Uses of triglyceride and phospholipid compositions

Abstract

Provided herein are compositions comprising triglycerides and phospholipids and methods of using them for various medical applications, for example, as an imaging agent, a coupling agent (e.g., for invasive ultrasound imaging), a contrast agent, a light-dispersive agent, a delivery agent, and / or a lubricant. The compositions and methods disclosure herein may be used for diagnosing and / or treating various diseases such as cancer.

Description

USES OF TRIGLYCERIDE AND PHOSPHOLIPID COMPOSITIONSCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority to U.S. Application No. 63 / 514,974, filed on July 21 , 2023, which is incorporated by reference herein in its entirety for all purposes.BACKGROUND

[0002] There is a need in the art for safe and stable compositions that can be used in various in vivo medical applications, for example, as an imaging agent, a coupling agent, a contrast agent, a light-dispersive agent, a delivery agent, and / or a lubricant. Such compositions may be used in methods of imaging and / or treating various diseases, such as cancer.

[0003] For example, ultrasound imaging is widely used in medical examination to obtain real-time visualization of tissue and is used in various clinical fields. To ensure proper contact between the transducer / ultrasound probe and the skin / tissue to be examined an ultrasound coupling agent, which is typically a gel or liquid, is used. The ultrasound coupling agent is used to avoid air pockets between the transducer / probe and tissue, and to facilitate a good acoustic coupling at the interface between the ultrasound transducer and the tissue to be imaged. Ultrasound imaging is often used in invasive procedures, such as during surgery or during an invasive diagnostic procedure. For example, ultrasound imaging may be used for imaging of tumors in brain surgery. In this case, ultrasound imaging may be used to locate the tumor and anatomical structures, as well as to identify residual tumor during surgery. Ultrasound imaging may also be used to make sure that the damaged tissue, such as a tumor, is completely removed, and that unnecessary resection of healthy tissue is avoided. However, in vivo applications of invasive ultrasound imaging are still challenging due to the lack of suitable compositions that reduce artifacts.

[0004] Ideally, high image quality should be sustained throughout the medical procedure in order to monitor the progress of that procedure (e.g. of surgery for tumor resection). However, surgery may cause image noise and thus lead to an inaccurate display of the relevant part of the anatomy in the ultrasound images.

[0005] The term artifact is used in medical imaging to describe any part of the image that does not accurately represent the anatomy of the subject being investigated. It is well known that ultrasound imaging is prone to several different types of artifacts which maylead to adverse outcomes for the subject. For example, when using ultrasound in brain tumor surgery, the presence of artifacts may interfere with the surgeon’s interpretation of the images.

[0006] One artifact commonly encountered when using ultrasound for the invasive imaging of the body is an enhanced (anomalously bright) signal appearing below a fluid- filled cavity. The brightness enhancement of tissue located beneath fluid filled spaces has been observed in ultrasound imaging of cysts, blood vessels or other fluid filled spaces. Because of this apparent enhancement of the reflected echo, this frequently encountered image artifact is often referred to as a brightness artifact (sometimes also referred to as an “enhancement artefact”, “or “bright rim effect”). This type of artefact is a result of the difference in attenuation of acoustic waves by the fluid in the cavity and by the surrounding biological tissue.

[0007] For example, during brain tumor surgery a resection cavity is typically filled with saline water as an ultrasound coupling agent before ultrasound imaging, to enable propagation of sound and to prevent air artifacts. The difference in attenuation between brain and isotonic saline may cause artifacts that degrade the ultrasound images, potentially affecting surgical accuracy (e.g. resection grades and safety). The acoustic waves travel through the cavity filled with saline water before reaching the biological tissue. The attenuation of acoustic waves in saline water is very low compared to the attenuation of acoustic waves in biological tissue. The attenuation coefficient (a) for water is 0.0022 dB / (MHz cm) while for e.g. brain it is reportedly measured by various groups to be within approximately 0.4 - 1.0 (Duck FA, In Physical properties of tissue, Academic Press, LTD).

[0008] A major component of the attenuation of sound in tissue is caused by absorption, in which part of the acoustic energy is converted to heat. Scattering also contributes to the attenuation of acoustic waves. These combined effects cause the acoustic waves propagating in saline water to have higher amplitudes than acoustic waves propagating an equal distance in biological tissue. The total attenuation is estimated by the equation:

[0009] Attenuation [dB] = a [dB / (MHz*cm)] * I [cm] * f [MHz] Wherein a is the attenuation coefficient of the medium;I is the medium length (or propagating distance); and f is the frequency of the transmitted ultrasound wave.

[0010] For example, selecting a frequency of 8 MHz and a propagating distance of 10 cm, and assuming an attenuation coefficient of 0.8 for brain tissue this will result in an attenuation of 0.18 dB for ultrasound propagating in water and an attenuation of 64 dB for waves propagating in brain tissue.

[0011] This difference in attenuation can generate noise in the ultrasound images e.g. when ultrasound is used intraoperatively in brain tumor surgery. The ultrasound waves transmitted through the water-filled resection cavity will have a large amplitude when arriving at the cavity walls, due to the low attenuation of water. Thus, the sound waves reflected from the cavity wall will also have relatively high amplitudes. Further, the sound waves propagating further into the tissue will have relatively high amplitudes. In comparison to sound waves that have propagated entirely in brain tissue, with a relatively high attenuation coefficient, these transmitted and reflected waves that have travelled through saline will be less damped and thereby have significantly higher amplitudes. The fluctuations in intensity observed in the ultrasound images make it very difficult to interpret the images. The bright rim observed at the cavity wall may mask the presence of residual tumor, or the high intensity regions extending from the cavity wall may be interpreted as hyperechoic tumor when it is actually normal brain tissue.

[0012] The presence of the hyperechoic rim in ultrasound imaging of a resection cavity is described in several papers regarding the use of ultrasound in brain tumor surgery. This enhanced signal appearing below the fluid filled cavity in the ultrasound images is regarded as one of the major imaging artifacts encountered in peroperative ultrasound imaging.

[0013] There is a need in the art for new compositions that are safe, stable, and do not lead to imaging artifacts.

[0014] Many in vivo medical applications other than ultrasound are also in need of better compositions. For example, photodynamic therapy (PDT), a promising cancer therapy, is limited for the treatment of cancer because light can only penetrate tissue from 0.7 to 1 cm. Transmission is limited because of light-tissue interactions, including absorption, scattering, refraction, and reflection. There is a need for compositions which improve light transmission in PDT.

[0015] There is also a need in the art for new contrast agents and solutions for suspending contrast agents. Contrast agents allow doctors to distinguish and identify abnormalities within tissue. Without a contrast agent, diagnostic images may be blurry and indistinct, preventing effective treatment.

[0016] The present disclosure provides such compositions, methods of using such compositions in various medical applications, and more.SUMMARY OF THE INVENTION

[0017] In one aspect, the disclosure provides compositions comprising: (a) at least one triglyceride; (b) at least one phospholipid; (c) water; (d) pH buffer; and (e) a humectant. In one aspect, the disclosure provides compositions comprising: (a) at least one triglyceride; (b) a lecithin comprising at least one phospholipid; (c) water; (d) pH buffer; and (e) a humectant. In embodiments, the composition comprises no more than 5% w / v, no more than 2% w / v, no more than 1 % w / v, no more than 0.5% w / v, no more than 0.2% w / v, or no more than 0.1% w / v, of substance(s) other than the (a)-(e). In embodiments, the composition consists essentially of all of the (a)-(e). In embodiments, the composition consists of all of the (a)-(e).

[0018] In one aspect, the disclosure provides compositions comprising (a) at least one triglyceride; (b) at least one phospholipid; (c) water; (d) pH buffer; (e) a humectant; and (f) a diagnostic agent, a therapeutic agent, or any combination thereof. In one aspect, the disclosure provides compositions comprising: (a) at least one triglyceride; (b) a lecithin comprising at least one phospholipid; (c) water; (d) pH buffer; (e) a humectant; and (f) a diagnostic agent, a therapeutic agent, or any combination thereof. In embodiments, the composition comprises no more than 5% w / v, no more than 2% w / v, no more than 1 % w / v, no more than 0.5% w / v, no more than 0.2% w / v, or no more than 0.1% w / v, of substance(s) other than the (a)-(f). In embodiments, the composition consists essentially of all of the (a)-(f). In embodiments, the composition consists of all of the (a)-(f).

[0019] In embodiments, the concentration of the at least one triglyceride is from about 5 % w / v to about 9 % w / v. In embodiments, the concentration of the at least one triglyceride is from about 6 % w / v to about 8 % w / v. In embodiments, the concentration of the at least one triglyceride is about 7 % w / v.

[0020] In embodiments, the concentration of the at least one triglyceride is from about 0.05 % w / v to about 1 % w / v, or from about 0.1 % w / v to about 0.5 % w / v. In embodiments, the concentration of the at least one triglyceride is about 0.1 % w / v, about 0.2 % w / v, or about 0.5 % w / v.

[0021] In embodiments, the at least one triglyceride is from one or more of olive oil, coconut oil, palm oil, canola oil, soybean oil, sunflower oil, corn oil, peanut oil, safflower oil, cottonseed oil, sesame oil, flaxseed oil, walnut oil, avocado oil, rice bran oil,grapeseed oil, almond oil, hazelnut oil, macadamia nut oil, pumpkin seed oil, hemp seed oil, camelina oil, mustard oil, pistachio oil, pecan oil, poppy seed oil, black seed oil, apricot kernel oil, cherry kernel oil, peach kernel oil, tamanu oil, borage oil, evening primrose oil, sea buckthorn oil, peri Ila oil, moringa oil, neem oil, karanja oil, jojoba oil, tung oil, camellia oil, tea seed oil, babassu oil, murumuru oil, safflower oil, shea butter, cocoa butter, sal butter, kokum butter, mango butter, illipe butter, or fish oil. In embodiments, the at least one triglyceride is from soybean oil. In embodiments, the at least one triglyceride is selected from the group consisting of: tristearin, triolein, tripalmitin, triacetin, trilinolein, tricaprin, trilaurin, triarachidin, tridecanoin, trilinolenin, tricaprylin, tridecanoin, trimyristin, tricaprylin, trivalerate, tricaprate, trilinolenin, tridecanoate, triundecanoin, trinonanoin, and any combination thereof. In embodiments, the at least one triglyceride is selected from the group consisting of: linolenic-oleic-linolenic, linoleic-linoleic-linoleic, oleic- linoleic-oleic, linoleic-oleic-linoleic, linolenic-linoleic-linolenic, palmitic-oleic-linoleic, palmitic-linoleic-palmitic, stearic-oleic-linoleic, linoleic-linolenic-linoleic, linoleic-oleic- oleic, and any combination thereof. In embodiments, the at least one triglyceride comprises, consists essentially of, or consists of medium chain triglycerides.

[0022] In embodiments, the concentration of the at least one phospholipid is up to about 1.2 % w / v. In embodiments, the concentration of the at least one phospholipid is from about 0.1 % w / v to about 1.2 % w / v. In embodiments, the concentration of the at least one phospholipid is from about 0.2 % w / v to about 1.2 % w / v. In embodiments, the concentration of the at least one phospholipid is from about 0.4 % w / v to about 1 .2 % w / v. In embodiments, the concentration of the at least one phospholipid is from about 0.42 % w / v to about 0.84 % w / v. In embodiments, the concentration of the at least one phospholipid is from about 3.2 g / L to about 5.2 g / L. In embodiments, the concentration of the at least one phospholipid is about 0.42 % w / v (about 4.2 g / L). In embodiments, the concentration of the at least one phospholipid is from about 7.4 g / L to about 9.4 g / L. In embodiments, the concentration of the at least one phospholipid is about 0.84 % w / v (about 8.4 g / L).

[0023] In embodiments, the composition comprises lecithin comprising the at least one phospholipid. In embodiments, the lecithin comprises from about 20 % to about 90 % the at least one phospholipid by weight. In embodiments, the lecithin comprises from about 60 % to about 70 % the at least one phospholipid by weight. In embodiments, the lecithin is from one or more of soybeans, sunflower seeds, rapeseeds, egg yolks, wheat germ, corn, peanuts, sesame seeds, rice bran, flaxseeds, pumpkin seeds, cashews, almonds, hazelnuts, pistachios, walnuts, pecans, macadamia nuts, brazil nuts, chia seeds, hempseeds, poppy seeds, quinoa, oats, barley, rye, millet, sorghum, buckwheat, amaranth, avocado, olives, cocoa beans, coconut, milk, butter, cheese, yogurt, beef liver, chicken liver, fish roe, mackerel, salmon, sardines, herring, anchovies, trout, halibut, tuna, and egg whites. In embodiments, the lecithin is egg yolk lecithin.

[0024] In embodiments, the composition comprises up to about 1.2 % w / v the lecithin. In embodiments, the composition comprises from about 0.1 % w / v to about 1.2 % w / v the lecithin. In embodiments, the composition comprises from about 0.4 % w / v to about 1.2 % w / v the lecithin. In embodiments, the composition comprises about 0.42 % w / v or about 0.84 % w / v the lecithin.

[0025] In embodiments, the lecithin comprises phosphatidylcholine. In embodiments, the lecithin comprises from about 10 % to about 75 % phosphatidylcholine by weight. In embodiments, the lecithin comprises from about 20 % to about 70 % phosphatidylcholine by weight. In embodiments, the lecithin comprises from about 60 % to about 75 % phosphatidylcholine by weight.

[0026] In embodiments, the at least one phospholipid comprises phosphatidylcholine. In embodiments, the at least one phospholipid comprises from about 10 % to about 70 % phosphatidylcholine by weight. In embodiments, the at least one phospholipid comprises from about 20 % to about 70 % phosphatidylcholine by weight. In embodiments, the at least one phospholipid comprises from about 60 % to about 75 % phosphatidylcholine by weight.

[0027] In embodiments, the concentration of the at least one triglyceride is from about 60.0 g / L to about 80.0 g / L, and / or wherein the concentration of the at least one phospholipid is from about 3.2 g / L to about 5.2 g / L. In embodiments, the concentration of the at least one triglyceride is from about 60.0 g / L to about 80.0 g / L, and / or wherein the concentration of the at least one phospholipid is from about 7.4 g / L to about 9.4 g / L.

[0028] In embodiments, the humectant is glycerol. In embodiments, the concentration of the humectant is from about 10 g / L to about 35 g / L. In embodiments, the concentration of the humectant is from about 14 g / L to about 26 g / L. In embodiments, the concentration of the humectant is about 16 g / L. In embodiments, the concentration of the humectant is from about 21 g / L to about 26 g / L. In embodiments, the concentration of the humectant is about 23.7 g / L.

[0029] In embodiments, the concentration of the at least one phospholipid or the lecithin, and the concentration of the glycerol, is selected from one of the formulations in Table 3.

[0030] In embodiments, the ratio of the at least one triglyceride to the at least one phospholipid or the lecithin is from about 6.5:1 to about 30:1 by weight. In embodiments,the ratio of the at least one triglyceride to the at least one phospholipid or the lecithin is from about 20:1 to about 30:1 by weight. In embodiments, the ratio of the at least one triglyceride to the at least one phospholipid or the lecithin is from about 13: 1 to about 20: 1 by weight. In embodiments, the ratio of the at least one triglyceride to the at least one phospholipid or the lecithin is about 16.7:1 by weight. In embodiments, the ratio of the at least one triglyceride to the at least one phospholipid or the lecithin is from about 6.5: 1 to about 10:1 by weight. In embodiments, the ratio of the at least one triglyceride to the at least one phospholipid or the lecithin is about 8.3:1 by weight.

[0031] In embodiments, the concentration of the at least one triglyceride is from about 0.05 % w / v to about 1 % w / v, or from about 0.1 % w / v to about 0.5 % w / v, wherein the ratio of the at least one triglyceride to the at least one phospholipid or the lecithin is from about 6.5: 1 to about 20: 1 by weight, and wherein the pH of the composition is from about 6.5 to about 8.5. In embodiments, the pH of the composition is about 7.0. In embodiments, the composition has an osmolality of less than 100 mOsm / kg, less than 90 mOsm / kg, less than 80 mOsm / kg, less than 70 mOsm / kg, less than 60 mOsm / kg, less than 50 mOsm / kg, less than 40 mOsm / kg, less than 30 mOsm / kg, less than 20 mOsm / kg, or less than 10 mOsm / kg, but greater than 0 mOsm / kg. In embodiments, the composition has an osmolality of less than 10 mOsm / kg, less than 9 mOsm / kg, less than 8 mOsm / kg, less than 7 mOsm / kg, less than 6 mOsm / kg, less than 5 mOsm / kg, less than 4 mOsm / kg, less than 3 mOsm / kg, less than 2 mOsm / kg, or less than 1 mOsm / kg, but greater than 0 mOsm / kg.

[0032] In embodiments, the concentration of the at least one triglyceride is from about 0.05 % w / v to about 1 % w / v, or from about 0.1 % w / v to about 0.5 % w / v, wherein the ratio of the at least one triglyceride to the at least one phospholipid or the lecithin is from about 6.5:1 to about 20:1 by weight, wherein the concentration of glycerol is about 25% to about 30%. In embodiments, the composition has an osmolality of from about 270 mOsm / kg to about 330 mOsm / kg, from about 284 mOsm / kg to about 296 mOsm / kg, from about 290 mOsm / kg to about 311 mOsm / kg, or from about 290 mOsm / kg to about 305 mOsm / kg. In embodiments, the pH of the composition is about 7.0.

[0033] In embodiments, the composition comprises less than 0.2 % w / v, less than 0.1 % w / v, less than 0.05 % w / v, less than 0.02 % w / v, or less than 0.01 % w / v, sodium chloride. In embodiments, the composition does not contain sodium chloride. In embodiments, the composition comprises less than 0.2 % w / v, less than 0.1 % w / v, less than 0.05 % w / v, less than 0.02 % w / v, or less than 0.01 % w / v, salt. In embodiments, the composition does not contain any salt.

[0034] In embodiments, the composition comprises less than 0.2 % w / v, less than 0.1 % w / v, less than 0.05 % w / v, less than 0.02 % w / v, or less than 0.01 % w / v, polysorbate(s). In embodiments, the composition does not contain polysorbate 80 (PS80). In embodiments, the composition does not contain any polysorbate.

[0035] In embodiments, the composition comprises less than 0.2 % w / v, less than 0.1 % w / v, less than 0.05 % w / v, less than 0.02 % w / v, or less than 0.01 % w / v, stabilizer(s). In embodiments, the composition does not contain a stabilizer.

[0036] In embodiments, the pH of the composition is 9-12, or 10-11. In embodiments, the composition has not been sterilized by gamma irradiation.

[0037] In embodiments, the pH of the composition is from about 6.5 to about 8.5. In embodiments, the pH of the composition is from about 6.9 to about 7.6. In embodiments, the pH of the composition is from about 6.9 to about 7.5. In embodiments, the pH of the composition is about 7.3. In embodiments, the pH of the composition is about 7.5. In embodiments, the pH of the composition is about 6.9.

[0038] In embodiments, the pH buffer is or comprises NaOH.

[0039] In embodiments, the pH of the composition is measured after sterilization by gamma irradiation and storage for at least 5 days.

[0040] In embodiments, the composition is sterilized by gamma irradiation.

[0041] In embodiments, the composition is an ultrasound coupling agent. In embodiments, the composition is a contrast agent. In embodiments, the composition is an aqueous composition. In embodiments, the composition is a lubricant.

[0042] In embodiments, the composition has an attenuation coefficient of from about 0.002 dB / (MHz*cm) to about 1.0 dB / (MHz*cm). In embodiments, the composition has an attenuation coefficient from about 0.05 dB / (MHz*cm) to about 15 dB / (MHz*cm). In embodiments, the composition has an attenuation coefficient of from about 3 dB / (MHz*cm) to about 15 dB / (MHz*cm). In embodiments, the composition has an attenuation coefficient from about 0.05 dB / (MHz*cm) to about 1.8 dB / (MHz*cm). In embodiments, the composition has an attenuation coefficient of from about 0.5 dB / (MHz*cm) to about 1.5 dB / (MHz*cm). In embodiments, the composition has an attenuation coefficient of from about 0.1 dB / (MHz*cm) to about 1.5 dB / (MHz*cm). In embodiments, the composition has an attenuation coefficient of from about 0.1 dB / (MHz*cm) to about 0.5 dB / (MHz*cm). In embodiments, the composition has an attenuation coefficient of from about 0.15 dB / (MHz*cm) to about 0.60 dB / (MHz*cm).

[0043] In embodiments, the composition has an attenuation coefficient that is substantially similar to an attenuation coefficient of a tissue or organ selected from abone, brain, lung, liver, kidney, heart, cerebrospinal fluid, a soft tissue, a bladder, and a colon. In embodiments, the tissue or organ is of human origin.

[0044] In embodiments, the composition has an osmolality of from about 270 mOsm / kg to about 330 mOsm / kg. In embodiments, the composition has an osmolality of from about284 mOsm / kg to about 296 mOsm / kg. In embodiments, the composition has an osmolality of from about 290 mOsm / kg to about 311 mOsm / kg. In embodiments, the composition has an osmolality of from about 290 mOsm / kg to about 305 mOsm / kg.

[0045] In embodiments, the composition has a volume mean weighted droplet size of from about 0.2 pm to about 0.55 pm. In embodiments, the composition has a volume mean weighted droplet size of from about 0.26 pm to about 0.50 pm. In embodiments, the composition has a volume mean weighted droplet size of from about 228 nm to about 342 nm. In embodiments, the composition has a volume mean weighted droplet size of about 258 nm.

[0046] In embodiments, the composition forms oil droplets, and wherein 100 % of the oil droplets have a diameter that is less than 0.84 pm. In embodiments, the composition forms oil droplets, and wherein 100 % of the oil droplets have a diameter that is less than 0.96 pm. In embodiments, the composition forms oil droplets, and wherein 100 % of the oil droplets have a diameter that is less than 1.91 pm. In embodiments, the composition forms oil droplets, and wherein substantially none of the droplets comprise a diameter of greater than 5000 nm.

[0047] In embodiments, the composition forms oil droplets, and wherein the oil droplets have an average size of from 200 nm to about 750 nm. In embodiments, the composition forms oil droplets, and wherein the oil droplets have an average size of from 250 nm to about 500 nm. In embodiments, the composition has an average droplet size of about285 nm ±20%. In embodiments, the average droplet size is measured by dynamic light scattering.

[0048] In embodiments, the diagnostic agent comprised within the composition is a contrast agent. In embodiments, the contrast agent is near infrared (IR) fluorophore. In embodiments, the near IR fluorophore is indocyanine green.

[0049] In embodiments, the therapeutic agent within the composition comprises an antibiotic.

[0050] In embodiments, the shelf life of the composition is at least about 10 hours, at least about 16 hours, at least about 24 hours, at least about 2 days, at least about 3 days, at least about 4 days, at least about 5 days, at least about 7 days, at least about 2 weeks, at least about 3 weeks, at least about 4 weeks, at least about 2 months, at least about 3months, at least about 4 months, at least about 6 months, at least about 9 months, at least about 1 years, at least about 2 years, at least about 3 years, at least about 4 years, at least about 5 years, or at least about 6 years, at room temperature. In embodiments, the shelf life of the composition is from about six months to about five years, from about 1 year to about 5 years, from about 2 years to about 5 years, from about 3 years to about 5 years, from about 6 months to about 4 years, from about 6 months to about 3 years, from about 6 months to about 2 years, from about six months to about one year, from about 1 year to about 4 years, from about 1 year to about 3 years, from about 1 year to about 2 years, or from about 2 years to about 4 years, at room temperature.

[0051] In one aspect, the disclosure provides methods of preparing the composition of the disclosure, comprising mixing components (a) - (e) or (a) - (f).

[0052] In one aspect, the disclosure provides imaging methods comprising administering the composition of the disclosure to a subject in need thereof, and performing imaging. In embodiments, the composition is administered into a wound, an organ, a tumor, a blood vessel, an area of blood circulation, or a cavity inside the subject.

[0053] In one aspect, the disclosure provides methods of obtaining an image of a wound, organ, tumor, blood vessel, or cavity, comprising: i) contacting the wound, organ, tumor, blood vessel, or cavity with a composition of the disclosure; ii) obtaining the image with an instrument.

[0054] In embodiments, the imaging is invasive ultrasound imaging. In embodiments, the imaging is Doppler based flow imaging. In embodiments, the imaging is laser speckle imaging. In embodiments, the imaging is optical coherence tomography, photoacoustic imaging (PAI), computed tomography (CT), magnetic resonance imaging (MRI), or echocardiography. In embodiments, the imaging is fluorescence imaging, radioimaging, positron emission tomography (PET), or magnetic particle imaging (MPI).

[0055] In one aspect, the disclosure provides methods of performing a surgery for a subject in need thereof, comprising administering the composition of the disclosure to a wound, organ, tumor, blood vessel, area of blood circulation, or cavity of the subject to obtain an image, and performing the surgery based on the image.

[0056] In one aspect, the disclosure provides methods of resecting a tumor, comprising administering the composition of the disclosure to a tissue proximal to the tumor, obtaining an ultrasound image of the tumor and the proximal tissue, identifying the tumor, and resecting the tumor.

[0057] In embodiments, the tumor is in or proximal to a bladder, uterus, cervix, colon, or spine.

[0058] In embodiments, the composition is contained in a balloon catheter.

[0059] In one aspect, the disclosure provides methods of performing a surgery for a subject in need thereof, comprising contacting an instrument used for the surgery with the composition of the disclosure and inserting the instrument into a wound, an organ, a tumor, a blood vessel, or a cavity inside the subject.

[0060] In one aspect, the disclosure provides methods of performing a surgery for a subject in need thereof, comprising administering the composition of the disclosure into a wound, organ, tumor, blood vessel, or cavity inside the subject, and inserting an instrument used for the surgery into the wound, organ, tumor, blood vessel, or cavity.

[0061] In embodiments, the surgery is a brain surgery or a neurosurgery.

[0062] In one aspect, the disclosure provides methods of placing an instrument inside a subject in need thereof, comprising, sequentially or concurrently, contacting a site on the subject with the composition of the disclosure and inserting the instrument into the subject.

[0063] In embodiments, the instrument is for preventing or treating a disease.

[0064] In embodiments, the instrument is a catheter. In embodiments, the catheter is a subdural pressure catheter, a drainage catheter, a cerebral flow catheter, a microdialysis catheter, or a brain tissue oxygen catheter.

[0065] In embodiments, the instrument is an intracranial pressure sensor. In embodiments, the instrument is an implantable brain-computer interface (BCI).

[0066] In embodiments, the composition acts as a lubricant for the instrument.

[0067] In one aspect, the disclosure provides methods of delivering a diagnostic or therapeutic agent to a subject in need thereof, comprising administering the composition of the disclosure, wherein the composition comprises the diagnostic or therapeutic agent. In embodiments, the method is for treating a disease, and wherein the agent comprises the therapeutic agent.

[0068] In one aspect, the disclosure provides methods of delivering a diagnostic or therapeutic agent to a subject in need thereof, comprising administering the composition of the disclosure, and the agent. In embodiments, the composition and the agent are administered sequentially.

[0069] In embodiments, the therapeutic agent comprises a photosensitizing agent. In embodiments, the method comprises exposing the photosensitizing agent to light.

[0070] In one aspect, the disclosure provides methods of treating a disease in a subject in need thereof using a focused ultrasound therapy, comprising administering thecomposition of the disclosure to the subject and performing the focused ultrasound therapy.

[0071] In one aspect, the disclosure provides methods of treating a disease in a subject in need thereof, comprising administering the composition of the disclosure to the subject.

[0072] In embodiments, the composition comprises a therapeutic agent.

[0073] In embodiments, the method comprises treating the subject with a photodynamic therapy after administering the composition.

[0074] In embodiments, the method comprises diluting the composition with water and glycerol to obtain a low triglyceride composition comprising about 0.005% w / v to about 0.5% w / v the triglyceride. In embodiments, the low triglyceride composition has an osmolality of from about 270 mOsm / kg to about 330 mOsm / kg, from about 284 mOsm / kg to about 296 mOsm / kg, from about 290 mOsm / kg to about 311 mOsm / kg, or from about 290 mOsm / kg to about 305 mOsm / kg.

[0075] In embodiments, the composition is a light-dispersing agent.

[0076] In embodiments, the therapeutic agent comprises a photosensitizing agent.

[0077] In one aspect, the disclosure provides methods of treating a disease, comprising: i) contacting a wound, organ, tumor, blood vessel, area of blood circulation or cavity that contains tissue of the disease with the composition of the disclosure; ii) obtaining an image of the wound, organ, tumor, blood vessel, area of blood circulation, or cavity; and iii) treating the disease or removing a disease tissue based on the image. In embodiments, the image is an ultrasound image.

[0078] In embodiments, the composition comprises a contrast agent that enables obtaining the image. In embodiments, the contrast agent is a near infrared (IR) fluorophore. In embodiments, the near IR fluorophore is indocyanine green.

[0079] In embodiments, the composition comprises a fluorophore.

[0080] In embodiments, the image is for identifying a target tissue or a disease tissue inside the subject. In embodiments, the disease tissue is a residual tumor.

[0081] In embodiments, the method further comprises removing and / or treating an abnormal or diseased tissue. In embodiments, the method comprises removing the abnormal or diseased tissue via surgery. In embodiments, the method comprising treating the abnormal or diseased tissue via a chemotherapy, a targeted therapy, a photodynamic therapy, or a radiotherapy.

[0082] In embodiments, the disease is cancer. In embodiments, the diseased tissue comprises a tumor tissue.

[0083] In embodiments, the tumor is a brain tumor. In embodiments, the tumor is glioma, glioblastoma, or neuroblastoma.

[0084] In embodiments, the method comprises administering one or more methods of cancer treatment. In embodiments, the one or more methods are selected from the group consisting of chemotherapy, immunotherapy, alternating electric tumor treating fields, laser induced interstitial thermotherapy (LITT), magnetic hyperthermia therapy (MHT), focused ultrasound, radiofrequency microwaves, photodynamic therapy (PDT), intraoperative magnetic resonance imaging, fluorescence guided resection, surgical resection, and magnetic resonance imaging. In embodiments, treating the disease comprises exposing the cancer cells to light.

[0085] In embodiments, the method comprises conducting an invasive procedure before administration of the composition to allow access of the wound, the organ, the blood vessel, or the cavity to the composition and / or instrument.

[0086] In embodiments, the cavity is selected from any one of oral cavity, nasal cavity, orbital cavity, thoracic cavity, pericardial cavity, pleural cavities, abdominal cavity, pelvic cavity, cranial cavity, spinal cavity, articular cavities, synovial cavities, buccal cavity, cranial fossae, mandibular fossa, maxillary sinus, frontal sinus, ethmoidal sinus, sphenoidal sinus, mastoid air cells, auditory canal, middle ear cavity, tympanic cavity, vestibular system, cochlear duct, olfactory epithelium, oral vestibule, palatine tonsil, pharyngeal tonsil, lingual tonsil, sinus venosus, infundibulum , alveolar sacs, bronchioles , laryngeal cavity, tracheal cavity, gastric pits, crypts of lieberkuhn, gallbladder fossa, renal sinus, ureteral opening, bladder trigone, ovarian follicles, testicular lobules, vaginal fornix, anal canal, vertebral foramen, intervertebral foramina, foramen magnum, and jugular foramen.

[0087] In embodiments, the organ is selected from any one of brain, heart, lungs, liver, kidneys, stomach, small intestine, large intestine, pancreas, spleen, gallbladder, colon, spine, bladder, skin, eyes, ears, nose, mouth, tongue, throat, trachea, breast, esophagus, diaphragm, adrenal gland, thyroid, parathyroid gland, pituitary gland, pineal gland, hypothalamus, ovaries, testes, uterus, prostate, penis, vagina, cervix, urethra, rectum, anus, skeletal muscles, smooth muscle, cardiac muscle, bone marrow, bones, blood vessel, lymph node, lymphatic vessel, tonsils, appendix, adipose tissue, nerves, and connective tissue. In embodiments, the organ is a brain, kidney, liver, pancreas, ovary, breast, bladder, uterus, cervix, or colon. In embodiments, the organ is a brain.

[0088] In embodiments, the organ or the cavity comprises a tumor.

[0089] In embodiments, the method comprises resecting the tumor.

[0090] In embodiments, the method reduces an artifact of ultrasound imaging compared to a control method that does not administer the composition. In embodiments, the artifact is or comprises a brightening artifact. In embodiments, the control method uses saline water instead of the composition as an ultrasound coupling agent.

[0091] In embodiments, the composition is contained in a balloon catheter. In embodiments, the cavity is created by the balloon catheter.

[0092] In embodiments, the subject is a human.

[0093] In embodiments, provided herein are containers comprising the composition of the disclosure.

[0094] In embodiments, provided herein are kits comprising the composition of the disclosure and a container. In embodiments, the container comprises the composition. In embodiments, the kit contains a bag spike. In embodiments, the kit comprises a syringe. In embodiments, the kit comprises a filter.

[0095] In embodiments, the container is a syringe. In embodiments, the container is glass. In embodiments, the container is stainless steel. In embodiments, the container is a bag. In embodiments, the container lacks one or more of dyes, preservatives, rubber, butyl, silica, polyvinyl chloride (PVC), and di(2-ethylhexyl)phthalate (DEHP).

[0096] In embodiments, the kit further comprises a bag spike. In embodiments, the kit further comprises a filter. In embodiments, the filter has a pore size of about 1.2 pm.

[0097] Provided herein is a composition consisting of: a) from about 60.0 to about 80.0 g / L of at least one triglyceride; b) from about 3.2 to about 5.2 g / L of at least one phospholipid; c) water; d) a pH buffer; and e) glycerol; wherein the composition has an attenuation constant from about 0.15 dB / (MHz*cm) to about 0.60 dB / (MHz*cm) or from about 0.002 to about 1.0 dB / (MHz*cm).

[0098] Provided here in a composition consisting of: a) at least one triglyceride; b) at least one phospholipid; c) water, d) pH buffer; and e) glycerol; wherein the composition has an attenuation constant from about 0.15 dB / (MHz*cm) to about 0.60 dB / (MHz*cm) or from about 0.002 to about 1.0 dB / (MHz*cm); and wherein the ratio of the at least one triglyceride to the at least one phospholipid is from about 13:1 to about 20:1 by weight.

[0099] Provided herein is a composition consisting of: a) at least one triglyceride, wherein the at least one triglyceride is present at about 7 % w / v; b) at least one phospholipid, wherein the at least one phospholipid is present at about 0.4 % w / v; c) water, wherein the water is present at about 92 % w / v; d) pH buffer; and e) glycerol.

[0100] Provided herein is a composition comprising: a) from about 60.0 g / L to about 80.0 g / L of at least one triglyceride; b) from about 3.2 g / L to 5.2 g / L of at least onephospholipid, wherein the composition does not include a stabilizer and does not include sodium chloride, and wherein the composition has an attenuation constant from about 0.15 dB / (MHz*cm) to about 0.60 dB / (MHz*cm) or from about 0.002 to about 1.0 dB / (MHz*cm).

[0101] Provided herein is a composition comprising: a) at least one triglyceride; and b) at least one phospholipid; wherein the composition does not include a stabilizer and does not include sodium chloride; wherein the composition has an attenuation constant from about 0.15 dB / (MHz*cm) to about 0.60 dB / (MHz*cm) or from about 0.002 to about 1.0 dB / (MHz*cm); and wherein the ratio of the at least one triglyceride to the at least one phospholipid is from about 13:1 to about 20:1 by weight.

[0102] Provided herein is a composition comprising: a) at least one triglyceride, wherein the at least one triglyceride is present at about 7 % w / v; and b) at least one phospholipid, wherein the at least one phospholipid is present at about 0.4 % w / v; wherein the composition does not include a stabilizer and does not include sodium chloride; and wherein the composition has an attenuation constant from about 0.15 dB / (MHz*cm) to about 0.60 dB / (MHz*cm) or from about 0.002 to about 1 .0 dB / (MHz*cm).

[0103] In embodiments, the compositions provided herein comprise about 70 g / L of at least one triglyceride.

[0104] In embodiments, the at least one triglyceride of the compositions provided herein is selected from one or more of soybean oil, olive oil, or fish oil. In embodiments, the at least one triglyceride of the compositions provided herein is soybean oil.

[0105] In embodiments, the compositions provided herein comprise at least one humectant. In embodiments, the at least one humectant is glycerol.

[0106] In embodiments, the compositions provided herein do not comprise PS80.

[0107] In embodiments, the compositions provided herein have a pH from about 6.5 to about 8.5. In embodiments, the compositions provided herein have a pH of about 7.3.

[0108] In embodiments, the compositions provided herein have an osmolality from 270- 330 mOsm / L.

[0109] In embodiments, the compositions provided herein have an average droplet size of about 285 nm ±20%, wherein the average droplet size is measured by dynamic light scattering.

[0110] In embodiments, the compositions provided herein have a shelf life of the composition is at least about 10 hours.

[0111] In embodiments, the ratio of the at least one triglyceride to the at least one phospholipid in the compositions provided herein is about 16.7:1 by weight.

[0112] In embodiments, provided herein is a method of obtaining an ultrasound image of an organ comprising i) contacting the organ with a composition provided herein; ii) obtaining an ultrasound image of the organ, wherein the composition has an attenuation constant from about 0.15 dB / (MHz*cm) to about 0.60 dB / (MHz*cm) or from about 0.002 to about 1.0 dB / (MHz*cm).

[0113] In embodiments, the organ is a brain, breast, colon, or heart. In embodiments, the organ is a brain.

[0114] In embodiments, provided herein are compositions consisting of: (a) from about 60.0 g / L to about 80.0 g / L of at least one triglyceride; (b) from about 3.2 g / L to about 5.2 g / L of at least one phospholipid; (c) water; (d) pH buffer; and (e) glycerol. In embodiments, provided herein are compositions consisting of: (a) at least one triglyceride; (b) at least one phospholipid; (c) water, (d) pH buffer; and (e) glycerol; and wherein the ratio of the at least one triglyceride to the at least one phospholipid is from about 13:1 to about 20:1 by weight. In embodiments, provided herein are compositions consisting of: (a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) from about 0.2 % w / v to about 1 .2 % w / v of at least one phospholipid; (c) water; (d) pH buffer; and (e) glycerol. In embodiments, provided herein are compositions consisting of: (a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) at least one phospholipid, wherein the at least one phospholipid is present at about 0.42 % w / v; (c) water; (d) pH buffer; and (e) glycerol. In embodiments, provided herein are compositions consisting of: (a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) at least one phospholipid; (c) water; (d) pH buffer; and (e) glycerol. In embodiments, provided herein are compositions consisting of: (a) about 7 % w / v of a triglyceride; (b) about 4.2 g / L of a phospholipid; (c) about 23.7 g / L of glycerol; (d) water; and (e) a pH buffer. In embodiments, provided herein are compositions comprising: (a) from about 60.0 g / L to about 80.0 g / L of at least one triglyceride; (b) from about 3.2 g / L to about 5.2 g / L of at least one phospholipid; (c) water; (d) pH buffer; and (e) glycerol, wherein the composition does not include a stabilizer and does not include sodium chloride. In embodiments, provided herein are compositions comprising: (a) at least one triglyceride; (b) at least one phospholipid; (c) water, (d) pH buffer; and (e) glycerol; and wherein the ratio of the at least one triglyceride to the at least one phospholipid is from about 13:1 to about 20:1 by weight, wherein the composition does not include a stabilizer and does not include sodium chloride. In embodiments, provided herein are compositions comprising: (a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) from about 0.2 % w / v to about 1.2 % w / v of at least one phospholipid; (c) water; (d) pH buffer; and (e) glycerol,wherein the composition does not include a stabilizer and does not include sodium chloride. In embodiments, provided herein are compositions comprising: (a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) at least one phospholipid, wherein the at least one phospholipid is present at about 0.42 % w / v; (c) water; (d) pH buffer; and (e) glycerol, wherein the composition does not include a stabilizer and does not include sodium chloride. In embodiments, provided herein are compositions comprising: (a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) at least one phospholipid; (c) water; (d) pH buffer; and (e) glycerol, wherein the composition does not include a stabilizer and does not include sodium chloride. In embodiments, provided herein are compositions comprising: (a) about 7 % w / v of a triglyceride; (b) about 4.2 g / L of a phospholipid; (c) about 23.7 g / L of glycerol; (d) water; and (e) a pH buffer, wherein the composition does not include a stabilizer and does not include sodium chloride. In embodiments, provided herein are compositions consisting essentially of: (a) from about 60.0 g / L to about 80.0 g / L of at least one triglyceride; (b) from about 3.2 g / L to about 5.2 g / L of at least one phospholipid; (c) water; (d) pH buffer; and (e) glycerol. In embodiments, provided herein are compositions consisting essentially of: (a) at least one triglyceride; (b) at least one phospholipid; (c) water, (d) pH buffer; and (e) glycerol; and wherein the ratio of the at least one triglyceride to the at least one phospholipid is from about 13:1 to about 20:1 by weight. In embodiments, provided herein are compositions consisting essentially of: (a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) from about 0.2 % w / v to about 1.2 % w / v of at least one phospholipid; (c) water; (d) pH buffer; and (e) glycerol. In embodiments, provided herein are compositions consisting essentially of: (a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) at least one phospholipid, wherein the at least one phospholipid is present at about 0.42 % w / v; (c) water; (d) pH buffer; and (e) glycerol. In embodiments, provided herein are compositions consisting essentially of: (a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) at least one phospholipid; (c) water; (d) pH buffer; and (e) glycerol. In embodiments, provided herein are compositions consisting essentially of: (a) about 7 % w / v of a triglyceride; (b) about 4.2 g / L of a phospholipid; (c) about 23.7 g / L of glycerol; (d) water; and (e) a pH buffer. In embodiments, provided herein are compositions comprising: (a) about 7 % w / v of a triglyceride; (b) about 4.2 g / L of at least one phospholipid; (c) about 23.7 g / L of glycerol; (d) water; and (e) a pH buffer. In embodiments, the stabilizer is polysorbate 80 (PS80).

