Improved tissue spacer with visual additives

Abstract

Provided herein is a method for reducing the toxicity of advanced resection cancer treatments to adjacent organs. The method provides spacing between single or multiple tumor sites and surrounding healthy organs while maintaining or improving the patient's quality of life. Such isolation of toxicity can be achieved by inserting a spacer around one or more tumor sites.

Description

[Technical field]

[0001] REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 63 / 309,430, filed February 11, 2022, which is incorporated by reference in its entirety. [Background technology]

[0002] Generally, radiation therapy is considered a palliative treatment option for severe or rare cases of melanoma. However, there has been a recent demand for new systems and methods for the management of melanoma. Brachytherapy techniques also include balloon or strut multicatheter brachytherapy, where applicators are placed into the surgical cavity by the breast surgeon at the time of or shortly after wide local excision.

[0003] Current treatments have a number of drawbacks known in the art, including difficulty in imaging in all imaging modalities across all cavity locations, difficulty in application, and migration of the balloon, structure, or spacer after placement. Summary of the Invention

[0004] The formulations and methods described herein include improved methods of radiation therapy. More specifically, the formulations and methods described herein include reducing the dose of radiation therapy to tissues adjacent to the site of radiation therapy.

[0005] Aspects of the disclosure described herein include a viscoelastic medium and a first visual additive, the first visual additive comprising a metal, the metal having a particle diameter of 80 micrometers (μm) or greater. In some embodiments, the metal is a precious metal. In some embodiments, the metal or precious metal is selected from the group consisting of gold (Au), iodine (I), gadolinium (Gd), iron (Fe), barium (Ba), calcium (Ca), magnesium (Mg), and combinations thereof. In some embodiments, the metal or precious metal is an isotope of gold (Au), iodine (I), gadolinium (Gd), iron (Fe), barium (Ba), calcium (Ca), magnesium (Mg), or combinations thereof. In some embodiments, the metal or precious metal is a powder. In some embodiments, the first visual additive has a radiographic density of about 1.0 g / cm3 to 2.0 g / cm3. In some embodiments, half of the first visual additive is configured to disperse in tissue within 9 months. In some embodiments, the particle size of the metal or precious metal is between about 80 μm and about 120 μm. In some embodiments, the particle size of the metal or precious metal is about 100 μm. In some embodiments, the first visual additive further comprises one or more microbubbles. In some embodiments, the composition comprises a second visual additive. In some embodiments, the second visual additive is different from the second visual additive. In some embodiments, the second visual additive comprises one or more microbubbles. In some embodiments, the metal or precious metal is about 0.015% to about 1.5% by weight of the composition. In some embodiments, the composition is configured to be present on an imaging modality for at least 9 months. In some embodiments, the first visual additive is configured to not substantially migrate prior to or during imaging. In some embodiments, the composition is configured to be imaged within 30 minutes, 90 minutes, 4 hours, 8 hours, or 4 days of placement.

[0006] Another aspect of the disclosure described herein includes a method of spacing a first tissue site of a subject in need thereof from a second tissue site of a subject in need thereof, the method comprising disposing a viscoelastic medium in a space between the first tissue site and the second tissue site, the viscoelastic medium comprising one or more visualization additives. In some embodiments, the method further comprises monitoring or imaging the space between the first tissue site and the second tissue site. In some embodiments, the space between the first tissue site and the second tissue site is within a range of about 0.1 cm to about 10 cm. In some embodiments, a visualization additive is present in an amount sufficient to generate contrast when imaged by an imaging modality. In some embodiments, the viscoelastic medium comprises a volume of about 1 ml to about 50 ml. In some embodiments, the viscoelastic medium is disposed through a 10-25 gauge needle. In some embodiments, the viscoelastic medium comprises hyaluronic acid, polyethylene glycol, or dextranoma in a concentration ranging from about 5 mg / ml to about 100 mg / ml. In some embodiments, the viscoelastic medium comprises gel particles ranging in size from about 0.08 mm to about 5 mm. In some embodiments, the viscoelastic medium is administered subcutaneously or subepidermally. In some embodiments, the first tissue site and the second tissue site are selected from the group consisting of breast, head and neck, cervix, vagina, uterus, ovaries, spinal base, skin, pancreas, liver, rectum, or lung of a subject. In some embodiments, the imaging comprises real-time imaging. In some embodiments, the imaging is performed within 30 minutes, 90 minutes, 4 hours, 8 hours, or 4 days of the placement of the viscoelastic medium. In some embodiments, the imaging comprises MRI, CT, ultrasound, or a combination thereof. In some embodiments, the imaging modality comprises MRI, CT, ultrasound, or a combination thereof. In some embodiments, the viscoelastic medium does not move substantially before and during the imaging.In some embodiments, the visualization additive comprises one or more nanoparticles.In some embodiments, the visualization additive comprises a precious metal. In some embodiments, the precious metal comprises iron or gold. In some embodiments, the viscoelastic medium is bioabsorbable. In some embodiments, the visualization additive comprises gold, iodine, gadolinium, iron, barium, calcium, magnesium, or combinations thereof. In some embodiments, the visualization additive is gold particles.