[0115] In embodiments, provided herein are compositions consisting of: (a) from about 60.0 g / L to about 80.0 g / L of at least one triglyceride; (b) from about 3.2 g / L to about 5.2g / L of lecithin; (c) water; (d) pH buffer; and (e) glycerol. In embodiments, provided herein are compositions consisting of: (a) at least one triglyceride; (b) lecithin; (c) water, (d) pH buffer; and (e) glycerol; and wherein the ratio of the at least one triglyceride to the lecithin is from about 13:1 to about 20:1 by weight. In embodiments, provided herein are compositions consisting of: (a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) from about 0.2 % w / v to about 1.2 % w / v of lecithin; (c) water; (d) pH buffer; and (e) glycerol. In embodiments, provided herein are compositions consisting of: (a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) lecithin, wherein the lecithin is present at about 0.42 % w / v; (c) water; (d) pH buffer; and (e) glycerol. In embodiments, provided herein are compositions consisting of: (a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) lecithin; (c) water; (d) pH buffer; and (e) glycerol. In embodiments, provided herein are compositions consisting of: (a) about 7 % w / v of a triglyceride; (b) about 4.2 g / L of lecithin; (c) about 23.7 g / L of glycerol; (d) water; and (e) a pH buffer. In embodiments, provided herein are compositions comprising: (a) from about 60.0 g / L to about 80.0 g / L of at least one triglyceride; (b) from about 3.2 g / L to about 5.2 g / L of lecithin; (c) water; (d) pH buffer; and (e) glycerol, wherein the composition does not include a stabilizer and does not include sodium chloride. In embodiments, provided herein are compositions comprising: (a) at least one triglyceride; (b) lecithin; (c) water, (d) pH buffer; and (e) glycerol; and wherein the ratio of the at least one triglyceride to the lecithin is from about 13:1 to about 20:1 by weight, wherein the composition does not include a stabilizer and does not include sodium chloride. In embodiments, provided herein are compositions comprising: (a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) from about 0.2 % w / v to about 1.2 % w / v of lecithin; (c) water; (d) pH buffer; and (e) glycerol, wherein the composition does not include a stabilizer and does not include sodium chloride. In embodiments, provided herein are compositions comprising: (a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) lecithin, wherein the lecithin is present at about 0.42 % w / v; (c) water; (d) pH buffer; and (e) glycerol, wherein the composition does not include a stabilizer and does not include sodium chloride. In embodiments, provided herein are compositions comprising: (a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) lecithin; (c) water; (d) pH buffer; and (e) glycerol, wherein the composition does not include a stabilizer and does not include sodium chloride. In embodiments, provided herein are compositions comprising: (a) about 7 % w / v of a triglyceride; (b) about 4.2 g / L of lecithin; (c) about 23.7 g / L of glycerol; (d) water; and (e) a pH buffer, wherein the composition does not include a stabilizer and does not include sodium chloride. In embodiments, provided herein arecompositions consisting essentially of: (a) from about 60.0 g / L to about 80.0 g / L of at least one triglyceride; (b) from about 3.2 g / L to about 5.2 g / L of lecithin; (c) water; (d) pH buffer; and (e) glycerol. In embodiments, provided herein are compositions consisting essentially of: (a) at least one triglyceride; (b) lecithin; (c) water, (d) pH buffer; and (e) glycerol; and wherein the ratio of the at least one triglyceride to the lecithin is from about 13:1 to about 20:1 by weight. In embodiments, provided herein are compositions consisting essentially of: (a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) from about 0.2 % w / v to about 1.2 % w / v of lecithin; (c) water; (d) pH buffer; and (e) glycerol. In embodiments, provided herein are compositions consisting essentially of: (a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) lecithin, wherein the lecithin is present at about 0.42 % w / v; (c) water; (d) pH buffer; and (e) glycerol. In embodiments, provided herein are compositions consisting essentially of: (a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) lecithin; (c) water; (d) pH buffer; and (e) glycerol. In embodiments, provided herein are compositions consisting essentially of: (a) about 7 % w / v of a triglyceride; (b) about 4.2 g / L of lecithin; (c) about 23.7 g / L of glycerol; (d) water; and (e) a pH buffer. In embodiments, provided herein are compositions comprising: (a) about 7 % w / v of a triglyceride; (b) about 4.2 g / L of lecithin; (c) about 23.7 g / L of glycerol; (d) water; and (e) a pH buffer. In embodiments, the stabilizer is polysorbate 80 (PS80). In embodiments, the composition has an attenuation coefficient of from about 0.15 dB / (MHz*cm) to about 0.60 dB / (MHz*cm). In embodiments, the composition has an attenuation coefficient of from about 0.002 dB / (MHz*cm) to about 1.0 dB / (MHz*cm). In embodiments, the composition has an attenuation coefficient of from about 0.05 dB / (MHz*cm) to about 15 dB / (MHz*cm).

[0116] In embodiments, provided herein are methods of obtaining an ultrasound image of an organ or a cavity comprising i) contacting the organ or the cavity with a composition described herein; and ii) obtaining an ultra sound image of the organ or the cavity.

[0117] In embodiments, provided herein are methods of performing neurosurgery comprising contacting an instrument used for surgery with a composition described herein and inserting the instrument into a brain.BRIEF DESCRIPTION OF THE DRAWINGS

[0118] Figs. 1A-1G show ultrasound images of a brain tissue-mimicking phantom filled with saline (Fig. 1A), Formulation 2 (Fig. 1B), Formulation 3 (Fig. 1C), Formulation 4(Fig. 1D), Formulation 5 (Fig. 1 E), Formulation 6 (Fig. 1 F), and Formulation 7 (Fig. 1G). The components of each of Formulations 1-7 are provided in Example 2.

[0119] Figs. 2A-2B show ultrasound images of a cavity filled containing a tumor. The cavity is filled with saline (Fig. 2A) or Formulation 7 (Fig. 2B). The components of Formulation 7 are provided in Example 2.

[0120] Fig. 3 shows an exemplary kit of the disclosure containing a syringe, a bag spike, and a composition.DETAILED DESCRIPTIONA. Definitions

[0121] As used in this specification and the appended claims, the singular forms “a,” “an” and “the” include plural references unless the content clearly dictates otherwise.

[0122] As used in this specification, the term “and / or” is used in this disclosure to either “and” or “or” unless indicated otherwise.

[0123] As used herein, the term “ultrasound coupling agent” refers to a medium used to exclude air between the ultrasound probe and the tissue to be imaged. The main purpose of the ultrasound coupling agent is thus to provide acoustic coupling between the ultrasound transducer / probe and the tissue to be investigated. In embodiments, the ultrasound coupling agent described herein is in the form of a liquid or gel under standard conditions of temperature and pressure and / or at physiological temperatures and ambient pressure. Typically the ultrasound coupling agent is in the form of an emulsion.

[0124] The term “aqueous” as used herein refers to a solution or mixture comprising water as the solvent or continuous phase. This includes cases where an aqueous phase can diffuse freely within the confines of a free-standing three-dimensional structure such as a hydrogel or an emulsion-based hydrogel (e.g. an emulgel). The term does not exclude solvents other than water from being present in the solution / mixture, however typically water is the principal solvent present (e.g.. forming at least 50% by weight of the solvent present in the solution / mixture). In a preferred embodiment, the term “aqueous” refers to a solution or mixture comprising water as the solvent or continuous phase, and in which water forms at least 90% by weight of the solvent (or continuous phase) present in the solution / mixture. In one embodiment, water is the only solvent present in the solution / mixture (or continuous phase). Aqueous solutions or mixtures may contain salts such as sodium and / or potassium salts and may, for example be isotonic. Aqueous solutions or mixtures may be sterile, as appropriate.

[0125] As used herein, the term “invasive ultrasound imaging” refers to any method for imaging of a body, particularly the human body, which involves the detection of ultrasound and which involves the introduction of a device (such as the tip of an ultrasonic probe / transducer) into the body either through a body orifice or through an opening in the body other than a body orifice, such as a break or rupture in the skin. The term “body orifice” means any natural opening in the body, as well as the external surface of the eyeball, or any permanent artificial opening, such as a stoma. Invasive ultrasound imaging thus includes both the imaging of a body via the introduction of a device through a natural opening in the body and the imaging of a body via the introduction of a device through an artificial opening, such an incision made during surgery or as part of an invasive diagnostic procedure.

[0126] As used herein, the term “ultrasound” refers to sound waves with frequencies higher than the upper audible limit of human hearing. Typically, this is about 20 kHz and so in general ultrasound waves have a frequency greater than 20kHz. In the applications described herein, however, frequencies in the range of about 5 to about 20 MHz are contemplated. Preferably therefore, the term “ultrasound imaging” as used herein refers to any method for imaging involving the detection of sound waves having frequencies in the range of 5 to 20 MHz.

[0127] “Imaging” may involve the display of a static and / or moving visual image, such as on paper or a display screen, or may involve a computer or artificial intelligence device generating and / or processing data that could be rendered as a visual image, whether or not such an image is in fact generated.

[0128] As used herein, amounts which are indicated as “about”, “approximately”, etc. may be the exact value stated or may vary by ±10%, preferably ±5% or ±1%. The same applies to the ends of ranges. Formulations “comprising” certain components may also “consist essentially” of such components or consist solely of such components. Similarly, compositions “consisting essentially of” listed components may consist solely of such components or may contain less than 10%, or preferably 5% or 1% of other materials. All % are by weight where context allows, unless indicated otherwise.

[0129] Ranges in this document should be understood to be inclusive of their end points. A content range of from 1 % w / v to 5% w / v of an ingredient, for example, includes contents of 1.0% w / v and 5.0% w / v. Sections of this document will reference various possible values and will then recite that this list of values also includes all ranges and subrangestherebetween. This should be interpreted as also disclosing the total range of values listed in the text as well as any subrange from any one number to another number listed in the relevant text. For example, a recitation of 1%, 2%, 3%, 4%, 5%, or 6% content of a particular ingredient, including all “ranges and subranges” therebetween, would also encompass the range of values of 1 % to 6%, and / or subranges, such as 3% to 4%.

[0130] Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the disclosure. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges, and are also encompassed within the disclosure, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the disclosure.

[0131] As used herein, the terms “treatment,” “treating,” or “ameliorating” refers to either a therapeutic treatment or prophylactic / preventative treatment. A treatment is therapeutic if at least one symptom of disease in an individual receiving treatment improves or a treatment can delay worsening of a progressive disease in an individual, or prevent onset of additional associated diseases.

[0132] As used herein, the term “substantially” refers to the qualitative condition of exhibiting total or near-total extent or degree of a characteristic or property of interest. One of ordinary skill in the biological arts will understand that biological and chemical phenomena rarely, if ever, go to completion and / or proceed to completeness or achieve or avoid an absolute result. The term “substantially” is therefore used herein to capture the potential lack of completeness inherent in many biological and chemical phenomena.B. Compositions

[0133] Provided herein are compositions and methods of using them in various medical applications.

[0134] In embodiments, the composition of the disclosure comprises (a) at least one triglyceride; (b) at least one phospholipid; (c) water; (d) pH buffer; and (e) a humectant. In embodiments, the composition of the disclosure comprises (a) at least one triglyceride; (b) a lecithin comprising at least one phospholipid; (c) water; (d) pH buffer; and (e) a humectant. In embodiments, the composition comprises no more than 5% w / v, no morethan 2% w / v, no more than 1% w / v, no more than 0.5% w / v, no more than 0.2% w / v, or no more than 0.1% w / v, of substance(s) other than components (a)-(e). In embodiments, the composition consists essentially of components (a)-(e). In embodiments, the composition consists of components (a)-(e). In embodiments, the composition further comprises a diagnostic and / or therapeutic agent. In embodiments, the composition further comprises a diagnostic agent. In embodiments, the composition further comprises a therapeutic agent.

[0135] In embodiments, the composition of the disclosure comprises (a) at least one triglyceride; (b) at least one phospholipid; (c) water; (d) pH buffer; (e) a humectant; and (f) a diagnostic agent, a therapeutic agent, or any combination thereof. In embodiments, the composition of the disclosure comprises (a) at least one triglyceride; (b) a lecithin comprising at least one phospholipid; (c) water; (d) pH buffer; (e) a humectant; and (f) a diagnostic agent, a therapeutic agent, or any combination thereof. In embodiments, the composition comprises no more than 5% w / v, no more than 2% w / v, no more than 1 % w / v, no more than 0.5% w / v, no more than 0.2% w / v, or no more than 0.1% w / v, of substance(s) other than components (a)-(f). In embodiments, the composition consists essentially of components (a)-(f). In embodiments, the composition consists of components (a)-(f).

[0136] In embodiments, the composition is a contrast agent. In embodiments, the composition is an ultrasound coupling agent. In embodiments, the composition is a lubricant. In embodiments, the composition is an aqueous composition.

[0137] In embodiments, the compositions and methods are for ultrasound imaging of a subject. In embodiments, the ultrasound imaging is invasive ultrasound imaging. The compositions described herein are unexpectedly effective in reducing the appearance of artifacts such as brightening artifacts when used in the invasive ultrasound imaging of body tissues, particularly human body tissues, compared to saline, and also safe. In embodiments, advantageously, the composition does not contain sodium chloride or a stabilizing agent like polysorbate 80 (also known as PS80 or tween 80). Prior to the present disclosure, it was believed that sodium chloride and polysorbate 80 were needed to produce a stable and effective composition. Sodium chloride was selected to maintain osmolality of the solution. However, sodium chloride disrupts fat and an emulsifier (PS80) must be used to stabilize the solution, by preventing fat separation. The prior formulation thus included triglyceride, phospholipid, NaCI and PS80, while providing an attenuation constant appropriate for providing an ultrasound image with minimal artifacts. However, applicant discovered the prior formulations were not safe for ultrasound imaging of thebrain. Advantageously, applicant discovered that an effective composition can be prepared without polysorbate 80 and sodium chloride. The compositions described herein that lacked PS80 and sodium chloride were superior to or substantially similar to formulations that contained PS80 and sodium chloride for ultrasound imaging of the brain. (Example 2).

[0138] In embodiments, provided herein are compositions consisting of: (a) from about 60.0 g / L to about 80.0 g / L of at least one triglyceride; (b) from about 3.2 g / L to about 5.2 g / L of at least one phospholipid; (c) water; (d) pH buffer; and (e) glycerol. In embodiments, provided herein are compositions consisting of: (a) at least one triglyceride; (b) at least one phospholipid; (c) water, (d) pH buffer; and (e) glycerol; and wherein the ratio of the at least one triglyceride to the at least one phospholipid is from about 13:1 to about 20:1 by weight. In embodiments, provided herein are compositions consisting of: (a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) from about 0.2 % w / v to about 1 .2 % w / v of at least one phospholipid; (c) water; (d) pH buffer; and (e) glycerol. In embodiments, provided herein are compositions consisting of: (a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) at least one phospholipid, wherein the at least one phospholipid is present at about 0.42 % w / v; (c) water; (d) pH buffer; and (e) glycerol. In embodiments, provided herein are compositions consisting of: (a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) at least one phospholipid; (c) water; (d) pH buffer; and (e) glycerol. In embodiments, provided herein are compositions consisting of: (a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) from about 0.2 % w / v to about 1.2 % w / v of at least one phospholipid; (c) water; (d) pH buffer; and (e) from about 21 g / L to about 26 g / L of glycerol. In embodiments, provided herein are compositions consisting of: (a) about 7 % w / v of a triglyceride; (b) about 4.2 g / L of a phospholipid; (c) about 23.7 g / L of glycerol; (d) water; and (e) a pH buffer. In embodiments, the pH buffer is NaOH.

[0139] In embodiments, provided herein are compositions consisting of: (a) from about 60.0 to about 80.0 g / L of at least one triglyceride; (b) from about 3.2 to about 5.2 g / L of lecithin; (c) water; (d) pH buffer; and (e) glycerol. In embodiments, provided herein are compositions consisting of: (a) at least one triglyceride; (b) lecithin; (c) water, (d) pH buffer; and (e) glycerol; and wherein the ratio of the at least one triglyceride to the at least one phospholipid is from about 13:1 to about 20:1 by weight. In embodiments, provided herein are compositions consisting of: (a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) from about 0.2 % w / v to about 1 .2 % w / v of lecithin; (c) water; (d) pH buffer; and (e) glycerol. In embodiments, provided herein are compositions consisting of:(a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) about 0.42 % w / v lecithin; (c) water; (d) pH buffer; and (e) glycerol. In embodiments, provided herein are compositions consisting of: (a) between 5 % w / v and 9 % w / v of at least one triglyceride;(b) lecithin; (c) water; (d) pH buffer; and (e) glycerol. In embodiments, provided herein are compositions consisting of: (a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) from about 0.2 % w / v to about 1 .2 % w / v of lecithin; (c) water; (d) pH buffer; and (e) from about 21 g / L to about 26 g / L of glycerol. In embodiments, provided herein are compositions consisting of: (a) 7 % w / v of a triglyceride; (b) about 4.2 g / L lecithin; (c) about 23.7 g / L of glycerol; (d) water; and (e) a pH buffer. In embodiments, the pH buffer is NaOH.

[0140] In embodiments, provided herein are compositions comprising: (a) from about 60.0 to about 80.0 g / L of at least one triglyceride; (b) from about 3.2 to about 5.2 g / L of at least one phospholipid; (c) water; (d) pH buffer; and (e) glycerol; wherein the composition does not include a stabilizer and does not include sodium chloride. In embodiments, provided herein are compositions comprising: (a) at least one triglyceride;(b) at least one phospholipid; (c) water; (d) pH buffer; and(e) glycerol; and wherein the ratio of the at least one triglyceride to the at least one phospholipid is from about 13:1 to about 20: 1 by weight; wherein the composition does not include a stabilizer and does not include sodium chloride. In embodiments, provided herein are compositions comprising:(a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) from about 0.2 % w / v to about 1.2 % w / v of at least one phospholipid; (c) water; (d) pH buffer; and (e) glycerol; wherein the composition does not include a stabilizer and does not include sodium chloride. In embodiments, provided herein are compositions comprising: (a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) at least one phospholipid, wherein the at least one phospholipid is present at about 0.42 % w / v; (c) water; (d) pH buffer; and (e) glycerol; wherein the composition does not include a stabilizer and does not include sodium chloride. In embodiments, provided herein are compositions comprising: (a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) at least one phospholipid;(c) water; (d) pH buffer; and (e) glycerol; wherein the composition does not include a stabilizer and does not include sodium chloride. In embodiments, provided herein are compositions comprising: (a) between 5 % w / v and 9 % w / v of at least one triglyceride;(b) from about 0.2 % w / v to about 1.2 % w / v of at least one phospholipid; (c) water; (d) pH buffer; and (e) from about 21 g / L to about 26 g / L of glycerol; wherein the composition does not include a stabilizer and does not include sodium chloride. In embodiments, provided herein are compositions comprising: (a) about 7 % w / v of a triglyceride; (b)about 4.2 g / L of a phospholipid; (c) about 23.7 g / L of glycerol; (d) water; and (e) a pH buffer; wherein the composition does not include a stabilizer and does not include sodium chloride. In embodiments, the pH buffer is NaOH. In embodiments, the stabilizer is PS80.

[0141] In embodiments, provided herein are compositions comprising: (a) from about 60.0 to about 80.0 g / L of at least one triglyceride; (b) from about 3.2 to about 5.2 g / L of lecithin; (c) water; (d) pH buffer; and (e) glycerol; wherein the composition does not include a stabilizer and does not include sodium chloride. In embodiments, provided herein are compositions comprising: (a) at least one triglyceride; (b) lecithin; (c) water; (d) pH buffer; and (e) glycerol; and wherein the ratio of the at least one triglyceride to the at least one phospholipid is from about 13:1 to about 20:1 by weight; wherein the composition does not include a stabilizer and does not include sodium chloride. In embodiments, provided herein are compositions comprising: (a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) from about 0.2 % w / v to about 1.2 % w / v of lecithin; (c) water; (d) pH buffer; and (e) glycerol; wherein the composition does not include a stabilizer and does not include sodium chloride. In embodiments, provided herein are compositions comprising: (a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) about 0.42 % w / v lecithin; (c) water; (d) pH buffer; and (e) glycerol; wherein the composition does not include a stabilizer and does not include sodium chloride. In embodiments, provided herein are compositions comprising: (a) between 5 % w / v and 9 % w / v of at least one triglyceride; (b) lecithin; (c) water; (d) pH buffer; and (e) glycerol; wherein the composition does not include a stabilizer and does not include sodium chloride. In embodiments, provided herein are compositions comprising: (a) between 5 % w / v and 9 % w / v of triglyceride; (b) from about 0.2 % w / v to about 1 .2 % w / v of at least one lecithin; (c) water; (d) pH buffer; and (e) from about 21 g / L to about 26 g / L of glycerol; wherein the composition does not include a stabilizer and does not include sodium chloride. In embodiments, provided herein are compositions comprising: (a) about 7 % w / v of a triglyceride; (b) about 4.2 g / L lecithin; (c) about 23.7 g / L of glycerol; (d) water; and (e) a pH buffer; wherein the composition does not include a stabilizer and does not include sodium chloride. In embodiments, the pH buffer is NaOH. In embodiments, the stabilizer is PS80.

[0142] In embodiments, provided herein are compositions comprising: (a) about 7 % w / v of a triglyceride; (b) about 4.2 g / L of at least one phospholipid; (c) about 23.7 g / L of glycerol; (d) water; and (e) a pH buffer. In embodiments, provided herein are compositions comprising (a) about 7 % w / v of a triglyceride; (b) about 4.2 g / L lecithin; (c)about 23.7 g / L of glycerol; (d) water; and (e) a pH buffer. In embodiments, the pH buffer is NaOH.

[0143] In embodiments, the composition of the disclosure comprises less than 0.5 % w / v, less than 0.4 % w / v, less than 0.3 % w / v, less than 0.2 % w / v, less than 0.1 % w / v, less than 0.05 % w / v, less than 0.02 % w / v, or less than 0.01 % w / v, sodium chloride. In embodiments, the composition does not comprise sodium chloride.

[0144] In embodiments, the composition of the disclosure comprises less than 0.5 % w / v, less than 0.4 % w / v, less than 0.3 % w / v, less than 0.2 % w / v, less than 0.1 % w / v, less than 0.05 % w / v, less than 0.02 % w / v, or less than 0.01 % w / v, salt. In embodiments, the composition does not comprise any salt. As used herein, the term “salt” refers to any chemical compound that can be formed from the reaction of an acid with a base, with all or part of the hydrogen of the acid replaced by a metal or other cation.

[0145] In embodiments, the composition of the disclosure comprises less than 0.5 % w / v, less than 0.4 % w / v, less than 0.3 % w / v, less than 0.2 % w / v, less than 0.1 % w / v, less than 0.05 % w / v, less than 0.02 % w / v, or less than 0.01 % w / v, polysorbate 80 (PS80). In embodiments, the composition does not comprise polysorbate 80 (PS80).

[0146] In embodiments, the composition of the disclosure comprises less than 0.5 % w / v, less than 0.4 % w / v, less than 0.3 % w / v, less than 0.2 % w / v, less than 0.1 % w / v, less than 0.05 % w / v, less than 0.02 % w / v, or less than 0.01 % w / v, polysorbate. In embodiments, the composition does not comprise any polysorbate. In embodiments, the composition of the disclosure comprises less than 0.5 % w / v, less than 0.4 % w / v, less than 0.3 % w / v, less than 0.2 % w / v, less than 0.1 % w / v, less than 0.05 % w / v, less than 0.02 % w / v, or less than 0.01 % w / v, stabilizer. In embodiments, the composition does not comprise any stabilizer.

[0147] In embodiments, the composition described in the preceding paragraphs is diluted with water and / or glycerol to prepare a low triglyceride composition (e.g., as lightdispersing agent in photodynamic therapy). In embodiments, the composition is diluted by about 2-fold, about 3-fold, about 4-fold, about 5-fold, about 6-fold, about 7-fold, about 8-fold, about 9-fold, about 10-fold, about 11-fold, about 12-fold, about 13-fold, about 14- fold, about 15-fold, about 16-fold, about 17-fold, about 18-fold, about 19-fold, about 20- fold, about 22-fold, about 25-fold, about 30-fold, about 35-fold, about 40-fold, about 45- fold, about 50-fold, about 60-fold, about 70-fold, about 80-fold, about 90-fold, about 100- fold, about 200-fold, about 250-fold, about 300- fold, about 400-fold, about 500-fold, about 600-fold, about 700-fold, about 800-fold, about 900-fold, or about 1000-fold. In embodiments, the composition is diluted by about 2-fold to about 5-fold, about 5-fold toabout 10-fold, about 10-fold to about 15-fold, about 15-fold to about 20-fold, about 20- fold to about 30-fold, about 30-fold to about 40-fold, about 40-fold to about 60-fold, about 60-fold to about 80-fold, about 80-fold to about 100-fold, about 100-fold to about 150- fold, about 150-fold to about 200-fold, about 200-fold to about 300-fold, about 300-fold to about 400-fold, about 400-fold to about 600-fold, about 600-fold to about 800-fold, or about 800-fold to about 1000-fold, including all ranges and subranges in between. In embodiments, the ratio of the triglyceride : the phospholipid or lecithin remain the same after dilution. In embodiments, glycerol is added to the diluted composition to compensate for the decrease of osmolality due to dilution.Triglycerides

[0148] In embodiments, the composition comprises 20.0 to 90.0 g / L of at least one triglyceride. As used herein, the term “triglyceride” (sometimes also “triacylglycerol” or “triacylglyceride”) refers to a neutral tri-ester derived from glycerol and three fatty acids. The triglyceride as defined herein therefore contains a polar glycerol-derived “head group” and three non-polar fatty-acid derived “tail groups”. The three non-polar tail groups may have the same or a differing number of carbon atoms and may each independently be saturated or unsaturated. It is preferred however that at least one of the three nonpolar tail groups is unsaturated.

[0149] Examples of suitable non-polar groups include C6-C32 alkyl and alkenyl groups, which are typically present as the esters of long chain carboxylic acids. These are often described by reference to the number of carbon atoms and the number of unsaturations in the carbon chain. Thus, CX:Z indicates a hydrocarbon chain having X carbon atoms and Z unsaturations. Examples particularly include lauroyl (C12:0), myristoyl (C14:0), palmitoyl (C16:0), phytanoyl (C16:0), palmitoleoyl (C16:1), stearoyl (C18:0), oleoyl (C18:1), elaidoyl (C18:1), linoleoyl (C18:2), linolenoyl (C18:3), arachidonoyl (C20:4), behenoyl (C22:0) and lignoceroyl (C24:9) groups. Thus, typical non-polar chains are based on the fatty acids of natural ester lipids, including caproic, caprylic, capric, lauric, myristic, palmitic, phytanic, palmitolic, stearic, oleic, elaidic, linoleic, linolenic, arachidonic, behenic or lignoceric acids, or the corresponding alcohols. Preferable nonpolar chains are palmitic, stearic, oleic and linoleic acids, particularly linoleic acid. In one preferred embodiment, component a) comprises at least one triglyceride having one or more C16 to C18 alkyl groups, particularly such groups having zero, one or twounsaturations. In particular, component a) may comprise at least 50% of triglycerides having such alkyl groups.

[0150] The at least one triglyceride used as part of component a) may be synthetic or may be derived from a purified and / or chemically modified natural source. In one particularly preferred embodiment, the at least one triglyceride is derived from a natural source. For example, the triglyceride used may be selected from vegetable oils or animal fats. Vegetable oils may preferably be selected from the group consisting of soybean oil, olive oil, palm oil and copra oil. Examples of animal fats that may be used are milk fats, fish oils and fish liver oils. The use of soybean oil (which is typically a mixture of neutral triglycerides) is especially preferred.

[0151] In embodiments, the triglyceride is present in the composition in an amount of 20.0 to 90.0 g / L (e.g., 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, or 90 g / L). In embodiments, the triglyceride is present in an amount of 40.0 to 90.0 g / L, 50.0 to 90.0 g / L, 55.0 to 85.0 g / L, or 60.0 to 80.0 g / L. Where a mixture of triglycerides is used, the amount (g / L) of triglyceride refers to the sum of the amount of each of the triglycerides in the composition as a whole.

[0152] When using triglycerides obtained from commercial sources, particular natural products such as soybean oil, there is generally a certain proportion of “impurity” lipid having other chain lengths etc. In embodiments, the compositions and methods described herein encompass such “impurities,” and the use of “consistent of” or “consisting essentially of’ does not exclude the presence of such “impurities.” In embodiments, a triglyceride may be any pharmaceutically acceptable grade of triglyceride with concomitant impurities (i.e. a triglyceride of commercial purity). These impurities may be separated and removed by purification but providing the grade is consistent this is rarely necessary. If necessary, however, a triglyceride may be essentially chemically pure triglyceride, such as at least 80% pure, at least 85% pure, at least 90% pure (e.g., 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) triglyceride.

[0153] Given that the composition is intended for use on the body, it will be readily appreciated by the skilled person in the art that certain additional requirements must also typically be satisfied by the at least one triglyceride. In particular, the at least one triglyceride and its component fatty acids must generally be non-toxic, sterile and biocompatible. In a preferred embodiment therefore, the at least one triglyceride is at least one pharmaceutical grade triglyceride.

[0154] In embodiments, the at least one triglyceride is from one or more of olive oil, coconut oil, palm oil, canola oil, soybean oil, sunflower oil, corn oil, peanut oil, safflower oil, cottonseed oil, sesame oil, flaxseed oil, walnut oil, avocado oil, rice bran oil, grapeseed oil, almond oil, hazelnut oil, macadamia nut oil, pumpkin seed oil, hemp seed oil, camelina oil, mustard oil, pistachio oil, pecan oil, poppy seed oil, black seed oil, apricot kernel oil, cherry kernel oil, peach kernel oil, tamanu oil, borage oil, evening primrose oil, sea buckthorn oil, peri Ila oil, moringa oil, neem oil, karanja oil, jojoba oil, tung oil, camellia oil, tea seed oil, babassu oil, murumuru oil, safflower oil, shea butter, cocoa butter, sal butter, kokum butter, mango butter, illipe butter, or fish oil. In embodiments, the at least one triglyceride is from soybean oil.

[0155] In embodiments, the one or more triglycerides are selected from any one of: tristearin, triolein, tripalmitin, triacetin, trilinolein, tricaprin, trilaurin, triarachidin, tridecanoin, trilinolenin, tricaprylin, tridecanoin, trimyristin, tricaprylin, trivalerate, tricaprate, trilinolenin, tridecanoate, triundecanoin, and trinonanoin.

[0156] In embodiments, the one or more triglycerides have a structure of Formula I: CH2OC(O)R1R2C(O)OCH

[0157] CH2OC(O)R3 (l)wherein, R1, R2, and R3 are each independently a C6-C32 saturated or unsaturated alkyl.In embodiments, RiC(O), R2C(O), and RsC(O) of Formula I each independently comprise a fatty acid residue. In embodiments, the at least one triglycerides of the compositions comprise a residue of linoleic acid (44-62 % by weight), oleic acid (19-30 % by weight), palmitic acid (7-14 % by weight), a-linolenic acid (4-11 % by weight), and stearic acid (1.4-5.5 % by weight). In embodiments, the compositions described herein comprise one or more triglycerides selected from any one of: linolenic-oleic-linolenic, linoleic-linoleic-linoleic, oleic-linoleic-oleic, linoleic-oleic-linoleic, linolenic-linoleic- linolenic, palmitic-oleic-linoleic, palmitic-linoleic-palmitic, stearic-oleic-linoleic, linoleic- linolenic-linoleic, and linoleic-oleic-oleic.

[0158] In embodiments, the at least one triglyceride is a medium-chain triglyceride. A medium chain triglyceride comprises a glycerol backbone and three fatty acid chains that are 6-12 carbons long.

[0159] In embodiments, the one or more triglycerides comprise linoleic acid , oleic acid, palmitic acid, a-linolenic acid, and stearic acid.

[0160] In embodiments, the at least one triglyceride is present in the composition at a concentration of from about 1 % w / v and 15 % w / v. In embodiments, the at least one triglyceride is present in the composition at a concentration of about 1 % w / v, about 1.5 % w / v, about 2 % w / v, about 2.5 % w / v, about 3 % w / v, about 3.5 % w / v, about 4 % w / v, about 4.5 % w / v, about 5 % w / v, about 5.5 % w / v, about 6.0 % w / v, about 6.5 % w / v, about 7.0 % w / v, about 7.5 % w / v, about 8.0 % w / v, about 8.5 % w / v, about 9 % w / v, about 9.5 % w / v, about 10 % w / v, about 10.5 % w / v, about 11 % w / v, about 11.5 % w / v, about 12 % w / v, about 12.5 % w / v, about 13 % w / v, about 13.5 % w / v, about 14 % w / v, about 14.5 % w / v, about 15 % w / v, or any value or range therebetween.

[0161] In embodiments, the at least one triglyceride is present in the composition at a concentration of between 5 % w / v and 9 % w / v. In embodiments, the at least one triglyceride is present in the composition at a concentration of 5.1 % w / v, 5.2 % w / v, 5.3 % w / v, 5.4 % w / v, 5.5 % w / v, 5.6 % w / v, 5.7 % w / v, 5.8 % w / v, 5.9 % w / v, 6.0 % w / v, 6.1% w / v, 6.2 % w / v, 6.3 % w / v, 6.4 % w / v, 6.5 % w / v, 6.6 % w / v, 6.7 % w / v, 6.8 % w / v, 6.9% w / v, 7.0 % w / v, 7.1 % w / v, 7.2 % w / v, 7.3 % w / v, 7.4 % w / v, 7.5 % w / v, 7.6 % w / v, 7.7% w / v, 7.8 % w / v, 7.9 % w / v, 8.0 % w / v, 8.1 % w / v, 8.2 % w / v, 8.3 % w / v, 8.4 % w / v, 8.5% w / v, 8.6 % w / v, 8.7 % w / v, 8.8 % w / v, 8.9 % w / v, or any value or range therebetween. In embodiments, the at least one triglyceride is present in the composition at a concentration of about 7 % w / v.

[0162] In embodiments, the at least one triglyceride is present in the composition at a concentration of between 50 g / L and 90 g / L. In embodiments, the at least one triglyceride is present in the composition at a concentration of about 50 g / L, about 51 g / L, about 52 g / L, about 53 g / L, about 54 g / L, about 55 g / L, about 56 g / L, about 57 g / L, about 58 g / L, about 59 g / L, about 60 g / L, about 61 g / L, about 62 g / L, about 63 g / L, about 64 g / L, about 65 g / L, about 66 g / L, about 67 g / L, about 68 g / L, about 69 g / L, about 70 g / L, about 71 g / L, about 72 g / L, about 73 g / L, about 74 g / L, about 75 g / L, about 76 g / L, about 77 g / L, about 78 g / L, about 79 g / L, about 80 g / L, about 81 g / L, about 82 g / L, about 83 g / L, about 84 g / L, about 85 g / L, about 86 g / L, about 87 g / L, about 88 g / L, about 89 g / L, about 90 g / L, or any concentration or range therebetween. In embodiments, the at least one triglyceride is present in the composition at a concentration of about 70 g / L.

[0163] In embodiments, the composition is diluted to prepare a low triglyceride composition (e.g., as light-dispersing agent in photodynamic therapy). In embodiments, the composition is diluted with water. In embodiments, the composition is diluted withwater containing glycerol. In embodiments, the composition is diluted with Lactated Ringer's solution (containing 6 g / L sodium chloride, 3.1 g / L sodium lactate, 0.3 g / L potassium chloride; 0.2 g / L calcium chloride dihydrate - see www.accessdata.fda.gov / drugsatfda_docs / label / 2019 / 016682s117lbl.pdf). In embodiments, the composition is diluted with 0.9% saline (0.9 gram of NaCI per 100 ml of solution). Accordingly, in embodiments, the low triglyceride composition contains salt(s) at concentrations that corresponds to the dilution ratios — for example, a diluted triglyceride composition with 1 :9 ratio of the composition : 0.9% saline (1 part of the composition mixed with 9 parts of 0.9% saline) has about 0.81% w / v NaCI.

[0164] In embodiments, the low triglyceride composition comprises the triglyceride at a concentration of about 6 % w / v, about 5 % w / v, about 4 % w / v, about 3 % w / v, about 2.5 % w / v, about 2.2 % w / v, about 2 % w / v, about 1.8 % w / v, about 1.6 % w / v, about 1.4 % w / v, about 1.2 % w / v, about 1 % w / v, about 0.9 % w / v, about 0.8 % w / v, about 0.7 % w / v, about 0.6 % w / v, about 0.5 % w / v, about 0.4 % w / v, about 0.3 % w / v, about 0.2 % w / v, about 0.1 % w / v, about 0.09 % w / v, about 0.08 % w / v, about 0.07 % w / v, about 0.06 % w / v, about 0.05 % w / v, about 0.04 % w / v, about 0.03 % w / v, about 0.02 % w / v, about 0.01 % w / v, about 0.009 % w / v, about 0.008 % w / v, about 0.007 % w / v, about 0.006 % w / v, or about 0.005 % w / v. In embodiments, the low triglyceride composition comprises the triglyceride at a concentration within about 6 % w / v to about 4 % w / v, about 4 % w / v to about 2 % w / v, about 2 % w / v to about 1 % w / v, about 1 % w / v to about 0.8 % w / v, about 0.8 % w / v to about 0.6 % w / v, about 0.6 % w / v to about 0.4 % w / v, about 0.4 % w / v to about 0.3 % w / v, about 0.3 % w / v to about 0.2 % w / v, about 0.2 % w / v to about 0.1 % w / v, about 0.1 % w / v to about 0.08 % w / v, about 0.08 % w / v to about 0.05 % w / v, about 0.06 % w / v to about 0.04 % w / v, about 0.04 % w / v to about 0.03 % w / v, about 0.03 % w / v to about 0.02 % w / v, about 0.02 % w / v to about 0.01 % w / v, about 0.01 % w / v to about 0.008 % w / v, or about 0.008 % w / v to about 0.005 % w / v.

[0165] In embodiments, the low triglyceride composition comprises the triglyceride at a concentration of about 1 % w / v, about 0.9 % w / v, about 0.8 % w / v, about 0.7 % w / v, about 0.6 % w / v, about 0.5 % w / v, about 0.4 % w / v, about 0.3 % w / v, about 0.2 % w / v, about 0.1 % w / v, about 0.09 % w / v, about 0.08 % w / v, about 0.07 % w / v, about 0.06 % w / v, about 0.05 % w / v, about 0.04 % w / v, about 0.03 % w / v, about 0.02 % w / v, about 0.01 % w / v, about 0.009 % w / v, about 0.008 % w / v, about 0.007 % w / v, about 0.006 % w / v, or about 0.005 % w / v. In embodiments, the low triglyceride composition comprises the triglyceride at a concentration within about 1 % w / v to about 0.8 % w / v, about 0.8 % w / v to about 0.6 % w / v, about 0.6 % w / v to about 0.4 % w / v, about 0.4 % w / v to about 0.3 %w / v, about 0.3 % w / v to about 0.2 % w / v, about 0.2 % w / v to about 0.1 % w / v, about 0.1 % w / v to about 0.08 % w / v, about 0.08 % w / v to about 0.05 % w / v, about 0.06 % w / v to about 0.04 % w / v, about 0.04 % w / v to about 0.03 % w / v, about 0.03 % w / v to about 0.02 % w / v, about 0.02 % w / v to about 0.01 % w / v, about 0.01 % w / v to about 0.008 % w / v, or about 0.008 % w / v to about 0.005 % w / v. In embodiments, the low triglyceride composition comprises the triglyceride at a concentration of about 0.1 % w / v to about 0.5 % w / v. In embodiments, the composition comprises the triglyceride at a concentration of about 0.1 % w / v. In embodiments, the composition comprises the triglyceride at a concentration of about 0.2 % w / v. In embodiments, the composition comprises the triglyceride at a concentration of about 0.5 % w / v.