[0007] Another aspect of the disclosure described herein includes a method of preventing or reducing damage to tissue adjacent to a site of radiation treatment in a subject undergoing radiation therapy, the method comprising injecting a bioabsorbable viscoelastic medium into the site of radiation treatment, the bioabsorbable viscoelastic medium including a visualization additive. In some embodiments, the injection displaces the tissue a distance ranging from about 0.1 cm to about 10 cm. In some embodiments, the viscoelastic medium includes gel particles. In some embodiments, the gel particles include hyaluronic acid or a derivative thereof. In some embodiments, the injection includes a volume of about 1 ml to about 50 ml. In some embodiments, the injection is performed with a 10-25 gauge needle. In some embodiments, the concentration of hyaluronic acid is in the range of about 5 mg / ml to about 100 mg / ml. In some embodiments, the gel particles have a size ranging from about 0.2 mm to about 5 mm. In some embodiments, the injection is subcutaneous or subepidermal. In some embodiments, migration of the viscoelastic medium is prevented or reduced. In some embodiments, the visualization additive comprises one or more nanoparticles. In some embodiments, the nanoparticles comprise a precious metal. In some embodiments, the visualization additive comprises gold, iodine, gadolinium, iron, barium, calcium, magnesium, or a combination thereof. In some embodiments, the precious metal is gold. In some embodiments, the dose of radiation therapy contacting tissue adjacent to the site of radiation treatment is reduced by about 10% to about 80%. In some embodiments, the site of radiation treatment is selected from the group consisting of the subject's breast, head and neck, cervix, vagina, spinal base, skin, pancreas, liver, rectum, or lung. The method of any one of embodiments 35-48 further comprises administration of hyaluronidase at the site of radiation treatment. In some embodiments, the volume of the viscoelastic medium at the site of radiation treatment is reduced by about 1% to about 95%. In some embodiments, the administration of hyaluronidase occurs about 0.1 hours to about 24 hours after injection of the bioabsorbable viscoelastic medium. In some embodiments, the method further comprises imaging the site of radiation treatment, hi some embodiments, the imaging comprises continuous imaging.In some embodiments, the imaging includes an MRI, a CT scan, an ultrasound, or a combination thereof.

[0008] Another aspect of the disclosure described herein includes a method of reducing a dose of radiation therapy to tissue proximate to a site of radiation treatment in a subject undergoing radiation therapy, the method comprising injecting a bioabsorbable viscoelastic medium into the site of radiation treatment. In some embodiments, the injection displaces the tissue a distance ranging from about 0.1 cm to about 10 cm. In some embodiments, the viscoelastic medium comprises gel particles. In some embodiments, the gel particles comprise hyaluronic acid or a derivative thereof. In some embodiments, the injection comprises a volume of about 1 ml to about 50 ml. In some embodiments, the injection is administered through a 10-25 gauge needle. In some embodiments, the concentration of hyaluronic acid ranges from about 5 mg / ml to about 100 mg / ml. In some embodiments, the gel particles have a size ranging from about 0.2 mm to about 5 mm. In some embodiments, the injection is subcutaneous or subepidermal. In some embodiments, migration of the viscoelastic medium is prevented or reduced. In some embodiments, the viscoelastic medium further comprises one or more nanoparticles. In some embodiments, the nanoparticles comprise a precious metal. In some embodiments, the dose of radiation therapy is reduced by about 10% to about 80%. In some embodiments, the site of radiation therapy is selected from the group consisting of the subject's breast, head and neck, cervix, vagina, spinal base, skin, pancreas, liver, rectum, or lung. In some embodiments, the method further comprises administration of hyaluronidase at the site of radiation therapy. In some embodiments, the volume of the viscoelastic medium at the site of radiation therapy is reduced by about 1% to about 95%. In some embodiments, administration of hyaluronidase is performed about 0.1 hours to about 24 hours after injection of the bioabsorbable viscoelastic medium.

[0009] Another aspect of the disclosure described herein includes a method of temporarily super-spacing tissue adjacent to a site of radiation treatment, comprising injecting a formulation comprising cross-linked hyaluronic acid or a derivative thereof and a quantity of degradable nanoparticles encapsulating hyaluronidase. In some embodiments, the amount of degradable nanoparticles encapsulating hyaluronidase is directly proportional to the desired super-spacing distance for the desired super-spacing duration. In some embodiments, the method further comprises injecting a bioabsorbable viscoelastic medium into a blood vessel, where the blood vessel is directly coupled to a tumor. In some embodiments, the viscoelastic medium comprises gel particles. In some embodiments, the gel particles comprise hyaluronic acid or a derivative thereof. In some embodiments, the injection comprises a volume of about 1 ml to about 50 ml. In some embodiments, the injection is performed with a 10-25 gauge needle. In some embodiments, the concentration of hyaluronic acid ranges from about 5 mg / ml to about 100 mg / ml. In some embodiments, the gel particles have a size ranging from about 0.2 mm to about 5 mm. In some embodiments, blood flow to the tumor is prevented or reduced. In some embodiments, migration of the viscoelastic medium is prevented or reduced. In some embodiments, the method further comprises administration of hyaluronidase at the site of radiation treatment. In some embodiments, administration of hyaluronidase occurs about 0.1 hours to about 24 hours to 30 days after injection of the bioabsorbable viscoelastic medium. In some embodiments, the method further comprises excising residual tumor cells from the subject.

[0010] Another aspect of the disclosure described herein includes a composition comprising a viscoelastic medium and a visualization additive. In some embodiments, the visualization additive is present in an amount sufficient to generate contrast when imaged by an imaging modality. In some embodiments, the viscoelastic medium comprises a volume of about 1 ml to about 50 ml. In some embodiments, the viscoelastic medium is configured to be placed by a 10-25 gauge syringe needle. In some embodiments, the viscoelastic medium comprises hyaluronic acid, polyethylene glycol, or dextranoma in a concentration ranging from about 5 mg / ml to about 100 mg / ml. In some embodiments, the viscoelastic medium comprises gel particles ranging in size from about 0.08 mm to about 5 mm. In some embodiments, the visualization additive comprises the viscoelastic medium to be imaged, where the imaging comprises real-time imaging. In some embodiments, the visualization additive comprises the viscoelastic medium to be imaged within 30 minutes, within 90 minutes, within 4 hours, within 8 hours, or within 4 days of the placement of the viscoelastic medium. In some embodiments, the visualization additive constitutes the viscoelastic medium to be imaged, and the imaging comprises MRI, CT, ultrasound, or a combination thereof. In some embodiments, the imaging modality comprises MRI, CT, ultrasound, or a combination thereof. In some embodiments, the viscoelastic medium is configured to not move substantially upon displacement. In particular, in these embodiments, the viscoelastic medium is configured to not collect in organs that are not where the viscoelastic medium is injected. In some embodiments, the visualization additive comprises one or more nanoparticles. In some embodiments, the visualization additive comprises a precious metal. In some embodiments, the precious metal comprises gold. In some embodiments, the precious metal comprises gold, iodine, gadolinium, iron, barium, calcium, or a combination thereof. In some embodiments, the particles of the visualization additive are between about 80 micrometers and about 120 micrometers. In some embodiments, the viscoelastic medium is bioabsorbable.

[0011] Also provided herein is the use of a viscoelastic medium for the manufacture of a medicament. In some embodiments, more than 70% (v / v) of the particles are within a given size limit under physiological conditions, including physiological conditions relevant to humans. Provided herein are particles of a viscoelastic medium that are injectable gel particles having a size in the range of 1-5 mm when exposed to saline. Subcutaneous administration of an implant comprising gel particles made from a viscoelastic medium that are much larger than conventionally used in implants made from a viscoelastic medium is useful to avoid migration and / or displacement of the implant or a portion thereof from the site of desired radiation protection. Furthermore, the limited displacement of the implant combined with the appreciable particle size can facilitate easy removal of the implant, if desired. In an embodiment herein, the particle size is in the range of 1-2.5 mm. In some embodiments, the size is in the range of 2.5-5 mm. In embodiments herein, the viscoelastic medium is selected from the group consisting of polysaccharides and derivatives thereof. In some embodiments, the viscoelastic medium is selected from stabilized glycosaminoglycans and derivatives thereof. In some embodiments, the viscoelastic medium is selected from the group consisting of stabilized hyaluronic acid, stabilized chondroitin sulfate, stabilized heparin, and derivatives thereof. In some embodiments herein, the viscoelastic medium is selected from the group consisting of cross-linked hyaluronic acid and derivatives thereof. In some embodiments, the concentration of said viscoelastic medium in the gel particles ranges from 5 to 100 mg / ml when provided in saline. In some embodiments, the particles herein are injectable through a 20 gauge or larger needle by applying a pressure of 15 to 50 N.

[0012] Further provided herein is a method for producing injectable gel particles of a viscoelastic medium, comprising the steps of: (i) producing a gel having a desired concentration of said viscoelastic medium; and (ii) mechanically disrupting said gel into gel particles having a size in the range of 1-5 mm when subjected to saline.

[0013] Further provided herein is a radioprotective implant comprising particles of a viscoelastic medium, the majority of said particles being injectable gel particles having a size in the range of 1-5 mm when subjected to saline. In one embodiment of the implant, said size is in the range of 1-2.5 mm. In one embodiment of the implant, said size is in the range of 2.5-5 mm.