[0166] In embodiments, the composition forms small-sized oil droplets. In embodiments, such a composition has superior light dispersive effect. In embodiments, the small-sized oil droplets have an average size of from about 100 nm to about 500 nm, from about 200 nm to about 400 nm, from about 250 nm to about 350 nm, or about 285 nm. In embodiments, the small-sized oil droplets have an average size ranging from about 250 nm to about 350 nm. In embodiments, the small-sized oil droplets are produced under high pressure. In embodiments, essentially all oil droplets in the composition have a size of less than 500 nm. In embodiments, the composition is a low triglyceride composition as described herein.

[0167] In embodiments, the low triglyceride composition contains a triglyceride to phospholipid (or lecithin) ratio as described herein (e.g., a ratio by weight of triglycerides to phospholipids in the composition in the range of 6.5:1 to 30:1 , or a ratio by weight of triglycerides to lecithin in the composition in the range of 6.5:1 to 30:1). In embodiments, the low triglyceride composition has an osmolality of less than 100 mOsm / kg, less than 90 mOsm / kg, less than 80 mOsm / kg, less than 70 mOsm / kg, less than 60 mOsm / kg, less than 50 mOsm / kg, less than 40 mOsm / kg, less than 30 mOsm / kg, less than 20 mOsm / kg, or less than 10 mOsm / kg, but greater than 0 mOsm / kg. In embodiments, the low triglyceride composition has an osmolality of less than 10 mOsm / kg, less than 9 mOsm / kg, less than 8 mOsm / kg, less than 7 mOsm / kg, less than 6 mOsm / kg, less than 5 mOsm / kg, less than 4 mOsm / kg, less than 3 mOsm / kg, less than 2 mOsm / kg, or less than 1 mOsm / kg, but greater than 0 mOsm / kg.

[0168] In embodiments, the low triglyceride composition contains a triglyceride to phospholipid (or lecithin) ratio as described herein, and further comprises glycerol at a concentration that adjusts the osmolality of the composition to a suitable level (e.g., from about 270 mOsm / kg to about 330 mOsm / kg, from about 290 mOsm / kg to about 311mOsm / kg, or from about 290 mOsm / kg to about 305 mOsm / kg). In embodiments, the osmolality of the composition is about 290 + / - 6 mOsm / kg. In embodiments, the osmolality of the composition is 290 + / - 6 mOsm / kg. In embodiments, the composition comprises a relatively higher concentration of triglyceride and phospholipid, and a relatively lower concentration of glycerol, that keeps the osmolality of the composition at a suitable level. In embodiments, the composition is formulated such that the composition is biocompatible (e.g., osmolality corresponds to physiological osmolality). In embodiments, the composition is formulated such that its osmolality is at a suitable level that can match physiological osmolality at the site of application. Non-limiting examples of the lipids and glycerol concentrations are provided in Table 3.Phospholipids or Lecithin

[0169] Phospholipid comprises a polar head group and at least one non-polar tail group. The difference between components triglycerides and phospholipid lies principally in the polar group. The non-polar portions may be derived from the fatty acids or corresponding alcohols considered above for the triglycerides. In particular C16 to C18 acyl groups having zero, one or two unsaturations are suitable as moieties forming the non-polar group of the phospholipids. It will typically be the case that the phospholipid will contain two non-polar groups, although one or more constituents of this component may have only one non-polar moiety. Where more than one non-polar group is present these may be the same or different.

[0170] The at least one phospholipid comprises a negatively charged phosphate group. The phospholipid is thus an ionic species. Preferred phospholipid polar “head” groups include phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS) and phosphatidylinositol(PI). PC and PE are preferred lipids, both individually and as a mixture. In one embodiment, component b) may comprise at least 70% PC, PE or mixtures thereof. In embodiments, the phospholipid is phosphatidylcholine (PC). In a preferred embodiment, component b) thus comprises at least 50% PC, preferably at least 70% PC and most preferably at least 80% PC.

[0171] The phospholipid may be synthetic or derived from a natural source. In an embodiment, the phospholipid is derived from a natural source. Suitable natural sources of phospholipids include egg, heart (e.g. bovine), brain, liver (e.g. bovine) and plant sources including soybean. Such sources may comprise any mixture of phospholipids.In an embodiment, the phospholipid is lecithin, preferably egg yolk lecithin, soy lecithin or a mixture thereof. Egg yolk lecithin is preferred.

[0172] When using phospholipids from natural sources, there is generally a certain proportion of “impurity” lipid or other component, such as triglycerides, tocoopherols, sterols, phosphatides, metals, pigments, and protein fragments. In embodiments, the compositions and methods described herein encompass such “impurities,” and the use of “consistent of” or “consisting essentially of” does not exclude the presence of such “impurities.” In embodiments, a phospholipid may be any pharmaceutically acceptable grade of phospholipid with concomitant impurities (i.e. a triglyceride of commercial purity). These impurities may be separated and removed by purification but providing the grade is consistent this is rarely necessary. If necessary, however, a triglyceride may be essentially chemically pure triglyceride, such as at least 80% pure, at least 85% pure, at least 90% pure, at least 95 % pure, (e.g., 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) triglyceride.

[0173] In embodiments, the at least one phospholipid is non-toxic, biocompatible and sterile. In embodiments, the at least one phospholipid is any pharmaceutically acceptable phospholipid.

[0174] In embodiments, the compositions described herein comprise from about 1 g / L to about 12 g / L phospholipid. In embodiments, the compositions described herein comprise from about 4.2 g / L to about 12 g / L phospholipid. In embodiments, the compositions described herein comprise up to about 12 g / L phospholipid. In embodiments, the compositions described herein comprise about 1 g / L, about 1.2 g / L, about 1.4 g / L, about 1.6 g / L, about 1.8 g / L, about 2 g / L, about 2.2 g / L, about 2.5 g / L, about 3 g / L, about 3.5 g / L, about 4 g / L, about 4.5 g / L, about 5 g / L, about 6 g / L, about 7 g / L, about 8 g / L, about 9 g / L, about 10 g / L, about 11 g / L, or about 12 g / L phospholipid, or any concentration or subrange in between. In embodiments, the compositions described herein comprise about 3 g / L, about 3.1 g / L, about 3.2 g / L, about 3.3 g / L, about 3.4 g / L, about 3.5 g / L, about 3.6 g / L, about 3.7 g / L, about 3.8 g / L, about 3.9 g / L, about 4 g / L, about 4.1 g / L, about 4.2 g / L, about 4.3 g / L, about 4.4 g / L, about 4.5 g / L, about 4.6 g / L, about 4.7 g / L, about 4.8 g / L, about 4.9 g / L, about 5 g / L, about 5.1 g / L, about 5.2 g / L, about 5.3 g / L, about 5.4 g / L, about 5.5 g / L, about 5.6 g / L, about 5.7 g / L, about 5.8 g / L, about 5.9 g / L, about 6 g / L, about 6.1 g / L, about 6.2 g / L, about 6.3 g / L, about 6.4 g / L, about 6.5 g / L, about 6.6 g / L, about 6.7 g / L, about 6.8 g / L, about 6.9 g / L, about 7 g / L, about 7.1 g / L, about 7.2 g / L, about 7.3 g / L, about 7.4 g / L, about 7.5 g / L, about 7.6 g / L, about 7.7 g / L, about 7.8 g / L, about 7.9 g / L, about 8 g / L, about 8.1 g / L, about 8.2 g / L, about 8.3 g / L,about 8.4 g / L, about 8.5 g / L, about 8.6 g / L, about 8.7 g / L, about 8.8 g / L, about 8.9 g / L, about 9 g / L, about 9.1 g / L, about 9.2 g / L, about 9.3 g / L, about 9.4 g / L, about 9.5 g / L, about 9.6 g / L, about 9.7 g / L, about 9.8 g / L, about 9.9 g / L, or about 10 g / L, phospholipid.

[0175] In embodiments, the phospholipid is present in an amount of 2.5 to 5.2 g / L of the composition, e.g. 3.0 to 5.0 g / L. In embodiments, the compositions described herein comprise from about 3.2 g / L to about 5.2 g / L phospholipid. In embodiments, the phospholipid is present in an amount of 3.5 to 4.8 g / L, or 3.8 to 4.5 g / L of the composition. In embodiments, the composition comprises about 4.2 g / L phospholipid.

[0176] In embodiments, the phospholipid is present in an amount of 5. O to 10.4 g / L of the composition, e.g. 6.0 to 10.0 g / L. In embodiments, the compositions described herein comprise from about 6.4 g / L to about 10.4 g / L phospholipid. In embodiments, the phospholipid is present in an amount of 7.0 to 9.6 g / L, or 7.6 to 9.0 g / L of the composition. In embodiments, the composition comprises about 8.4 g / L phospholipid.

[0177] Where the composition comprises a mixture of phospholipids, the amount of phospholipid refers to the sum of the amount of each of the phospholipids in the composition as a whole. The composition may contain low levels of impurities (i.e. lipids other than phospholipids) or if desired may be substantially pure.

[0178] In embodiments, the ratio by weight of triglycerides to phospholipids in the composition is in the range of 4:1 to 30:1. In embodiments, the ratio by weight of triglycerides to phospholipids in the composition is in the range of about 4:1 to about 6:1 , about 6:1 to about 8:1 , about 8:1 to about 10:1 , about 10:1 to about 12:1 , about 12:1 to about 15:1 , about 15:1 to about 18:1 , about 18:1 to about 21 :1 , about 21 :1 to about 25:1 , or about 25:1 to about 30:1. In embodiments, the ratio by weight of triglycerides to phospholipids in the composition is about 4: 1 , about 4.5:1 , about 5: 1 , about 5.5:1 , about 6:1 , about 6.5:1 , about 7:1 , about 7.5:1 , about 8:1 , about 8.5:1 , about 9:1 , about 9.5:1 , about 10:1 , about 10.5:1 , about 11 :1 , about 11.5:1 , about 12:1 , about 12.5:1 , about 13:1 , about 13.5:1 , about 14:1 , about 14.5:1 , about 15:1 , about 15.5:1 , about 16:1 , about 16.5:1 , about 17:1 , about 17.5:1 , about 18:1 , about 18.5:1 , about 19:1 , about 19.5:1 , about 20:1 , about 20.5:1 , about 21:1, about 21.5:1 , about 22:1 , about 22.5:1 , about 23:1 , about 23.5:1 , about 24:1 , about 24.5:1 , about 25:1 , about 26:1 , about 27:1 , about 28:1 , about 29: 1 , or about 30: 1 .

[0179] In embodiments, the ratio by weight of triglycerides to lecithin in the composition is in the range of 4: 1 to 30: 1. In embodiments, the ratio by weight of triglycerides to lecithin in the composition is in the range of about 4: 1 to about 6: 1 , about 6: 1 to about 8:1 , about 8: 1 to about 10:1 , about 10: 1 to about 12:1 , about 12: 1 to about 15:1 , about 15: 1 to about18:1, about 18:1 to about 21:1, about 21:1 to about 25:1, or about 25:1 to about 30:1. In embodiments, the ratio by weight of triglycerides to lecithin in the composition is about 4:1, about 4.5:1, about 5:1, about 5.5:1, about 6:1, about 6.5:1, about 7:1, about 7.5:1, about 8:1, about 8.5:1, about 9:1, about 9.5:1, about 10:1, about 10.5:1, about 11:1, about 11.5:1, about 12:1, about 12.5:1, about 13:1, about 13.5:1, about 14:1, about 14.5:1, about 15:1, about 15.5:1, about 16:1, about 16.5:1, about 17:1, about 17.5:1, about 18:1, about 18.5:1, about 19:1, about 19.5:1, about 20:1, about 20.5:1, about 21:1, about 21.5:1, about 22:1, about 22.5:1, about 23:1, about 23.5:1, about 24:1, about 24.5:1, about 25:1, about 26:1, about 27:1, about 28:1, about 29:1, or about 30:1.

[0180] In embodiments, the ratio by weight of triglycerides to phospholipids in the composition is in the range of 20: 1 to 30: 1 , preferably 21:1 to 29: 1 , more preferably 22: 1 to 28:1, most preferably 23:1 to 27:1. In embodiments, the ratio of triglycerides to phospholipids by weight ranges from about 24:1 to about 26:1. In embodiments, the ratio of triglycerides to phospholipids by weight is about 25:1.

[0181] In embodiments, the ratio by weight of triglycerides to lecithin in the composition is in the range of 20: 1 to 30: 1 , preferably 21 : 1 to 29: 1 , more preferably 22: 1 to 28: 1 , most preferably 23:1 to 27:1. In embodiments, the ratio of triglycerides to lecithin by weight ranges from about 24:1 to about 26:1. In embodiments, the ratio of triglycerides to lecithin by weight is about 25: 1.

[0182] In embodiments, the ratio by weight of triglycerides to phospholipids in the composition is in the range of 8:1 to 25:1, preferably 10:1 to 22:1, more preferably 12:1 to 20:1, most preferably 14:1 to 18:1. In embodiments, the ratio of triglycerides to phospholipids by weight ranges from about 13:1 to about 20:1. In embodiments, the ratio of triglycerides to phospholipids by weight is about 16.7:1.

[0183] In embodiments, the ratio by weight of triglycerides to lecithin in the composition is in the range of 8: 1 to 25: 1 , preferably 10:1 to 22: 1 , more preferably 12:1 to 20: 1 , most preferably 14:1 to 18:1. In embodiments, the ratio of triglycerides to lecithin by weight ranges from about 13:1 to about 20:1. In embodiments, the ratio of triglycerides to lecithin by weight is about 16.7:1.

[0184] In embodiments, the ratio by weight of triglycerides to phospholipids in the composition is in the range of 4:1 to 12.5:1, preferably 5:1 to 11:1, more preferably 6:1 to 10:1, most preferably 7:1 to 9:1. In embodiments, the ratio of triglycerides to phospholipids by weight ranges from about 6.5:1 to about 10:1. In embodiments, the ratio of triglycerides to phospholipids by weight is about 8.3:1.

[0185] In embodiments, the ratio by weight of triglycerides to lecithin in the composition is in the range of 4:1 to 12.5:1 , preferably 5:1 to 11 :1 , more preferably 6:1 to 10:1 , most preferably 7:1 to 9:1. In embodiments, the ratio of triglycerides to lecithin by weight ranges from about 6.5:1 to about 10:1. In embodiments, the ratio of triglycerides to lecithin by weight is about 8.3:1.

[0186] In embodiments, the composition comprises at least one phospholipid in combination with at least one triglyceride. In embodiments, the composition comprises at least one lecithin in combination with at least one triglyceride.

[0187] In embodiments, the compositions provided herein comprises lecithin comprising at least one phospholipid (e.g., phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol). In embodiments, the lecithin further comprises glycerol, choline, glycolipids, triglycerides. In embodiments, the lecithin comprises from about 20 % to about 70 % phospholipids by weight. In embodiments, the lecithin comprises from about 60 % to about 70 % phospholipids by weight. In embodiments, the lecithin comprises about 20 %, about 20 %, about 21 %, about 22 %, about 23 %, about 24 %, about 25 %, about 26 %, about 27 %, about 28 %, about 29 %, about 30 %, about 31 %, about 32 %, about 33 %, about 34 %, about 35 %, about 36 %, about 37 %, about 38 %, about 39 %, about 40 %, about 41 %, about 42 %, about 43 %, about 44 %, about 45 %, about 46 %, about 47 %, about 48 %, about 49 %, about 50 %, about 51 %, about 52 %, about 53 %, about 54 %, about 55 %, about 56 %, about 57 %, about 58 %, about 59 %, about 60 %, about 61 %, about 62 %, about 63 %, about 64 %, about 65 %, about 66 %, about 67 %, about 68 %, about 69 %, or about 70 % phospholipids by weight of the lecithin, including all ranges and values therebetween.

[0188] In embodiments, the lecithin is from one or more of soybeans, sunflower seeds, rapeseeds, egg yolks, wheat germ, corn, peanuts, sesame seeds, rice bran, flaxseeds, pumpkin seeds, cashews, almonds, hazelnuts, pistachios, walnuts, pecans, macadamia nuts, brazil nuts, chia seeds, hemp seeds, poppy seeds, quinoa, oats, barley, rye, millet, sorghum, buckwheat, amaranth, avocado, olives, cocoa beans, coconut, milk, butter, cheese, yogurt, beef liver, chicken liver, fish roe, mackerel, salmon, sardines, herring, anchovies, trout, halibut, tuna, and egg whites. In embodiments, the lecithin is from egg yolk.

[0189] In embodiments, the lecithin comprises phosphatidylcholine and / or phosphatidylethanolamine and / or lysophosphatidyl choline.

[0190] In embodiments, the lecithin comprises phosphatidylcholine. In embodiments, the lecithin comprises from about 10 % to about 100 % phosphatidylcholine by weight. In embodiments, the lecithin comprises from about 10 % to about 90 % phosphatidylcholine by weight. In embodiments, the lecithin comprises from about 10 % to about 80 % phosphatidylcholine by weight. In embodiments, the lecithin comprises from about 10 % to about 70 % phosphatidylcholine by weight. In embodiments, the lecithin comprises from about 20 % to about 70 % phosphatidylcholine by weight. In embodiments, the lecithin comprises from about 60 % to about 70 % phosphatidylcholine by weight. In embodiments, the lecithin comprises about 10 %, about 11 %, about 12 %, about 13 %, about 14 %, about 15 %, about 16 %, about 17 %, about 18 %, about 19 %, about 20 %, about 21 %, about 22 %, about 23 %, about 24 %, about 25 %, about 26 %, about 27 %, about 28 %, about 29 %, about 30 %, about 31 %, about 32 %, about 33 %, about 34 %, about 35 %, about 36 %, about 37 %, about 38 %, about 39 %, about 40 %, about 41 %, about 42 %, about 43 %, about 44 %, about 45 %, about 46 %, about 47 %, about 48 %, about 49 %, about 50 %, about 51 %, about 52 %, about 53 %, about 54 %, about 55 %, about 56 %, about 57 %, about 58 %, about 59 %, about 60 %, about 61 %, about 62 %, about 63 %, about 64 %, about 65 %, about 66 %, about 67 %, about 68 %, about 69 %, about 70 %, about 71 %, about 72 %, about 73 %, about 74 %, about 75 %, about 76 %, about 77 %, about 78 %, about 79 %, about 80 %, about 81 %, about 82 %, about 83 %, about 84 %, about 85 %, about 86 %, about 87 %, about 88 %, about 89 %, about 90 %, about 91 %, about 92 %, about 93 %, about 94 %, about 95 %, about 96 %, about 97 %, about 98 %, about 99 %, or about 100 % phosphatidylcholine by weight of the lecithin, including all ranges and values therebetween.

[0191] In embodiments, the lecithin comprises phosphatidylethanolamine. In embodiments, the lecithin comprises from about 5 % to about 30 % phosphatidylethanolamine by weight. In embodiments, the lecithin comprises about 5 %, about 6 %, about 7 %, about 8 %, about 9 %, about 10 %, about 11 %, about 12 %, about 13 %, about 14 %, about 15 %, about 16 %, about 17 %, about 18 %, about 19 %, about 20 %, about 20 %, about 21 %, about 22 %, about 23 %, about 24 %, about 25 %, about 26 %, about 27 %, about 28 %, about 29 %, about 30 % phosphatidylethanolamine by weight of the lecithin, including all ranges and values therebetween. In embodiments, the lecithin comprises from about 7 % to about 10 % phosphatidylethanolamine. In embodiments, the lecithin comprises from about 10 % to about 18 % phosphatidylethanolamine. In embodiments, the lecithin comprises from 0 % to about 2 % phosphatidylethanolamine. In embodiments, the lecithin comprises from about 12 %to about 18 % phosphatidylethanolamine. In embodiments, the lecithin comprises about 14.6 % phosphatidylethanolamine. In embodiments, the lecithin comprises a minimum of about 5 % phosphatidylethanolamine.

[0192] In embodiments, the lecithin comprises lysophosphatidyl choline. In embodiments, the lecithin comprises from about 0 % to about 10 % lysophosphatidyl choline by weight. In embodiments, the lecithin comprises about 5 %, about 6 %, about 7 %, about 8 %, about 9 %, about 10 %, about 11 %, about 12 %, about 13 %, about 14 %, about 15 %, about 16 %, about 17 %, about 18 %, about 19 %, about 20 %, about 20 %, about 21 %, about 22 %, about 23 %, about 24 %, about 25 %, about 26 %, about 27 %, about 28 %, about 29 %, about 30 % phosphatidylethanolamine by weight of the lecithin, including all ranges and values therebetween. In embodiments, the lecithin comprises a maximum of about 3 % lysophosphatidyl choline by weight. In embodiments, the lecithin comprises a maximum of about 4 % lysophosphatidyl choline by weight. In embodiments, the lecithin comprises a maximum of about 1.5 % lysophosphatidyl choline by weight.

[0193] In embodiments, the lecithin comprises about 70 % phosphatidylcholine, from 7 to about 10 % phosphatidylethanolamine, and a maximum of 3 % of lysophosphatidylcholine by weight of the lecithin. In embodiments, the lecithin comprises at least 45 % phosphatidylcholine, from 10 to about 18 % phosphatidylethanolamine, and a maximum of 4 % of lysophosphatidylcholine by weight of the lecithin. In embodiments, the lecithin comprises about 92 % phosphatidylcholine, from 0 to about 2 % phosphatidylethanolamine, and a maximum of 3 % of lysophosphatidylcholine by weight of the lecithin. In embodiments, the lecithin comprises about 70 % phosphatidylcholine, from about 12 % to about 18 % phosphatidylethanolamine, and a maximum of 3 % of lysophosphatidylcholine by weight of the lecithin. In embodiments, the lecithin comprises about 69.8 % phosphatidylcholine, about 14.6 % phosphatidylethanolamine, and about 1.5 % of lysophosphatidylcholine by weight of the lecithin. In embodiments, the lecithin comprises a minimum of 50 % of phosphatidylcholine and a minimum of 5 % phosphatidylethanolamine by weight of the lecithin. In embodiments, the lecithin comprises a minimum of 20 % of phosphatidylcholine and a minimum of 20 % lysophosphatidyl choline by weight of the lecithin.

[0194] In embodiments, the compositions described herein comprise from about 1 g / L to about 12 g / L lecithin. In embodiments, the compositions described herein comprise from about4.2 g / L to about 12 g / L lecithin. In embodiments, the compositions described herein comprise from about 3.2 g / L to about 5.2 g / L lecithin. In embodiments, the compositions described herein comprise from about 6.4 g / L to about 10.4 g / L lecithin. In embodiments,the compositions described herein comprise up to about 12 g / L lecithin. In embodiments, the compositions described herein comprise about 1 g / L, about 1.2 g / L, about 1.4 g / L, about 1.6 g / L, about 1.8 g / L, about 2 g / L, about 2.2 g / L, about 2.5 g / L, about 3 g / L, about 3.5 g / L, about 4 g / L, about 4.5 g / L, about 5 g / L, about 6 g / L, about 7 g / L, about 8 g / L, about 9 g / L, about 10 g / L, about 11 g / L, or about 12 g / L lecithin, or any concentration or subrange in between. In embodiments, the compositions described herein comprise about 3 g / L, about 3.1 g / L, about 3.2 g / L, about 3.3 g / L, about 3.4 g / L, about 3.5 g / L, about 3.6 g / L, about 3.7 g / L, about 3.8 g / L, about 3.9 g / L, about 4 g / L, about 4.1 g / L, about 4.2 g / L, about 4.3 g / L, about 4.4 g / L, about 4.5 g / L, about 4.6 g / L, about 4.7 g / L, about 4.8 g / L, about 4.9 g / L, about 5 g / L, about 5.1 g / L, about 5.2 g / L, about 5.3 g / L, about 5.4 g / L, about 5.5 g / L, about 5.6 g / L, about 5.7 g / L, about 5.8 g / L, about 5.9 g / L, about 6 g / L, about 6.1 g / L, about 6.2 g / L, about 6.3 g / L, about 6.4 g / L, about 6.5 g / L, about 6.6 g / L, about 6.7 g / L, about 6.8 g / L, about 6.9 g / L, about 7 g / L, about 7.1 g / L, about 7.2 g / L, about 7.3 g / L, about 7.4 g / L, about 7.5 g / L, about 7.6 g / L, about 7.7 g / L, about 7.8 g / L, about 7.9 g / L, about 8 g / L, about 8.1 g / L, about 8.2 g / L, about 8.3 g / L, about 8.4 g / L, about 8.5 g / L, about 8.6 g / L, about 8.7 g / L, about 8.8 g / L, about 8.9 g / L, about 9 g / L, about 9.1 g / L, about 9.2 g / L, about 9.3 g / L, about 9.4 g / L, about 9.5 g / L, about 9.6 g / L, about 9.7 g / L, about 9.8 g / L, about 9.9 g / L, or about 10 g / L, lecithin. In embodiments, the composition comprises about 4.2 g / L lecithin. In embodiments, the composition comprises about 8.4 g / L lecithin.

[0195] In embodiments, the compositions described herein comprise from about 0.1 % w / v to about 1.2 % w / v lecithin. In embodiments, the compositions described herein comprise from about 0.4 % w / v to about 1.2 % w / v lecithin. In embodiments, the compositions described herein comprise from about 0.3 % w / v to about 0.6 % w / v lecithin. In embodiments, the compositions described herein comprise from about 0.6 % w / v to about 1.2 % w / v lecithin. In embodiments, the compositions described herein comprise up to about 1.2 % w / v lecithin. In embodiments, the composition comprises about 0.42 % w / v lecithin. In embodiments, the composition comprises about 0.84 % w / v lecithin.

[0196] In embodiments, the compositions described herein comprise from about 1 g / L to about 12 g / L of phospholipid. In embodiments, the compositions described herein comprise from about 4.2 g / L to about 12 g / L of phospholipid. In embodiments, the compositions described herein comprise from about 3.2 g / L to about 5.2 g / L of phospholipid. In embodiments, the compositions described herein comprise from about 6.4 g / L to about 10.4 g / L of phospholipid. In embodiments, the compositions described herein comprise up to about 12 g / L of phospholipid. In embodiments, the compositionsdescribed herein comprise from about 1 g / L, about 2 g / L, about 3 g / L, about 4 g / L, about 5 g / L, about 6 g / L, about 7 g / L, about 8 g / L, about 9 g / L, about 10 g / L, about 11 g / L, about 12 g / L of phospholipid, or any concentration or subrange thereof. In embodiments, the composition comprises about 4.2 g / L of phospholipid. In embodiments, the composition comprises about 8.4 g / L of phospholipid.

[0197] In embodiments, the compositions described herein comprise from about 0.1 % w / v to about 1.2 % w / v of phospholipid. In embodiments, the compositions described herein comprise from about 0.4 % w / v to about 1.2 % w / v of phospholipid. In embodiments, the compositions described herein comprise up to about 1.2 % w / v of phospholipid. In embodiments, the compositions described herein comprise from about 0.3 % w / v to about 0.6 % w / v of phospholipid. In embodiments, the composition comprises about 0.42 % w / v of phospholipid. In embodiments, the compositions described herein comprise from about 0.6 % w / v to about 1.2 % w / v of phospholipid. In embodiments, the composition comprises about 0.84 % w / v of phospholipid.

[0198] In embodiments, the composition comprises: a) 60.0 to 80.0 g / L of at least one triglyceride; and b) 3.8 to 4.5 g / L of at least one phospholipid.

[0199] In embodiments, the composition comprises: a) 60.0 to 80.0 g / L of at least one triglyceride; and b) 7.6 to 9.0 g / L of at least one phospholipid.

[0200] In embodiments, the composition comprises: a) 20.0 to 90.0 g / L soybean oil; and b) 1.2 to 5.4 g / L lecithin.

[0201] In embodiments, the composition comprises: a) 20.0 to 90.0 g / L soybean oil; and b) 2.4 to 10.8 g / L lecithin.

[0202] In embodiments, the composition comprises: a) 60.0 to 80.0 g / L soybean oil; and b) 3.8 to 4.5 g / L lecithin.

[0203] In embodiments, the composition comprises: a) 60.0 to 80.0 g / L soybean oil; and b) 7.6 to 9.0 g / L lecithin.

[0204] In a preferred embodiment, the lecithin is egg yolk lecithin, soy lecithin or a mixture thereof.

[0205] In embodiments, the composition comprises triglyceride(s) and phospholipid(s) each at the concentration level according to one of the formulations listed in Table 1 below:Table 1. Exemplary Concentrations of Triglycerides and Phospholipids

[0206] In embodiments, the composition comprises triglyceride(s) and lecithin(s) each at the concentration level according to one of the formulations listed in Table 2 below:Table 2. Exemplary Concentrations of Triglycerides and Lecithins

[0207] In embodiments, the composition comprises a diluted triglyceride (e.g., at a concentration of less than about 1 % w / v). In embodiments, the ratio of the triglyceride : the phospholipid or lecithin remain the same in the low triglyceride composition as in the non-diluted composition.Humectants (e.g., Glycerol)

[0208] In embodiments, the composition comprises at least one humectant. As used herein, the term “humectant” refers to a hygroscopic substance which is capable of controlling the water content within a material. Humectants typically therefore comprise molecules having one or more hydrophilic groups, such as hydroxyl groups. In an embodiment, the humectant is a polyol.

[0209] In an embodiment, the composition comprises at least one humectant. In an embodiment, the humectant is biocompatible, sterile, and non-toxic. Any pharmaceutically acceptable humectant may be used. In a preferred embodiment, the at least one humectant is selected from the group consisting of polyols, lactic acid and mixtures thereof, especially polyols. Example of polyols include glycerol (also known as glycerin / glycerine), propylene glycol, and sorbitol. The use of glycerol is especially preferred.

[0210] In embodiments, the humectant is typically present in the composition in an amount of 2.2 to 9.5 g / L, 4.5 to 9.2 g / L, 5.5 to 9.0 g / L, or 6.5 to 8.5 g / L. Where a mixture of humectants is used, the amount of humectant refers to the sum of the amount of eachhumectant present in the composition. In embodiments, the humectant is biocompatible, sterile and non-toxic.

[0211] The humectant may contribute to controlling the osmotic pressure of the composition, as described herein.

[0212] In embodiments, the composition comprises: a) 60.0 to 80.0 g / L of at least one triglyceride; b) 3.8 to 4.5 g / L of at least one phospholipid; and c) 6.5 to 8.5 g / L of at least one humectant.

[0213] In embodiments, the composition comprises: a) 60.0 to 80.0 g / L of at least one triglyceride; b) 3.8 to 4.5 g / L of at least one phospholipid; and c) 6.5 to 8.5 g / L of glycerol.

[0214] In embodiments, the composition comprises: a) 20.0 to 90.0 g / L soybean oil; b) 1.2 to 5.4 g / L lecithin; and c) 2.2 to 9.5 g / L glycerol.

[0215] In embodiments, the composition comprises: a) 60.0 to 80.0 g / L soybean oil; b) 3.8 to 4.5 g / L lecithin; and c) 6.5 to 8.5 g / L glycerol.

[0216] In embodiments, the composition comprises: a) 60.0 to 80.0 g / L soybean oil; b) 3.8 to 4.5 g / L lecithin; and c) 22 to 25 g / L glycerol.

[0217] In embodiments, the composition comprises: a) 60.0 to 80.0 g / L of at least one triglyceride; b) 7.6 to 9.0 g / L of at least one phospholipid; and c) 6.5 to 8.5 g / L of at least one humectant.

[0218] In embodiments, the composition comprises: a) 60.0 to 80.0 g / L of at least one triglyceride; b) 7.6 to 9.0 g / L of at least one phospholipid; and c) 6.5 to 8.5 g / L of glycerol.

[0219] In embodiments, the composition comprises: a) 20.0 to 90.0 g / L soybean oil; b) 2.4 to 10.8 g / L lecithin; andc) 2.2 to 9.5 g / L glycerol.

[0220] In embodiments, the composition comprises: a) 60.0 to 80.0 g / L soybean oil; b) 7.6 to 9.0 g / L lecithin; and c) 6.5 to 8.5 g / L glycerol.

[0221] In embodiments, the composition comprises: a) 60.0 to 80.0 g / L soybean oil; b) 7.6 to 9.0 g / L lecithin; and c) 22 to 25 g / L glycerol.

[0222] In embodiments, the compositions described herein comprise from about 8 g / L to about 26 g / L of glycerol. In embodiments, the compositions described herein comprise from about 14 g / L to about 26 g / L of glycerol. In embodiments, the compositions described herein comprise about 8 g / L, about 9 g / L, about 10 g / L, about 11 g / L, about 12 g / L, about 13 g / L, about 14 g / L, about 15 g / L, about 16 g / L, about 17 g / L, about 18 g / L, about 19 g / L, about 20 g / L, about 21 g / L, about 22 g / L, about 23 g / L, about 24 g / L, about 25 g / L, about 26 g / L glycerol, or any value or range therebetween. In embodiments, the compositions described herein comprise about 16 g / L glycerol. In embodiments, the compositions described herein comprise about 23.7 g / L glycerol.

[0223] In embodiments, the compositions described herein comprise from about 8 g / L to about 30 g / L of glycerol. In embodiments, the compositions described herein comprise from about 14 g / L to about 30 g / L of glycerol. In embodiments, the compositions described herein comprise about 8 g / L, about 9 g / L, about 10 g / L, about 11 g / L, about 12 g / L, about 13 g / L, about 14 g / L, about 15 g / L, about 16 g / L, about 17 g / L, about 18 g / L, about 19 g / L, about 20 g / L, about 21 g / L, about 22 g / L, about 23 g / L, about 24 g / L, about 25 g / L, about 26 g / L glycerol, about 27 g / L glycerol, about 28 g / L glycerol, about 29 g / L glycerol, about 30 g / L glycerol, or any value or range therebetween.

[0224] In embodiments, the composition of the disclosure comprising (a) triglyceride(s) and (b) phospholipid(s) or lecithin(s) also comprises glycerol at a concentration that adjusts the osmolality of the composition to be the same as that of a target organ or tissue. In embodiments, the composition comprises glycerol at a concentration that adjusts the osmolality of the composition to be from about 270 mOsm / kg to about 330 mOsm / kg, preferably from about 290 mOsm / kg to about 311 mOsm / kg, and more preferably from about 290 mOsm / kg to about 305 mOsm / kg. In embodiments, the compositions have an osmolality of about 270 mOsm / kg, about 275 mOsm / kg, about 280 mOsm / kg, about 285 mOsm / kg, about 290 mOsm / kg, about 295 mOsm / kg, about 300mOsm / kg, about 305 mOsm / kg, about 310 mOsm / kg, about 320 mOsm / kg, about 325 mOsm / kg, or about 330 mOsm / kg, including all values and ranges therebetween. In embodiments, the composition has an osmolality of about 290 mOsm / kg. In embodiments, the composition has an osmolality of from about 284 mOsm / kg to about 296 mOsm / kg. In embodiments, the composition is formulated such that the composition is biocompatible (e.g., osmolality corresponds to physiological osmolality). In embodiments, the composition is formulated such that its osmolality is at a suitable level that can match physiological osmolality at the site of application. In embodiments, the glycerol of the composition is at the concentration level according to one of the formulations listed in Table 3 below:Table 3. Exemplary Concentrations of Glycerol| C70 | about 5 % to about 5.1 % | about 2.43 % to about 2.53 %, or about 2.45 % to about 2.5 %

[0225] In embodiments, the composition comprises a diluted triglyceride (e.g., at a concentration of less than about 1 % w / v). In embodiments, the ratio of the triglyceride : the phospholipid or lecithin remain the same in the diluted composition as in the nondiluted composition, but the composition comprises more glycerol to compensate for the decrease of osmolality due to the decrease of the triglyceride and the phospholipid or lecithin. In embodiments, the low triglyceride composition comprises from about 24 g / L to about 40 g / L of glycerol. In embodiments, the composition comprises from about 26 g / L to about 30 g / L of glycerol. In embodiments, the composition comprises about 27 g / L glycerol. In embodiments, the composition comprises about 24 g / L, about 25 g / L, about 26 g / L glycerol, about 27 g / L glycerol, about 28 g / L glycerol, about 29 g / L glycerol, about30 g / L glycerol, about 31 g / L glycerol, about 32 g / L glycerol, about 33 g / L glycerol, about34 g / L glycerol, about 35 g / L glycerol, about 36 g / L glycerol, about 37 g / L glycerol, about38 g / L glycerol, about 39 g / L glycerol, about 40 g / L glycerol, or any value or range therebetween. In embodiments, the low triglyceride composition has an osmolality of from about 270 mOsm / kg to about 330 mOsm / kg. In embodiments, the low triglyceride composition has an osmolality of about 290 mOsm / kg. In embodiments, the low triglyceride composition has an osmolality of from about 284 mOsm / kg to about 296 mOsm / kg. In embodiments, the low triglyceride composition has an osmolality of from about 290 mOsm / kg to about 311 mOsm / kg. In embodiments, the low triglyceride composition has an osmolality of from about 290 mOsm / kg to about 305 mOsm / kg. In embodiments, the low triglyceride composition has an osmolality that is substantially the same as that of a target organ or tissue. In embodiments, the low triglyceride composition is formulated such that the composition is biocompatible (e.g., osmolality corresponds to physiological osmolality). In embodiments, the low triglyceride composition is formulated such that its osmolality is at a suitable level that can match physiological osmolality at the site of application.Additional Ingredients

[0226] In embodiments the composition comprises at least one pH-adjusting additive in order to adjust the pH of the composition to a level suitable for the intended clinical use. In one embodiment, the pH-adjusting additive (also called a “pH buffer”) is a metal hydroxide, preferably a group (I) metal hydroxide such as sodium hydroxide, potassiumhydroxide or a mixture thereof. In a preferred embodiment, the pH-adjusting additive is sodium hydroxide. Alternatively, a base such as a tertiary amine (e.g. trimethylamine) can be added to the composition to adjust its pH. Optionally the composition (e.g. fluid) can be buffered, however the use of a buffer is not required.

[0227] In embodiments, the solvent used to prepare the composition is water.

[0228] In one embodiment, the composition may be sterilized by gamma irradiation and adjusted to pH 9-12, preferably pH 10-11 prior to gamma irradiation. This is believed to compensate for the observed drop in pH when the formulation is irradiated and / or stored. In another embodiment, the composition may have a pH of 6.0 to 9.0, preferably 6.5 to 8.0 after sterilization by gamma irradiation and storage for at least 5 days. Most bacteria are neutrophiles and grow best at near neutral pH, i.e. around 7. Where the pH of the formulation after manufacturing but before irradiation is above 9.0 this will reduce as much as possible the risk of bacterial growth occurring between mixing and sterilization. The reduction of pH (e.g. to 6.5 to 8.0) after sterilization makes the formulation compatible for use without further adjustment.

[0229] Thus, in embodiments, the composition has a pH from about 9 to about 12. In embodiments, the composition has a pH from about 9 to about 10, about 10 to about 11 , or about 11 to about 12. In embodiments, the composition has a pH from about 10 to about 11. In embodiments, such a composition has not been sterilized by gamma irradiation. In embodiments, such a composition is to ber sterilized by gamma irradiation.

[0230] In embodiments, where technically viable, the composition may be a fluid or a gel. Correspondingly, the composition may additionally comprise any appropriate gelling agent. Examples of gelling agents are well known in the art and include protein-based gelling agents such as gelatine, and polysaccharide-based gelling agents such as pectin, agar and alginates. Mixtures of gelling agents may be used.

[0231] In embodiments, the composition is preferably biocompatible, sterile and nontoxic.