[0014] In some embodiments, the injectable gel particles have a size of about 0.5 mm to about 5 mm. In some embodiments, the injectable gel particles are from about 0.5 mm to about 1 mm, from about 0.5 mm to about 1.5 mm, from about 0.5 mm to about 2 mm, from about 0.5 mm to about 2.5 mm, from about 0.5 mm to about 3 mm, from about 0.5 mm to about 3.5 mm, from about 0.5 mm to about 4 mm, from about 0.5 mm to about 4.5 mm, from about 0.5 mm to about 5 mm, from about 1 mm to about 1.5 mm, from about 1 mm to about 2 mm, from about 1 mm to about 2.5 mm, from about 1 mm to about 3 mm, from about 1 mm to about 3.5 mm, from about 1 mm to about 4 mm, from about 1 mm to about 4.5 mm, from about 1 mm to about 5 mm, from about 1.5 mm to about 2 mm, from about 1.5 mm to about 2.5 mm, from about 1.5 mm to about 3 mm, from about 1.5 mm to about 3.5 mm, from about 1.5 mm to about and about 4 mm, about 1.5 mm to about 4.5 mm, about 1.5 mm to about 5 mm, about 2 mm to about 2.5 mm, about 2 mm to about 3 mm, about 2 mm to about 3.5 mm, about 2 mm to about 4 mm, about 2 mm to about 4.5 mm, about 2 mm to about 5 mm, about 2.5 mm to about 3 mm, about 2.5 mm to about 3.5 mm, about 2.5 mm to about 4 mm, about 2.5 mm to about 4.5 mm, about 2.5 mm to about 5 mm, about 3 mm to about 3.5 mm, about 3 mm to about 4 mm, about 3 mm to about 4.5 mm, about 3 mm to about 5 mm, about 3.5 mm to about 4 mm, about 3.5 mm to about 4.5 mm, about 3.5 mm to about 5 mm, about 4 mm to about 4.5 mm, about 4 mm to about 5 mm, or about 4.5 mm to about 5 mm. In some embodiments, the injectable gel particles have a size of about 0.5 mm, about 1 mm, about 1.5 mm, about 2 mm, about 2.5 mm, about 3 mm, about 3.5 mm, about 4 mm, about 4.5 mm, or about 5 mm. In some embodiments, the injectable gel particles have a size of at least about 0.5 mm, about 1 mm, about 1.5 mm, about 2 mm, about 2.5 mm, about 3 mm, about 3.5 mm, about 4 mm, or about 4.5 mm. In some embodiments, the injectable gel particles have a size of at most about 1 mm, about 1.5 mm, about 2 mm, about 2.5 mm, about 3 mm, about 3.5 mm, about 4 mm, about 4.5 mm, or about 5 mm. In some embodiments, the injectable gel particles have a size of about 1 mm to about 2 mm.In some embodiments, the injectable gel particles are from about 1 mm to about 1.1 mm, from about 1 mm to about 1.2 mm, from about 1 mm to about 1.3 mm, from about 1 mm to about 1.4 mm, from about 1 mm to about 1.5 mm, from about 1 mm to about 1.6 mm, from about 1 mm to about 1.7 mm, from about 1 mm to about 1.8 mm, from about 1 mm to about 1.9 mm, from about 1 mm to about 2 mm, from about 1.1 mm to about 1.2 mm, from about 1.1 mm to about 1.3 mm, from about 1.1 mm to about 1.4 mm, from about 1.1 mm to about 1.5 mm, from about 1 mm to about 1.6 mm, from about 1 mm to about 1.7 mm, from about 1 mm to about 1.8 mm, from about 1 mm to about 1.9 mm, Approximately 1.5mm, approximately 1.1mm to approximately 1.6mm, approximately 1.1mm to approximately 1.7mm, approximately 1.1mm to approximately 1.8mm, approximately 1.1mm to approximately 1.9mm, approximately 1.1mm to approximately 2mm, approximately 1.2mm to approximately 1.3mm, approximately 1.2mm to approximately 1.4mm, approximately 1.2mm to approximately 1.5mm, approximately 1.2mm to approximately 1.6mm, approximately 1.2mm to approximately 1.7mm, approximately 1.2mm to approximately 1.8mm, approximately 1.2mm to approximately 1.9mm, approximately 1.2mm to approximately 2mm, approximately 1.3mm m ~ about 1.4mm, about 1.3mm - about 1.5mm, about 1.3mm - about 1.6mm, about 1.3mm - about 1.7mm, about 1.3mm - about 1.8mm, about 1.3mm - about 1.9mm, about 1.3mm - about 2mm, about 1.4 mm ~ approx. 1.5 mm, approx. 1.4 mm ~ approx. 1.6 mm, approx. 1.4 mm ~ approx. 1.7 mm, approx. 1.4 mm ~ approx. 1.8 mm, approx. 1.4 mm ~ approx. 1.9 mm, approx. 1.4 mm ~ approx. 2 mm, approx. The injectable gel particles have a size of about 5 mm to about 1.7 mm, about 1.5 mm to about 1.8 mm, about 1.5 mm to about 1.9 mm, about 1.5 mm to about 2 mm, about 1.6 mm to about 1.7 mm, about 1.6 mm to about 1.8 mm, about 1.6 mm to about 1.9 mm, about 1.6 mm to about 2 mm, about 1.7 mm to about 1.8 mm, about 1.7 mm to about 1.9 mm, about 1.7 mm to about 2 mm, about 1.8 mm to about 1.9 mm, about 1.8 mm to about 2 mm, about 1.9 mm to about 2 mm. In some embodiments, the injectable gel particles have a size of about 1 mm, 1.1 mm, about 1.2 mm, about 1.3 mm, about 1.4 mm, about 1.5 mm, about 1.6 mm, about 1.7 mm, about 1.8 mm, about 1.9 mm, or about 2 mm. In some embodiments, the injectable gel particles have a size of at least about 1 mm, about 1.1 mm, about 1.2 mm, about 1.3 mm, about 1.4 mm, about 1.5 mm, about 1.6 mm, about 1.7 mm, about 1.8 mm, or about 1.9 mm.In some embodiments, the injectable gel particles have a size of at most about 1.1 mm, about 1.2 mm, about 1.3 mm, about 1.4 mm, about 1.5 mm, about 1.6 mm, about 1.7 mm, about 1.8 mm, about 1.9 mm, or about 2 mm.

[0015] Further provided herein is a method of radioprotection of adjacent organs in a mammal, including a human, comprising subepidermal administration at a site in the mammal where soft tissue radioprotection is desired of an implant comprising injectable gel particles of a viscoelastic medium, the majority of said particles having a size in the range of 1-5 mm when placed in saline. In some embodiments, said administration is selected from the group consisting of subcutaneous administration, submuscular administration, and supraperiostal administration. In some embodiments, said size is in the range of 1-2.5 mm. In some embodiments, said radioprotected site is selected from facial tissues and other tissues covered by exposed skin. In some embodiments, said size is in the range of 2.5-5 mm. In some embodiments, said administration is selected from the group consisting of single administration and multi-layer administration.

[0016] Further provided herein is an injectable gel particle according to an embodiment herein for use as a medicament. Further provided herein is an injectable radioprotective implant comprising an injectable gel particle according to an embodiment herein for use as a medicament.

[0017] Further provided herein are methods of using injectable gel particles of a viscoelastic medium according to embodiments herein. In some embodiments, the particles have an average size in the range of 1-5 mm when subjected to aqueous physiological solution for the manufacture of a medicament for therapeutic radioprotection in a mammal, including a human, wherein the medicament is suitable for subepidermal administration according to embodiments herein at a site in the mammal where therapeutic radioprotection is desired.