[0232] In embodiments, the composition of the disclosure comprises a diagnostic agent (e.g., a contrast agent). In embodiments, the compositions of the disclosure are used to suspend a contrast agent. In embodiments, the contrast agent is a near infrared (IR) fluorophore. Near IR fluorophores absorb light having a wavelength from 700 to 2000 nm. Non-limiting examples of near I R fluorophores include indocyanine green, methylene blue, the cyanine derivative Cy5.5, and the cyanine derivative Cy7. The following publication describes additional near IR fluorophores and is incorporated by reference inits entirety for all purposes: Zhang et al. Expert Opin Med Diagn. 2011 May 1 ; 5(3): 241- 251. In embodiments, the near IR fluorophore is conjugated to a targeting molecule. The targeting molecule enables the conjugate to reach the area of interest (e.g., a tumor). In embodiments, the targeting agent is chlorotoxin, is a 36-amino acid peptide isolated from the venom of Leiurus quinquestriatus. In embodiments, the near IR fluorophore is indocyanine green and the targeting agent is chlorotoxin. This conjugate is referred to as BLZ-100 and is described in the following reference which is incorporated by reference herein in its entirety for all purposes: Butte et al. Near-infrared imaging of brain tumors using the Tumor Paint BLZ-100 to achieve near-complete resection of brain tumors. Neurosurg Focus 36(2): E1 , 2014. In embodiments, BLZ-100 is suspended in a composition containing from 5 % to about 20 % triglycerides by weight. In embodiments, BLZ-100 is suspended in a composition containing 20 % triglycerides by weight. In embodiments, BLZ-100 is suspended in a composition containing 5 % triglycerides by weight. In embodiments, BLZ-100 is suspended in a composition containing 7 % triglycerides by weight. In embodiments, the triglycerides are soybean oil.

[0233] In embodiments, near infrared contrast agents are used in laparoscopy, hepatology, coronary artery surgery, vascular surgery, and surgical oncology.

[0234] In embodiments, the composition is used to suspend fluorophores.

[0235] In embodiments, the composition comprises a photosensitizing agent. In embodiments, the composition with the photosensitizing agent is for photodynamic therapy. In embodiments, the photosensitizing agent is selected from any one of riboflavin, verteporfin, methoxsalen, porfimer sodium, carprofen, aminolevulinic acid, tiaprofenic acid, benzophenone, protoporphyrin, trioxsalen, acetophenone, motexafin lutetium, motexafin gadolinium, hexaminolevulinate, rostaporfin, cyamemazine, titanium dioxide, temoporfin, talaporfin, bergapten, methyl aminolevulinate, dihematoporphyrin ether, efaproxiral, padeliporfin, indapamide, leuprolide, lovastatin, polythiazide, hydroflumethiazide, pitolisant, lamotrigine, chloroquine, trimethoprim, sulfamethoxazole, minocycline, levofloxacin, diclofenac, promethazine, amiodarone, furosemide, ketoconazole, dronedarone, prochlorperazine, enalapril, bupropion, diltiazem, triamterene, simvastatin, methotrexate, misoprostol, hydrochlorothiazide, nadolol, gemfibrozil, hydroxychloroquine, lisinopril, losartan, oxcarbazepine, gabapentin, cyclobenzaprine, escitalopram, enalaprilat, stiripentol, simeprevir, cobimetinib, enoximone, febuxostat, nilotinib, thiothixene, pipotiazine, methotrimeprazine, isocarboxazid, dasatinib, estazolam, captopril, zopiclone, itraconazole, sertraline, flucytosine, diphenhydramine, thalidomide, ketoprofen, cromoglicic acid, doxorubicin,oxaprozin, lomefloxacin, tipranavir, quinidine, chlorothiazide, flupentixol, tacrolimus, diflunisal, perphenazine, trifluoperazine, acetazolamide, mefenamic acid, tetracycline, etodolac, carbinoxamine, hexachlorophene, esomeprazole, paroxetine, flurbiprofen, methazolamide, moexipril, pentosan polysulfate, thioridazine, fluphenazine, demeclocycline, ethionamide, sulindac, piroxicam, benazepril, fluorouracil, haloperidol, fosinopril, nabilone, chlorpromazine, nabumetone, ketorolac, acitretin, cyproheptadine, loxapine, eszopiclone, nisoldipine, clozapine, pyrazinamide, chlorthalidone, valproic acid, metoprolol, sulfisoxazole, doxycycline, methyclothiazide, azithromycin, ramipril, pravastatin, interferon alfa-2b, clofazimine, methylene blue, trovafloxacin, dapsone, naproxen, nalidixic acid, vemurafenib, voriconazole, ciprofloxacin, celecoxib, bumetanide, isotretinoin, glyburide, etretinate, dabrafenib, imatinib, vandetanib, hemoporfin, fosdenopterin, rezafungin, amotosalen, and 5-aminolevulinic acid. The following references describe photodynamic therapy and are incorporated by reference herein in their entireties: International Publication No. 2022 / 258727; Dupont et al. Future Oncol. A novel device for intraoperative photodynamic therapy dedicated to glioblastoma treatment. 2017; Dupont et al. Intraoperative photodynamic Therapy for GliOblastomas: Study Protocol for a Phase I Clinical Trial, Neurosurgery, 2018; Vermandel et al. Standardized Intraoperative 5-ALA photodynamic therapy for newly diagnosed glioblastoma patients: a preliminary analysis of the INDYGO clinical trial. Journal of Neuro-Oncology (2021) 152:501-514; and Mahmoudi et al. 5-Aminolevulinic Acid Photodynamic Therapy for the Treatment of High-Grade Gliomas, J Neurooncol. 2019 141(3): 595-607. In embodiments, the photosensitizing agent is one or more of 5- aminolevulinic acid, hematoporphyrin derivative (HpD), temoporfin, verteporfin, and porfimer sodium. In embodiments, the photosensitizer is a porphyrin, chlorin, pheophorbide, bacteriopheophorbide, metalloporphyrin, purpurin, or a phthalocyanine. Mahmoudi et al. (Mahmoudi et al. 5-Aminolevulinic Acid Photodynamic Therapy for the Treatment of High-Grade Gliomas, J Neurooncol. 2019 141 (3): 595-607) describes multiple photosensitizing agents and is incorporated by reference herein in its entirety.

[0236] In embodiments, the composition of the disclosure comprises a therapeutic agent.

[0237] In embodiments, the therapeutic agent is an antibiotic. In embodiments, the antibiotic is selected from the group consisting of an aminoglycoside, an ansamycin, a carbacephem, a carbapenem, a cephalosporin, a glycopeptide, a lincosamide, a lipopeptide, a macrolide, a monbactam, a nitrofuran, an oxazolidonone, a penicillin, a polypeptide, a quinolone, a sulfonamide, and a tetracycline. In embodiments, the antibiotic is selected from vancomycin, rifamycin, rifampicin, teicoplanin, sulfacetamide,amoxicillin, novobiocin, a tetracycline compound, tetracycline, oxytetracycline, methacycline, minocycline, chlorotetracycline, doxycycline, rolitetracycline, demeclocycline, sulfanilamide, sulfamethoxazole, norfloxacin, gatifloxacin, gemifloxacin, trimethoprim, pyrimethamine, cefadroxil, an anti-tubercular compound, isoniazid, rifampicin; streptomycin, ciprofloxacin, moxifloxacin, and aminosalicylic acid.

[0238] In embodiments, the therapeutic agent is a chemotherapeutic agent. In embodiments, the chemotherapeutic agent is selected from the group consisting of a protein synthesis inhibitor, a DNA-damaging chemotherapeutic, an akylating agent, a topoisomerase inhibitor, an RNA synthesis inhibitor, a DNA complex binder, a thiolate alkylating agent, a guanine alkylating agent, a tubulin binder, a DNA polymerase inhibitor, an anticancer enzyme, a RAC1 inhibitor, a thymidylate synthase inhibitor, an oxazophosphorine compound, an integrin inhibitor, an antifolate, a folate antimetabolite, and a combination thereof. In embodiments, the chemotherapeutic agent is selected from the group consisting of carboplatin, cisplatin, oxaliplatin, 5-fluorouracil, floxuridine, capecitabine, gemcitabine, mytomycin, cyclophosphamide, decarbazine, abraxane, ifosfamide, topotecan, irinotecan, docetaxel, temozolomide, paclitaxel, etoposide, pemetrexed, and a combination thereof.

[0239] In embodiments, the compositions are used in cancer surgery. In embodiments, the compositions are used as drug delivery vehicles.C. Properties of Compositions

[0240] In embodiments, the composition of the disclosure has a property (e.g., attenuation coefficient) that match the target tissue, so as to enhance the signal of the target tissue (e.g., blood). In embodiments, the composition of the disclosure enhances the measures of flow or flow rates of a moving fluid in the subject. In embodiments, the moving fluid is an arterial blood. In embodiments, the moving fluid is a venous blood. In embodiments, the moving fluid is a cerebrospinal fluid (CSF). In embodiments, the composition of the disclosure has a property (e.g., attenuation coefficient) that match the surrounding I encapsulating tissue, so as to enhance the signal of the surrounding tissue (e.g., in bladder, uterus, cervix, colon, or spine).Attenuation Coefficients

[0241] In embodiments, a composition described herein comprises an attenuation coefficient that is substantially similar (i.e., within 20 %, 15%, 10% or 5%) of anattenuation coefficient of a tissue, organ, or cavity that is being imaged. In embodiments, a composition described herein comprises an attenuation coefficient that is the same as the attenuation coefficient of a tissue, organ, or cavity that is being imaged. In embodiments, using a composition that is substantially similar to or the same as an attenuation coefficient of a tissue, organ, or cavity that is being imaged results in a reduction of ultrasound artifacts.

[0242] In embodiments, the use of the composition of the disclosure reduces an artifact by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98%, or at least 99%, compared to the use of a control. In embodiments, the control is saline water (e.g., 0.9% saline that has 0.9 gram of NaCI per 100 ml of solution). In embodiments, the artifact is brightening artifact.

[0243] In embodiments, a composition described herein comprises an attenuation coefficient that is within 5 %, within 10 %, within 15 %, within 20 %, within 25 %, or within 30 % of the attenuation coefficient of an attenuation coefficient of a tissue, organ, or cavity that is being imaged. For example, if the attenuation coefficient of a tissue, organ, or cavity is 1 .5 dB / (MHz*cm), a composition that has an attenuation coefficient that is within 20 % of the tissue, organ, or cavity has an attenuation coefficient from about 1.2-1.8 dB / (MHz*cm). In embodiments, a composition has an attenuation coefficient that is substantially similar to an attenuation coefficient of bone, brain, lung, liver, kidney, heart, cerebrospinal fluid, a soft tissue, a bladder, or a colon. The attenuation coefficient of various tissues and organs is shown in the table below:

[0244] In embodiments, the attenuation coefficient of a composition described herein is from about 0.05 dB / (MHz*cm) to about 15 dB / (MHz*cm). In embodiments, the attenuation coefficient of a composition described herein is from about 3 dB / (MHz*cm) to about 15 dB / (MHz*cm). In embodiments, the attenuation coefficient of a composition described herein is from about 0.002 dB / (MHz*cm) to about 1.0 dB / (MHz*cm). In embodiments, the attenuation coefficient of a composition described herein is from about 0.05 dB / (MHz*cm) to about 1.8 dB / (MHz*cm). In embodiments, the attenuation coefficient of a composition described herein is from about 0.1 dB / (MHz*cm) to about 1.5 dB / (MHz*cm). In embodiments, the attenuation coefficient of a composition described herein is from about 0.5 dB / (MHz*cm) to about 1.5 dB / (MHz*cm). In embodiments, the attenuation coefficient of a composition described herein is from about 0.1 dB / (MHz*cm) to about 0.5 dB / (MHz*cm). In embodiments, the attenuation coefficient of a composition described herein is from about 0.1 dB / (MHz*cm) to about 0.7 dB / (MHz*cm). In embodiments, the attenuation coefficient of a composition described herein is from about 0.1 dB / (MHz*cm) to about 1.0 dB / (MHz*cm). In embodiments, the attenuation coefficient of a composition described herein is from about 0.3 dB / (MHz*cm) to about 0.7 dB / (MHz*cm). In embodiments, the attenuation coefficient of a composition described herein is from about 0.5 dB / (MHz*cm) to about 0.7 dB / (MHz*cm).

[0245] In embodiments, the attenuation coefficient of a composition described herein is about 0.001 dB / (MHz*cm), about 0.005 dB / (MHz*cm), about 0.01 dB / (MHz*cm), about 0.02 dB / (MHz*cm), about 0.03 dB / (MHz*cm), about 0.04 dB / (MHz*cm), about 0.05 dB / (MHz*cm), about 0.06 dB / (MHz*cm), about 0.07 dB / (MHz*cm), about 0.08 dB / (MHz*cm), about 0.09 dB / (MHz*cm), about 0.1 dB / (MHz*cm), about 0.15 dB / (MHz*cm), about 0.2 dB / (MHz*cm), about 0.25 dB / (MHz*cm), about 0.3 dB / (MHz*cm), about 0.35 dB / (MHz*cm), about 0.4 dB / (MHz*cm), about 0.45 dB / (MHz*cm), about 0.5 dB / (MHz*cm), about 0.55 dB / (MHz*cm), about 0.6 dB / (MHz*cm), about 0.65 dB / (MHz*cm), about 0.7 dB / (MHz*cm), about 0.75 dB / (MHz*cm), about 0.8 dB / (MHz*cm), about 0.85 dB / (MHz*cm), about 0.9 dB / (MHz*cm), about 0.95 dB / (MHz*cm), about 1 dB / (MHz*cm), about 1.05 dB / (MHz*cm), about 1.1 dB / (MHz*cm), about 1.15 dB / (MHz*cm), about 1.2 dB / (MHz*cm), about 1.25 dB / (MHz*cm), about 1.3 dB / (MHz*cm), about 1.35 dB / (MHz*cm), about 1.4 dB / (MHz*cm), about 1.45 dB / (MHz*cm), about 1.5 dB / (MHz*cm), about 1.55dB / (MHz*cm), about 1.6 dB / (MHz*cm), about 1.65 dB / (MHz*cm), about 1.7 dB / (MHz*cm), about 1.75 dB / (MHz*cm), about 1.8 dB / (MHz*cm), about 1.85 dB / (MHz*cm), about 1.9 dB / (MHz*cm), about 1.95 dB / (MHz*cm), about 2 dB / (MHz*cm), about 2.05 dB / (MHz*cm), about 2.1 dB / (MHz*cm), about 2.15 dB / (MHz*cm), about 2.2 dB / (MHz*cm), about 2.25 dB / (MHz*cm), about 2.3 dB / (MHz*cm), about 2.35 dB / (MHz*cm), about 2.4 dB / (MHz*cm), about 2.45 dB / (MHz*cm), about 2.5 dB / (MHz*cm), about 2.55 dB / (MHz*cm), about 2.6 dB / (MHz*cm), about 2.65 dB / (MHz*cm), about 2.7 dB / (MHz*cm), about 2.75 dB / (MHz*cm), about 2.8 dB / (MHz*cm), about 2.85 dB / (MHz*cm), about 2.9 dB / (MHz*cm), about 2.95 dB / (MHz*cm), about 3 dB / (MHz*cm), about 3.05 dB / (MHz*cm), about 3.1 dB / (MHz*cm), about 3.15 dB / (MHz*cm), about 3.2 dB / (MHz*cm), about 3.25 dB / (MHz*cm), about 3.3 dB / (MHz*cm), about 3.35 dB / (MHz*cm), about 3.4 dB / (MHz*cm), about 3.45 dB / (MHz*cm), about 3.5 dB / (MHz*cm), about 3.55 dB / (MHz*cm), about 3.6 dB / (MHz*cm), about 3.65 dB / (MHz*cm), about 3.7 dB / (MHz*cm), about 3.75 dB / (MHz*cm), about 3.8 dB / (MHz*cm), about 3.85 dB / (MHz*cm), about 3.9 dB / (MHz*cm), about 3.95 dB / (MHz*cm), about 4 dB / (MHz*cm), about 4.05 dB / (MHz*cm), about 4.1 dB / (MHz*cm), about 4.15 dB / (MHz*cm), about 4.2 dB / (MHz*cm), about 4.25 dB / (MHz*cm), about 4.3 dB / (MHz*cm), about 4.35 dB / (MHz*cm), about 4.4 dB / (MHz*cm), about 4.45 dB / (MHz*cm), about 4.5 dB / (MHz*cm), about 4.55 dB / (MHz*cm), about 4.6 dB / (MHz*cm), about 4.65 dB / (MHz*cm), about 4.7 dB / (MHz*cm), about 4.75 dB / (MHz*cm), about 4.8 dB / (MHz*cm), about 4.85 dB / (MHz*cm), about 4.9 dB / (MHz*cm), about 4.95 dB / (MHz*cm), about 5 dB / (MHz*cm), about 5.05 dB / (MHz*cm), about 5.1 dB / (MHz*cm), about 5.15 dB / (MHz*cm), about 5.2 dB / (MHz*cm), about 5.25 dB / (MHz*cm), about 5.3 dB / (MHz*cm), about 5.35 dB / (MHz*cm), about 5.4 dB / (MHz*cm), about 5.45 dB / (MHz*cm), about 5.5 dB / (MHz*cm), about 5.55 dB / (MHz*cm), about 5.6 dB / (MHz*cm), about 5.65 dB / (MHz*cm), about 5.7 dB / (MHz*cm), about 5.75 dB / (MHz*cm), about 5.8 dB / (MHz*cm), about 5.85 dB / (MHz*cm), about 5.9 dB / (MHz*cm), about 5.95 dB / (MHz*cm), about 6 dB / (MHz*cm), about 6.05 dB / (MHz*cm), about 6.1 dB / (MHz*cm), about 6.15 dB / (MHz*cm), about 6.2 dB / (MHz*cm), about 6.25 dB / (MHz*cm), about 6.3 dB / (MHz*cm), about 6.35 dB / (MHz*cm), about 6.4 dB / (MHz*cm), about 6.45 dB / (MHz*cm), about 6.5 dB / (MHz*cm), about 6.55 dB / (MHz*cm), about 6.6 dB / (MHz*cm), about 6.65 dB / (MHz*cm), about 6.7 dB / (MHz*cm), about 6.75 dB / (MHz*cm), about 6.8 dB / (MHz*cm), about 6.85 dB / (MHz*cm), about 6.9 dB / (MHz*cm), about 6.95 dB / (MHz*cm), about 7 dB / (MHz*cm), about 7.05 dB / (MHz*cm),about 7.1 dB / (MHz*cm), about 7.15 dB / (MHz*cm), about 7.2 dB / (MHz*cm), about 7.25 dB / (MHz*cm), about 7.3 dB / (MHz*cm), about 7.35 dB / (MHz*cm), about 7.4 dB / (MHz*cm), about 7.45 dB / (MHz*cm), about 7.5 dB / (MHz*cm), about 7.55 dB / (MHz*cm), about 7.6 dB / (MHz*cm), about 7.65 dB / (MHz*cm), about 7.7 dB / (MHz*cm), about 7.75 dB / (MHz*cm), about 7.8 dB / (MHz*cm), about 7.85 dB / (MHz*cm), about 7.9 dB / (MHz*cm), about 7.95 dB / (MHz*cm), about 8 dB / (MHz*cm), about 8.05 dB / (MHz*cm), about 8.1 dB / (MHz*cm), about 8.15 dB / (MHz*cm), about 8.2 dB / (MHz*cm), about 8.25 dB / (MHz*cm), about 8.3 dB / (MHz*cm), about 8.35 dB / (MHz*cm), about 8.4 dB / (MHz*cm), about 8.45 dB / (MHz*cm), about 8.5 dB / (MHz*cm), about 8.55 dB / (MHz*cm), about 8.6 dB / (MHz*cm), about 8.65 dB / (MHz*cm), about 8.7 dB / (MHz*cm), about 8.75 dB / (MHz*cm), about 8.8 dB / (MHz*cm), about 8.85 dB / (MHz*cm), about 8.9 dB / (MHz*cm), about 8.95 dB / (MHz*cm), about 9 dB / (MHz*cm), about 9.05 dB / (MHz*cm), about 9.1 dB / (MHz*cm), about 9.15 dB / (MHz*cm), about 9.2 dB / (MHz*cm), about 9.25 dB / (MHz*cm), about 9.3 dB / (MHz*cm), about 9.35 dB / (MHz*cm), about 9.4 dB / (MHz*cm), about 9.45 dB / (MHz*cm), about 9.5 dB / (MHz*cm), about 9.55 dB / (MHz*cm), about 9.6 dB / (MHz*cm), about 9.65 dB / (MHz*cm), about 9.7 dB / (MHz*cm), about 9.75 dB / (MHz*cm), about 9.8 dB / (MHz*cm), about 9.85 dB / (MHz*cm), about 9.9 dB / (MHz*cm), about 9.95 dB / (MHz*cm), about 10 dB / (MHz*cm), about 10.05 dB / (MHz*cm), about 10.1 dB / (MHz*cm), about 10.15 dB / (MHz*cm), about 10.2 dB / (MHz*cm), about 10.25 dB / (MHz*cm), about 10.3 dB / (MHz*cm), about 10.35 dB / (MHz*cm), about 10.4 dB / (MHz*cm), about 10.45 dB / (MHz*cm), about 10.5 dB / (MHz*cm), about 10.55 dB / (MHz*cm), about 10.6 dB / (MHz*cm), about 10.65 dB / (MHz*cm), about 10.7 dB / (MHz*cm), about 10.75 dB / (MHz*cm), about 10.8 dB / (MHz*cm), about 10.85 dB / (MHz*cm), about 10.9 dB / (MHz*cm), about 10.95 dB / (MHz*cm), about 11 dB / (MHz*cm), about 11.05 dB / (MHz*cm), about 11.1 dB / (MHz*cm), about 11.15 dB / (MHz*cm), about 11.2 dB / (MHz*cm), about 11.25 dB / (MHz*cm), about 11.3 dB / (MHz*cm), about 11.35 dB / (MHz*cm), about 11.4 dB / (MHz*cm), about 11.45 dB / (MHz*cm), about 11.5 dB / (MHz*cm), about 11.55 dB / (MHz*cm), about 11.6 dB / (MHz*cm), about 11.65 dB / (MHz*cm), about 11.7 dB / (MHz*cm), about 11.75 dB / (MHz*cm), about 11.8 dB / (MHz*cm), about 11.85 dB / (MHz*cm), about 11.9 dB / (MHz*cm), about 11.95 dB / (MHz*cm), about 12 dB / (MHz*cm), about 12.05 dB / (MHz*cm), about 12.1 dB / (MHz*cm), about 12.15 dB / (MHz*cm), about 12.2 dB / (MHz*cm), about 12.25 dB / (MHz*cm), about 12.3 dB / (MHz*cm), about 12.35 dB / (MHz*cm), about 12.4 dB / (MHz*cm), about 12.45dB / (MHz*cm), about 12.5 dB / (MHz*cm), about 12.55 dB / (MHz*cm), about 12.6 dB / (MHz*cm), about 12.65 dB / (MHz*cm), about 12.7 dB / (MHz*cm), about 12.75 dB / (MHz*cm), about 12.8 dB / (MHz*cm), about 12.85 dB / (MHz*cm), about 12.9 dB / (MHz*cm), about 12.95 dB / (MHz*cm), about 13 dB / (MHz*cm), about 13.05 dB / (MHz*cm), about 13.1 dB / (MHz*cm), about 13.15 dB / (MHz*cm), about 13.2 dB / (MHz*cm), about 13.25 dB / (MHz*cm), about 13.3 dB / (MHz*cm), about 13.35 dB / (MHz*cm), about 13.4 dB / (MHz*cm), about 13.45 dB / (MHz*cm), about 13.5 dB / (MHz*cm), about 13.55 dB / (MHz*cm), about 13.6 dB / (MHz*cm), about 13.65 dB / (MHz*cm), about 13.7 dB / (MHz*cm), about 13.75 dB / (MHz*cm), about 13.8 dB / (MHz*cm), about 13.85 dB / (MHz*cm), about 13.9 dB / (MHz*cm), about 13.95 dB / (MHz*cm), about 14 dB / (MHz*cm), about 14.05 dB / (MHz*cm), about 14.1 dB / (MHz*cm), about 14.15 dB / (MHz*cm), about 14.2 dB / (MHz*cm), about 14.25 dB / (MHz*cm), about 14.3 dB / (MHz*cm), about 14.35 dB / (MHz*cm), about 14.4 dB / (MHz*cm), about 14.45 dB / (MHz*cm), about 14.5 dB / (MHz*cm), about 14.55 dB / (MHz*cm), about 14.6 dB / (MHz*cm), about 14.65 dB / (MHz*cm), about 14.7 dB / (MHz*cm), about 14.75 dB / (MHz*cm), about 14.8 dB / (MHz*cm), about 14.85 dB / (MHz*cm), about 14.9 dB / (MHz*cm), about 14.95 dB / (MHz*cm), about 15 dB / (MHz*cm), or any value or subrange therebetween. In embodiments, the attenuation coefficient of a composition described herein is about 0.5886 dB / (MHz*cm).

[0246] In embodiments, the purpose of the composition described herein is not only to avoid air pockets between the ultrasound transducer / probe and tissue to be imaged and to facilitate a good acoustic coupling between the probe and tissue, but also to minimize the appearance of artifacts by matching the attenuation of the composition and that of the tissue to be imaged. The attenuation of a particular tissue / composition is however in part a function of the frequency of the ultrasound used for imaging (as well as the propagation length), and so a more common parameter used to determine the degree to which the composition is suitable for use with certain tissue types is the attenuation coefficient (a). This has units dB / (MHz cm) and is a property of the material itself i.e. is not dependent on frequency or propagation length. The attenuation coefficient is measured by measuring the amplitude of signals obtained using pulse-echo measurements applied to the composition and comparing this to the amplitude using pulse-echo measurements applied to a specific reference material (e.g. water).

[0247] In embodiments, the composition has an attenuation coefficient (a) that is at least a factor of 30 larger than the attenuation coefficient for water, (i.e. a > 0.066 dB / (MHz cm)). In one embodiment, the attenuation coefficient is from about 0.10 to about1.10, about 0.15 to about 1.00 dB / (MHz cm), or about 0.20 to about 0.90 dB / (MHz cm). In embodiments, the attenuation coefficient is from about 0.30 to about 0.80 dB / (MHz*cm). In embodiments, the attenuation coefficient is from about 0.15 to about 0.60 dB / (MHz*cm). In embodiments, the composition has an attenuation coefficient targeted at about 0.60 dB / (MHz cm) (±0.10 dB / MHz*cm), which is in the same order as the attenuation coefficient of the adult human brain.

[0248] In embodiments, the composition has an attenuation coefficient between that of water (i.e. 0.002 dB / (MHz*cm)) and the attenuation coefficient of the target tissue (i.e. the tissue to be imaged). For example, when the composition is for use in invasive ultrasound imaging of the brain, the attenuation constant of the composition is from about 0.002 to about 1 dB / (MHz*cm), from about 0.10 to about 0.60 dB / (MHz*cm), from about 0.002 to about 0.8 dB / (MHz*cm), or from about 0.15 to about 0.60 dB / (MHz*cm).Shelf Life

[0249] The “shelf life” of a composition described herein refers to the length of time in which the oil droplets within the composition (e.g., the phospholipid and / or triglycerides) are homogenous with the water (i.e., when the oil droplets and water are not phase separated) of the composition. In embodiments, the shelf life of a composition is observed visually. The shelf life of a composition must be sufficient such that surgery or ultrasound imaging can be performed without the composition phase separating. In embodiments, the shelf life is measured at room temperature. In embodiments, the room temperature is between 20 °C and 25 °C. In embodiments, the room temperature is about 25 °C.

[0250] In embodiments, compositions described herein have a shelf life of from about six months to about ten years, from about six months to about five years, from about 1 year to about 5 years, from about 2 years to about 5 years, from about 3 years to about 5 years, from about 6 months to about 4 years, from about 6 months to about 3 years, from about 6 months to about 2 years, from about six months to about one year, from about 1 year to about 4 years, from about 1 year to about 3 years, from about 1 year to about 2 years, or from about 2 years to about 4 years.

[0251] In embodiments, the shelf life is at least about 6 months, at least about 1 year, at least about 2 years, at least about 3 years, at least about 4 years, at least about 5 years, at least about 6 years, at least about 7 years, at least about 8 years, at least about 9 years, at least about 10 years, or more.Osmolality

[0252] The amount of solute (including any dissolved ions) in the composition can be expressed as the osmotic concentration (also known as osmolality) of the composition. In embodiments, the composition has an osmotic concentration from about 200 to about 500 mOsm / kg, from about 225 to about 400 mOsm / kg, from about 250 to about 350 mOsm / kg, from about 275 to about 325 mOsm / kg, from about 270 to about 330 mOsm / kg, or from about 280 to about 300 mOsm / kg of composition. In embodiments, the composition has an osmotic concentration of about 200 mOsm / kg, about 201 mOsm / kg, about 202 mOsm / kg, about 203 mOsm / kg, about 204 mOsm / kg, about 205 mOsm / kg, about 206 mOsm / kg, about 207 mOsm / kg, about 208 mOsm / kg, about 209 mOsm / kg, about 210 mOsm / kg, about 211 mOsm / kg, about 212 mOsm / kg, about 213 mOsm / kg, about 214 mOsm / kg, about 215 mOsm / kg, about 216 mOsm / kg, about 217 mOsm / kg, about 218 mOsm / kg, about 219 mOsm / kg, about 220 mOsm / kg, about 221 mOsm / kg, about 222 mOsm / kg, about 223 mOsm / kg, about 224 mOsm / kg, about 225 mOsm / kg, about 226 mOsm / kg, about 227 mOsm / kg, about 228 mOsm / kg, about 229 mOsm / kg, about 230 mOsm / kg, about 231 mOsm / kg, about 232 mOsm / kg, about 233 mOsm / kg, about 234 mOsm / kg, about 235 mOsm / kg, about 236 mOsm / kg, about 237 mOsm / kg, about 238 mOsm / kg, about 239 mOsm / kg, about 240 mOsm / kg, about 241 mOsm / kg, about 242 mOsm / kg, about 243 mOsm / kg, about 244 mOsm / kg, about 245 mOsm / kg, about 246 mOsm / kg, about 247 mOsm / kg, about 248 mOsm / kg, about 249 mOsm / kg, about 250 mOsm / kg, about 251 mOsm / kg, about 252 mOsm / kg, about 253 mOsm / kg, about 254 mOsm / kg, about 255 mOsm / kg, about 256 mOsm / kg, about 257 mOsm / kg, about 258 mOsm / kg, about 259 mOsm / kg, about 260 mOsm / kg, about 261 mOsm / kg, about 262 mOsm / kg, about 263 mOsm / kg, about 264 mOsm / kg, about 265 mOsm / kg, about 266 mOsm / kg, about 267 mOsm / kg, about 268 mOsm / kg, about 269 mOsm / kg, about 270 mOsm / kg, about 271 mOsm / kg, about 272 mOsm / kg, about 273 mOsm / kg, about 274 mOsm / kg, about 275 mOsm / kg, about 276 mOsm / kg, about 277 mOsm / kg, about 278 mOsm / kg, about 279 mOsm / kg, about 280 mOsm / kg, about 281 mOsm / kg, about 282 mOsm / kg, about 283 mOsm / kg, about 284 mOsm / kg, about 285 mOsm / kg, about 286 mOsm / kg, about 287 mOsm / kg, about 288 mOsm / kg, about 289 mOsm / kg, about 290 mOsm / kg, about 291 mOsm / kg, about 292 mOsm / kg, about 293 mOsm / kg, about 294 mOsm / kg, about 295 mOsm / kg, about 296 mOsm / kg, about 297 mOsm / kg, about 298 mOsm / kg, about 299 mOsm / kg, about 300 mOsm / kg, about 301 mOsm / kg, about 302 mOsm / kg, about 303 mOsm / kg, about 304 mOsm / kg, about 305 mOsm / kg, about 306 mOsm / kg, about 307 mOsm / kg, about 308 mOsm / kg, about 309mOsm / kg, about 310 mOsm / kg, about 311 mOsm / kg, about 312 mOsm / kg, about 313 mOsm / kg, about 314 mOsm / kg, about 315 mOsm / kg, about 316 mOsm / kg, about 317 mOsm / kg, about 318 mOsm / kg, about 319 mOsm / kg, about 320 mOsm / kg, about 321 mOsm / kg, about 322 mOsm / kg, about 323 mOsm / kg, about 324 mOsm / kg, about 325 mOsm / kg, about 326 mOsm / kg, about 327 mOsm / kg, about 328 mOsm / kg, about 329 mOsm / kg, about 330 mOsm / kg, about 331 mOsm / kg, about 332 mOsm / kg, about 333 mOsm / kg, about 334 mOsm / kg, about 335 mOsm / kg, about 336 mOsm / kg, about 337 mOsm / kg, about 338 mOsm / kg, about 339 mOsm / kg, about 340 mOsm / kg, about 341 mOsm / kg, about 342 mOsm / kg, about 343 mOsm / kg, about 344 mOsm / kg, about 345 mOsm / kg, about 346 mOsm / kg, about 347 mOsm / kg, about 348 mOsm / kg, about 349 mOsm / kg, about 350 mOsm / kg, about 351 mOsm / kg, about 352 mOsm / kg, about 353 mOsm / kg, about 354 mOsm / kg, about 355 mOsm / kg, about 356 mOsm / kg, about 357 mOsm / kg, about 358 mOsm / kg, about 359 mOsm / kg, about 360 mOsm / kg, about 361 mOsm / kg, about 362 mOsm / kg, about 363 mOsm / kg, about 364 mOsm / kg, about 365 mOsm / kg, about 366 mOsm / kg, about 367 mOsm / kg, about 368 mOsm / kg, about 369 mOsm / kg, about 370 mOsm / kg, about 371 mOsm / kg, about 372 mOsm / kg, about 373 mOsm / kg, about 374 mOsm / kg, about 375 mOsm / kg, about 376 mOsm / kg, about 377 mOsm / kg, about 378 mOsm / kg, about 379 mOsm / kg, about 380 mOsm / kg, about 381 mOsm / kg, about 382 mOsm / kg, about 383 mOsm / kg, about 384 mOsm / kg, about 385 mOsm / kg, about 386 mOsm / kg, about 387 mOsm / kg, about 388 mOsm / kg, about 389 mOsm / kg, about 390 mOsm / kg, about 391 mOsm / kg, about 392 mOsm / kg, about 393 mOsm / kg, about 394 mOsm / kg, about 395 mOsm / kg, about 396 mOsm / kg, about 397 mOsm / kg, about 398 mOsm / kg, about 399 mOsm / kg, about 400 mOsm / kg, about 401 mOsm / kg, about 402 mOsm / kg, about 403 mOsm / kg, about 404 mOsm / kg, about 405 mOsm / kg, about 406 mOsm / kg, about 407 mOsm / kg, about 408 mOsm / kg, about 409 mOsm / kg, about 410 mOsm / kg, about 411 mOsm / kg, about 412 mOsm / kg, about 413 mOsm / kg, about 414 mOsm / kg, about 415 mOsm / kg, about 416 mOsm / kg, about 417 mOsm / kg, about 418 mOsm / kg, about 419 mOsm / kg, about 420 mOsm / kg, about 421 mOsm / kg, about 422 mOsm / kg, about 423 mOsm / kg, about 424 mOsm / kg, about 425 mOsm / kg, about 426 mOsm / kg, about 427 mOsm / kg, about 428 mOsm / kg, about 429 mOsm / kg, about 430 mOsm / kg, about 431 mOsm / kg, about 432 mOsm / kg, about 433 mOsm / kg, about 434 mOsm / kg, about 435 mOsm / kg, about 436 mOsm / kg, about 437 mOsm / kg, about 438 mOsm / kg, about 439 mOsm / kg, about 440 mOsm / kg, about 441 mOsm / kg, about 442 mOsm / kg, about 443 mOsm / kg, about 444 mOsm / kg, about 445 mOsm / kg, about 446 mOsm / kg, about 447 mOsm / kg, about 448 mOsm / kg, about 449mOsm / kg, about 450 mOsm / kg, about 451 mOsm / kg, about 452 mOsm / kg, about 453 mOsm / kg, about 454 mOsm / kg, about 455 mOsm / kg, about 456 mOsm / kg, about 457 mOsm / kg, about 458 mOsm / kg, about 459 mOsm / kg, about 460 mOsm / kg, about 461 mOsm / kg, about 462 mOsm / kg, about 463 mOsm / kg, about 464 mOsm / kg, about 465 mOsm / kg, about 466 mOsm / kg, about 467 mOsm / kg, about 468 mOsm / kg, about 469 mOsm / kg, about 470 mOsm / kg, about 471 mOsm / kg, about 472 mOsm / kg, about 473 mOsm / kg, about 474 mOsm / kg, about 475 mOsm / kg, about 476 mOsm / kg, about 477 mOsm / kg, about 478 mOsm / kg, about 479 mOsm / kg, about 480 mOsm / kg, about 481 mOsm / kg, about 482 mOsm / kg, about 483 mOsm / kg, about 484 mOsm / kg, about 485 mOsm / kg, about 486 mOsm / kg, about 487 mOsm / kg, about 488 mOsm / kg, about 489 mOsm / kg, about 490 mOsm / kg, about 491 mOsm / kg, about 492 mOsm / kg, about 493 mOsm / kg, about 494 mOsm / kg, about 495 mOsm / kg, about 496 mOsm / kg, about 497 mOsm / kg, about 498 mOsm / kg, about 499 mOsm / kg, or about 500 mOsm / kg, including all values and ranges therebetween.

[0253] In embodiments, the compositions have an osmolality of from about 270 mOsm / kg to about 330 mOsm / kg. In embodiments, the compositions have an osmolality of about 290 mOsm / kg. In embodiments, the compositions have an osmolality of from about 284 mOsm / kg to about 296 mOsm / kg. In embodiments, the compositions have an osmolality of from about 290 mOsm / kg to about 311 mOsm / kg. In embodiments, the compositions have an osmolality of from about 290 mOsm / kg to about 305 mOsm / kg. In embodiments, the compositions have an osmolality of about 270 mOsm / kg, about 275 mOsm / kg, about 280 mOsm / kg, about 285 mOsm / kg, about 290 mOsm / kg, about 295 mOsm / kg, about 300 mOsm / kg, about 305 mOsm / kg, about 310 mOsm / kg, about 320 mOsm / kg, about 325 mOsm / kg, or about 330 mOsm / kg, including all values and ranges therebetween. In embodiments, the composition is formulated such that the composition is biocompatible (e.g., osmolality corresponds to physiological osmolality). In embodiments, the composition is formulated such that its osmolality is at a suitable level that can match physiological osmolality at the site of application. Unless otherwise indicated, the osmolality of the compositions described herein is measured on an OSMOMAT 030-D- D3P from GonoTec®, Ser. No. 08 02 22 osmometer.

[0254] In embodiments, the composition is isotonic with the fluid, tissue, or organ that is being imaged. In embodiments, the composition is isotonic with cerebral spinal fluid (~ 290-292 mOsm / kg).PH

[0255] In embodiments, the composition should have a pH which matches the pH of the tissue to which it is intended to be contacted with or is substantially similar to the pH of the tissue that it contacts. In embodiments, the composition has a pH is from about 6.0 to about 9.0, from about 6.5 to about 8.5, or from about 6.5 to about 8.0. In embodiments, the pH is about 6.0, about 6.1 , about 6.2, about 6.3, about 6.4, about 6.5, about 6.6, about 6.7, about 6.8, about 6.9, about 7.0, about 7.1 , about 7.2, about 7.3, about 7.4, about 7.5, about 7.6, about 7.7, about 7.8, about 7.9, about 8.0, about 8.1 , about 8.2, about 8.3, about 8.4, about 8.5, or any pH or range therebetween. In embodiments, the compositions described herein have a pH from about 6.5 to about 8.5, from about 6.5 to about 8, from about 6.9 to about 7.5, or from about 6.9 to about 7.5. In embodiments, the pH of the composition is about 6.9. In embodiments, the pH of the composition is about 7.3. In embodiments, the pH of the composition is about 7.5. In embodiments, the pH of the composition is substantially similar to the pH of cerebrospinal fluid (~pH 7.3).

[0256] The skilled person knows that the pH of the composition may gradually change over time depending on storage conditions etc. For example, in general the pH of the composition directly after manufacture is higher than that of the composition after a period of prolonged storage. For the avoidance of doubt therefore, by the pH of the composition is meant the pH of the composition shortly before its intended application (i.e. , about 1 hour), as it is this that is important in determining the suitability of the composition for use on certain tissue types.

[0257] In embodiments, the pH buffer is or comprises citrate, phosphate (e.g., dihydrogen phosphate, monohydrogen phosphate), acetate, histidine, glycine, bicarbonate, HEPES, Tris, HCI, NaOH, or any combinations thereof. In embodiments, the pH buffer is or comprises NaOH.Droplet Size

[0258] In embodiments, the triglycerides and phospholipids typically form an emulsion when added to a suitable solvent. In embodiments, triglycerides and phospholipids of the composition form an oil-in-water (o / w) type emulsion i.e. wherein droplets of oil (comprising at least component a)) are dispersed within a continuous aqueous phase. The amphiphilic phospholipid component b) helps to stabilize the interface formed between the dispersed triglyceride / oil phase and the continuous aqueous phase.

[0259] In embodiments, the droplet size of the emulsion can be tuned by varying the nature and / or relative amount of triglyceride and phospholipid components (as well as any optional co-emulsifier(s) that may be present). Additionally or alternatively, the droplet size can be tuned by controlling the shear forces applied during emulsification.