[0018] Further provided herein are particles of a viscoelastic medium, which are injectable gel particles having a size in the range of 1-5 mm when exposed to saline. The particles are useful in a radioprotective implant comprising particles of a viscoelastic medium, the majority of the particles being injectable gel particles having a specific size, a size in the range of 1-5 mm, when exposed to saline. The implant is then useful in a method of radioprotection in a mammal, including a human, comprising subcutaneous administration at a site in the mammal, where radioprotection is desired of an implant comprising injectable gel particles of a viscoelastic medium, the majority of the particles having a size in the range of 1-5 mm when exposed to saline.

[0019] Another aspect provided herein is a method of preventing or reducing damage to tissue adjacent to a site of radiation treatment in a subject undergoing radiation therapy, the method comprising injecting a bioabsorbable viscoelastic medium into the site of radiation treatment. In some embodiments, the viscoelastic medium comprises gel particles. In some embodiments, the gel particles comprise hyaluronic acid or a derivative thereof.

[0020] In some embodiments, the injection displaces the tissue a distance of about 0.1 cm to about 10 cm. In some embodiments, the injection displaces the tissue a distance of about 0.1 cm to about 0.2 cm, about 0.1 cm to about 0.5 cm, about 0.1 cm to about 1 cm, about 0.1 cm to about 2 cm, about 0.1 cm to about 3 cm, about 0.1 cm to about 4 cm, about 0.1 cm to about 5 cm, about 0.1 cm to about 6 cm, about 0.1 cm to about 7 cm, about 0.1 cm to about 8 cm, about 0.1 cm to about 10 cm, about 0.2 cm to about 0.5 cm, about 0.2 cm to about 1 cm, about 0.2 cm to about 2 cm, about 0.2cm to 3cm, 0.2cm to 4cm, 0.2cm to 5cm, 0.2cm to 6cm, 0.2cm to 7cm, 0.2cm to 8cm, 0.2cm to 10cm, 0.5cm to 1cm, Approximately 0.5cm to approximately 2cm, approximately 0.5cm to approximately 3cm, approximately 0.5cm to approximately 4cm, approximately 0.5cm to approximately 5cm, approximately 0.5cm to approximately 6cm, approximately 0.5cm to approximately 7cm, approximately 0.5cm to approximately 8cm, approximately 0.5cm to approximately 10cm , about 1cm to about 2cm, about 1cm to about 3cm, about 1cm to about 4cm, about 1cm to about 5cm, about 1cm to about 6cm, about 1cm to about 7cm, about 1cm to about 8cm, about 1cm to about 10cm, about 2cm to about 3cm, about 2cm ~4cm, 2cm~5cm, 2cm~6cm, 2cm~7cm, 2cm~8cm, 2cm~10cm, 3cm~4cm, 3cm~5cm, 3cm~6cm, 3cm~7cm , about 3 cm to about 8 cm, about 3 cm to about 10 cm, about 4 cm to about 5 cm, about 4 cm to about 6 cm, about 4 cm to about 7 cm, about 4 cm to about 8 cm, about 4 cm to about 10 cm, about 5 cm to about 6 cm, about 5 cm to about 7 cm, about 5 cm to about 8 cm, about 5 cm to about 10 cm, about 6 cm to about 7 cm, about 6 cm to about 8 cm, about 6 cm to about 10 cm, about 7 cm to about 8 cm, about 7 cm to about 10 cm, or about 8 cm to about 10 cm. In some embodiments, the injection displaces the tissue a distance of about 0.1 cm, about 0.2 cm, about 0.5 cm, about 1 cm, about 2 cm, about 3 cm, about 4 cm, about 5 cm, about 6 cm, about 7 cm, about 8 cm, or about 10 cm.In some embodiments, the injection displaces the tissue a distance of at least about 0.1 cm, about 0.2 cm, about 0.5 cm, about 1 cm, about 2 cm, about 3 cm, about 4 cm, about 5 cm, about 6 cm, about 7 cm, or about 8 cm. In some embodiments, the injection displaces the tissue a distance of at most about 0.2 cm, about 0.5 cm, about 1 cm, about 2 cm, about 3 cm, about 4 cm, about 5 cm, about 6 cm, about 7 cm, about 8 cm, or about 10 cm. In some embodiments, the injection comprises a volume of about 1 ml to about 50 ml.In some embodiments, the injection is from about 1 ml to about 2 ml, from about 1 ml to about 5 ml, from about 1 ml to about 10 ml, from about 1 ml to about 15 ml, from about 1 ml to about 20 ml, from about 1 ml to about 25 ml, from about 1 ml to about 30 ml, from about 1 ml to about 35 ml, from about 1 ml to about 40 ml, from about 1 ml to about 45 ml, from about 1 ml to about 50 ml, from about 2 ml to about 5 ml, from about 2 ml to about 10 ml, from about 2 ml to about 15 ml, from about 2 ml to about 20 ml, from about 2 ml to about 25 ml, from about 2 ml to about 30 ml, from about 2 ml to about 35 ml, from about 2 ...35 ml, from about 2 ml to about 40 ml, from about 2 ml to about 45 ml, from about 2 ml to about 50 ml, from about 2 ml to about 50 ml, from about 2 ml to about 50 ml, from about 2 ml to about 10 ml, from about 2 ml to about 15 ml, from about 2 ml to about 20 ml, from about 2 ml to about 25 ml, from about 2 ml to about 30 ml, from about 2 ml to about 35 ml, from about 2 ml to about 35 ml, from about 2 ml to about 35 ml, from about 2 0ml, about 2ml to about 35ml, about 2ml to about 40ml, about 2ml to about 45ml, about 2ml to about 50ml, about 5ml to about 10ml, about 5ml to about 15ml, about 5ml to about 20ml, about 5ml to about 25ml, about 5ml to about 30ml, approximately 5ml to approximately 35ml, approximately 5ml to approximately 40ml, approximately 5ml to approximately 45ml, approximately 5ml to approximately 50ml, approximately 10ml to approximately 15ml, approximately 10ml to approximately 20ml, approximately 10ml to approximately 25ml, approximately 10ml to approximately 30ml, approximately 10ml to about 35ml, about 10ml to about 40ml, about 10ml to about 45ml, about 10ml to about 50ml, about 15ml to about 20ml, about 15ml to about 25ml, about 15ml to about 30ml, about 15ml to about 35ml, about 15 ml~about 40ml, about 15ml~about 45ml, about 15ml~about 50ml, about 20ml~about 25ml, about 20ml~about 30ml, about 20ml~about 35ml, about 20ml~about 40ml, about 20ml~about 45ml, about 20ml In some embodiments, the injection comprises a volume of about 1 ml, about 2 ml, about 5 ml, about 10 ml, about 15 ml, about 20 ml, about 25 ml, about 30 ml, about 35 ml, about 40 ml, about 45 ml, about 50 ml, about 45 ml, about 50 ml, about 50 ml, about 4 ... In some embodiments, the injection comprises a volume of at least about 1 ml, about 2 ml, about 5 ml, about 10 ml, about 15 ml, about 20 ml, about 25 ml, about 30 ml, about 35 ml, about 40 ml, or about 45 ml.In some embodiments, the injection comprises a volume of at most about 2 ml, about 5 ml, about 10 ml, about 15 ml, about 20 ml, about 25 ml, about 30 ml, about 35 ml, about 40 ml, about 45 ml, or about 50 ml.