[0260] In embodiments, the number average (mean) droplet diameter is from about 100 nm to about 1000 nm, from about 200 nm to about 700 nm, or from about 230 nm to about 340 nm, including all values and ranges therebetween. In embodiments, the number average droplet diameter is from about 250 nm to about 320 nm, such as about 285 nm ± 35 nm, preferably 285 nm ± 5nm. In embodiments, the number average droplet diameter is 285 nm ± 20 %. Average droplet diameters are measured by Dynamic Light Scattering using a Malvern Zetasizer. In embodiments, the number average droplet diameter is about 100 nm, about 110 nm, about 120 nm, about 130 nm, about 140 nm, about 150 nm, about 160 nm, about 170 nm, about 180 nm, about 190 nm, about 200 nm, about 210 nm, about 220 nm, about 230 nm, about 240 nm, about 250 nm, about 260 nm, about 270 nm, about 280 nm, about 290 nm, about 300 nm, about 310 nm, about 320 nm, about 330 nm, about 340 nm, about 350 nm, about 360 nm, about 370 nm, about 380 nm, about 390 nm, about 400 nm, about 410 nm, about 420 nm, about 430 nm, about 440 nm, about 450 nm, about 460 nm, about 470 nm, about 480 nm, about 490 nm, about 500 nm, about 510 nm, about 520 nm, about 530 nm, about 540 nm, about 550 nm, about 560 nm, about 570 nm, about 580 nm, about 590 nm, about 600 nm, about 61 O nm, about 620 nm, about 630 nm, about 640 nm, about 650 nm, about 660 nm, about 670 nm, about 680 nm, about 690 nm, about 700 nm, about 710 nm, about 720 nm, about 730 nm, about 740 nm, about 750 nm, about 760 nm, about 770 nm, about 780 nm, about 790 nm, about 800 nm, about 810 nm, about 820 nm, about 830 nm, about 840 nm, about 850 nm, about 860 nm, about 870 nm, about 880 nm, about 890 nm, about 900 nm, about 910 nm, about 920 nm, about 930 nm, about 940 nm, about 950 nm, about 960 nm, about 970 nm, about 980 nm, about 990 nm, or about 1000 nm.

[0261] In embodiments, the composition has a volume mean weighted droplet size (i.e. , diameter) of from about 0.2 pm to 5 pm, from about 0.2 pm to 4.5 pm, from about 0.2 pm to about 4 pm, from about 0.2 pm to about 3.5 pm, from about 0.2 pm to about 3 pm, from about 0.2 pm to about 2.5 pm, from about 0.2 pm to about 2 pm, from about 0.2 pm to about 1.5 pm, from about 0.2 pm to about 1 pm, from about 0.2 pm to about 0.9 pm, from about 0.2 pm to about 0.8 pm, from about 0.2 pm to about 0.7 pm, or from about 0.2 pm to about 0.6 pm. In embodiments, the composition has a volume mean weighted droplet size of from about 0.2 pm to about 0.55 pm. In embodiments, the compositionhas a volume mean weighted droplet size of from about 0.26 pm to about 0.50 pm. In embodiments, the composition has a volume mean weighted droplet size of from about 228 nm to about 342 nm. In embodiments, the composition has a volume mean weighted droplet size of about 258 nm. In embodiments, volume mean weighted droplet size is measured by laser diffraction.

[0262] In embodiments, the composition forms oil droplets, wherein 100 % of the oil droplets have a diameter of less than 5 pm, less than 4.5 pm, less than 4 pm, less than3.5 pm, less than 3 pm, less than 2.5 pm, less than 2 pm, less than 1.5 pm, less than 1 pm, less than 0.9 pm, less than 0.8 pm, less than 0.7 pm, less than 0.6 pm, or less than 0.5 pm. In embodiments, 100 % of the oil droplets have a diameter that is less than 0.84 pm. In embodiments, 100 % of the oil droplets have a diameter that is less than 0.96 pm. In embodiments, 100 % of the oil droplets have a diameter that is less than 1.91 pm. In embodiments, none (of the droplets comprise a diameter of greater than 5000 nm.

[0263] In embodiments, the composition forms oil droplets with an average size of from about 200 nm to about 750 nm or from about 250 nm to about 500 nm. In embodiments, the composition forms oil droplets with an average size of about 285 nm ±20%. In embodiments, the composition forms oil droplets with an average size of about 369 nm. In embodiments, size is measured by dynamic light scattering. In embodiments, the size is measured by laser diffraction.

[0264] In embodiments, the droplets in the emulsion are monodisperse or essentially monodisperse. As used herein, the term “monodisperse” means that at least 90% by number of the droplets (D90) have a particular diameter or less. In embodiments, the D90 is in the range of 200 to 400nm. In embodiments the D90 of the emulsion is in the range of 220 to 350 nm. In embodiments, the D90 of the emulsion is in the range of 230 to 340 nm. In embodiments, the D90 is from about 0.2 pm to 5 pm, from about 0.2 pm to4.5 pm, from about 0.2 pm to about 4 pm, from about 0.2 pm to about 3.5 pm, from about 0.2 pm to about 3 pm, from about 0.2 pm to about 2.5 pm, from about 0.2 pm to about 2 pm, from about 0.2 pm to about 1.5 pm, from about 0.2 pm to about 1 pm, from about 0.2 pm to about 0.9 pm, from about 0.2 pm to about 0.8 pm, from about 0.2 pm to about 0.7 pm, about 0.2 pm to about 0.6 pm, from about 0.2 pm to about 1 pm, or from about 0.4 pm to about 1.4 pm. In embodiments, the D90 is about 200 nm, about 210 nm, about 220 nm, about 230 nm, about 240 nm, about 250 nm, about 260 nm, about 270 nm, about 280 nm, about 290 nm, about 300 nm, about 310 nm, about 320 nm, about 330 nm, about 340 nm, about 350 nm, about 360 nm, about 369 nm, about 370 nm, about 380 nm, about 390 nm, about 400 nm, about 410 nm, about 420 nm, about 430 nm, about 440 nm, about450 nm, about 460 nm, about 470 nm, about 480 nm, about 490 nm, about 500 nm, about510 nm, about 520 nm, about 530 nm, about 540 nm, about 550 nm, about 560 nm, about570 nm, about 580 nm, about 590 nm, about 600 nm, about 610 nm, about 620 nm, about630 nm, about 640 nm, about 650 nm, about 660 nm, about 670 nm, about 680 nm, about690 nm, about 700 nm, about 710 nm, about 720 nm, about 730 nm, about 740 nm, about750 nm, about 760 nm, about 770 nm, about 780 nm, about 790 nm, about 800 nm, about810 nm, about 820 nm, about 830 nm, about 840 nm, about 850 nm, about 860 nm, about870 nm, about 880 nm, about 890 nm, about 900 nm, about 910 nm, about 920 nm, about930 nm, about 940 nm, about 950 nm, about 960 nm, about 970 nm, about 980 nm, about990 nm, about 1000 nm, about 1010 nm, about 1020 nm, about 1030 nm, about 1040 nm, about 1050 nm, about 1060 nm, about 1070 nm, about 1080 nm, about 1090 nm, about 1100 nm, about 1110 nm, about 1120 nm, about 1130 nm, about 1140 nm, about 1150 nm, about 1160 nm, about 1170 nm, about 1180 nm, about 1190 nm, about 1200 nm, about 1210 nm, about 1220 nm, about 1230 nm, about 1240 nm, about 1250 nm, about 1260 nm, about 1270 nm, about 1280 nm, about 1290 nm, about 1300 nm, about 1310 nm, about 1320 nm, about 1330 nm, about 1340 nm, about 1350 nm, about 1360 nm, about 1370 nm, about 1380 nm, about 1390 nm, about 1400 nm, about 1410 nm, about 1420 nm, about 1430 nm, about 1440 nm, about 1450 nm, about 1460 nm, about 1470 nm, about 1480 nm, about 1490 nm, about 1500 nm, about 1510 nm, about 1520 nm, about 1530 nm, about 1540 nm, about 1550 nm, about 1560 nm, about 1570 nm, about 1580 nm, about 1590 nm, about 1600 nm, about 1610 nm, about 1620 nm, about 1630 nm, about 1640 nm, about 1650 nm, about 1660 nm, about 1670 nm, about 1680 nm, about 1690 nm, about 1700 nm, about 1710 nm, about 1720 nm, about 1730 nm, about 1740 nm, about 1750 nm, about 1760 nm, about 1770 nm, about 1780 nm, about 1790 nm, about 1800 nm, about 1810 nm, about 1820 nm, about 1830 nm, about 1840 nm, about 1850 nm, about 1860 nm, about 1870 nm, about 1880 nm, about 1890 nm, about 1900 nm, about 1910 nm, about 1920 nm, about 1930 nm, about 1940 nm, about 1950 nm, about 1960 nm, about 1970 nm, about 1980 nm, about 1990 nm, about 2000 nm, about 2010 nm, about 2020 nm, about 2030 nm, about 2040 nm, about 2050 nm, about 2060 nm, about 2070 nm, about 2080 nm, about 2090 nm, about 2100 nm, about 2110 nm, about 2120 nm, about 2130 nm, about 2140 nm, about 2150 nm, about 2160 nm, about 2170 nm, about 2180 nm, about 2190 nm, about 2200 nm, about 2210 nm, about 2220 nm, about 2230 nm, about 2240 nm, about 2250 nm, about 2260 nm, about 2270 nm, about 2280 nm, about 2290 nm, about 2300 nm, about 2310 nm, about 2320 nm, about 2330 nm, about 2340 nm, about 2350 nm, about 2360 nm, about 2370 nm,about 2380 nm, about 2390 nm, about 2400 nm, about 2410 nm, about 2420 nm, about 2430 nm, about 2440 nm, about 2450 nm, about 2460 nm, about 2470 nm, about 2480 nm, about 2490 nm, about 2500 nm, about 2510 nm, about 2520 nm, about 2530 nm, about 2540 nm, about 2550 nm, about 2560 nm, about 2570 nm, about 2580 nm, about 2590 nm, about 2600 nm, about 2610 nm, about 2620 nm, about 2630 nm, about 2640 nm, about 2650 nm, about 2660 nm, about 2670 nm, about 2680 nm, about 2690 nm, about 2700 nm, about 2710 nm, about 2720 nm, about 2730 nm, about 2740 nm, about 2750 nm, about 2760 nm, about 2770 nm, about 2780 nm, about 2790 nm, about 2800 nm, about 2810 nm, about 2820 nm, about 2830 nm, about 2840 nm, about 2850 nm, about 2860 nm, about 2870 nm, about 2880 nm, about 2890 nm, about 2900 nm, about 2910 nm, about 2920 nm, about 2930 nm, about 2940 nm, about 2950 nm, about 2960 nm, about 2970 nm, about 2980 nm, about 2990 nm, or about 3000 nm, including all values and ranges therebetween.D. Containers and Kits Containing Compositions

[0265] In embodiments, the composition is contained in a balloon. In embodiments, the balloon is a balloon catheter. In embodiments, the composition is delivered to a cavity of the subject via the balloon. In embodiments, the cavity is created by the balloon.

[0266] In embodiments, provided herein is a pre-filled syringe containing a composition described herein. A suitable syringe may be, for example, 10 to 250ml in capacity, such as 25 to 100 ml in capacity. In one embodiment, the composition is sterilized by gamma irradiation of the pre-filled syringe containing said composition. Pre-filled syringes may optionally be provided with a filter to reduce the probability that larger droplets and any presence of larger particles in the composition can enter the cavity during use. Typical filters will have a pore size around 0.1 to 5 pm, preferably 0.8 to 1.5pm.

[0267] Advantageously, the kit is suitable for carrying out the method for preparing or method for formulating the composition as defined herein.

[0268] In another aspect, provided herein is a kit comprising: a mixture comprising at least one triglyceride, at least one phospholipid and optionally at least one humectant; and water. The mixture and aqueous solution are preferably as defined in any aspect described herein.

[0269] In embodiments, provided herein are kits comprising a composition and a container. In embodiments, the container is a syringe. In embodiments, the container isglass. In embodiments, the container is stainless steel. In embodiments, the container is a bag. In embodiments, the container lacks one or more of dyes, preservatives, rubber, butyl, silica, polyvinyl chloride (PVC), and di(2-ethylhexyl)phthalate (DEHP). In embodiments, the container contains polypropylene, polyethylene, polycarbonate, cyclic olefin copolymer, cyclic olefin polymer, polymethyl methacrylate, or glass. In embodiments, the container contains cyclin olefin copolymer and cyclic olefin polymer.

[0270] In embodiments, provided herein are kits comprising a composition, a container, and a filter. In embodiments, the pore size of the filter is small enough to prevent microbial growth and large enough to allow oil droplets from the composition to pass through the filter. In embodiments, the filter comprises pores that are greater than 0.5 pm and smaller than 5 pm. In embodiments, the filter has a pore size of about 0.6 pm, about 0.7 pm, about 0.8 pm, about 0.9 pm, about 1 pm, about 1.1 pm, about 1.2 pm, about 1.3 pm, about 1.4 pm, about 1.5 pm, about 1.6 pm, about 1.7 pm, about 1.8 pm, about 1.9 pm, about 2 pm, about 2.1 pm, about 2.2 pm, about 2.3 pm, about 2.4 pm, about 2.5 pm, about 2.6 pm, about 2.7 pm, about 2.8 pm, about 2.9 pm, about 3 pm, about 3.1 pm, about 3.2 pm, about 3.3 pm, about 3.4 pm, about 3.5 pm, about 3.6 pm, about 3.7 pm, about 3.8 pm, about 3.9 pm, about 4 pm, about 4.1 pm, about 34.2 pm, about 4.3 pm, about 4.4 pm, about 4.5 pm, about 4.6 pm, about 4.7 pm, about 4.8 pm, about 4.9 pm, or about 5 pm, including all values and ranges therebetween. In embodiments, the filter has a pore size of about 2 pm. In embodiments, the filter has a pore size of about 1.2 pm.

[0271] In embodiments, the kit comprises a bag spike and a bag containing the composition. A bag spike is used to puncture the bag containing the composition. In embodiments the kit further comprises an inline, vented filter. Inline filters are placed directly in the bag. In embodiments, the filter is vented to allow air to escape from the fluid path and to prevent air bubbles from entering the bloodstreams and causing embolisms.

[0272] In embodiments, the kit comprises a composition, a syringe, a bag spike, and a filter. In embodiments, the filter is a 1.2 pm filter.

[0273] In embodiments, provided herein are containers comprising a composition described herein. In embodiments, the container is a syringe. In embodiments, the container is glass. In embodiments, the container is stainless steel. In embodiments, thecontainer is a bag. In embodiments, the container lacks one or more of dyes, preservatives, rubber, butyl, silica, polyvinyl chloride (PVC), and di(2- ethyl hexyl) phthalate (DEHP). In embodiments, the container contains polypropylene, polyethylene, polycarbonate, cyclic olefin copolymer, cyclic olefin polymer, polymethyl methacrylate, or glass. In embodiments, the container contains cyclin olefin copolymer and cyclic olefin polymer.

[0274] In embodiments, the container is a syringe. In embodiments, the syringe is a 50 mL syringe. In embodiments, the syringe contains one or more of polypropylene, polyethylene, polycarbonate, cyclic olefin copolymer, cyclic olefin polymer, polymethyl methacrylate, or glass. In embodiments, the syringe comprises a plunger. In embodiments, the plunger comprises one or more of rubber (e.g., natural or synthetic), thermoplastic elastomers, silicone rubber, polyisoprene, ethylene propylene diene monomer, chlorobutyl rubber, or bromobutyl rubber.

[0275] In embodiments, the container is a bag. In embodiments, a composition is present in a sterile inline bag spike and infusion kit. In embodiments, the bag is a pressure bag.E. Methods of Using Compositions

[0276] The disclosure provides methods of using the composition. In embodiments, the composition is used for imaging (e.g., via ultrasound or other imaging methods). In embodiments, the composition is used for providing guidance to surgeries. In embodiments, the composition is used as a delivery vehicle (e.g., delivering a diagnostic or therapeutic agent). In embodiments, the composition is used for diagnosing or treating a disease. In embodiments, the composition is used as lubricant (e.g., for assisting the insertion of an instrument into a body part). The composition may be used for a particular method of the disclosure, or for a combination of methods for a subject (e.g., both as a composition for imaging and subsequently as a lubricant for a surgery instrument).

[0277] In embodiments, the disclosure provides imaging methods using the composition of the disclosure. In embodiments, the method comprises administering the composition of the disclosure to a subject in need thereof, and then performing imaging. In embodiments, the composition is administered into a wound, an organ, a tumor, a blood vessel, or a cavity inside the subject. In embodiments, the composition is administered into a blood vessel or area of blood circulation of the subject. In embodiments, the methodobtains an image of a wound, organ, tumor, blood vessel or area of blood circulation, or cavity, and comprises i) contacting the wound, organ, tumor, blood vessel, or cavity with a composition of the disclosure and ii) obtaining the image (imaging) with an instrument.

[0278] In embodiments, the image is an ultrasound image. In embodiments, the imaging method is invasive ultrasound imaging.

[0279] In embodiments, the imaging method is a Doppler based flow imaging method. In embodiments, the method is optical coherence tomography. In embodiments, the method is a laser speckle imaging method. In embodiments, the oil droplets comprised within the composition are strong back-scatterers that enhance backscattering signals. In embodiments, the composition of the disclosure enhances the Doppler detection and reduce imaging latency. In embodiments, the composition of the disclosure functions as a contrast agent. Additional information of the methods can be found, for example, in Liu et al., CS Appl. Nano Mater. 2023, 6, 19, 17691-17697, the content of which is incorporated by reference in its entirety.

[0280] In embodiments, the compositions and suspensions described herein are used in methods of laser speckle contrast imaging. In embodiments, a composition described herein is diluted in water and / or glycerol and used in methods of laser speckle contrast imaging. Laser speckle contrast imaging is described in the following article which is incorporated by reference herein in its entirety: Wang et al. Assessment of Optical Clearing Induced Improvement of Laser Speckle Contrast Imaging, Vol. 3, No.3, 2010, p. 159-167. In embodiments, the suspensions and compositions are used to visualize blood vessels. In embodiments, the suspensions and compositions are used to visualize blood flow.

[0281] In embodiments, the method is a photoacoustic imaging (PAI) method. In PAI, laser illumination is generally used to induce rapid thermoelastic expansion in the tissue volume that produces ultrasonic signals, the amplitude of which is proportional to the absorbed optical intensity. In embodiments, an image that maps the original optical energy deposition inside the target is formed by detecting and processing the ultrasonic signals. In embodiments, the composition of the disclosure functions as a contrast agent. Additional information of PAI can be found, for example, in Zhang et al., Biomed Opt Express. 2019 Nov 1 ; 10(11): 5744-5754, the content of which is incorporated by reference in its entirety.

[0282] In embodiments, the method is a computed tomography (CT) method. In embodiments, the composition of the disclosure functions as a contrast agent. Additionalinformation of CT can be found, for example, in Hildell et al., AJR Am J Roentgenol. 1981 Oct;137(4):777-80, the content of which is incorporated by reference in its entirety.

[0283] In embodiments, the method is an echocardiography method. In embodiments, the method is myocardial contrast two-dimensional echocardiography. Additional information of echocardiography can be found, for example, in Myocardial Contrast Two- dimensional Echocardiography (Developments in Cardiovascular Medicine Book 99) by Meerbaum and Richard S. Meltzer (2012), the content of which is incorporated by reference in its entirety.

[0284] In embodiments, the method is a magnetic field-based imaging method. In embodiments, the method is magnetic resonance imaging (MRI). In embodiments, the method is magnetic particle imaging (MPI). In embodiments, the composition comprises a magnetic substance (e.g., superparamagnetic nanoparticles) for the magnetic fieldbased imaging.

[0285] In embodiments, the method is a fluorescence imaging method. In embodiments, the composition comprises a fluorescent substance (e.g., as a diagnostic agent) for the fluorescence imaging.

[0286] In embodiments, the method is a radioimaging method. In embodiments, the method is positron emission tomography (PET). In embodiments, the composition comprises a radioactive substance (e.g., as a diagnostic agent) for such imaging methods.

[0287] In embodiments, the compositions of the disclosure are used as a contrast agent. In embodiments, the compositions are used to image blood vessels. In embodiments, the compositions are used to image blood flow.

[0288] In embodiments, the composition is administered into the bloodstream of the subject. In embodiments, the composition supplies back-scatterers in the bloodstream that allowed improved imaging of blood vessels or areas of blood circulation. In embodiments, the composition serves as a contrast agent. In embodiments, the method comprises (i) injecting the composition into the bloodstream of the subject, (ii) imaging the blood vessels or area of blood circulation by an imaging method; and optionally (iii) calculating the blood flow velocity in the blood vessels. In embodiments, the imaging method is Optical Doppler Tomography (ODT). In embodiments, the imaging method is Laser Speckle Contrast Imaging (LSCI). Further description of blood flow imaging can be found, for example, in W02014012042, the content of which is incorporated by reference in its entirety.

[0289] In embodiments, the blood vessel is a capillary. In embodiments, the area of blood circulation is a microvasculature (e.g., a tumor microvasculature).

[0290] Additional description of various imaging methods can be found, for example, in Theek et al., Radiologe. 2020 Nov;60(Suppl 1):41-53, the content of which is incorporated by reference in its entirety.

[0291] In embodiments, the method of the disclosure is for measuring one or more of the following: neurovascular hemodynamics, pharmacological effects on the brain, tumor vasculature imaging, surgical confirmation of curtailing of tumor vascular supply during brain surgery, assessment of wounding healing (e.g., noninvasive imaging of angiogeneisis), and OCT imaging of vascular abnormality in retina.

[0292] In embodiments, the imaging method is connected with surgery. In embodiments, once the image is obtained (e.g., for the blood vessel / blood circulation, wound, organ, tumor, or cavity of interest), the surgeon can perform surgery based on information provided by the image. In embodiments, the disclosure provides methods of performing a surgery for a subject in need thereof, comprising administering the composition of the disclosure to a wound, organ, tumor, or cavity, or a blood vessel or area of blood circulation, of the subject to obtain an image, and performing the surgery based on the image. In embodiments, the surgery is resecting a tumor.

[0293] In embodiments, the composition of the disclosure is used to assist inserting an instrument into a subject in need thereof. In embodiments, the composition of the disclosure functions as a lubricant. In embodiments, the composition can help deliver instruments to the target site without causing the instrument and the tissue to snag on each other. Advantageously, as discussed herein, the composition can be formulated such that the composition is biocompatible (e.g., osmolality corresponds to physiological osmolality). In embodiments, the disclosure provides methods of performing a surgery for a subject in need thereof, comprising contacting an instrument used for the surgery with the composition of the disclosure and inserting the instrument into a wound, an organ, a tumor, a blood vessel, or a cavity inside the subject. In embodiments, the composition is in contact with the instrument before the instrument is inserted into the subject. In embodiments, the composition is first administered into the target area before the instrument is inserted into it.

[0294] In embodiments, the disclosure provides methods of performing a surgery for a subject in need thereof, comprising administering the composition of the disclosure into a wound, organ, tumor, blood vessel, or cavity inside the subject, and inserting a surgery instrument into the wound, organ, tumor, blood vessel, or cavity. In embodiments, thedisclosure provides methods of placing an instrument inside a subject in need thereof, comprising, sequentially or concurrently, contacting a site in the subject with the composition of the disclosure and inserting the instrument into the subject. In embodiments, contacting the site with the composition occurs before placing the instrument. In embodiments, contacting the site with the composition is concurrent with placing the instrument. In embodiments, contacting the site with the composition is after placing the instrument.

[0295] In embodiments, the instrument is for treating a disease. In embodiments, the instrument is for preventing a disease.

[0296] In embodiments, the instrument is a catheter. In embodiments, the catheter is a subdural pressure catheter, a drainage catheter, a cerebral flow catheter, a microdialysis catheter, or a brain tissue oxygen catheter.

[0297] In embodiments, the instrument is an intracranial pressure sensor.

[0298] In embodiments, the instrument is an implantable brain-computer interface (BCI). Additional description of BCI can be found, for example, in Shih et al., Mayo Clin Proc. 2012 Mar; 87(3): 268-279, the content of which is incorporated by reference in its entirety.

[0299] In embodiments, the surgery is angioplasty, stent placement, embolization, injection of a clot-dissolving medicine, catheter placement, gastrostomy tube placement, I VC filter placement, removal of a foreign body (e.g., a shrapnel), drainage of a cyst, or needle biopsy. In embodiments, the surgery is an endovascular surgery or endoscopic surgery. Additional description of surgeries can be found, for example, in Mashoufi and Mashoufi, Cureus. 2023 Nov; 15(11): e48603, the content of which is incorporated by reference in its entirety.

[0300] In embodiments, the surgery is a brain surgery or a neurosurgery. In embodiments, the instrument is inserted into the brain of a subject.

[0301] In one embodiment, the surgery is for resecting a tumor (for example, removing a residual tumor embedded in a tissue). In embodiments, the method comprises administering the composition of the disclosure to a tissue proximal to the tumor, obtaining an image of the proximal tissue that is suspected to contain a tumor, identifying the tumor, and resecting the tumor. In embodiments, the tumor is in or proximal to a bladder, uterus, cervix, colon, or spine.

[0302] In embodiments, the composition of the disclosure has a property (e.g., attenuation coefficient) that match the target tissue, so as to enhance the signal of the target tissue (e.g., blood). In embodiments, the composition of the disclosure enhancesthe measures of flow or flow rates of a moving fluid in the subject. In embodiments, the moving fluid is an arterial blood. In embodiments, the moving fluid is a venous blood. In embodiments, the moving fluid is a cerebrospinal fluid (CSF). In embodiments, the composition of the disclosure has a property (e.g., attenuation coefficient) that match the surrounding I encapsulating tissue, so as to enhance the signal of the surrounding tissue (e.g., in bladder, uterus, cervix, colon, or spine).

[0303] In embodiments, the subject is a patient. In embodiments, the subject is a mammal. In embodiments, the subject is a primate. In embodiments, the subject is a human.

[0304] In embodiments, delivery of the composition is achieved using a balloon that contains the composition. In embodiments, the balloon is a balloon catheter. In embodiments, the composition is delivered to a cavity of the subject via the balloon. In embodiments, the cavity is created by the balloon.

[0305] In embodiments, the composition is for use in invasive ultrasound imaging of a subject. Examples of such uses include invasive ultrasound imaging during surgery, as well as non-surgical uses such as invasive diagnostic procedures (e.g. colorectal examination).

[0306] In embodiments, the composition is for use as an ultrasound coupling agent in focused ultrasound therapy. Focused ultrasound therapy concentrates ultrasound energy on a target on the body (e.g., cancer cells). By focusing on the target, focused ultrasound does not harm healthy tissue.

[0307] Various tissues / materials may be imaged using the compositions described herein. In embodiments, the composition is for use in invasive ultrasound imaging of the brain, such as during brain surgery. In embodiments, the brain contains a tumor. In embodiments, a composition described herein is used to image a tumor via ultrasound. In embodiments, the tumor is resected. In embodiments, use of a composition allows a neurosurgeon to ensure removal of tumor tissue and not healthy tissue.

[0308] In embodiments, the composition is for use in invasive ultrasound imaging of other tissues such as heart tissue or breast tissue. In embodiments, the composition described herein has an attenuation coefficient which makes it particularly suitable for imaging of the heart i.e. which composition (e.g. fluid) generates fewer artifacts during invasive ultrasound imaging of the heart.

[0309] In embodiments, provided herein is a method of ultrasound imaging of a subject, comprising administering to the subject a composition described herein through an opening in the body of the subject, applying ultrasound to said composition, and detectingultrasound reflected from said composition. In embodiments, the method is a method of ultrasound imaging of a subject during surgery, such as brain surgery, breast cancer surgery, or open-heart surgery. In embodiments, the method is a method of ultrasound imaging of a subject during an invasive diagnostic procedure, such as colorectal examination.

[0310] In embodiments, provided herein is a composition comprising: a) 20.0 to 90.0 g / L of at least one triglyceride; b) 1 .2 to 5.4 g / L of at least one phospholipid; and c) optionally at least one humectant; for use in invasive ultrasound imaging of the heart, such as during open-heart surgery, and wherein the attenuation coefficient (a) of the composition is in the range of 0.1 to 1.0 dB / (MHz*cm), preferably 0.1 to 0.8 dB(MHz*cm). Unexpectedly, when the composition having an attenuation coefficient within this range is used in invasive ultrasound imaging of the heart, the intensity and prevalence of image artifacts such as brightness artifacts is reduced.

[0311] In embodiments, provided herein is a composition comprising: a) 20.0 to 90.0 g / L of at least one triglyceride; b) 5.5 to 10.8 g / L of at least one phospholipid; and c) optionally at least one humectant; for use in invasive ultrasound imaging of the heart, such as during open-heart surgery, and wherein the attenuation coefficient (a) of the composition is in the range of 0.1 to 1.0 dB / (MHz*cm), preferably 0.1 to 0.8 dB(MHz*cm). Unexpectedly, when the composition having an attenuation coefficient within this range is used in invasive ultrasound imaging of the heart, the intensity and prevalence of image artifacts such as brightness artifacts is reduced.

[0312] In embodiments, provided herein is a composition comprising: a) 20.0 to 90.0 g / L of at least one triglyceride; b) 1 .2 to 5.4 g / L of at least one phospholipid; and c) optionally at least one humectant; for use in invasive ultrasound imaging of the breast, such as during breast cancer surgery, wherein the attenuation coefficient (a) of the composition is in the range of 0.1 to 1.2 dB / (MHz*cm), preferably 0.1 to 0.8 dB(MHz*cm). Unexpectedly, when the composition having an attenuation coefficient within this range is used in invasive ultrasound imaging of the breast, the intensity and prevalence of image artefacts such as brightness artifacts is reduced. The nature and amount of each of components a)-d) in the composition of this aspect may be as recited for the composition of any other aspect described herein.

[0313] In embodiments, provided herein is a composition comprising: a) 20.0 to 90.0 g / L of at least one triglyceride; b) 5.5 to 10.8 g / L of at least one phospholipid; and c) optionally at least one humectant;

[0314] for use in invasive ultrasound imaging of the breast, such as during breast cancer surgery, wherein the attenuation coefficient (a) of the composition is in the range of 0.1 to 1.2 dB / (MHz*cm), preferably 0.1 to 0.8 dB(MHz*cm). Unexpectedly, when the composition having an attenuation coefficient within this range is used in invasive ultrasound imaging of the breast, the intensity and prevalence of image artefacts such as brightness artifacts is reduced. The nature and amount of each of components a)-d) in the composition of this aspect may be as recited for the composition of any other aspect described herein.

[0315] In embodiments, provided herein is a composition for ultrasound imaging of the brain, comprising: a) about 60 g / L to about 80.0 g / L of at least one triglyceride; b) about 1 .2 g / L to 12 g / L of at least one phospholipid; and c) about 21 g / L to about 26 g / L of glycerol.

[0316] In embodiments, provided herein is a composition as hereinbefore defined for use in invasive ultrasound imaging of the colon in colorectal cancer staging using a balloon stand-off system, wherein the attenuation coefficient (a) of the composition is in the range of 0.1 to 0.6 dB(MHz*cm). Unexpectedly, when the composition having an attenuation coefficient within this range is used in colorectal cancer staging using a balloon stand-off system, the intensity and prevalence of image artefacts such as brightness artifacts is reduced.

[0317] The balloon standoff may comprise an outer “balloon” sheath surrounding at least a part of an ultrasound transducer and a liquid or gel ultrasound coupling material between the ultrasound transducer and the sheath. In one embodiment, the volume of ultrasound coupling material between the ultrasound transducer and the sheath may be varied in order to allow ease of positioning and conform the shape of the balloon to the biological structure being examined. The ultrasound coupling material of this embodiment will be the composition as described herein in any appropriate aspect or embodiment. The material of the sheath may be any appropriate material, such as an elastomeric polymer material. In one embodiment the material of the sheath may be latex-free.

[0318] In one aspect, the composition is for use in the invasive ultrasound imaging of the brain, heart, breast, veins, or colon.

[0319] In embodiments, provided herein are methods comprising: (i) contacting an organ or a cavity with a composition described herein; and (ii) obtaining an ultrasound image of the organ or the cavity. In embodiments, the organ or cavity comprises a tumor. In embodiments, the method further comprises resecting the tumor.

[0320] In embodiments, methods of the disclosures comprise conducting an invasive procedure before administration of the composition. In embodiments, the invasive procedure allows access of the wound, the organ, the blood vessel, or the cavity to the composition and / or instrument.

[0321] In embodiments, the cavity is selected from any one of oral cavity, nasal cavity, orbital cavity, thoracic cavity, pericardial cavity, pleural cavities, abdominal cavity, pelvic cavity, cranial cavity, spinal cavity, articular cavities, synovial cavities, buccal cavity, cranial fossae, mandibular fossa, maxillary sinus, frontal sinus, ethmoidal sinus, sphenoidal sinus, mastoid air cells, auditory canal, middle ear cavity, tympanic cavity, vestibular system, cochlear duct, olfactory epithelium, oral vestibule, palatine tonsil, pharyngeal tonsil, lingual tonsil, sinus venosus, infundibulum , alveolar sacs, bronchioles , laryngeal cavity, tracheal cavity, gastric pits, crypts of lieberkuhn, gallbladder fossa, renal sinus, ureteral opening, bladder trigone, ovarian follicles, testicular lobules, vaginal fornix, anal canal, vertebral foramen, intervertebral foramina, foramen magnum, and jugular foramen. In embodiments, the cavity comprises a tumor. In embodiments, the method comprises resecting the tumor.

[0322] In embodiments, compositions are delivered to one or more cavities in the body selected from the group consisting of the cranial cavity, the vertebral canal, the thoracic cavity, the abdominal cavity, the pelvic cavity, the abdominopelvic cavity, the ventral body cavity, the dorsal body cavity, and the pericardial cavity.

[0323] In embodiments, the organ is selected from any one of brain, heart, lungs, liver, kidneys, stomach, small intestine, large intestine, pancreas, spleen, gallbladder, colon, spine, bladder, skin, eyes, ears, nose, mouth, tongue, throat, trachea, breast, esophagus, diaphragm, adrenal gland, thyroid, parathyroid gland, pituitary gland, pineal gland, hypothalamus, ovaries, testes, uterus, prostate, penis, vagina, cervix, urethra, rectum, anus, skeletal muscles, smooth muscle, cardiac muscle, bone marrow, bones, blood vessel, lymph node, lymphatic vessel, tonsils, appendix, adipose tissue, nerves, and connective tissue. In embodiments, the organ is a brain, kidney, liver, pancreas, ovary, breast, bladder, uterus, cervix, or colon. In embodiments, the organ is the brain. In embodiments, the organ comprises a tumor. In embodiments, the method comprises resecting the tumor.

[0324] In embodiments, the compositions are used in cancer surgery. In embodiments, the compositions are used as drug delivery vehicles.

[0325] In embodiments, the disclosure provides methods of delivering a diagnostic or therapeutic agent to a subject in need thereof, comprising administering the composition of the disclosure, wherein the composition comprises the diagnostic or therapeutic agent. In embodiments, the disclosure provides methods of delivering a diagnostic or therapeutic agent to a subject in need thereof, comprising administering both the composition of the disclosure and the diagnostic or therapeutic agent. In embodiments, the composition and the agent are administered sequentially. In embodiments, the composition and the agent are administered concurrently. In embodiments, the composition and the agent are administered to the same site.

[0326] In embodiments, the method delivers a diagnostic agent. In embodiments, the diagnostic agent is a contrast agent. In embodiments, the diagnostic agent is a near infrared (I R) fluorophore. In embodiments, the near IR fluorophore is indocyanine green. In embodiments, the diagnostic agent is a fluorophore.

[0327] In embodiments, the method is for identifying a target tissue or a disease tissue inside the subject. In embodiments, the disease tissue is a residual tumor. In embodiments, the method further comprises removing and / or treating the abnormal region or the disease tissue. In embodiments, the method comprises removing the abnormal region or the disease tissue via surgery. In embodiments, the method comprises treating the abnormal region via a therapy (e.g., a photodynamic therapy, a radiotherapy, or a chemotherapy). In embodiments, the composition comprises a therapeutic agent for the therapy (e.g., a photosensitizing agent, a radioactive agent, or a chemotherapeutic agent).

[0328] In embodiments, the method is for treating a disease, and wherein the agent is a therapeutic agent. In embodiments, the therapeutic agent comprises a photosensitizing agent. In embodiments, the method comprises exposing the photosensitizing agent to light. In embodiments, the method comprises a photodynamic therapy. In embodiments, a composition described herein is diluted in water and / or glycerol and used in methods of photodynamic therapy. Photodynamic therapy is described, for example, in Hu et al., Proc SPIE Int Soc Opt Eng. 2013 Jul 13; 7380: 73801W, the content of which is incorporated by reference in its entirety.

[0329] In embodiments, the compositions are used as light dispersing agents for photodynamic therapy. The term “light dispersing agent” refers to a solution which diffuses light. Photodynamic therapy comprises administering a photosensitizing agentto cancer cells and exposing the photosensitizing agent to light. When the photosensitizing agent is exposed to light, it kills the cancer cells. In embodiments, the photosensitizing agent is delivered to cancer cells via a balloon. In embodiments, the balloon is also filled with a composition described herein, which acts as a light dispersing agent. In embodiments, the photosensitizing agent and / or a composition described herein is applied directly to a cavity in the human body. In embodiments, the light dispersing agent and / or photosensitizing agent is applied directly on a tumor. In embodiments, the photosensitizing agent and / or compositions described herein are delivered to cancer cells via a system described in any one of WO2022258727, Dupont et al. Neurosurgery 84(6):p E414-E419, June 2019, and Vermandel et al. Journal of Neuro-Oncology (2021) 152:501-514; Dupont et al. Future Oncol. 2017 Nov;13(27):2441-2454; the contents of these references are incorporated by reference herein in their entirety.

[0330] In embodiments, the method comprises diluting the composition with water and / or glycerol. In embodiments, the method comprises diluting the composition with water and glycerol. In embodiments, the method comprises diluting the composition by about 2-fold, about 3-fold, about 4-fold, about 5-fold, about 6-fold, about 7-fold, about 8-fold, about 9- fold, about 10-fold, about 11-fold, about 12-fold, about 13-fold, about 14-fold, about 15- fold, about 16-fold, about 17-fold, about 18-fold, about 19-fold, about 20-fold, about 22- fold, about 25-fold, about 30-fold, about 35-fold, about 40-fold, about 45-fold, about 50- fold, about 60-fold, about 70-fold, about 80-fold, about 90-fold, or about 100-fold. In embodiments, the method comprises diluting the composition by about 2-fold to about 5- fold, about 5-fold to about 10-fold, about 10-fold to about 15-fold, about 15-fold to about 20-fold, about 20-fold to about 30-fold, about 30-fold to about 40-fold, about 40-fold to about 60-fold, about 60-fold to about 80-fold, or about 80-fold to about 100-fold. In embodiments, the method comprises diluting the composition to a final concentration of triglyceride of about 6 % w / v, about 5 % w / v, about 4 % w / v, about 3 % w / v, about 2.5 % w / v, about 2.2 % w / v, about 2 % w / v, about 1.8 % w / v, about 1.6 % w / v, about 1.4 % w / v, about 1.2 % w / v, about 1 % w / v, about 0.9 % w / v, about 0.8 % w / v, about 0.7 % w / v, about 0.6 % w / v, about 0.5 % w / v, about 0.4 % w / v, about 0.3 % w / v, about 0.2 % w / v, about 0.1 % w / v, about 0.09 % w / v, about 0.08 % w / v, about 0.07 % w / v, about 0.06 % w / v, or about 0.05 % w / v. In embodiments, the method comprises diluting the composition to a final concentration of triglyceride of about 6 % w / v to about 4 % w / v, about 4 % w / v to about 2 % w / v, about 2 % w / v to about 1 % w / v, about 1 % w / v to about 0.8 % w / v, about 0.8 % w / v to about 0.6 % w / v, about 0.6 % w / v to about 0.4 % w / v, about 0.4 %w / v to about 0.3 % w / v, about 0.3 % w / v to about 0.2 % w / v, about 0.2 % w / v to about 0.1 % w / v, about 0.1 % w / v to about 0.08 % w / v, or about 0.08 % w / v to about 0.05 % w / v. In embodiments, the method comprises diluting the composition to a final concentration of triglyceride of about 0.1 % w / v to about 0.5 % w / v. In embodiments, the method comprises diluting the composition to a final concentration of triglyceride of about 0.1 % w / v. In embodiments, the method comprises diluting the composition to a final concentration of triglyceride of about 0.2 % w / v. In embodiments, the method comprises diluting the composition to a final concentration of triglyceride of about 0.5 % w / v. In embodiments, the ratio of the triglyceride : the phospholipid or lecithin remain the same.

[0331] In embodiments, the low triglyceride composition has an osmolality of from about 270 mOsm / kg to about 330 mOsm / kg. In embodiments, the diluted composition has an osmolality of about 290 mOsm / kg. In embodiments, the diluted composition has an osmolality of from about 284 mOsm / kg to about 296 mOsm / kg. In embodiments, the diluted composition has an osmolality of from about 290 mOsm / kg to about 311 mOsm / kg. In embodiments, the diluted composition has an osmolality of from about 290 mOsm / kg to about 305 mOsm / kg. In embodiments, the low triglyceride composition has an osmolality that is substantially the same as that of a target organ or tissue. In embodiments, the low triglyceride composition is formulated such that the composition is biocompatible (e.g., osmolality corresponds to physiological osmolality). In embodiments, the low triglyceride composition is formulated such that its osmolality is at a suitable level that can match physiological osmolality at the site of application. In embodiments, glycerol is added during the dilution of the composition by water to increase the osmolality to the target level.

[0332] In embodiments, the disclosure provides methods of treating a disease in a subject in need thereof, comprising administering the composition of the disclosure. In embodiments, the composition comprises a therapeutic agent. In embodiments, the method comprises performing a treatment (e.g., photodynamic therapy or focused ultrasound therapy).

[0333] In embodiments, the disclosure provides methods of treating a disease in a subject in need thereof using a focused ultrasound therapy, comprising administering the composition of the disclosure to the subject and performing the focused ultrasound therapy.

[0334] In embodiments, the disclosure provides methods of treating a disease in a subject in need thereof, comprising: i) contacting a wound, organ, tumor, or cavity that contains tissue of the disease with the composition of the disclosure; ii) obtaining an image of thewound, organ, tumor, or cavity; and iii) treating the disease or removing a disease tissue based on the image.

[0335] In embodiments, the disclosure provides methods of treating a disease related to blood flow or blood circulation in a subject in need thereof, comprising: i) contacting a blood vessel or area of blood circulation with the composition of the disclosure; ii) obtaining an image of the blood vessel or area of blood circulation; and iii) treating the disease or removing a disease tissue based on the image.

[0336] In embodiments, the disease related to blood flow or blood circulation is selected from atherosclerosis, myocardial infarction, angina pectoris, arrhythmia, dysrhythmia, cardiac ischemia, a stroke, a vascular disease, a peripheral artery disease, a coronary artery disease, Buerger’s disease, Mitral valve prolapse, Mitral valve regurgitation, or Mitral stenosis. In embodiments, the treatment method comprises angioplasty, stent placement, embolization, injection of a clot-dissolving medicine, catheter placement, and / or IVC filter placement.

[0337] The route of administration will vary, naturally, with the location and nature of the disease being treated or condition being diagnosed, and may include, for example, auricular, buccal, conjunctival, cutaneous, dental, endocervical, endosinusial, endotracheal, enteral, epidural, interstitial, intra-articular, intra-arterial, intra-abdominal, intraauricular, intrabiliary, intrabronchial, intrabursal, intracavernous, intracerebral, intracisternal, intracorneal, intracronal, intracoronary, intracranial, intradermal, intradiscal, intraductal, intraduodenal, intraduodenal, intradural, intraepicardial, intraepidermal, intraesophageal, intragastric, intragingival, intrahepatic, intraileal, intralesional, intralingual, intraluminal, intralymphatic, intramammary, intramedulleray, intrameningeal, intramuscular, intranasal, intranodal, intraocular, intraomentum, intraovarian, intraperitoneal, intrapericardial, intrapleural, intraprostatic, intrapulmonary, intraruminal, intrasinal, intraspinal, intrasynovial, intratendinous, intratesticular, intratracheal, intrathecal, intrathoracic, intratubular, intratumoral, intratympanic, intrauterine, intraperitoneal, intravascular, intraventricular, intravesical, intravestibular, intravenous, intravitreal, larangeal, nasal, nasogastric, oral, ophthalmic, oropharyngeal, parenteral, percutaneous, periarticular, peridural, perineural, periodontal, respiratory, retrotubular, rectal, spinal, subarachnoid, subconjunctival, subcutaneous, subdermal, subgingival, sublingual, submucosal, subretinal, topical, transdermal, transendocardial, transmucosal, transplacental, trantracheal, transtympanic, ureteral, urethral, vaginal perfusion, lavage, direct injection, oral administration, or any combination thereof.Cancer or Tumor related Applications

[0338] In embodiments, the methods of the disclosure are related to identifying and / or treating a tumor. In embodiments, the tumor is a residual tumor. In embodiments, the method comprises identifying the tumor using an imaging method of the disclosure. In embodiments, the method further comprises removing or treating the tumor identified by the imaging method. In embodiments, the methods of the disclosure comprise removing the tumor by surgery. In embodiments, the methods of the disclosure comprise treating the tumor with the composition of the disclosure (e.g., a composition that contains a therapeutic agent). In embodiments, the methods of the disclosure comprise treating the tumor with the assistance of the composition of the disclosure (e.g., the composition that serves as a light-dispersing agent for a photodynamic therapy).

[0339] In embodiments, the tumor is in or proximal to a bladder, uterus, cervix, colon, or spine. In embodiments, the tumor is a brain tumor. In embodiments, the tumor is glioma, glioblastoma, or neuroblastoma.

[0340] In embodiments, the methods described herein may be combined with one or more alternative methods of treating cancer. Non-limiting examples of alternative methods for treating cancer include chemotherapy, immunotherapy, alternating electric tumor treating fields, laser-induced interstitial thermotherapy (LITT), magnetic hyperthermia therapy (MHT), focused ultrasound, radiofrequency microwaves, photodynamic therapy (PDT), intraoperative magnetic resonance imaging, fluorescence guided resection, surgical resection, and magnetic resonance imaging. In embodiments, the method comprises administering one or more methods of cancer treatment. In embodiments, the one or more methods are selected from the group consisting of chemotherapy, immunotherapy, alternating electric tumor treating fields, laser induced interstitial thermotherapy (LITT), magnetic hyperthermia therapy (MHT), focused ultrasound, radiofrequency microwaves, photodynamic therapy (PDT), intraoperative magnetic resonance imaging, fluorescence guided resection, surgical resection, and magnetic resonance imaging. In embodiments, treating the cancer comprises exposing the cancer cells to light (e.g., via photodynamic therapy).F. Methods of Preparing Compositions

[0341] In one aspect, provided herein is a method of preparing a composition of the disclosure. In embodiments, the method comprises mixing (a) the at least one triglyceride; (b) the at least one phospholipid; (c) water; (d) the pH buffer; and (e) thehumectant. In embodiments, the method comprises mixing (a) the at least one triglyceride; (b) the lecithin comprising at least one phospholipid; (c) water; (d) the pH buffer; and (e) the humectant. In embodiments, the method comprises mixing (a) the at least one triglyceride; (b) the at least one phospholipid; (c) water; (d) the pH buffer; (e) the humectant; and (f) the diagnostic agent and / or therapeutic agent. In embodiments, the method comprises mixing (a) the at least one triglyceride; (b) the lecithin comprising at least one phospholipid; (c) water; (d) the pH buffer; (e) the humectant; and (f) the diagnostic agent and / or therapeutic agent.

[0342] In embodiments, the method comprises: i) providing a mixture comprising at least one triglyceride, at least one phospholipid and optionally at least one humectant; and ii) diluting said mixture with water.

[0343] The mixture provided in step i) is preferably an aqueous solution of the at least one triglyceride, at least one phospholipid and optionally at least one humectant. Optionally further components such as a pH-adjusting additive can also be present in the mixture. As to the nature of the triglyceride, phospholipid and optional humectant components, these can be any of the options recited in earlier aspects. A mixture comprising soybean oil, lecithin, and optionally glycerol is particularly preferred.

[0344] The amount of water = used to dilute said mixture can be adjusted so as to achieve the desired concentrations of triglyceride, phospholipid, and optional other components in the composition.

[0345] In one embodiment, any of the methods described herein include sterilization of the composition (of any embodiment disclosed herein). This may be by heat, gamma irradiation etc. In embodiments, sterilization comprises gamma irradiation and the radiation dose is fromIO to 100 kGy. In embodiments, method comprises filling the composition into a syringe and sterilizing the composition by gamma irradiation of a prefilled syringe containing said composition.

[0346] In embodiments, provided herein is a method of formulating a composition described herein, the method comprising: i) providing a mixture comprising at least one triglyceride, at least one phospholipid and optionally at least one humectant; ii) determining the attenuation coefficient (a) of the mixture; iii) calculating the difference (d) between the attenuation coefficient of the mixture determined in step ii) and a reference attenuation coefficient (ar);iv) forming a diluted mixture by diluting the mixture provided in step i) with water, in an amount which is determined by a function f(d) of the difference (d) calculated in step iii); and v) optionally repeating steps ii)-iv) on the diluted mixture obtained in step iv).

[0347] By starting with a concentrated mixture of at least one triglyceride, at least one phospholipid and optionally other components, it is possible to arrive at a composition (generally a fluid) having the desired attenuation coefficient i.e. the reference attenuation coefficient, simply by varying the amount of water or aqueous solution added to the mixture. Preferably the reference attenuation coefficient (ar) corresponds to the attenuation coefficient of a target tissue in a subject to be imaged, such as brain tissue, heart tissue or breast tissue. The value of these reference attenuation coefficients for any particular tissue may be found in published reference tables. The nature of the mixture / aqueous solution may be the same as in the method for preparing the composition according to the aspect previously described. Preferably the mixture comprises soybean oil, lecithin and glycerol.

[0348] Regarding the function f(d) used to determine the amount of water / aqueous solution to be added to the mixture to form the diluted mixture, this may be determined experimentally, e.g. using calibration curves etc. In one embodiment, the function is a linear function i.e. represented by the equation:

[0349] wherein k and c are constants. The value of the constant k and c can be determined experimentally.ExamplesExample 1 - Preparation of an exemplary composition

[0350] A concentrate of a composition described herein was formulated as an emulsion. The concentrate contained at least one triglyceride, at least one phospholipid, water, and glycerol. The concentrate was then diluted to the appropriate concentration with water. The concentrate did not include a stabilizer (e.g., no polysorbate 80 was present) or saline (i.e., no sodium chloride was present). The pH was adjusted to about 6.5 to about 8.5 with NaOH. The table below provides an exemplary concentrate formulation.Table A

[0351] The droplet size, osmolality, and pH of the emulsion were measured as described below.

[0352] Samples were stored at room temperature, with no direct exposure to sunlight. Visual analysis was done by observation of the syringe prior to extraction for further analysis, without any agitation of the samples which might cause redispersion or temporary mixing. For every measurement point, 5 ml of the emulsion was squeezed from each syringe after visual analysis. The 5 ml aliquots were subsequently used for all analyses of a specific time point. The autoclave (CertoClav® CVEL 12 L) temperature was controlled manually via a pressure gauge, and the duration of each cycle was controlled via a timer. The conditions used were 20 minutes at 121 °C.

[0353] pH measurements were collected using a Mettler Toledo SevenEasy pH-meter calibrated with AVS TITRINORM Buffer solution pH 4 and AVS TITRINORM Buffer solution pH 7, and controlled with AVS TITRJNORM Buffer solution pH 5 as part of a daily routine.

[0354] Dynamic light scattering measurements were collected using a Malvern Zetasizer Nano Series Nano- ZS. Here, the sample was diluted by a factor of 100 in DI water immediately prior to analysis. For size control and calibration, a Nanosphere size Standard 203 ± 5 nm was used. This is made fresh and run every day the measurement was done. Average droplet size reported from ZetaSizer measurements is the Z-average diameter.

[0355] The microscope used is an Olympos BX43 equipped with an Olympus XM10 camera with pre-calibrated measurements (embedded in images). Osmolality measurements were made using an OSMOMAT 030-D-D3P from GonoTec, Ser. No. 08 02 22. Here, 50 microliter of the sample was pipetted into the measuring vessel, making sure to avoid any formation of air bubbles. Prior to sample analysis, the instrument wascalibrated with a GonoTec calibration standard with an expected value of 300 mOsmol / kg NaCI / H20 (acceptable range 298-302 mOsmol / kg). The calibration standard was run in triplicate.Example 2 - Evaluation of an exemplary composition for ultrasound-guided imaging of the brain

[0356] Compositions are critical for ultrasound-guided resection of brain tumors. In the absence of a composition (e.g., in the presence of saline alone), ultrasound images are difficult to interpret due to the presence of enhancement artefacts that make it difficult to determine if residual tumor exists in the cavity. Developing compositions for the brain is challenging because they must have substantially similar acoustic properties to cerebrospinal fluid and be safe. The ideal composition for the brain allows a neurosurgeon to precisely identify and remove tumor cells. One composition that has been used for this purpose is Formulation 7 of Table B, below. In comparison to saline, the use of Formulation 7 as a composition results in removal of enhancement artefacts and improvement of tumor visualization, (compare Fig. 2A (use of saline) to Fig. 2B (use of Formulation 7 as a composition). While Formulation 7 has ideal acoustic properties for imaging and thus allows neurosurgeons to precisely identify and remove tumor cells, safety concerns were identified with this formulation due to the presence of polysorbate 80 (PS80) in the formulation. PS80 is a surfactant that is used to stabilize fat emulsions and may unsafely alter lipid content in the brain.

[0357] The development of alternative formulations that exhibit acoustic properties that are equivalent or better than those of Formulation 7, but also that lack PS80, is challenging. Because PS80 was used as a stabilizer, to stabilize droplets in the emulsion and create a homogeneous solution, removal of PS80 was expected to cause triglycerides and phospholipids in the composition to come out of solution (phase separate), which could make the composition ineffective for tumor imaging.

[0358] In the prior versions of the ultrasound coupling agent, sodium chloride was used to modify osmolality of the coupling agent such that it was isotonic to cerebral spinal fluid. However, if PS80 was removed to address the safety issues, the sodium chloride would have destabilized the emulsion, causing the triglycerides and phospholipids to phase separate. The resulting composition would not be suitable for use as an ultrasound coupling agent. Further, removing sodium chloride from the formulation would havechanged the osmolality of the coupling agent such that it was no longer isotonic to cerebral spinal fluid. Contrast agents must be isotonic with their environment to prevent them from affecting surrounding cells. For instance, if the contrast agent was hypertonic with its environment, water would be drawn out of cells and cells would collapse. This would be a serious safety risk.

[0359] The inventor herein has unexpectedly discovered that formulations lacking both PS80 and sodium chloride can effectively serve as compositions and can be used to accurately visualize a brain tissue-mimicking phantom (Cirs Multipurpose Phantom). The advantage of these formulations is that they lack PS80 and thus do not present safety concerns.

[0360] The formulations of Table B were evaluated for imaging the tissue mimicking phantom:Table B

[0361] The phantom had an attenuation coefficient of 0.5 dB / cm-MHz ± 0.07, a speed of sound of 1540 m / s ± 10 m / s, and a scatter or relative contrast of -15 dB to + 15 dB. The phantom has tubular hyperechoic and hypoechoic structures of between 3 cm and 4 cm. The phantom also contained a cubic cavity of about 2 cm length, 1 cm width, and 2 cm depth, in premade tubular structures.

[0362] The cubic cavity of the phantom was filled with one of the formulations from Table B and imaged on an ultrasound device (a BK5000 using Autogain or Fixed Gain). A neurosurgeon evaluated the (1) enhancement artifacts, (2) visual CNR, (3) overall image quality, and (4) similarity of Formulations 1-6 to Formulation 7 on a scale of 1 to 5, with a higher score being most desirable for imaging. Table C shows the scores for each Formulation using a BK5000 ultrasound device.Table C

[0363] Formulations that contained 7 % w / v triglycerides (Formulations 3 (Fig. 1C), 5 (Fig. 1 E), and 6 (Fig. 1F)) were superior compositions to formulations that contained 5 % w / v (Formulation 2, Fig. 1B) or 9 % w / v triglycerides (Formulation 4, Fig. 1D). Surprisingly, formulations that lacked salt and stabilizing agent were substantially similar to or improved compared to Formulation 7, which contained salt (i.e., NaCI) and stabilizing agent (i.e., PS80). Also surprising was the fact that Formulations 3, 5, and 6 contained 207 % more glycerol than Formulation 7 but still were suitable compositions.Example 3 - Ultrasound Fluid Characteristics of Exemplary Compositions

[0364] The particle size of a composition must be under 5 pm to safely administer a composition via intravenous administration. The osmolality of a composition must be from 270-330 mOsm / L to ensure that the composition is isotonic with cerebral spinal fluid. The pH of the composition should be from about 6.5 to about 8.5. Multiple compositions were evaluated to determine if they exhibited ideal particle size, osmolality, and pH.

[0365] Initial formulations were generated by adding glycerol to three different lipid emulsion stock solutions. Each of the lipid emulsion stock solutions contains different sources of triglycerides. For example, the triglyceride source for Lipid Emulsion 1 is soybean oil. The triglyceride source for Emulsion 2 is medium-chain triglcyerides, olive oil, and fish oil, and the triglyceride source for Emulsion 3 is highly refined fish oil. Each of the lipid emulsion stock solutions also contains a different source of phospholipid. The formulations of each lipid emulsion stock solutions are in Table D.Table D

[0366] The formulations of Table D were diluted to 5 %, 7 %, or 9% w / v triglyceride and a various amounts of glycerol was added to each formulation. Table E shows the pH and osmolality of each formulation with varying amounts of glycerol.Table E

[0367] Formulations with osmolalities from about 290 mOsm / kg - 311 mOsm / kg were then generated, and the oil droplet size was characterized. Table F shows the Mastersizer 100 % < x pm value and the D [4,3] value for each formulation. The Mastersizer 100 % < x pm value (“Mastersizer”) describes the oil droplet diameter, where 100 % of the oil droplets are smaller. The D[4,3] is the volume weighted mean droplet size.Table Fdroplet size distribution for imaging brain tumors.Example 4 - Use of Compositions in Photodynamic Therapy

[0369] Selected compositions disclosed herein (e.g., a composition containing 70 g / l soybean oil, 4.2 g / l egg yolk phospholipids, and 23.7 g / l glycerol) are diluted with a diluent to reach a series of final triglyceride concentrations between 0.005% w / v and 5% w / v — for example, 0.005% w / v, 0.01% w / v, 0.05% w / v, 0.1% w / v, 0.2% w / v, 0.5% w / v, 1% w / v, 2% w / v, and 5% w / v. Essentially all oil droplets in the low triglyceride composition have a size of less than 500 nm, with an average size of from about 250 nm to about 350 nm (e.g., about 285 nm ±20%). Prior to administering the low triglyceride composition, the patients ingest a photosensitizing agent that is preferentially absorbed by the target cells. The low triglyceride composition is then injected into the target site and / or into a conformable container such as a balloon, where the target site can be a cavity created by the resection of a tumor inside the patient. A laser light is then activated at a specific wavelength to activate the photosensitizing agent where the low triglyceride composition acts to disperse the laser light evenly around the cavity to achieve improved activation of the absorbed photosensitizing agent at the target site.Example 5 - Use of Compositions as Lubricants

[0370] Selected compositions disclosed herein (e.g., a composition containing 70 g / l soybean oil, 4.2 g / l egg yolk phospholipids, and 23.7 g / l glycerol) are used to provide a lubricant external and / or internal coating on a medical device being positioned in a vessel, such as a stent or valve, or between tissues such as positioning a pressure transducer I monitor in the ventricles of the brain to allow the free movement the device against the tissue without any snagging or irritation. For some procedures, the composition is applied sterile to the medical device external to the body prior to its entry into the body. For some procedures, the composition is applied during the procedure at the target site via a syringe and catheter combination. The use of the composition as lubricant help position the device more safely and with more predictable movements of hand and device.Example 6 - Use of Compositions as Contrast Agents

[0371] Selected compositions disclosed herein (e.g., a composition containing 70 g / l soybean oil, 4.2 g / l egg yolk phospholipids, and 23.7 g / l glycerol) that contain small oil droplets are used as contrast agents. Essentially all oil droplets in the compositions havea size of less than 500 nm, with an average size of from about 150 nm to about 250 nm, about 250 nm to about 350 nm (e.g., 285 nm ±20%), about 350 nm to about 450 nm, or about 450 nm to about 500 nm. Each of the compositions is injected into a vessel or a cavity under an ultrasound investigation to increase the contrast between the tissue and the vessel and to improve the image quality and diagnostic accuracy of the imaging.

[0372] In another study, selected compositions disclosed herein (e.g., a composition containing 70 g / l soybean oil, 4.2 g / l egg yolk phospholipids, and 23.7g / l glycerol) that contain small oil droplets are used as contrast agents. Essentially all oil droplets in the compositions have a size of less than 500 nm, with an average size of from about 150 nm to about 250 nm, about 250 nm to about 350 nm (e.g., 285 nm ±20%), about 350 nm to about 450 nm, or about 450 nm to about 500 nm. Each of the compositions is injected into a vessel or a cavity under to improve the flow measurements using doppler ultrasound. The oil droplets of the composition increase the echogenicity of the blood to give a better assessment of blood flow, as well as the measurements of structure and movement of vessel / wall, by the doppler ultrasound.Attorney Docket No. SQAS-002 / 01 WO 349370-2010NUMBERED EMBODIMENTS OF THE DISCLOSURE

[0373] Notwithstanding the appended claims, the disclosure sets for the following numbered embodiments:

[0374] Embodiment 1. A composition comprising: (a) at least one triglyceride; (b) at least one phospholipid; (c) water; (d) pH buffer; and (e) a humectant.

[0375] Embodiment 2. A composition comprising: (a) at least one triglyceride; (b) a lecithin comprising at least one phospholipid; (c) water; (d) pH buffer; and(e) a humectant.

[0376] Embodiment 3. The composition of Embodiment 1 or 2, wherein the composition comprises no more than 5% w / v, no more than 2% w / v, no more than 1% w / v, no more than 0.5% w / v, no more than 0.2% w / v, or no more than 0.1% w / v, of substance(s) other than the (a)-(e).

[0377] Embodiment 4. The composition of Embodiment 1 or 2, wherein the composition consists essentially of all of the (a)-(e).

[0378] Embodiment 5. The composition of Embodiment 1 or 2, wherein the composition consists of all of the (a)-(e).

[0379] Embodiment 6. A composition comprising: (a) at least one triglyceride; (b) at least one phospholipid; (c) water; (d) pH buffer; (e) a humectant; and (f) a diagnostic agent, a therapeutic agent, or any combination thereof.

[0380] Embodiment 7. A composition comprising: (a) at least one triglyceride; (b) a lecithin comprising at least one phospholipid; (c) water; (d) pH buffer; (e) a humectant; and (f) a diagnostic agent, a therapeutic agent, or any combination thereof.

[0381] Embodiment 8. The composition of Embodiment 6 or 7, wherein the composition comprises no more than 5% w / v, no more than 2% w / v, no more than 1% w / v, no more than 0.5% w / v, no more than 0.2% w / v, or no more than 0.1% w / v, of substance(s) other than the (a)-(f).

[0382] Embodiment 9. The composition of Embodiment 6 or 7, wherein the composition consists essentially of all of the (a)-(f).

[0383] Embodiment 10. The composition of Embodiment 6 or 7, wherein the composition consists of all of the (a)-(f).

[0384] Embodiment 11. The composition of any one of Embodiments 1-10, wherein the concentration of the at least one triglyceride is from about 5 % w / v to about 9 % w / v.Attorney Docket No. SQAS-002 / 01 WO 349370-2010

[0385] Embodiment 12. The composition of any one of Embodiments 1-10, wherein the concentration of the at least one triglyceride is from about 6 % w / v to about 8 % w / v.

[0386] Embodiment 13. The composition of any one of Embodiments 1-10, wherein the concentration of the at least one triglyceride is about 7 % w / v.

[0387] Embodiment 14. The composition of any one of Embodiments 1-10, wherein the concentration of the at least one triglyceride is from about 0.05 % w / v to about 1 % w / v, or from about 0.1 % w / v to about 0.5 % w / v.

[0388] Embodiment 15. The composition of any one of Embodiments 1-10, wherein the concentration of the at least one triglyceride is about 0.1 % w / v, about 0.2 % w / v, or about 0.5 % w / v.

[0389] Embodiment 16. The composition of any one of Embodiments 1-15, wherein the at least one triglyceride is from one or more of olive oil, coconut oil, palm oil, canola oil, soybean oil, sunflower oil, corn oil, peanut oil, safflower oil, cottonseed oil, sesame oil, flaxseed oil, walnut oil, avocado oil, rice bran oil, grapeseed oil, almond oil, hazelnut oil, macadamia nut oil, pumpkin seed oil, hemp seed oil, camelina oil, mustard oil, pistachio oil, pecan oil, poppy seed oil, black seed oil, apricot kernel oil, cherry kernel oil, peach kernel oil, tamanu oil, borage oil, evening primrose oil, sea buckthorn oil, perilla oil, moringa oil, neem oil, karanja oil, jojoba oil, tung oil, camellia oil, tea seed oil, babassu oil, murumuru oil, safflower oil, shea butter, cocoa butter, sal butter, kokum butter, mango butter, illipe butter, or fish oil.

[0390] Embodiment 17. The composition of any one of Embodiments 1-15, wherein the at least one triglyceride is from soybean oil.

[0391] Embodiment 18. The composition of any one of Embodiments 1-17, wherein the at least one triglyceride is selected from the group consisting of: tristearin, triolein, tripalmitin, triacetin, trilinolein, tricaprin, trilaurin, triarachidin, tridecanoin, trilinolenin, tricaprylin, tridecanoin, trimyristin, tricaprylin, trivalerate, tricaprate, trilinolenin, tridecanoate, triundecanoin, trinonanoin, and any combination thereof.

[0392] Embodiment 19. The composition of any one of Embodiments 1-18, wherein the at least one triglyceride is selected from the group consisting of: linolenic-oleic-linolenic, linoleic-linoleic-linoleic, oleic-linoleic-oleic, linoleic-oleic-linoleic, linolenic-linoleic- linolenic, palmitic-oleic-linoleic, palmitic-linoleic-palmitic, stearic-oleic-linoleic, linoleic- linolenic-linoleic, linoleic-oleic-oleic, and any combination thereof.Attorney Docket No. SQAS-002 / 01 WO 349370-2010

[0393] Embodiment 20. The composition of any one of Embodiments 1-19, wherein the at least one triglyceride comprises, consists essentially of, or consists of medium chain triglycerides.

[0394] Embodiment 21. The composition of any one of Embodiments 1-20, wherein the concentration of the at least one phospholipid is up to about 1.2 % w / v.

[0395] Embodiment 22. The composition of any one of Embodiments 1-20, wherein the concentration of the at least one phospholipid is from about 0.1 % w / v to about 1.2 % w / v.

[0396] Embodiment 23. The composition of any one of Embodiments 1-20, wherein the concentration of the at least one phospholipid is from about 0.2 % w / v to about 1.2 % w / v.

[0397] Embodiment 24. The composition of any one of Embodiments 1-20, wherein the concentration of the at least one phospholipid is from about 0.4 % w / v to about 1.2 % w / v.

[0398] Embodiment 25. The composition of any one of Embodiments 1-20, wherein the concentration of the at least one phospholipid is from about 0.42 % w / v to about 0.84 % w / v.

[0399] Embodiment 26. The composition of any one of Embodiments 1-20, wherein the concentration of the at least one phospholipid is from about 3.2 g / L to about 5.2 g / L.

[0400] Embodiment 27. The composition of any one of Embodiments 1-20, wherein the concentration of the at least one phospholipid is about 0.42 % w / v (about 4.2 g / L).

[0401] Embodiment 28. The composition of any one of Embodiments 1-20, wherein the concentration of the at least one phospholipid is from about 7.4 g / L to about 9.4 g / L.

[0402] Embodiment 29. The composition of any one of Embodiments 1-20, wherein the concentration of the at least one phospholipid is about 0.84 % w / v (about 8.4 g / L).

[0403] Embodiment 30. The composition of any one of Embodiments 1-29, wherein the composition comprises lecithin comprising the at least one phospholipid.

[0404] Embodiment 31. The composition of any one of Embodiments 2-5 and 7-30, wherein the lecithin comprises from about 20 % to about 90 % the at least one phospholipid by weight.Attorney Docket No. SQAS-002 / 01 WO 349370-2010

[0405] Embodiment 32. The composition of any one of Embodiments 2-5 and 7-31 , wherein the lecithin comprises from about 60 % to about 70 % the at least one phospholipid by weight.

[0406] Embodiment 33. The composition of any one of Embodiments 2-5 and 7-32, wherein the lecithin is from one or more of soybeans, sunflower seeds, rapeseeds, egg yolks, wheat germ, corn, peanuts, sesame seeds, rice bran, flaxseeds, pumpkin seeds, cashews, almonds, hazelnuts, pistachios, walnuts, pecans, macadamia nuts, brazil nuts, chia seeds, hemp seeds, poppy seeds, quinoa, oats, barley, rye, millet, sorghum, buckwheat, amaranth, avocado, olives, cocoa beans, coconut, milk, butter, cheese, yogurt, beef liver, chicken liver, fish roe, mackerel, salmon, sardines, herring, anchovies, trout, halibut, tuna, and egg whites.

[0407] Embodiment 34. The composition of any one of Embodiments 2-5 and 7-33, wherein the lecithin is egg yolk lecithin.

[0408] Embodiment 35. The composition of any one of Embodiments 2-5 and 7-34, wherein the composition comprises up to about 1.2 % w / v the lecithin.

[0409] Embodiment 36. The composition of any one of Embodiments 2-5 and 7-34, wherein the composition comprises from about 0.1 % w / v to about 1.2 % w / v the lecithin.

[0410] Embodiment 37. The composition of any one of Embodiments 2-5 and 7-34, wherein the composition comprises from about 0.4 % w / v to about 1.2 % w / v the lecithin.

[0411] Embodiment 37.1. The composition of any one of Embodiments 2-5 and 7-34, wherein the composition comprises from about 0.32 w / v to about 0.52 w / v the lecithin.

[0412] Embodiment 37.2. The composition of any one of Embodiments 2-5 and 7-34, wherein the composition comprises from about 0.37 w / v to about 0.47 w / v the lecithin.

[0413] Embodiment 37.3. The composition of any one of Embodiments 2-5 and 7-34, wherein the composition comprises from about 0.64 w / v to about 1.04 w / v the lecithin.

[0414] Embodiment 37.4. The composition of any one of Embodiments 2-5 and 7-34, wherein the composition comprises from about 0.74 w / v to about 0.94 w / v the lecithin.

[0415] Embodiment 38. The composition of any one of Embodiments 2-5 and 7-34, wherein the composition comprises about 0.42 % w / v or about 0.84 % w / v the lecithin.

[0416] Embodiment 39. The composition of any one of Embodiments 2-5 and 7-38, wherein the lecithin comprises phosphatidylcholine.Attorney Docket No. SQAS-002 / 01 WO 349370-2010

[0417] Embodiment 40. The composition of any one of Embodiments 2-5 and 7-39, wherein the lecithin comprises from about 10 % to about 75 % phosphatidylcholine by weight.

[0418] Embodiment 41. The composition of any one of Embodiments 2-5 and 7-40, wherein the lecithin comprises from about 20 % to about 70 % phosphatidylcholine by weight.

[0419] Embodiment 42. The composition of any one of Embodiments 2-5 and 7-41 , wherein the lecithin comprises from about 60 % to about 75 % phosphatidylcholine by weight.

[0420] Embodiment 43. The composition of any one of Embodiments 1-42, wherein the at least one phospholipid comprises phosphatidylcholine.

[0421] Embodiment 44. The composition of any one of Embodiments 1-43, wherein the at least one phospholipid comprises from about 10 % to about 70 % phosphatidylcholine by weight.

[0422] Embodiment 45. The composition of any one of Embodiments 1-43, wherein the at least one phospholipid comprises from about 20 % to about 70 % phosphatidylcholine by weight.

[0423] Embodiment 46. The composition of any one of Embodiments 1-43, wherein the at least one phospholipid comprises from about 60 % to about 75 % phosphatidylcholine by weight.

[0424] Embodiment 47. The composition of any one of Embodiments 1-46, wherein the concentration of the at least one triglyceride is from about 60.0 g / L to about 80.0 g / L, and / or wherein the concentration of the at least one phospholipid is from about 3.2 g / L to about 5.2 g / L.

[0425] Embodiment 48. The composition of any one of Embodiments 1-46, wherein the concentration of the at least one triglyceride is from about 60.0 g / L to about 80.0 g / L, and / or wherein the concentration of the at least one phospholipid is from about 7.4 g / L to about 9.4 g / L.

[0426] Embodiment 49. The composition of any one of Embodiments 1-48, wherein the humectant is glycerol.

[0427] Embodiment 50. The composition of any one of Embodiments 1-49, wherein the concentration of the humectant is from about 10 g / L to about 35 g / L.Attorney Docket No. SQAS-002 / 01 WO 349370-2010

[0428] Embodiment 51. The composition of any one of Embodiments 1-50, wherein the concentration of the humectant is from about 14 g / L to about 26 g / L.

[0429] Embodiment 52. The composition of any one of Embodiments 1-51 , wherein the concentration of the humectant is about 16 g / L.

[0430] Embodiment 53. The composition of any one of Embodiments 1-50, wherein the concentration of the humectant is from about 21 g / L to about 26 g / L.

[0431] Embodiment 54. The composition of any one of Embodiments 1-50, wherein the concentration of the humectant is about 23.7 g / L.

[0432] Embodiment 55. The composition of any one of Embodiments 1-54, wherein the concentration of the at least one phospholipid or the lecithin, and the concentration of the glycerol, is selected from one of the formulations in Table 3.

[0433] Embodiment 56. The composition of any one of Embodiments 1-55, wherein the ratio of the at least one triglyceride to the at least one phospholipid or the lecithin is from about 6.5:1 to about 30:1 by weight.

[0434] Embodiment 56.1. The composition of any one of Embodiments 1-56, wherein the ratio of the at least one triglyceride to the at least one phospholipid or the lecithin is from about 20:1 to about 30:1 by weight.

[0435] Embodiment 56.2 The composition of any one of Embodiments 1-56.1 , wherein the ratio of the at least one triglyceride to the at least one phospholipid or the lecithin is about 25:1 by weight.

[0436] Embodiment 57. The composition of any one of Embodiments 1-56, wherein the ratio of the at least one triglyceride to the at least one phospholipid or the lecithin is from about 13:1 to about 20:1 by weight.

[0437] Embodiment 58. The composition of any one of Embodiments 1-57, wherein the ratio of the at least one triglyceride to the at least one phospholipid or the lecithin is about 16.7:1 by weight.

[0438] Embodiment 59. The composition of any one of Embodiments 1-56, wherein the ratio of the at least one triglyceride to the at least one phospholipid or the lecithin is from about 6.5:1 to about 10:1 by weight.

[0439] Embodiment 60. The composition of any one of Embodiments 1-56, wherein the ratio of the at least one triglyceride to the at least one phospholipid or the lecithin is about 8.3:1 by weight.Attorney Docket No. SQAS-002 / 01 WO 349370-2010

[0440] Embodiment 61. The composition of any one of Embodiments 1-60, wherein the concentration of the at least one triglyceride is from about 0.05 % w / v to about 1 % w / v, or from about 0.1 % w / v to about 0.5 % w / v, wherein the ratio of the at least one triglyceride to the at least one phospholipid or the lecithin is from about 6.5:1 to about 20:1 by weight, and wherein the pH of the composition is from about 6.5 to about 8.5; optionally, the pH of the composition is about 7.

[0441] Embodiment 61.1. The composition of Embodiment 61, wherein the composition has an osmolality of less than 50 mOsm / kg, less than 40 mOsm / kg, less than 30 mOsm / kg, less than 20 mOsm / kg, less than 10 mOsm / kg, less than 5 mOsm / kg, less than 3 mOsm / kg, less than 2 mOsm / kg, or less than 1 mOsm / kg, but greater than 0 mOsm / kg.

[0442] Embodiment 61.2. The composition of any one of Embodiments 1-60, wherein the concentration of the at least one triglyceride is from about 0.05 % w / v to about 1 % w / v, or from about 0.1 % w / v to about 0.5 % w / v, wherein the ratio of the at least one triglyceride to the at least one phospholipid or the lecithin is from about 6.5:1 to about 20:1 by weight, wherein the concentration of glycerol is about 25% to about 30%.

[0443] Embodiment 61.3. The composition of Embodiment 61.2, wherein the composition has an osmolality of from about 270 mOsm / kg to about 330 mOsm / kg, from about 290 mOsm / kg to about 311 mOsm / kg, or from about 290 mOsm / kg to about 305 mOsm / kg.

[0444] Embodiment 61.4. The composition of Embodiment 61.2 or 61.3, wherein the composition has an osmolality of about 290 mOsm / kg, or from about 284 mOsm / kg to about 296 mOsm / kg.

[0445] Embodiment 62. The composition of any one of Embodiments 1-61.4, wherein the composition comprises less than 0.2 % w / v, less than 0.1 % w / v, less than 0.05 % w / v, less than 0.02 % w / v, or less than 0.01 % w / v, sodium chloride.

[0446] Embodiment 63. The composition of any one of Embodiments 1-62, wherein the composition does not contain sodium chloride.

[0447] Embodiment 64. The composition of any one of Embodiments 1-63, wherein the composition comprises less than 0.2 % w / v, less than 0.1 % w / v, less than 0.05 % w / v, less than 0.02 % w / v, or less than 0.01 % w / v, salt.Attorney Docket No. SQAS-002 / 01 WO 349370-2010

[0448] Embodiment 65. The composition of any one of Embodiments 1-64, wherein the composition does not contain any salt.

[0449] Embodiment 66. The composition of any one of Embodiments 1-65, wherein the composition comprises less than 0.2 % w / v, less than 0.1 % w / v, less than 0.05 % w / v, less than 0.02 % w / v, or less than 0.01 % w / v, polysorbate(s).

[0450] Embodiment 67. The composition of any one of Embodiments 1-66, wherein the composition does not contain polysorbate 80 (PS80).

[0451] Embodiment 68. The composition of any one of Embodiments 1-67, wherein the composition does not contain any polysorbate.

[0452] Embodiment 69. The composition of any one of Embodiments 1-68, wherein the composition comprises less than 0.2 % w / v, less than 0.1 % w / v, less than 0.05 % w / v, less than 0.02 % w / v, or less than 0.01 % w / v, stabilizer(s).

[0453] Embodiment 70. The composition of any one of Embodiments 1-69, wherein the composition does not contain a stabilizer.

[0454] Embodiment 71. The composition of any one of Embodiments 1-70, wherein the pH of the composition is 9-12, or 10-11.

[0455] Embodiment 72. The composition of any one of Embodiments 1-71, wherein the composition has not been sterilized by gamma irradiation.

[0456] Embodiment 73. The composition of any one of Embodiments 1-70, wherein the pH of the composition is from about 6.5 to about 8.5.

[0457] Embodiment 74. The composition of any one of Embodiments 1-70, wherein the pH of the composition is from about 6.9 to about 7.6.

[0458] Embodiment 75. The composition of any one of Embodiments 1-70, wherein the pH of the composition is from about 6.9 to about 7.5.

[0459] Embodiment 76. The composition of any one of Embodiments 1-70, wherein the pH of the composition is about 7.3.

[0460] Embodiment 77. The composition of any one of Embodiments 1-70, wherein the pH of the composition is about 7.5.

[0461] Embodiment 78. The composition of any one of Embodiments 1-70, wherein the pH of the composition is about 6.9.

[0462] Embodiment 79. The composition of any one of Embodiments 1-78, wherein the pH buffer is or comprises NaOH.Attorney Docket No. SQAS-002 / 01 WO 349370-2010

[0463] Embodiment 80. The composition of any one of Embodiments 1-70 and 73-79, wherein the pH of the composition is measured after sterilization by gamma irradiation and storage for at least 5 days.

[0464] Embodiment 81. The composition of any one of Embodiments 1-70 and 73-80, wherein the composition is sterilized by gamma irradiation.

[0465] Embodiment 82. The composition of any one of Embodiments 1-81 , wherein the composition is an ultrasound coupling agent.

[0466] Embodiment 83. The composition of any one of Embodiments 1-82, wherein the composition is a contrast agent.

[0467] Embodiment 84. The composition of any one of Embodiments 1-83, wherein the composition is an aqueous composition.

[0468] Embodiment 85. The composition of any one of Embodiments 1-84, wherein the composition is a lubricant.

[0469] Embodiment 86. The composition of any one of Embodiments 1-85, wherein the composition has an attenuation coefficient of from about 0.002 dB / (MHz*cm) to about 1 .0 dB / (MHz*cm).