[0021] In some embodiments, the injection is performed with a needle having a gauge of about 10 to about 26. In some embodiments, the injection is performed with a needle having a gauge of about 10 to about 11, about 10 to about 12, about 10 to about 13, about 10 to about 14, about 10 to about 15, about 10 to about 16, about 10 to about 18, about 10 to about 20, about 10 to about 22, about 10 to about 24, about 10 to about 26, about 11 to about 12, about 11 to about 13, about 11 to about 14, about 11 to about 15, about 11 to about 16, about 11 to about 18, about 11 to about 20, about 11 to about 22, about 11 to about 24, about 11 to about 26, about 12 to about 13, about 12 to about 14, about 12 to about 15, about 12 to about 16, about 12 to about 18, about 12 to about 20, about 12 to about 22, about 12 to about 24, about 12 to about 26, about 13 to about 14, about 13 to about 15, about 13 to about 16, about 1 3 to about 18, about 13 to about 20, about 13 to about 22, about 13 to about 24, about 13 to about 26, about 14 to about 15, about 14 to about 16, about 14 to about 18, about 14 to about 20, about 14 to about 22, about 14 to about 24, about 14 to about 26, about 15 to about 16, about 15 to about 18, about 15 to about 20, about 15 to about 22, about 15 to about 24, about 15 to about 26 , about 16 to about 18, about 16 to about 20, about 16 to about 22, about 16 to about 24, about 16 to about 26, about 18 to about 20, about 18 to about 22, about 18 to about 24, about 18 to about 26, about 20 to about 22, about 20 to about 24, about 20 to about 26, about 22 to about 24, about 22 to about 26, or about 24 to about 26. In some embodiments, the injection is performed with a needle having a gauge of about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 18, about 20, about 22, about 24, or about 26. In some embodiments, injection is performed with a needle having a gauge of at least about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 18, about 20, about 22, or about 24. In some embodiments, injection is performed with a needle having a gauge of at most about 11, about 12, about 13, about 14, about 15, about 16, about 18, about 20, about 22, about 24, or about 26.