[0470] Embodiment 87. The composition of any one of Embodiments 1-86, wherein the composition has an attenuation coefficient from about 0.05 dB / (MHz*cm) to about 15 dB / (MHz*cm).

[0471] Embodiment 88. The composition of any one of Embodiments 1-87, wherein the composition has an attenuation coefficient of from about 3 dB / (MHz*cm) to about 15 dB / (MHz*cm).

[0472] Embodiment 89. The composition of any one of Embodiments 1-88, wherein the composition has an attenuation coefficient from about 0.05 dB / (MHz*cm) to about 1.8 dB / (MHz*cm).

[0473] Embodiment 90. The composition of any one of Embodiments 1-89, wherein the composition has an attenuation coefficient of from about 0.5 dB / (MHz*cm) to about 1.5 dB / (MHz*cm).

[0474] Embodiment 91. The composition of any one of Embodiments 1-89, wherein the composition has an attenuation coefficient of from about 0.1 dB / (MHz*cm) to about 1.5 dB / (MHz*cm).Attorney Docket No. SQAS-002 / 01 WO 349370-2010

[0475] Embodiment 92. The composition of any one of Embodiments 1-89, wherein the composition has an attenuation coefficient of from about 0.1 dB / (MHz*cm) to about 0.5 dB / (MHz*cm).

[0476] Embodiment 93. The composition of any one of Embodiments 1-92, wherein the composition has an attenuation coefficient of from about 0.15 dB / (MHz*cm) to about 0.60 dB / (MHz*cm).

[0477] Embodiment 94. The composition of any one of Embodiments 1-93, wherein the composition has an attenuation coefficient that is substantially similar to an attenuation coefficient of a tissue or organ selected from a bone, brain, lung, liver, kidney, heart, cerebrospinal fluid, a soft tissue, a bladder, and a colon.

[0478] Embodiment 95. The composition of Embodiment 94, wherein the tissue or organ is of human origin.

[0479] Embodiment 96. The composition of any one of Embodiments 1-95, wherein the composition has an osmolality of from about 270 mOsm / kg to about 330 mOsm / kg.

[0480] Embodiment 96.1. The composition of any one of Embodiments 1-95, wherein the composition has an osmolality of about 290 mOsm / kg.

[0481] Embodiment 96.2. The composition of any one of Embodiments 1-95, wherein the composition has an osmolality of from about 284 mOsm / kg to about 296 mOsm / kg.

[0482] Embodiment 97. The composition of any one of Embodiments 1-95, wherein the composition has an osmolality of from about 290 mOsm / kg to about 311 mOsm / kg.

[0483] Embodiment 98. The composition of any one of Embodiments 1-95, wherein the composition has an osmolality of from about 290 mOsm / kg to about 305 mOsm / kg.

[0484] Embodiment 99. The composition of any one of Embodiments 1-98, wherein the composition has a volume mean weighted droplet size of from about 0.2 pm to about 0.55 pm.

[0485] Embodiment 100. The composition of any one of Embodiments 1-99, wherein the composition has a volume mean weighted droplet size of from about 0.26 pm to about 0.50 pm.

[0486] Embodiment 101. The composition of any one of Embodiments 1-100, wherein the composition has a volume mean weighted droplet size of from about 228 nm to about 342 nm.Attorney Docket No. SQAS-002 / 01 WO 349370-2010

[0487] Embodiment 102. The composition of any one of Embodiments 1-101 , wherein the composition has a volume mean weighted droplet size of about 258 nm.

[0488] Embodiment 103. The composition of any one of Embodiments 1-102, wherein the composition forms oil droplets, and wherein 100 % of the oil droplets have a diameter that is less than 0.84 pm.

[0489] Embodiment 104. The composition of any one of Embodiments 1-102, wherein the composition forms oil droplets, and wherein 100 % of the oil droplets have a diameter that is less than 0.96 pm.

[0490] Embodiment 105. The composition of any one of Embodiments 1-102, wherein the composition forms oil droplets, and wherein 100 % of the oil droplets have a diameter that is less than 1.91 pm.

[0491] Embodiment 106. The composition of any one of Embodiments 1-105, wherein the composition forms oil droplets, and wherein substantially none of the droplets comprise a diameter of greater than 5000 nm.

[0492] Embodiment 107. The composition of any one of Embodiments 1-106, wherein the composition forms oil droplets, and wherein the oil droplets have an average size of from 200 nm to about 750 nm.

[0493] Embodiment 108. The composition of any one of Embodiments 1-107, wherein the composition forms oil droplets, and wherein the oil droplets have an average size of from 250 nm to about 500 nm.

[0494] Embodiment 109. The composition of any one of Embodiments 1-108, wherein the composition has an average droplet size of about 285 nm ±20%.

[0495] Embodiment 110. The composition of any one of Embodiments 99-109, wherein the average droplet size is measured by dynamic light scattering.

[0496] Embodiment 111. The composition of any one of Embodiments 6-110, wherein the diagnostic agent is a contrast agent.

[0497] Embodiment 112. The composition of Embodiment 111 , wherein the contrast agent is near infrared (IR) fluorophore.

[0498] Embodiment 113. The composition of Embodiment 112, wherein the near IR fluorophore is indocyanine green.

[0499] Embodiment 114. The composition of any one of Embodiments 6-113, wherein the therapeutic agent comprises an antibiotic.Attorney Docket No. SQAS-002 / 01 WO 349370-2010

[0500] Embodiment 115. The composition of any one of Embodiments 1-114, wherein the shelf life of the composition is at least about 10 hours, at least about 16 hours, at least about 24 hours, at least about 2 days, at least about 3 days, at least about 4 days, at least about 5 days, at least about 7 days, at least about 2 weeks, at least about 3 weeks, at least about 4 weeks, at least about 2 months, at least about 3 months, at least about 4 months, at least about 6 months, at least about 9 months, at least about 1 years, at least about 2 years, at least about 3 years, at least about 4 years, at least about 5 years, or at least about 6 years, at room temperature.

[0501] Embodiment 116. The composition of any one of Embodiments 1-114, wherein the shelf life of the composition is from about six months to about five years, from about 1 year to about 5 years, from about 2 years to about 5 years, from about 3 years to about 5 years, from about 6 months to about 4 years, from about 6 months to about 3 years, from about 6 months to about 2 years, from about six months to about one year, from about 1 year to about 4 years, from about 1 year to about 3 years, from about 1 year to about 2 years, or from about 2 years to about 4 years, at room temperature.

[0502] Embodiment 117. A method of preparing the composition of any one of Embodiments 1-116, comprising mixing components (a) - (e) or (a) - (f).

[0503] Embodiment 118. An imaging method, comprising administering the composition of any one of Embodiments 1-116 to a subject in need thereof, and performing imaging.

[0504] Embodiment 119. The method of Embodiment 118, wherein the composition is administered into a wound, an organ, a tumor, a blood vessel, an area of blood circulation, or a cavity inside the subject.

[0505] Embodiment 120. A method of obtaining an image of a wound, organ, tumor, blood vessel, or cavity, comprising: i) contacting the wound, organ, tumor, blood vessel, or cavity with a composition of any one of Embodiments 1-116; ii) obtaining the image with an instrument.

[0506] Embodiment 121. The composition of any one of Embodiments 118-120, wherein the imaging is invasive ultrasound imaging.

[0507] Embodiment 122. The composition of any one of Embodiments 118-120, wherein the imaging is Doppler based flow imaging.

[0508] Embodiment 123. The composition of any one of Embodiments 118-120, wherein the imaging is laser speckle imaging.Attorney Docket No. SQAS-002 / 01 WO 349370-2010

[0509] Embodiment 124. The composition of any one of Embodiments 118-120, wherein the imaging is optical coherence tomography, photoacoustic imaging (PAI), computed tomography (CT), magnetic resonance imaging (MRI), or echocardiography.

[0510] Embodiment 125. The composition of any one of Embodiments 118-120, wherein the imaging is fluorescence imaging, radioimaging, positron emission tomography (PET), or magnetic particle imaging (MPI).

[0511] Embodiment 126. A method of performing a surgery for a subject in need thereof, comprising administering the composition of any one of Embodiments 1-116 to a wound, organ, tumor, blood vessel, area of blood circulation, or cavity of the subject to obtain an image, and performing the surgery based on the image.

[0512] Embodiment 127. A method of resecting a tumor, comprising administering the composition of any one of Embodiments 1-116 to a tissue proximal to the tumor, obtaining an ultrasound image of the tumor and the proximal tissue, identifying the tumor, and resecting the tumor.

[0513] Embodiment 128. The method of Embodiment 127, wherein the tumor is in or proximal to a bladder, uterus, cervix, colon, or spine.

[0514] Embodiment 129. The method of any one of Embodiments 118-128, wherein the composition is contained in a balloon catheter.

[0515] Embodiment 130. A method of performing a surgery for a subject in need thereof, comprising contacting an instrument used for the surgery with the composition of any one of Embodiments 1-116 and inserting the instrument into a wound, an organ, a tumor, a blood vessel, or a cavity inside the subject.

[0516] Embodiment 131. A method of performing a surgery for a subject in need thereof, comprising administering the composition of any one of Embodiments 1-116 into a wound, organ, tumor, blood vessel, or cavity inside the subject, and inserting an instrument used for the surgery into the wound, organ, tumor, blood vessel, or cavity.

[0517] Embodiment 132. The method of Embodiment 130 or 131 , wherein the surgery is a brain surgery or a neurosurgery.

[0518] Embodiment 133. A method of placing an instrument inside a subject in need thereof, comprising, sequentially or concurrently, contacting a site on the subject with the composition of any one of Embodiments 1-116 and inserting the instrument into the subject.Attorney Docket No. SQAS-002 / 01 WO 349370-2010

[0519] Embodiment 134. The method of any one of Embodiments 130-133, wherein the instrument is for preventing or treating a disease.

[0520] Embodiment 135. The method of any one of Embodiments 130-134, wherein the instrument is a catheter.

[0521] Embodiment 136. The method of Embodiment 135, wherein the catheter is a subdural pressure catheter, a drainage catheter, a cerebral flow catheter, a microdialysis catheter, or a brain tissue oxygen catheter.

[0522] Embodiment 137. The method of any one of Embodiments 130-134, wherein the instrument is an intracranial pressure sensor.

[0523] Embodiment 138. The method of any one of Embodiments 130-134, wherein the instrument is an implantable brain-computer interface (BCI).

[0524] Embodiment 139. The method of any one of Embodiments 130-138, wherein the composition acts as a lubricant for the instrument.

[0525] Embodiment 140. A method of delivering a diagnostic or therapeutic agent to a subject in need thereof, comprising administering: i) the composition of any one of Embodiments 1-116, wherein the composition comprises the diagnostic or therapeutic agent; or ii) the composition of any one of Embodiments 1-116, and the agent.

[0526] Embodiment 141. The method of Embodiment 140, wherein the method is for treating a disease, and wherein the agent comprises the therapeutic agent.

[0527] Embodiment 142. The method of Embodiment 140 or 141 , wherein the composition and the agent are administered sequentially.

[0528] Embodiment 143. The method of any one of Embodiments 140-142, wherein the therapeutic agent comprises a photosensitizing agent.

[0529] Embodiment 144. The method of Embodiment 143, comprising exposing the photosensitizing agent to light.

[0530] Embodiment 145. A method of treating a disease in a subject in need thereof using a focused ultrasound therapy, comprising administering the composition of any one of Embodiments 1-116 to the subject and performing the focused ultrasound therapy.

[0531] Embodiment 146. A method of treating a disease in a subject in need thereof, comprising administering the composition of any one of Embodiments 1-116 to the subject.Attorney Docket No. SQAS-002 / 01 WO 349370-2010

[0532] Embodiment 147. The method of any one of Embodiments 145-146, wherein the composition comprises a therapeutic agent.

[0533] Embodiment 148. The method of any one of Embodiments 145-147, wherein the method comprises treating the subject with a photodynamic therapy after administering the composition.

[0534] Embodiment 149. The method of any one of Embodiments 145-148, wherein the method comprises diluting the composition with water and glycerol to obtain a low triglyceride composition comprising about 0.005% w / v to about 0.5% w / v the triglyceride.

[0535] Embodiment 149.1. The method of Embodiment 149, wherein the low triglyceride composition has an osmolality of less than 50 mOsm / kg, less than 40 mOsm / kg, less than 30 mOsm / kg, less than 20 mOsm / kg, less than 10 mOsm / kg, less than 5 mOsm / kg, less than 3 mOsm / kg, less than 2 mOsm / kg, or less than 1 mOsm / kg, but greater than 0 mOsm / kg.

[0536] Embodiment 150. The method of Embodiment 149, wherein the low triglyceride composition has an osmolality of from about 270 mOsm / kg to about 330 mOsm / kg, from about 290 mOsm / kg to about 311 mOsm / kg, or from about 290 mOsm / kg to about 305 mOsm / kg.

[0537] Embodiment 150.1 The method of Embodiment 149, wherein the low triglyceride composition has an osmolality of about 290 mOsm / kg, or from about 284 mOsm / kg to about 296 mOsm / kg.

[0538] Embodiment 151. The method of any one of Embodiments 146-150.1 , wherein the composition is a light-dispersing agent.

[0539] Embodiment 152. The method of any one of Embodiments 146-151 , wherein the therapeutic agent comprises a photosensitizing agent.

[0540] Embodiment 153. A method of treating a disease, comprising: i) contacting a wound, organ, tumor, blood vessel, area of blood circulation or cavity that contains tissue of the disease with the composition of any one of Embodiments 1-116; ii) obtaining an image of the wound, organ, tumor, blood vessel, area of blood circulation, or cavity; and iii) treating the disease or removing a disease tissue based on the image.

[0541] Embodiment 154. The method of Embodiments 153, wherein the image is an ultrasound image.Attorney Docket No. SQAS-002 / 01 WO 349370-2010

[0542] Embodiment 155. The method of any one of Embodiments 153-154, wherein the composition comprises a contrast agent that enables obtaining the image.

[0543] Embodiment 156. The method of Embodiment 155, wherein the contrast agent is a near infrared (IR) fluorophore.

[0544] Embodiment 157. The method of Embodiment 156, wherein the near IR fluorophore is indocyanine green.

[0545] Embodiment 158. The method of any one of Embodiments 153-157, wherein the composition comprises a fluorophore.

[0546] Embodiment 159. The method of any one of Embodiments 153-158, wherein the image is for identifying a target tissue or a disease tissue inside the subject.

[0547] Embodiment 160. The method of Embodiment 159, wherein the disease tissue is a residual tumor.

[0548] Embodiment 161. The method of any one of Embodiments 140-160, wherein the method further comprises removing and / or treating an abnormal or diseased tissue.

[0549] Embodiment 162. The method of Embodiment 161, wherein the method comprises removing the abnormal or diseased tissue via surgery.

[0550] Embodiment 163. The method of Embodiment 161 or 162, wherein the method comprising treating the abnormal or diseased tissue via a chemotherapy, a targeted therapy, a photodynamic therapy, or a radiotherapy.

[0551] Embodiment 164. The method of any one of Embodiments 141-163, wherein the disease is cancer and / or the diseased tissue comprises a tumor tissue.

[0552] Embodiment 165. The method of any one of Embodiments 119-132 and 153-164, wherein the tumor is a brain tumor.

[0553] Embodiment 166. The method of any one of Embodiments 119-132 and 153-164, wherein the tumor is glioma, glioblastoma, or neuroblastoma.

[0554] Embodiment 167. The method of any one of Embodiments 118-166, comprising administering one or more methods of cancer treatment.

[0555] Embodiment 168. The method of Embodiment 167, wherein the one or more methods are selected from the group consisting of chemotherapy, immunotherapy, alternating electric tumor treating fields, laser induced interstitial thermotherapy (LITT), magnetic hyperthermia therapy (MHT), focused ultrasound, radiofrequency microwaves,Attorney Docket No. SQAS-002 / 01 WO 349370-2010 photodynamic therapy (PDT), intraoperative magnetic resonance imaging, fluorescence guided resection, surgical resection, and magnetic resonance imaging.

[0556] Embodiment 169. The method of Embodiment 167 or 168, wherein treating the disease comprises exposing the cancer cells to light.

[0557] Embodiment 170. The method of any one of Embodiments 118-169, wherein the method comprises conducting an invasive procedure before administration of the composition to allow access of the wound, the organ, the blood vessel, or the cavity to the composition and / or instrument.

[0558] Embodiment 171. The method of any one of Embodiments 119-126, 128-132, 134-139 and 153-170, wherein the cavity is selected from any one of oral cavity, nasal cavity, orbital cavity, thoracic cavity, pericardial cavity, pleural cavities, abdominal cavity, pelvic cavity, cranial cavity, spinal cavity, articular cavities, synovial cavities, buccal cavity, cranial fossae, mandibular fossa, maxillary sinus, frontal sinus, ethmoidal sinus, sphenoidal sinus, mastoid air cells, auditory canal, middle ear cavity, tympanic cavity, vestibular system, cochlear duct, olfactory epithelium, oral vestibule, palatine tonsil, pharyngeal tonsil, lingual tonsil, sinus venosus, infundibulum , alveolar sacs, bronchioles , laryngeal cavity, tracheal cavity, gastric pits, crypts of lieberkuhn, gallbladder fossa, renal sinus, ureteral opening, bladder trigone, ovarian follicles, testicular lobules, vaginal fornix, anal canal, vertebral foramen, intervertebral foramina, foramen magnum, and jugular foramen.

[0559] Embodiment 172. The method of any one of Embodiments 119-126, 128-132, 134-139 and 153-170, wherein the organ is selected from any one of brain, heart, lungs, liver, kidneys, stomach, small intestine, large intestine, pancreas, spleen, gallbladder, colon, spine, bladder, skin, eyes, ears, nose, mouth, tongue, throat, trachea, breast, esophagus, diaphragm, adrenal gland, thyroid, parathyroid gland, pituitary gland, pineal gland, hypothalamus, ovaries, testes, uterus, prostate, penis, vagina, cervix, urethra, rectum, anus, skeletal muscles, smooth muscle, cardiac muscle, bone marrow, bones, blood vessel, lymph node, lymphatic vessel, tonsils, appendix, adipose tissue, nerves, and connective tissue.

[0560] Embodiment 173. The method of any one of Embodiments 119-126, 128-132, 134-139 and 153-170, wherein the organ is a brain, kidney, liver, pancreas, ovary, breast, bladder, uterus, cervix, or colon.Attorney Docket No. SQAS-002 / 01 WO 349370-2010

[0561] Embodiment 174. The method of Embodiment 173, wherein the organ is a brain.

[0562] Embodiment 175. The method of any one of Embodiments 119-126, 128-132, 134-139 and 153-174, wherein the organ or the cavity comprises a tumor.

[0563] Embodiment 176. The method of Embodiment 175, comprising resecting the tumor.

[0564] Embodiment 177. The method of any one of Embodiments 118-176, wherein the method reduces an artifact of ultrasound imaging compared to a control method that does not administer the composition.

[0565] Embodiment 178. The method of Embodiment 178, wherein the artifact is or comprises a brightening artifact.

[0566] Embodiment 179. The method of Embodiment 177 or 178, wherein the control method uses saline water instead of the composition as an ultrasound coupling agent.

[0567] Embodiment 180. The method of any one of Embodiments 130-179, wherein the composition is contained in a balloon catheter.

[0568] Embodiment 181. The method of Embodiment 180, wherein the cavity is created by the balloon catheter.

[0569] Embodiment 182. The method of any one of Embodiments 118-181 , wherein the subject is a human.

[0570] Embodiment 183. A container comprising the composition of any one of Embodiments 1-116.

[0571] Embodiment 184. The container of Embodiment 183, wherein the container is a syringe.

[0572] Embodiment 185. The container of Embodiment 183 or 184, wherein the container is glass.

[0573] Embodiment 185.1. The container of Embodiment 183 or 184, wherein the container is stainless steel.

[0574] Embodiment 186. The container of Embodiment 183 or 184, wherein the container is a bag.

[0575] Embodiment 187. The container of any one of Embodiments 183-186, wherein the container lacks one or more of dyes, preservatives, rubber, butyl, silica, polyvinyl chloride (PVC), and di(2-ethylhexyl)phthalate (DEHP).Attorney Docket No. SQAS-002 / 01 WO 349370-2010

[0576] Embodiment 188. A kit comprising the composition of any one of Embodiments 1- 116 and a container.

[0577] Embodiment 189. The kit of Embodiment 188, wherein the container is a syringe.

[0578] Embodiment 190. The kit of Embodiment 188 or 189, wherein the container is glass.

[0579] Embodiment 190.1. The kit of Embodiment 188 or 189, wherein the container is stainless steel.

[0580] Embodiment 191. The kit of Embodiment 188, wherein the container is a bag.

[0581] Embodiment 192. The kit of any one of Embodiments 188-191 , wherein the container lacks one or more of dyes, preservatives, rubber, butyl, silica, polyvinyl chloride (PVC), and di(2-ethylhexyl)phthalate (DEHP).

[0582] Embodiment 193. The kit of any one of Embodiments 188-192, further comprising a bag spike.

[0583] Embodiment 194. The kit of any one of Embodiments 188-193, further comprising a filter.

[0584] Embodiment 195. The kit of Embodiment 194, wherein the filter has a pore size of about 1.2 pm.FURTHER NUMBERED EMBODIMENTS

[0585] Notwithstanding the appended claims, the disclosure sets for the following further numbered embodiments:1. A composition consisting of: a) from about 60.0 to about 80.0 g / L of at least one triglyceride; b) from about 3.2 to about 5.2 g / L of at least one phospholipid; c) water; d) pH buffer; and e) glycerol; wherein the composition has an attenuation constant from about 0.15 dB / (MHz*cm) to about 0.60 dB / (MHz*cm) or from about 0.002 to about 1 .0 dB / (MHz*cm).2. A composition consisting of: a) at least one triglyceride; b) at least one phospholipid;Attorney Docket No. SQAS-002 / 01 WO 349370-2010 c) water, and d) pH buffer; and e) glycerol; wherein the composition has an attenuation constant from about 0.15 dB / (MHz*cm) to about 0.60 dB / (MHz*cm) or from about 0.002 to about 1.0 dB / (MHz*cm); and wherein the ratio of the at least one triglyceride to the at least one phospholipid is from about 13:1 to about 20:1 by weight.3. A composition consisting of: a) at least one triglyceride, wherein the at least one triglyceride is present at about 7 % w / v; b) at least one phospholipid, wherein the at least one phospholipid is present at about 0.4 % w / v; c) water, wherein the water is present at about 92 % w / v; d) pH buffer; and e) glycerol.4. A composition comprising: a) from about 60.0 g / L to about 80.0 g / L of at least one triglyceride; b) from about 3.2 g / L to 5.2 g / L of at least one phospholipid, wherein the composition does not include a stabilizer and does not include sodium chloride, and wherein the composition has an attenuation constant from about 0.15 dB / (MHz*cm) to about 0.60 dB / (MHz*cm) or from about 0.002 to about 1.0 dB / (MHz*cm).5. A composition comprising: a) at least one triglyceride; and b) at least one phospholipid; wherein the composition does not include a stabilizer and does not include sodium chloride;Attorney Docket No. SQAS-002 / 01 WO 349370-2010 wherein the composition has an attenuation constant from about 0.15 dB / (MHz*cm) to about 0.60 dB / (MHz*cm) or from about 0.002 to about 1.0 dB / (MHz*cm); and wherein the ratio of the at least one triglyceride to the at least one phospholipid is from about 13:1 to about 20:1 by weight.6. A composition comprising: a) at least one triglyceride, wherein the at least one triglyceride is present at about 7 % w / v; and b) at least one phospholipid, wherein the at least one phospholipid is present at about 0.4 % w / v; wherein the composition does not include a stabilizer and does not include sodium chloride; and wherein the composition has an attenuation constant from about 0.15 dB / (MHz*cm) to about 0.60 dB / (MHz*cm) or from about 0.002 to about 1.0 dB / (MHz*cm).7. The composition of embodiment 1 , 2, 4, and 5, comprising about 70 g / L of at least one triglyceride.8. The composition of any one of embodiments 1-7, wherein the at least one triglyceride is from one or more of soybean oil, olive oil, or fish oil.9. The composition of any one of embodiments 1-8, wherein the at least one triglyceride is from soybean oil.10. The composition of any one of embodiments 4-9, comprising at least one humectant.11. The composition of embodiment 10, wherein the at least one humectant is glycerol.Attorney Docket No. SQAS-002 / 01 WO 349370-201012. The composition of any one of embodiments 4-11 , wherein the composition does not comprise PS80.13. The composition of any one of embodiments 1-12, wherein the pH is from about 6.5 to about 8.5.14. The composition of any one of embodiments 1-12, wherein the pH is about 7.315. The composition of any one of embodiments 1-14, wherein the osmolality is from 270-330 mOsm / L.16. The composition of any one of embodiments 1-15, wherein the composition has an average droplet size of about 285 nm ±20%, wherein the average droplet size is measured by dynamic light scattering.17. The composition of any one of embodiments 1-15, wherein the shelf life of the composition is at least about 10 hours.18. The composition of any one of embodiments 1-17, wherein the ratio of the at least one triglyceride to the at least one phospholipid is about 16.7:1 by weight.19. A method of obtaining an ultrasound image of an organ comprising i) contacting the organ with a composition of any one of embodiments 1-18; ii) obtaining an ultra sound image of the organ, wherein the composition does not include a stabilizer and does not include sodium chloride, and wherein the composition has an attenuation constant from about 0.15 dB / (MHz*cm) to about 0.60 dB / (MHz*cm) or from about 0.002 to about 1.0 dB / (MHz*cm).20. The method of embodiment 19, wherein the organ is a brain.Attorney Docket No. SQAS-002 / 01 WO 349370-2010Additional Embodiments1. A composition consisting essentially of:(a) from about 60.0 g / L to about 80.0 g / L of at least one triglyceride;(b) from about 3.2 g / L to about 5.2 g / L of at least one phospholipid;(c) water;(d) pH buffer; and(e) glycerol.2. A composition consisting essentially of:(a) at least one triglyceride;(b) at least one phospholipid;(c) water,(d) pH buffer; and(e) glycerol; and wherein the ratio of the at least one triglyceride to the at least one phospholipid is from about 13:1 to about 20:1 by weight.3. A composition consisting essentially of:(a) between 5 % w / v and 9 % w / v of at least one triglyceride;(b) from about 0.2 % w / v to about 1.2 % w / v of at least one phospholipid;(c) water;(d) pH buffer; and(e) glycerol.4. A composition consisting essentially of:(a) between 5 % w / v and 9 % w / v of at least one triglyceride;(b) at least one phospholipid, wherein the at least one phospholipid is present at about 0.42 % w / v;(c) water;(d) pH buffer; and(e) glycerol.Attorney Docket No. SQAS-002 / 01 WO 349370-2010 A composition consisting essentially of:(a) between 5 % w / v and 9 % w / v of at least one triglyceride;(b) at least one phospholipid;(c) water;(d) pH buffer; and(e) glycerol. A composition consisting essentially of:(a) between 5 % w / v and 9 % w / v of at least one triglyceride;(b) from about 0.2 % w / v to about 1 .2 % w / v of at least one phospholipid;(c) water;(d) pH buffer; and(e) from about 21 g / L to about 26 g / L of glycerol. A composition consisting essentially of:(a) about 7 % w / v of a triglyceride;(b) about 4.2 g / L of a phospholipid;(c) about 23.7 g / L of glycerol;(d) water; and(e) a pH buffer. A composition consisting essentially of:(a) from about 60.0 to about 80.0 g / L of at least one triglyceride;(b) from about 3.2 to about 5.2 g / L of lecithin;(c) water;(d) pH buffer; and(e) glycerol. A composition consisting essentially of:(a) at least one triglyceride;(b) lecithin;(c) water,Attorney Docket No. SQAS-002 / 01 WO 349370-2010(d) pH buffer; and(e) glycerol; and wherein the ratio of the at least one triglyceride to the at least one phospholipid is from about 13:1 to about 20:1 by weight.10. A composition consisting essentially of:(a) between 5 % w / v and 9 % w / v of at least one triglyceride;(b) from about 0.2 % w / v to about 1.2 % w / v of lecithin;(c) water;(d) pH buffer; and(e) glycerol.11. A composition consisting essentially of:(a) between 5 % w / v and 9 % w / v of at least one triglyceride;(b) about 0.42 % w / v lecithin;(c) water;(d) pH buffer; and(e) glycerol.12. A composition consisting essentially of:(a) between 5 % w / v and 9 % w / v of at least one triglyceride;(b) lecithin;(c) water;(d) pH buffer; and(e) glycerol.13. A composition consisting essentially of:(a) between 5 % w / v and 9 % w / v of at least one triglyceride;(b) from about 0.2 % w / v to about 1.2 % w / v of lecithin;(c) water;(d) pH buffer; and(e) from about 21 g / L to about 26 g / L of glycerol.Attorney Docket No. SQAS-002 / 01 WO 349370-201014. A composition consisting essentially of:(a) 7 % w / v of a triglyceride;(b) about 4.2 g / L lecithin;(c) about 23.7 g / L of glycerol;(d) water; and(e) a pH buffer.15. A composition comprising:(a) from about 60.0 to about 80.0 g / L of at least one triglyceride;(b) from about 3.2 to about 5.2 g / L of at least one phospholipid;(c) water;(d) pH buffer; and(e) glycerol; wherein the composition does not include a stabilizer and does not include sodium chloride.16. A composition comprising:(a) at least one triglyceride;(b) at least one phospholipid;(c) water;(d) pH buffer; and(e) glycerol; and wherein the ratio of the at least one triglyceride to the at least one phospholipid is from about 13:1 to about 20:1 by weight; wherein the composition does not include a stabilizer and does not include sodium chloride.17. A composition comprising:(a) between 5 % w / v and 9 % w / v of at least one triglyceride;(b) from about 0.2 % w / v to about 1 .2 % w / v of at least one phospholipid;(c) water;Attorney Docket No. SQAS-002 / 01 WO 349370-2010(d) pH buffer; and(e) glycerol; wherein the composition does not include a stabilizer and does not include sodium chloride.18. A composition comprising:(a) between 5 % w / v and 9 % w / v of at least one triglyceride;(b) at least one phospholipid, wherein the at least one phospholipid is present at about 0.42 % w / v;(c) water;(d) pH buffer; and(e) glycerol; wherein the composition does not include a stabilizer and does not include sodium chloride.19. A composition comprising:(a) between 5 % w / v and 9 % w / v of at least one triglyceride;(b) at least one phospholipid;(c) water;(d) pH buffer; and(e) glycerol; wherein the composition does not include a stabilizer and does not include sodium chloride.20. A composition comprising:(a) between 5 % w / v and 9 % w / v of at least one triglyceride;(b) from about 0.2 % w / v to about 1 .2 % w / v of at least one phospholipid;(c) water;(d) pH buffer; and(e) from about 21 g / L to about 26 g / L of glycerol; wherein the composition does not include a stabilizer and does not include sodium chloride.Attorney Docket No. SQAS-002 / 01 WO 349370-201021. A composition comprising:(a) about 7 % w / v of a triglyceride;(b) about 4.2 g / L of a phospholipid;(c) about 23.7 g / L of glycerol;(d) water; and(e) a pH buffer; wherein the composition does not include a stabilizer and does not include sodium chloride.22. A composition comprising:(a) from about 60.0 to about 80.0 g / L of at least one triglyceride;(b) from about 3.2 to about 5.2 g / L of lecithin;(c) water;(d) pH buffer; and(e) glycerol; wherein the composition does not include a stabilizer and does not include sodium chloride.23. A composition comprising:(a) at least one triglyceride;(b) lecithin;(c) water,(d) pH buffer; and(e) glycerol; and wherein the ratio of the at least one triglyceride to the at least one phospholipid is from about 13:1 to about 20:1 by weight; wherein the composition does not include a stabilizer and does not include sodium chloride.24. A composition comprising:(a) between 5 % w / v and 9 % w / v of at least one triglyceride;(b) from about 0.2 % w / v to about 1.2 % w / v of lecithin;Attorney Docket No. SQAS-002 / 01 WO 349370-2010(c) water;(d) pH buffer; and(e) glycerol; wherein the composition does not include a stabilizer and does not include sodium chloride.25. A composition comprising:(a) between 5 % w / v and 9 % w / v of at least one triglyceride;(b) about 0.42 % w / v lecithin;(c) water;(d) pH buffer; and(e) glycerol; wherein the composition does not include a stabilizer and does not include sodium chloride.26. A composition comprising:(a) between 5 % w / v and 9 % w / v of at least one triglyceride;(b) lecithin;(c) water;(d) pH buffer; and(e) glycerol; wherein the composition does not include a stabilizer and does not include sodium chloride.27. A composition comprising:(a) between 5 % w / v and 9 % w / v of triglyceride;(b) from about 0.2 % w / v to about 1.2 % w / v of at least one lecithin;(c) water;(d) pH buffer; and(e) from about 21 g / L to about 26 g / L of glycerol; wherein the composition does not include a stabilizer and does not include sodium chlorideAttorney Docket No. SQAS-002 / 01 WO 349370-201028. A composition comprising:(a) about 7 % w / v of a triglyceride;(b) about 4.2 g / L lecithin;(c) about 23.7 g / L of glycerol;(d) water; and(e) a pH buffer; wherein the composition does not include a stabilizer and does not include sodium chloride.29. A composition comprising:(a) about 7 % w / v of a triglyceride;(b) about 4.2 g / L of at least one phospholipid;(c) about 23.7 g / L of glycerol;(d) water; and(e) a pH buffer.30. A composition comprising:(a) about 7 % w / v of a triglyceride;(b) about 4.2 g / L lecithin;(c) about 23.7 g / L of glycerol;(d) water; and(e) a pH buffer.31. The composition of any one of embodiments 15-28, wherein the stabilizer is polysorbate 80 (PS80).32. The composition of any one of embodiments 1-31, wherein the composition has an attenuation coefficient of from about 0.15 dB / (MHz*cm) to about 0.60 dB / (MHz*cm).33. The composition of any one of embodiments 1-31, wherein the composition has an attenuation coefficient of from about 0.002 dB / (MHz*cm) to about 1.0 dB / (MHz*cm).Attorney Docket No. SQAS-002 / 01 WO 349370-201034. The composition of any one of embodiments 1-31 , wherein the composition has an attenuation coefficient from about 0.05 dB / (MHz*cm) to about 15 dB / (MHz*cm).35. The composition of any one of embodiments 1-31 , wherein the composition has an attenuation coefficient from about 0.05 dB / (MHz*cm) to about 1.8 dB / (MHz*cm).36. The composition of any one of embodiments 1-31 , wherein the composition has an attenuation coefficient that is from about 0.5 dB / (MHz*cm) to about 1.5 dB / (MHz*cm).37. The composition of any one of embodiments 1-31 , wherein the composition has an attenuation coefficient that is from about 3 dB / (MHz*cm) to about 15 dB / (MHz*cm).38. The composition of any one of embodiments 1-31 , wherein the composition has an attenuation coefficient that is from about 0.1 dB / (MHz*cm) to about 0.5 dB / (MHz*cm).39. The composition of any one of embodiments 1-31 , wherein the composition has an attenuation coefficient that is from about 0.1 dB / (MHz*cm) to about 1.5 dB / (MHz*cm).40. The composition of any one of embodiments 1-31 , wherein the composition has an attenuation coefficient that is substantially similar to an attenuation coefficient of bone, brain, lung, liver, kidney, heart, cerebrospinal fluid, a soft tissue, a bladder, or a colon.41. The composition of any one of embodiments 1-40, wherein the at least one triglyceride is from one or more of olive oil, coconut oil, palm oil, canola oil, soybean oil, sunflower oil, corn oil, peanut oil, safflower oil, cottonseed oil, sesame oil, flaxseed oil, walnut oil, avocado oil, rice bran oil, grapeseed oil, almond oil, hazelnut oil, macadamia nut oil, pumpkin seed oil, hemp seed oil, camelina oil, mustard oil, pistachio oil, pecan oil, poppy seed oil, black seed oil, apricot kernel oil, cherry kernel oil, peach kernel oil, tamanu oil, borage oil, evening primrose oil, sea buckthorn oil, perilla oil, moringa oil, neem oil, karanja oil, jojoba oil, tung oil, camellia oil, tea seed oil, babassu oil, murumuruAttorney Docket No. SQAS-002 / 01 WO 349370-2010 oil, safflower oil, shea butter, cocoa butter, sal butter, kokum butter, mango butter, illipe butter, or fish oil.42. The composition of any one of embodiments 1-40, wherein the at least one triglyceride is from soybean oil.43. The composition of any one of embodiments 2, 9, 16, 23, and 31-42, comprising between 5 % w / v and 9 % w / v triglyceride.44. The composition of any one of embodiments 1-6, 8-13, 15-20, 22-27, and 31-42, comprising about 7 % w / v triglyceride.45. The composition of any one of embodiments 1-38, comprising one or more triglycerides selected from any one of: tristearin, triolein, tripalmitin, triacetin, trilinolein, tricaprin, trilaurin, triarachidin, tridecanoin, trilinolenin, tricaprylin, tridecanoin, trimyristin, tricaprylin, trivalerate, tricaprate, trilinolenin, tridecanoate, triundecanoin, and trinonanoin.46. The composition of any one of embodiments 1-38, comprising one or more triglycerides selected from any one of: linolenic-oleic-linolenic, linoleic-linoleic-linoleic, oleic-linoleic-oleic, linoleic-oleic-linoleic, linolenic-linoleic-linolenic, palmitic-oleic-linoleic, palmitic-linoleic-palmitic, stearic-oleic-linoleic, linoleic-linolenic-linoleic, and linoleic-oleic- oleic.47. The composition of any one of embodiments 1-40, comprising medium chain triglycerides.48. The composition of any one of embodiments 1-7, 15-21 , 29, and 31-47, comprising lecithin comprising the at least one phospholipid.49. The composition of any one of embodiments 8-14, 22-28, and 30-48, wherein the lecithin comprises from about 20 % to about 90 % phospholipids by weight.Attorney Docket No. SQAS-002 / 01 WO 349370-201050. The composition of any one of embodiments 8-14, 22-28, and 30-48, wherein the lecithin comprises from about 60 % to about 70 % phospholipids by weight.51 . The composition of any one of embodiments 8-14, 22-28, and 30-50, wherein the lecithin is from one or more of soybeans, sunflower seeds, rapeseeds, egg yolks, wheat germ, corn, peanuts, sesame seeds, rice bran, flaxseeds, pumpkin seeds, cashews, almonds, hazelnuts, pistachios, walnuts, pecans, macadamia nuts, brazil nuts, chia seeds, hemp seeds, poppy seeds, quinoa, oats, barley, rye, millet, sorghum, buckwheat, amaranth, avocado, olives, cocoa beans, coconut, milk, butter, cheese, yogurt, beef liver, chicken liver, fish roe, mackerel, salmon, sardines, herring, anchovies, trout, halibut, tuna, and egg whites.52. The composition of any one of embodiments 8-14, 22-28, and 30-50, wherein the lecithin is egg yolk lecithin.53. The composition of any one of embodiments 8-14, 22-28, and 30-52, wherein the lecithin comprises phosphatidylcholine.54. The composition of any one of embodiments 8-14, 22-28, and 30-52, wherein the lecithin comprises from about 10 % to about 75 % phosphatidylcholine by weight.55. The composition of any one of embodiments 8-14, 22-28, and 30-52, wherein the lecithin comprises from about 20 % to about 70 % phosphatidylcholine by weight.56. The composition of any one of embodiments 8-14, 22-28, and 30-52, wherein the lecithin comprises from about 60 % to about 75 % phosphatidylcholine by weight.56.1 The composition of any one of embodiments 8-14, 22-28, and 30-52, wherein the lecithin comprises about 70 % phosphatidylcholine, from 7 to about 10 % phosphatidylethanolamine, and a maximum of 3 % of lysophosphatidylcholine by weight of the lecithin.Attorney Docket No. SQAS-002 / 01 WO 349370-201056.2 The composition of any one of embodiments 8-14, 22-28, and 30-52, wherein the lecithin comprises at least 45 % phosphatidylcholine, from 10 to about 18 % phosphatidylethanolamine, and a maximum of 4 % of lysophosphatidylcholine by weight of the lecithin.56.3 The composition of any one of embodiments 8-14, 22-28, and 30-52, wherein the lecithin comprises about 92 % phosphatidylcholine, from 0 to about 2 % phosphatidylethanolamine, and a maximum of 3 % of lysophosphatidylcholine by weight of the lecithin.56.4 The composition of any one of embodiments 8-14, 22-28, and 30-52, wherein the lecithin comprises about 70 % phosphatidylcholine, from about 12 % to about 18 % phosphatidylethanolamine, and a maximum of 3 % of lysophosphatidylcholine by weight of the lecithin.56.5 The composition of any one of embodiments 8-14, 22-28, and 30-52, wherein the lecithin comprises about 69.8 % phosphatidylcholine, about 14.6 % phosphatidylethanolamine, and about 1.5 % of lysophosphatidylcholine by weight of the lecithin.56.6 The composition of any one of embodiments 8-14, 22-28, and 30-52, wherein the lecithin comprises a minimum of 50 % of phosphatidylcholine and a minimum of 5 % phosphatidylethanolamine by weight of the lecithin.56.7 The composition of any one of embodiments 8-14, 22-28, and 30-52, wherein the lecithin comprises a minimum of 20 % of phosphatidylcholine and a minimum of 20 % lysophosphatidyl choline by weight of the lecithin.57. The composition of any one of embodiments 1-7, 15-21, 29, and 31-48, wherein the at least one phospholipid comprises phosphatidylcholine.Attorney Docket No. SQAS-002 / 01 WO 349370-201058. The composition of any one of embodiments 1-7, 15-21, 29, and 31-48, wherein the at least one phospholipid comprises from about 10 % to about 70 % phosphatidylcholine by weight.59. The composition of any one of embodiments 1-7, 15-21, 29, and 31-48, wherein the at least one phospholipid comprises from about 20 % to about 70 % phosphatidylcholine by weight.60. The composition of any one of embodiments 1-7, 15-21, 29, and 31-48, wherein the at least one phospholipid comprises from about 60 % to about 70 % phosphatidylcholine by weight.61. The composition of any one of embodiments 9, 12, 23, 26, and 31-60, comprising from about 1 g / L to about 12 g / L lecithin.62. The composition of any one of embodiments 9, 12, 23, 26, and 31-60, comprising from about 4.2 g / L to about 12 g / L lecithin.63. The composition of any one of embodiments 9, 12, 23, 26, and 31-60, comprising up to about 12 g / L lecithin.64. The composition of any one of embodiments 8-10, 12-13, 22-24, 26-27, and 31- 60, comprising about 4.2 g / L lecithin.65. The composition of any one of embodiments 9, 12, 23, 26, and 31-60, comprising from about 0.1 % w / v to about 1.2 % w / v lecithin.66. The composition of any one of embodiments 9, 12, 23, 26, and 31-60, comprising from about 0.4 % w / v to about 1.2 % w / v lecithin.67. The composition of any one of embodiments 9, 12, 23, 26, and 31-60, comprising up to about 1.2 % w / v lecithin.Attorney Docket No. SQAS-002 / 01 WO 349370-201068. The composition of any one of embodiments 8-10, 12-13, 22-24, 26-27, and 31- 60, comprising about 0.42 % w / v lecithin.65. The composition of any one of embodiments 2, 5, 16, 19, and 31-60, comprising from about 1 g / L to about 12 g / L phospholipids.66. The composition of any one of embodiments 2, 5, 16, 19, and 31-60, comprising from about 4.2 g / L to about 12 g / L phospholipids.67. The composition of any one of embodiments 2, 5, 16, 19, and 31-60, comprising up to about 12 g / L phospholipids.68. The composition of any one of embodiments 1-3, 5-6, 15-17, 19-20, and 31-60 comprising about 4.2 g / L phospholipids.69. The composition of any one of embodiments 2, 5, 16, 19, and 31-60, comprising from about 0.1 % w / v to about 1.2 % w / v phospholipids.70. The composition of any one of embodiments 2, 5, 16, 19, and 31-60, comprising from about 0.4 % w / v to about 1.2 % w / v phospholipids.71. The composition of any one of embodiments 2, 5, 16, 19, and 31-60, comprising up to about 1.2 % w / v phospholipids.72. The composition of any one of embodiments 1-3, 5-6, 15-17, 19-20, and 31-60, comprising about 0.42 % w / v phospholipids.73. The composition of any one of embodiments 1-72, wherein the pH is from about 6.5 to about 8.5.Attorney Docket No. SQAS-002 / 01 WO 349370-201074. The composition of any one of embodiments 1-72, wherein the pH is from about 6.9 to about 7.6.75. The composition of any one of embodiments 1-72, wherein the pH is from about 6.9 to about 7.5.76. The composition of any one of embodiments 1-72, wherein the pH is about 7.3.77. The composition of any one of embodiments 1-72, wherein the pH is about 7.5.78. The composition of any one of embodiments 1-72, wherein the pH is about 6.9.79. The composition of any one of embodiments 1-78, wherein the osmolality is from about 270 mOsm / kg to about 330 mOsm / kg.80. The composition of any one of embodiments 1-78, wherein the osmolality is from about 290 mOsm / kg to about 311 mOsm / kg.81. The composition of any one of embodiments 1-78, wherein the osmolality is from about 290 mOsm / kg to about 305 mOsm / kg.82. The composition of any one of embodiments 1-5, 8-12, 15-19, 22-26, and 31-81, comprising from about 14 g / L to about 26 g / L glycerol.83. The composition of any one of embodiments 1-5, 8-12, 15-19, 22-26, and 31-81, comprising about 16 g / L glycerol.84. The composition of any one of embodiments 1-6, 8-13, 15-20, 22-27, and 31-81 comprising about 23.7 g / L glycerol.85. The composition of any one of embodiments 1-84, wherein the composition has a volume mean weighted droplet size of from about 0.2 pm to about 0.55 pm.Attorney Docket No. SQAS-002 / 01 WO 349370-201086. The composition of any one of embodiments 1-84, wherein the composition has a volume mean weighted droplet size of from about 0.26 pm to about 0.50 pm.87. The composition of any one of embodiments 1-84, wherein the composition has a volume mean weighted droplet size of from about 228 nm to about 342 nm.88. The composition of any one of embodiments 1-84, wherein the composition has a volume mean weighted droplet size of about 258 nm.89. The composition of any one of embodiments 1-84, wherein the composition forms oil droplets, and wherein 100 % of the oil droplets have a diameter that is less than 0.84 pm.90. The composition of any one of embodiments 1-84, wherein the composition forms oil droplets, and wherein 100 % of the oil droplets have a diameter that is less than 0.96 pm.91 . The composition of any one of embodiments 1-84, wherein the composition forms oil droplets, and wherein 100 % of the oil droplets have a diameter that is less than 1.91 pm.92. The composition of any one of embodiments 1-84, wherein the composition forms oil droplets, and wherein substantially none of the droplets comprise a diameter of greater than 5000 nm.93. The composition of any one of embodiments 1-84, wherein the composition forms oil droplets, and wherein the oil droplets have an average size of from 200 nm to about 750 nm.Attorney Docket No. SQAS-002 / 01 WO 349370-201094. The composition of any one of embodiments 1-84, wherein the composition forms oil droplets, and wherein the oil droplets have an average size of from 250 nm to about 500 nm.95. The composition of any one of embodiments 1-84, wherein the composition has an average droplet size of about 285 nm ±20%, wherein the average droplet size is measured by dynamic light scattering.96. The composition of any one of embodiments 2, 9, 16, 23, and 31-95, comprising between about 50 g / L and about 90 g / L of at least one triglyceride.97. The composition of any one of embodiments 1-6, 8-13, 15-20, 22-27, and 31-95, comprising about 70 g / L of at least one triglyceride.98. The composition of any one of embodiments 1-86, wherein the shelf life of the composition is from about six months to about five years, from about 1 year to about 5 years, from about 2 years to about 5 years, from about 3 years to about 5 years, from about 6 months to about 4 years, from about 6 months to about 3 years, from about 6 months to about 2 years, from about six months to about one year, from about 1 year to about 4 years, from about 1 year to about 3 years, from about 1 year to about 2 years, or from about 2 years to about 4 years.99. The composition of any one of embodiments 1-6, 15-20, and 31-98, wherein the ratio of the at least one triglyceride to the at least one phospholipid is about 16.7:1 by weight.100. The composition of any one of embodiments 8-13, 22-27, and 31-98, wherein the ratio of the at least one triglyceride to the lecithin is about 16.7:1 by weight.101. A method comprising i) contacting an organ or a cavity with a composition of any one of embodiments 1-100;Attorney Docket No. SQAS-002 / 01 WO 349370-2010 ii) obtaining an ultra sound image of the organ or the cavity.102. The method of embodiment 101, wherein the cavity is selected from any one of oral cavity, nasal cavity, orbital cavity, thoracic cavity, pericardial cavity, pleural cavities, abdominal cavity, pelvic cavity, cranial cavity, spinal cavity, articular cavities, synovial cavities, buccal cavity, cranial fossae, mandibular fossa, maxillary sinus, frontal sinus, ethmoidal sinus, sphenoidal sinus, mastoid air cells, auditory canal, middle ear cavity, tympanic cavity, vestibular system, cochlear duct, olfactory epithelium, oral vestibule, palatine tonsil, pharyngeal tonsil, lingual tonsil, sinus venosus, infundibulum , alveolar sacs, bronchioles , laryngeal cavity, tracheal cavity, gastric pits, crypts of lieberkuhn, gallbladder fossa, renal sinus, ureteral opening, bladder trigone, ovarian follicles, testicular lobules, vaginal fornix, anal canal, vertebral foramen, intervertebral foramina, foramen magnum, and jugular foramen.103. The method of embodiment 101 , wherein the organ is selected from any one of brain, heart, lungs, liver, kidneys, stomach, small intestine, large intestine, pancreas, spleen, gallbladder, colon, spine, bladder, skin, eyes, ears, nose, mouth, tongue, throat, trachea, breast, esophagus, diaphragm, adrenal gland, thyroid, parathyroid gland, pituitary gland, pineal gland, hypothalamus, ovaries, testes, uterus, prostate, penis, vagina, cervix, urethra, rectum, anus, skeletal muscles, smooth muscle, cardiac muscle, bone marrow, bones, blood vessel, lymph node, lymphatic vessel, tonsils, appendix, adipose tissue, nerves, and connective tissue.104. The method of any one of embodiments 103, wherein the organ or the cavity comprises a tumor.105. The method of embodiment 104, comprising resecting the tumor.106. The method of any one of embodiments 101-105, wherein the organ is the brain.104. A container comprising a composition of any one of embodiments 1-100.Attorney Docket No. SQAS-002 / 01 WO 349370-2010105. The container of embodiment 104, wherein the container is a syringe.106. The container of embodiment 103 or 104, wherein the container is glass.107. The container of embodiment 104 or 105, wherein the container is a bag.108. The container of any one of embodiments 104-107, wherein the container lacks one or more of dyes, preservatives, rubber, butyl, silica, polyvinyl chloride (PVC), and di(2-ethylhexyl)phthalate (DEHP).109. A kit comprising a composition of any one of embodiments 1-100 and a container.110. The kit of embodiment 109, wherein the container is a syringe.111. The kit of embodiment 109 or 110, wherein the container is glass.112. The kit of embodiment 109, wherein the container is a bag.113. The kit of any one of embodiments 109-112, wherein the container lacks one or more of dyes, preservatives, rubber, butyl, silica, polyvinyl chloride (PVC), and di(2- ethylhexyl)phthalate (DEHP).114. A method of performing neurosurgery comprising contacting an instrument used for surg...

Claims

Claims1. A composition comprising:(a) at least one triglyceride;(b) at least one phospholipid;(c) water;(d) pH buffer; and(e) a humectant.

2. A composition comprising:(a) at least one triglyceride;(b) a lecithin comprising at least one phospholipid;(c) water;(d) pH buffer; and(e) a humectant.

3. The composition of claim 1 or 2, wherein the composition comprises no more than 5% w / v, no more than 2% w / v, no more than 1% w / v, no more than 0.5% w / v, no more than 0.2% w / v, or no more than 0.1% w / v, of substance(s) other than the (a)-(e).

4. The composition of claim 1 or 2, wherein the composition consists essentially of all of the (a)-(e).

5. The composition of claim 1 or 2, wherein the composition consists of all of the (a)- (e).

6. A composition comprising:(a) at least one triglyceride;(b) at least one phospholipid;(c) water;(d) pH buffer;(e) a humectant; and(f) a diagnostic agent, a therapeutic agent, or any combination thereof.

7. A composition comprising:(a) at least one triglyceride;(b) a lecithin comprising at least one phospholipid;(c) water;(d) pH buffer;(e) a humectant; and(f) a diagnostic agent, a therapeutic agent, or any combination thereof.

8. The composition of claim 6 or 7, wherein the composition comprises no more than 5% w / v, no more than 2% w / v, no more than 1 % w / v, no more than 0.5% w / v, no more than 0.2% w / v, or no more than 0.1 % w / v, of substance(s) other than the (a)-(f).

9. The composition of claim 6 or 7, wherein the composition consists essentially of all of the (a)-(f).

10. The composition of claim 6 or 7, wherein the composition consists of all of the (a)- (f).

11. The composition of any one of claims 1-10, wherein the concentration of the at least one triglyceride is from about 5 % w / v to about 9 % w / v.

12. The composition of any one of claims 1-10, wherein the concentration of the at least one triglyceride is from about 6 % w / v to about 8 % w / v.

13. The composition of any one of claims 1-10, wherein the concentration of the at least one triglyceride is about 7 % w / v.

14. The composition of any one of claims 1-10, wherein the concentration of the at least one triglyceride is from about 0.05 % w / v to about 1 % w / v, or from about 0.1 % w / v to about 0.5 % w / v.

15. The composition of any one of claims 1-10, wherein the concentration of the at least one triglyceride is about 0.1 % w / v, about 0.2 % w / v, or about 0.5 % w / v.

16. The composition of any one of claims 1-15, wherein the at least one triglyceride is from one or more of olive oil, coconut oil, palm oil, canola oil, soybean oil, sunflower oil,corn oil, peanut oil, safflower oil, cottonseed oil, sesame oil, flaxseed oil, walnut oil, avocado oil, rice bran oil, grapeseed oil, almond oil, hazelnut oil, macadamia nut oil, pumpkin seed oil, hemp seed oil, camelina oil, mustard oil, pistachio oil, pecan oil, poppy seed oil, black seed oil, apricot kernel oil, cherry kernel oil, peach kernel oil, tamanu oil, borage oil, evening primrose oil, sea buckthorn oil, perilla oil, moringa oil, neem oil, karanja oil, jojoba oil, tung oil, camellia oil, tea seed oil, babassu oil, murumuru oil, safflower oil, shea butter, cocoa butter, sal butter, kokum butter, mango butter, illipe butter, or fish oil.

17. The composition of any one of claims 1-15, wherein the at least one triglyceride is from soybean oil.

18. The composition of any one of claims 1-17, wherein the at least one triglyceride is selected from the group consisting of: tristearin, triolein, tripalmitin, triacetin, trilinolein, tricaprin, trilaurin, triarachidin, tridecanoin, trilinolenin, tricaprylin, tridecanoin, trimyristin, tricaprylin, trivalerate, tricaprate, trilinolenin, tridecanoate, triundecanoin, trinonanoin, and any combination thereof.

19. The composition of any one of claims 1-18, wherein the at least one triglyceride is selected from the group consisting of: linolenic-oleic-linolenic, linoleic-linoleic-linoleic, oleic-linoleic-oleic, linoleic-oleic-linoleic, linolenic-linoleic-linolenic, palmitic-oleic-linoleic, palmitic-linoleic-palmitic, stearic-oleic-linoleic, linoleic-linolenic-linoleic, linoleic-oleic- oleic, and any combination thereof.

20. The composition of any one of claims 1-19, wherein the at least one triglyceride comprises, consists essentially of, or consists of medium chain triglycerides.

21. The composition of any one of claims 1-20, wherein the concentration of the at least one phospholipid is up to about 1.2 % w / v.

22. The composition of any one of claims 1-20, wherein the concentration of the at least one phospholipid is from about 0.1 % w / v to about 1 .2 % w / v.

23. The composition of any one of claims 1-20, wherein the concentration of the at least one phospholipid is from about 0.2 % w / v to about 1 .2 % w / v.

24. The composition of any one of claims 1-20, wherein the concentration of the at least one phospholipid is from about 0.4 % w / v to about 1.2 % w / v.

25. The composition of any one of claims 1-20, wherein the concentration of the at least one phospholipid is from about 0.42 % w / v to about 0.84 % w / v.

26. The composition of any one of claims 1-20, wherein the concentration of the at least one phospholipid is from about 3.2 g / L to about 5.2 g / L.

27. The composition of any one of claims 1-20, wherein the concentration of the at least one phospholipid is about 0.42 % w / v (about 4.2 g / L).

28. The composition of any one of claims 1-20, wherein the concentration of the at least one phospholipid is from about 7.4 g / L to about 9.4 g / L.

29. The composition of any one of claims 1-20, wherein the concentration of the at least one phospholipid is about 0.84 % w / v (about 8.4 g / L).

30. The composition of any one of claims 1-29, wherein the composition comprises lecithin comprising the at least one phospholipid.

31. The composition of any one of claims 2-5 and 7-30, wherein the lecithin comprises from about 20 % to about 90 % the at least one phospholipid by weight.

32. The composition of any one of claims 2-5 and 7-31 , wherein the lecithin comprises from about 60 % to about 70 % the at least one phospholipid by weight.

33. The composition of any one of claims 2-5 and 7-32, wherein the lecithin is from one or more of soybeans, sunflower seeds, rapeseeds, egg yolks, wheat germ, corn, peanuts, sesame seeds, rice bran, flaxseeds, pumpkin seeds, cashews, almonds, hazelnuts, pistachios, walnuts, pecans, macadamia nuts, brazil nuts, chia seeds, hemp seeds, poppy seeds, quinoa, oats, barley, rye, millet, sorghum, buckwheat, amaranth, avocado, olives, cocoa beans, coconut, milk, butter, cheese, yogurt, beef liver, chickenliver, fish roe, mackerel, salmon, sardines, herring, anchovies, trout, halibut, tuna, and egg whites.

34. The composition of any one of claims 2-5 and 7-33, wherein the lecithin is egg yolk lecithin.

35. The composition of any one of claims 2-5 and 7-34, wherein the composition comprises up to about 1.2 % w / v the lecithin.

36. The composition of any one of claims 2-5 and 7-34, wherein the composition comprises from about 0.1 % w / v to about 1.2 % w / v the lecithin.

37. The composition of any one of claims 2-5 and 7-34, wherein the composition comprises from about 0.4 % w / v to about 1.2 % w / v the lecithin.

38. The composition of any one of claims 2-5 and 7-34, wherein the composition comprises about 0.42 % w / v or about 0.84 % w / v the lecithin.

39. The composition of any one of claims 2-5 and 7-38, wherein the lecithin comprises phosphatidylcholine.

40. The composition of any one of claims 2-5 and 7-39, wherein the lecithin comprises from about 10 % to about 75 % phosphatidylcholine by weight.

41. The composition of any one of claims 2-5 and 7-40, wherein the lecithin comprises from about 20 % to about 70 % phosphatidylcholine by weight.

42. The composition of any one of claims 2-5 and 7-41 , wherein the lecithin comprises from about 60 % to about 75 % phosphatidylcholine by weight.

43. The composition of any one of claims 1-42, wherein the at least one phospholipid comprises phosphatidylcholine.

44. The composition of any one of claims 1-43, wherein the at least one phospholipid comprises from about 10 % to about 70 % phosphatidylcholine by weight.

45. The composition of any one of claims 1-43, wherein the at least one phospholipid comprises from about 20 % to about 70 % phosphatidylcholine by weight.

46. The composition of any one of claims 1-43, wherein the at least one phospholipid comprises from about 60 % to about 75 % phosphatidylcholine by weight.

47. The composition of any one of claims 1-46, wherein the concentration of the at least one triglyceride is from about 60.0 g / L to about 80.0 g / L, and / or wherein the concentration of the at least one phospholipid is from about 3.2 g / L to about 5.2 g / L.

48. The composition of any one of claims 1-46, wherein the concentration of the at least one triglyceride is from about 60.0 g / L to about 80.0 g / L, and / or wherein the concentration of the at least one phospholipid is from about 7.4 g / L to about 9.4 g / L.

49. The composition of any one of claims 1-48, wherein the humectant is glycerol.

50. The composition of any one of claims 1-49, wherein the concentration of the humectant is from about 10 g / L to about 35 g / L.

51. The composition of any one of claims 1-50, wherein the concentration of the humectant is from about 14 g / L to about 26 g / L.

52. The composition of any one of claims 1-51, wherein the concentration of the humectant is about 16 g / L.

53. The composition of any one of claims 1-50, wherein the concentration of the humectant is from about 21 g / L to about 26 g / L.

54. The composition of any one of claims 1-50, wherein the concentration of the humectant is about 23.7 g / L.

55. The composition of any one of claims 1-54, wherein the concentration of the at least one phospholipid or the lecithin, and the concentration of the glycerol, is selected from one of the formulations in Table 3.

56. The composition of any one of claims 1-55, wherein the ratio of the at least one triglyceride to the at least one phospholipid or the lecithin is from about 6.5:1 to about 30:1 by weight.

57. The composition of any one of claims 1-56, wherein the ratio of the at least one triglyceride to the at least one phospholipid or the lecithin is from about 13: 1 to about 20: 1 by weight.

58. The composition of any one of claims 1-57, wherein the ratio of the at least one triglyceride to the at least one phospholipid or the lecithin is about 16.7:1 by weight.

59. The composition of any one of claims 1-56, wherein the ratio of the at least one triglyceride to the at least one phospholipid or the lecithin is from about 6.5:1 to about 10:1 by weight.

60. The composition of any one of claims 1-56, wherein the ratio of the at least one triglyceride to the at least one phospholipid or the lecithin is about 8.3:1 by weight.

61. The composition of any one of claims 1-60, wherein the concentration of the at least one triglyceride is from about 0.05 % w / v to about 1 % w / v, or from about 0.1 % w / v to about 0.5 % w / v, wherein the ratio of the at least one triglyceride to the at least one phospholipid or the lecithin is from about 6.5:1 to about 20:1 by weight, and wherein the pH of the composition is from about 6.5 to about 8.5.

62. The composition of any one of claims 1-61 , wherein the composition comprises less than 0.2 % w / v, less than 0.1 % w / v, less than 0.05 % w / v, less than 0.02 % w / v, or less than 0.01 % w / v, sodium chloride.

63. The composition of any one of claims 1-62, wherein the composition does not contain sodium chloride.

64. The composition of any one of claims 1-63, wherein the composition comprises less than 0.2 % w / v, less than 0.1 % w / v, less than 0.05 % w / v, less than 0.02 % w / v, or less than 0.01 % w / v, salt.

65. The composition of any one of claims 1-64, wherein the composition does not contain any salt.

66. The composition of any one of claims 1-65, wherein the composition comprises less than 0.2 % w / v, less than 0.1 % w / v, less than 0.05 % w / v, less than 0.02 % w / v, or less than 0.01 % w / v, polysorbate(s).

67. The composition of any one of claims 1-66, wherein the composition does not contain polysorbate 80 (PS80).

68. The composition of any one of claims 1-67, wherein the composition does not contain any polysorbate.

69. The composition of any one of claims 1-68, wherein the composition comprises less than 0.2 % w / v, less than 0.1 % w / v, less than 0.05 % w / v, less than 0.02 % w / v, or less than 0.01 % w / v, stabilizer(s).

70. The composition of any one of claims 1-69, wherein the composition does not contain a stabilizer.

71. The composition of any one of claims 1-70, wherein the pH of the composition is 9-12, or 10-11.

72. The composition of any one of claims 1-71 , wherein the composition has not been sterilized by gamma irradiation.

73. The composition of any one of claims 1-70, wherein the pH of the composition is from about 6.5 to about 8.5.

74. The composition of any one of claims 1-70, wherein the pH of the composition is from about 6.9 to about 7.6.

75. The composition of any one of claims 1-70, wherein the pH of the composition is from about 6.9 to about 7.5.

76. The composition of any one of claims 1-70, wherein the pH of the composition is about 7.3.

77. The composition of any one of claims 1-70, wherein the pH of the composition is about 7.5.

78. The composition of any one of claims 1-70, wherein the pH of the composition is about 6.9.

79. The composition of any one of claims 1-78, wherein the pH buffer is or comprises NaOH.

80. The composition of any one of claims 1-70 and 73-79, wherein the pH of the composition is measured after sterilization by gamma irradiation and storage for at least 5 days.

81. The composition of any one of claims 1-70 and 73-80, wherein the composition is sterilized by gamma irradiation.

82. The composition of any one of claims 1-81, wherein the composition is an ultrasound coupling agent.

83. The composition of any one of claims 1-82, wherein the composition is a contrast agent.

84. The composition of any one of claims 1-83, wherein the composition is an aqueous composition.

85. The composition of any one of claims 1-84, wherein the composition is a lubricant.

86. The composition of any one of claims 1-85, wherein the composition has an attenuation coefficient of from about 0.002 dB / (MHz*cm) to about 1.0 dB / (MHz*cm).

87. The composition of any one of claims 1-86, wherein the composition has an attenuation coefficient from about 0.05 dB / (MHz*cm) to about 15 dB / (MHz*cm).

88. The composition of any one of claims 1-87, wherein the composition has an attenuation coefficient of from about 3 dB / (MHz*cm) to about 15 dB / (MHz*cm).

89. The composition of any one of claims 1-88, wherein the composition has an attenuation coefficient from about 0.05 dB / (MHz*cm) to about 1.8 dB / (MHz*cm).

90. The composition of any one of claims 1-89, wherein the composition has an attenuation coefficient of from about 0.5 dB / (MHz*cm) to about 1.5 dB / (MHz*cm).

91. The composition of any one of claims 1-89, wherein the composition has an attenuation coefficient of from about 0.1 dB / (MHz*cm) to about 1.5 dB / (MHz*cm).

92. The composition of any one of claims 1-89, wherein the composition has an attenuation coefficient of from about 0.1 dB / (MHz*cm) to about 0.5 dB / (MHz*cm).

93. The composition of any one of claims 1-92, wherein the composition has an attenuation coefficient of from about 0.15 dB / (MHz*cm) to about 0.60 dB / (MHz*cm).

94. The composition of any one of claims 1-93, wherein the composition has an attenuation coefficient that is substantially similar to an attenuation coefficient of a tissue or organ selected from a bone, brain, lung, liver, kidney, heart, cerebrospinal fluid, a soft tissue, a bladder, and a colon.

95. The composition of claim 94, wherein the tissue or organ is of human origin.

96. The composition of any one of claims 1-95, wherein the composition has an osmolality of from about 270 mOsm / kg to about 330 mOsm / kg, or from about 284 mOsm / kg to about 296 mOsm / kg.

97. The composition of any one of claims 1-95, wherein the composition has an osmolality of from about 290 mOsm / kg to about 311 mOsm / kg.

98. The composition of any one of claims 1-95, wherein the composition has an osmolality of from about 290 mOsm / kg to about 305 mOsm / kg.

99. The composition of any one of claims 1-98, wherein the composition has a volume mean weighted droplet size of from about 0.2 pm to about 0.55 pm.

100. The composition of any one of claims 1-99, wherein the composition has a volume mean weighted droplet size of from about 0.26 pm to about 0.50 pm.

101. The composition of any one of claims 1-100, wherein the composition has a volume mean weighted droplet size of from about 228 nm to about 342 nm.

102. The composition of any one of claims 1-101 , wherein the composition has a volume mean weighted droplet size of about 258 nm.

103. The composition of any one of claims 1-102, wherein the composition forms oil droplets, and wherein 100 % of the oil droplets have a diameter that is less than 0.84 pm.

104. The composition of any one of claims 1-102, wherein the composition forms oil droplets, and wherein 100 % of the oil droplets have a diameter that is less than 0.96 pm.

105. The composition of any one of claims 1-102, wherein the composition forms oil droplets, and wherein 100 % of the oil droplets have a diameter that is less than 1.91 pm.

106. The composition of any one of claims 1-105, wherein the composition forms oil droplets, and wherein substantially none of the droplets comprise a diameter of greater than 5000 nm.

107. The composition of any one of claims 1-106, wherein the composition forms oil droplets, and wherein the oil droplets have an average size of from 200 nm to about 750 nm.

108. The composition of any one of claims 1-107, wherein the composition forms oil droplets, and wherein the oil droplets have an average size of from 250 nm to about 500 nm.

109. The composition of any one of claims 1-108, wherein the composition has an average droplet size of about 285 nm ±20%.

110. The composition of any one of claims 99-109, wherein the average droplet size is measured by dynamic light scattering.

111. The composition of any one of claims 6-110, wherein the diagnostic agent is a contrast agent.

112. The composition of claim 111 , wherein the contrast agent is near infrared (I R) fluorophore.

113. The composition of claim 112, wherein the near IR fluorophore is indocyanine green.

114. The composition of any one of claims 6-113, wherein the therapeutic agent comprises an antibiotic.

115. The composition of any one of claims 1-114, wherein the shelf life of the composition is at least about 10 hours, at least about 16 hours, at least about 24 hours, at least about 2 days, at least about 3 days, at least about 4 days, at least about 5 days, at least about 7 days, at least about 2 weeks, at least about 3 weeks, at least about 4 weeks, at least about 2 months, at least about 3 months, at least about 4 months, at least about 6 months, at least about 9 months, at least about 1 years, at least about 2 years, at least about 3 years, at least about 4 years, at least about 5 years, or at least about 6 years, at room temperature.

116. The composition of any one of claims 1-114, wherein the shelf life of the composition is from about six months to about five years, from about 1 year to about 5 years, from about 2 years to about 5 years, from about 3 years to about 5 years, from about 6 months to about 4 years, from about 6 months to about 3 years, from about 6 months to about 2 years, from about six months to about one year, from about 1 year to about 4 years, from about 1 year to about 3 years, from about 1 year to about 2 years, or from about 2 years to about 4 years, at room temperature.

117. A method of preparing the composition of any one of claims 1-116, comprising mixing components (a) - (e) or (a) - (f).

118. An imaging method, comprising administering the composition of any one of claims 1-116 to a subject in need thereof, and performing imaging.

119. The method of claim 118, wherein the composition is administered into a wound, an organ, a tumor, a blood vessel, an area of blood circulation, or a cavity inside the subject.

120. A method of obtaining an image of a wound, organ, tumor, blood vessel, or cavity, comprising: i) contacting the wound, organ, tumor, blood vessel, or cavity with a composition of any one of claims 1-116; ii) obtaining the image with an instrument.

121. The composition of any one of claims 118-120, wherein the imaging is invasive ultrasound imaging.

122. The composition of any one of claims 118-120, wherein the imaging is Doppler based flow imaging.

123. The composition of any one of claims 118-120, wherein the imaging is laser speckle imaging.

124. The composition of any one of claims 118-120, wherein the imaging is optical coherence tomography, photoacoustic imaging (PAI), computed tomography (CT), magnetic resonance imaging (MRI), or echocardiography.

125. The composition of any one of claims 118-120, wherein the imaging is fluorescence imaging, radioimaging, positron emission tomography (PET), or magnetic particle imaging (MPI).

126. A method of performing a surgery for a subject in need thereof, comprising administering the composition of any one of claims 1-116 to a wound, organ, tumor, blood vessel, area of blood circulation, or cavity of the subject to obtain an image, and performing the surgery based on the image.

127. A method of resecting a tumor, comprising administering the composition of any one of claims 1-116 to a tissue proximal to the tumor, obtaining an ultrasound image of the tumor and the proximal tissue, identifying the tumor, and resecting the tumor.

128. The method of claim 127, wherein the tumor is in or proximal to a bladder, uterus, cervix, colon, or spine.

129. The method of any one of claims 118-128, wherein the composition is contained in a balloon catheter.

130. A method of performing a surgery for a subject in need thereof, comprising contacting an instrument used for the surgery with the composition of any one of claims 1-116 and inserting the instrument into a wound, an organ, a tumor, a blood vessel, or a cavity inside the subject.

131. A method of performing a surgery for a subject in need thereof, comprising administering the composition of any one of claims 1-116 into a wound, organ, tumor, blood vessel, or cavity inside the subject, and inserting an instrument used for the surgery into the wound, organ, tumor, blood vessel, or cavity.

132. The method of claim 130 or 131 , wherein the surgery is a brain surgery or a neurosurgery.

133. A method of placing an instrument inside a subject in need thereof, comprising, sequentially or concurrently, contacting a site on the subject with the composition of any one of claims 1-116 and inserting the instrument into the subject.

134. The method of any one of claims 130-133, wherein the instrument is for preventing or treating a disease.

135. The method of any one of claims 130-134, wherein the instrument is a catheter.

136. The method of claim 135, wherein the catheter is a subdural pressure catheter, a drainage catheter, a cerebral flow catheter, a microdialysis catheter, or a brain tissue oxygen catheter.

137. The method of any one of claims 130-134, wherein the instrument is an intracranial pressure sensor.

138. The method of any one of claims 130-134, wherein the instrument is an implantable brain-computer interface (BCI).

139. The method of any one of claims 130-138, wherein the composition acts as a lubricant for the instrument.

140. A method of delivering a diagnostic or therapeutic agent to a subject in need thereof, comprising administering: i) the composition of any one of claims 1-116, wherein the composition comprises the diagnostic or therapeutic agent; or ii) the composition of any one of claims 1-116, and the agent.

141. The method of claim 140, wherein the method is for treating a disease, and wherein the agent comprises the therapeutic agent.

142. The method of claim 140 or 141 , wherein the composition and the agent are administered sequentially.

143. The method of any one of claims 140-142, wherein the therapeutic agent comprises a photosensitizing agent.

144. The method of claim 143, comprising exposing the photosensitizing agent to light.

145. A method of treating a disease in a subject in need thereof using a focused ultrasound therapy, comprising administering the composition of any one of claims 1-116 to the subject and performing the focused ultrasound therapy.

146. A method of treating a disease in a subject in need thereof, comprising administering the composition of any one of claims 1-116 to the subject.

147. The method of any one of claims 145-146, wherein the composition comprises a therapeutic agent.

148. The method of any one of claims 145-147, wherein the method comprises treating the subject with a photodynamic therapy after administering the composition.

149. The method of any one of claims 145-148, wherein the method comprises diluting the composition with water and glycerol to obtain a diluted composition comprising about 0.005% w / v to about 0.5% w / v the triglyceride.

150. The method of claim 149, wherein the diluted composition has an osmolality of from about 270 mOsm / kg to about 330 mOsm / kg, from about 284 mOsm / kg to about 296 mOsm / kg, from about 290 mOsm / kg to about 311 mOsm / kg, or from about 290 mOsm / kg to about 305 mOsm / kg.

151. The method of any one of claims 146-150, wherein the composition is a lightdispersing agent.

152. The method of any one of claims 146-151 , wherein the therapeutic agent comprises a photosensitizing agent.

153. A method of treating a disease, comprising: i) contacting a wound, organ, tumor, blood vessel, area of blood circulation or cavity that contains tissue of the disease with the composition of any one of claims 1-116; ii) obtaining an image of the wound, organ, tumor, blood vessel, area of blood circulation, or cavity; and iii) treating the disease or removing a disease tissue based on the image.

154. The method of claims 153, wherein the image is an ultrasound image.

155. The method of any one of claims 153-154, wherein the composition comprises a contrast agent that enables obtaining the image.

156. The method of claim 155, wherein the contrast agent is a near infrared (IR) fluorophore.

157. The method of claim 156, wherein the near IR fluorophore is indocyanine green.

158. The method of any one of claims 153-157, wherein the composition comprises a fluorophore.

159. The method of any one of claims 153-158, wherein the image is for identifying a target tissue or a disease tissue inside the subject.

160. The method of claim 159, wherein the disease tissue is a residual tumor.

161. The method of any one of claims 140-160, wherein the method further comprises removing and / or treating an abnormal or diseased tissue.

162. The method of claim 161, wherein the method comprises removing the abnormal or diseased tissue via surgery.

163. The method of claim 161 or 162, wherein the method comprising treating the abnormal or diseased tissue via a chemotherapy, a targeted therapy, a photodynamic therapy, or a radiotherapy.

164. The method of any one of claims 141-163, wherein the disease is cancer and / or the diseased tissue comprises a tumor tissue.

165. The method of any one of claims 119-132 and 153-164, wherein the tumor is a brain tumor.

166. The method of any one of claims 119-132 and 153-164, wherein the tumor is glioma, glioblastoma, or neuroblastoma.

167. The method of any one of claims 118-166, comprising administering one or more methods of cancer treatment.

168. The method of claim 167, wherein the one or more methods are selected from the group consisting of chemotherapy, immunotherapy, alternating electric tumor treating fields, laser induced interstitial thermotherapy (LITT), magnetic hyperthermia therapy (MHT), focused ultrasound, radiofrequency microwaves, photodynamic therapy (PDT), intraoperative magnetic resonance imaging, fluorescence guided resection, surgical resection, and magnetic resonance imaging.

169. The method of claim 167 or 168, wherein treating the disease comprises exposing the cancer cells to light.

170. The method of any one of claims 118-169, wherein the method comprises conducting an invasive procedure before administration of the composition to allow access of the wound, the organ, the blood vessel, or the cavity to the composition and / or instrument.

171. The method of any one of claims 119-126, 128-132, 134-139 and 153-170, wherein the cavity is selected from any one of oral cavity, nasal cavity, orbital cavity, thoracic cavity, pericardial cavity, pleural cavities, abdominal cavity, pelvic cavity, cranial cavity, spinal cavity, articular cavities, synovial cavities, buccal cavity, cranial fossae, mandibular fossa, maxillary sinus, frontal sinus, ethmoidal sinus, sphenoidal sinus, mastoid air cells, auditory canal, middle ear cavity, tympanic cavity, vestibular system, cochlear duct, olfactory epithelium, oral vestibule, palatine tonsil, pharyngeal tonsil, lingual tonsil, sinus venosus, infundibulum , alveolar sacs, bronchioles , laryngeal cavity, tracheal cavity, gastric pits, crypts of lieberkuhn, gallbladder fossa, renal sinus, ureteral opening, bladder trigone, ovarian follicles, testicular lobules, vaginal fornix, anal canal, vertebral foramen, intervertebral foramina, foramen magnum, and jugular foramen.

172. The method of any one of claims 119-126, 128-132, 134-139 and 153-170, wherein the organ is selected from any one of brain, heart, lungs, liver, kidneys, stomach, small intestine, large intestine, pancreas, spleen, gallbladder, colon, spine, bladder, skin, eyes, ears, nose, mouth, tongue, throat, trachea, breast, esophagus, diaphragm, adrenal gland, thyroid, parathyroid gland, pituitary gland, pineal gland, hypothalamus, ovaries,testes, uterus, prostate, penis, vagina, cervix, urethra, rectum, anus, skeletal muscles, smooth muscle, cardiac muscle, bone marrow, bones, blood vessel, lymph node, lymphatic vessel, tonsils, appendix, adipose tissue, nerves, and connective tissue.

173. The method of any one of claims 119-126, 128-132, 134-139 and 153-170, wherein the organ is a brain, kidney, liver, pancreas, ovary, breast, bladder, uterus, cervix, or colon.

174. The method of claim 173, wherein the organ is a brain.

175. The method of any one of claims 119-126, 128-132, 134-139 and 153-174, wherein the organ or the cavity comprises a tumor.

176. The method of claim 175, comprising resecting the tumor.

177. The method of any one of claims 118-176, wherein the method reduces an artifact of ultrasound imaging compared to a control method that does not administer the composition.

178. The method of claim 178, wherein the artifact is or comprises a brightening artifact.

179. The method of claim 177 or 178, wherein the control method uses saline water instead of the composition as an ultrasound coupling agent.

180. The method of any one of claims 130-179, wherein the composition is contained in a balloon catheter.

181. The method of claim 180, wherein the cavity is created by the balloon catheter.

182. The method of any one of claims 118-181 , wherein the subject is a human.

183. A container comprising the composition of any one of claims 1-116.

184. The container of claim 183, wherein the container is a syringe.

185. The container of claim 183 or 184, wherein the container is glass or stainless steel.

186. The container of claim 183 or 184, wherein the container is a bag.

187. The container of any one of claims 183-186, wherein the container lacks one or more of dyes, preservatives, rubber, butyl, silica, polyvinyl chloride (PVC), and di(2- ethylhexyl)phthalate (DEHP).

188. A kit comprising the composition of any one of claims 1-116 and a container.

189. The kit of claim 188, wherein the container is a syringe.

190. The kit of claim 188 or 189, wherein the container is glass or stainless steel.

191. The kit of claim 188, wherein the container is a bag.

192. The kit of any one of claims 188-191, wherein the container lacks one or more of dyes, preservatives, rubber, butyl, silica, polyvinyl chloride (PVC), and di(2- ethylhexyl)phthalate (DEHP).

193. The kit of any one of claims 188-192, further comprising a bag spike.

194. The kit of any one of claims 188-193, further comprising a filter.

195. The kit of claim 194, wherein the filter has a pore size of about 1.2 pm.

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