[0022] In some embodiments, the concentration of hyaluronic acid in the spacer material is from about 1 mg / ml to about 100 mg / ml. In some embodiments, the concentration of hyaluronic acid in the spacer material is from about 1 mg / ml to about 5 mg / ml, from about 1 mg / ml to about 10 mg / ml, from about 1 mg / ml to about 15 mg / ml, from about 1 mg / ml to about 20 mg / ml, from about 1 mg / ml to about 25 mg / ml, from about 1 mg / ml to about 30 mg / ml, from about 1 mg / ml to about 40 mg / ml, from about 1 mg / ml to about 50 mg / ml, from about 1 mg / ml to about 60 mg / ml, from about 1 mg / ml to about 80 mg / ml, from about 1 mg / ml to about 100 mg / ml, from about 5 mg / ml to about 1 0mg / ml, about 5mg / ml to about 15mg / ml, about 5mg / ml to about 20mg / ml, about 5mg / ml to about 25mg / ml, about 5mg / ml to about 30mg / ml, about 5mg / ml to about 40mg / ml, about 5mg / ml to about 50mg / ml, about 5mg / ml ml~about 60mg / ml, about 5mg / ml~about 80mg / ml, about 5mg / ml~about 100mg / ml, about 10mg / ml~about 15mg / ml, about 10mg / ml~about 20mg / ml, about 10mg / ml~about 25mg / ml, about 10mg / ml~about 30mg / ml, about 10mg / ml to about 40mg / ml, about 10mg / ml to about 50mg / ml, about 10mg / ml to about 60mg / ml, about 10mg / ml to about 80mg / ml, about 10mg / ml to about 100mg / ml, about 15mg / ml to about 20mg / ml, about 15mg / ml to about 25mg / ml, about 15mg / ml to about 30mg / ml, about 15mg / ml to about 40mg / ml, about 15mg / ml to about 50mg / ml, about 15mg / ml to about 60mg / ml, about 15mg / ml to about 80mg / ml, about 15mg / m l ~ about 100mg / ml, about 20mg / ml - about 25mg / ml, about 20mg / ml - about 30mg / ml, about 20mg / ml - about 40mg / ml, about 20mg / ml - about 50mg / ml, about 20mg / ml - about 60mg / ml, about 20mg / ml - about 80 mg / ml, about 20 mg / ml to about 100 mg / ml, about 25 mg / ml to about 30 mg / ml, about 25 mg / ml to about 40 mg / ml, about 25 mg / ml to about 50 mg / ml, about 25 mg / ml to about 60 mg / ml, about 25 mg / ml to about 80 mg / ml,about 25mg / ml to about 100mg / ml, about 30mg / ml to about 40mg / ml, about 30mg / ml to about 50mg / ml, about 30mg / ml to about 60mg / ml, about 30mg / ml to about 80mg / ml, about 30mg / ml to about 100mg / ml, about 40mg / ml to about 50mg / ml, about 40mg / ml to about 60mg / ml, about 40mg / ml to about 80mg / ml, about 40mg / ml to about 100mg / ml, about 50mg / ml to about 60mg / ml, about 50mg / ml to about 80mg / ml, about 50mg / ml to about 100mg / ml, about 60mg / ml to about 80mg / ml, about 60mg / ml to about 100mg / ml, or about 80mg / ml to about 100mg / ml. In some embodiments, the concentration of hyaluronic acid in the spacer material is about 1 mg / ml, about 5 mg / ml, about 10 mg / ml, about 15 mg / ml, about 20 mg / ml, about 25 mg / ml, about 30 mg / ml, about 40 mg / ml, about 50 mg / ml, about 60 mg / ml, about 80 mg / ml, or about 100 mg / ml. In some embodiments, the concentration of hyaluronic acid in the spacer material is at least about 1 mg / ml, about 5 mg / ml, about 10 mg / ml, about 15 mg / ml, about 20 mg / ml, about 25 mg / ml, about 30 mg / ml, about 40 mg / ml, about 50 mg / ml, about 60 mg / ml, or about 80 mg / ml. In some embodiments, the concentration of hyaluronic acid in the spacer material is at most about 5 mg / ml, about 10 mg / ml, about 15 mg / ml, about 20 mg / ml, about 25 mg / ml, about 30 mg / ml, about 40 mg / ml, about 50 mg / ml, about 60 mg / ml, about 80 mg / ml, or about 100 mg / ml.

[0023] In some embodiments, the injectable gel particles have a size of about 0.1 mm to about 10 mm. In some embodiments, the particles have a size of about 0.1 mm to about 0.2 mm, about 0.1 mm to about 0.5 mm, about 0.1 mm to about 1 mm, about 0.1 mm to about 1.5 mm, about 0.1 mm to about 2 mm, about 0.1 mm to about 3 mm, about 0.1 mm to about 4 mm, about 0.1 mm to about 5 mm, about 0.1 mm to about 6 mm, about 0.1 mm to about 8 mm, about 0.1 mm to about 10 mm, about 0.2 mm to about 0.5 mm, about 0.2 mm to about 1 mm, about 0.2 mm to about 1.5 mm, about 0.2mm to about 2mm, about 0.2mm to about 3mm, about 0.2mm to about 4mm, about 0.2mm to about 5mm, about 0.2mm to about 6mm, about 0.2mm to about 8mm, about 0.2mm to about 10mm, about 0.5mm to about 1mm, about 0 .5mm to about 1.5mm, about 0.5mm to about 2mm, about 0.5mm to about 3mm, about 0.5mm to about 4mm, about 0.5mm to about 5mm, about 0.5mm to about 6mm, about 0.5mm to about 8mm, about 0.5mm to about 10mm, about 1mm to about 1.5mm, about 1mm to about 2mm, about 1mm to about 3mm, about 1mm to about 4mm, about 1mm to about 5mm, about 1mm to about 6mm, about 1mm to about 8mm, about 1mm to about 10mm, about 1.5mm to about 2mm, about 1.5 mm~3mm, 1.5mm~4mm, 1.5mm~5mm, 1.5mm~6mm, 1.5mm~8mm, 1.5mm~10mm, 2mm~3mm, 2mm~4mm, 2mm~5mm, The particles have a size of about 2 mm to about 6 mm, about 2 mm to about 8 mm, about 2 mm to about 10 mm, about 3 mm to about 4 mm, about 3 mm to about 5 mm, about 3 mm to about 6 mm, about 3 mm to about 8 mm, about 3 mm to about 10 mm, about 4 mm to about 5 mm, about 4 mm to about 6 mm, about 4 mm to about 8 mm, about 4 mm to about 10 mm, about 5 mm to about 6 mm, about 5 mm to about 8 mm, about 5 mm to about 10 mm, about 6 mm to about 8 mm, about 6 mm to about 10 mm, or about 8 mm to about 10 mm. In some embodiments, the particles have a size of about 0.1 mm, 0.2 mm, 0.5 mm, about 1 mm, about 1.5 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 8 mm, or about 10 mm.In some embodiments, the particles have a size of at least about 0.1 mm, about 0.2 mm, about 0.5 mm, about 1 mm, about 1.5 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, or about 8 mm. In some embodiments, the particles have a size of at most about 0.2 mm, about 0.5 mm, about 1 mm, about 1.5 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 8 mm, or about 10 mm.

[0024] In some embodiments, the injection is subcutaneous or subepidermal. In some embodiments, migration of the viscoelastic medium is prevented or reduced. In some embodiments, the viscoelastic medium additive further comprises nanoparticles. In some embodiments, the nanoparticles comprise a precious metal. In some embodiments, the dose of radiation therapy contacting tissue adjacent to the site of radiation treatment is reduced by about 10% to about 80%. In some embodiments, the site of radiation treatment is selected from the group consisting of the subject's breast, head and neck, cervix, vagina, base of the spine, skin, pancreas, liver, or lung. In some embodiments, the method further comprises administration of hyaluronidase at the site of radiation treatment.

[0025] In some embodiments, the volume of the viscoelastic medium at the site of radiation treatment is reduced by about 1% to about 95%. In some embodiments, the volume of the viscoelastic medium at the site of radiation treatment is reduced by about 1% to about 5%, about 1% to about 10%, about 1% to about 15%, about 1% to about 20%, about 1% to about 30%, about 1% to about 40%, about 1% to about 50%, about 1% to about 60%, about 1% to about 70%, about 1% to about 80%, about 1% to about 95%, about 5% to about 10%, about 5% to about 15%, about 5% to about 20%, about 5% to about 30%, about 5% to about 60%, about 5% to about 70%, about 5% to about 80%, about 5 ... % to about 40%, about 5% to about 50%, about 5% to about 60%, about 5% to about 70%, about 5% to about 80%, about 5% to about 95%, about 10% to about 15%, about 10% to about 20%, about 10% to about 30%, about 10% to about 40%, about 10% to about 50%, about 10% to about 60%, about 10% to about 70%, about 10% to about 80%, about 10% to about 95%, about 15% to about 20%, about 15% to about 30%, about 15% to about 40 %, about 15% to about 50%, about 15% to about 60%, about 15% to about 70%, about 15% to about 80%, about 15% to about 95%, about 20% to about 30%, about 20% to about 40%, about 20% to about 50%, about 20% to about 60%, about 20% to about 70%, about 20% to about 80%, about 20% to about 95%, about 30% to about 40%, about 30% to about 50%, about 30% to about 60%, about 30% to about 70%, about 30% to about 80 %, about 30% to about 95%, about 40% to about 50%, about 40% to about 60%, about 40% to about 70%, about 40% to about 80%, about 40% to about 95%, about 50% to about 60%, about 50% to about 70%, about 50% to about 80%, about 50% to about 95%, about 60% to about 70%, about 60% to about 80%, about 60% to about 95%, about 70% to about 80%, about 70% to about 95%, or about 80% to about 95%. In some embodiments, the volume of the viscoelastic medium at the site of radiation treatment is reduced by about 1%, about 5%, about 10%, about 15%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, or about 95%. In some embodiments, the volume of the viscoelastic medium at the site of radiation treatment is reduced by at least about 1%, about 5%, about 10%, about 15%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, or about 80%.In some embodiments, the volume of the viscoelastic medium at the site of radiation treatment is reduced by at most about 5%, about 10%, about 15%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, or about 95%.

[0026] In some embodiments, administration of hyaluronidase occurs at about 0.1 hours to about 95 hours after injection of the bioabsorbable viscoelastic medium. In some embodiments, administration of hyaluronidase occurs at about 0.1 hours to about 0.5 hours, about 0.1 hours to about 1 hour, about 0.1 hours to about 2 hours, about 0.1 hours to about 4 hours, about 0.1 hours to about 6 hours, about 0.1 hours to about 8 hours, about 0.1 hours to about 10 hours, about 0.1 hours to about 14 hours, about 0.1 hours to about 18 hours, about 0.1 hours to about 24 hours, about 0.1 hours to about 95 hours, about 0.5 hours to about 1 hour, or about 0.5 hours to about 2 hours after injection of the bioabsorbable viscoelastic medium. 0.5 hours to about 4 hours, about 0.5 hours to about 6 hours, about 0.5 hours to about 8 hours, about 0.5 hours to about 10 hours, about 0.5 hours to about 14 hours, about 0.5 hours to about 18 hours, about 0.5 hours to about 24 hours, about 0.5 hours to about 95 hours, about 1 hour to about 2 hours, about 1 hour to about 4 hours, about 1 hour to about 6 hours, about 1 hour to about 8 hours, about 1 hour to about 10 hours, about 1 hour to about 14 hours, about 1 hour to about 18 hours, about 1 hour to about 24 hours, about 1 hour to about 95 hours, about 2 hours ~about 4 hours, about 2 hours to about 6 hours, about 2 hours to about 8 hours, about 2 hours to about 10 hours, about 2 hours to about 14 hours, about 2 hours to about 18 hours, about 2 hours to about 24 hours, about 2 hours to about 95 hours, about 4 hours to about 6 hours, about 4 hours to about 8 hours, about 4 hours to about 10 hours, about 4 hours to about 14 hours, about 4 hours to about 18 hours, about 4 hours to about 24 hours, about 4 hours to about 95 hours, about 6 hours to about 8 hours, about 6 hours to about 10 hours, about 6 hours to about 14 hours, about 6 hours to about 18 hours, about 6 hours The incubation period may be from about 1 hour to about 24 hours, from about 6 hours to about 95 hours, from about 8 hours to about 10 hours, from about 8 hours to about 14 hours, from about 8 hours to about 18 hours, from about 8 hours to about 24 hours, from about 8 hours to about 95 hours, from about 10 hours to about 14 hours, from about 10 hours to about 18 hours, from about 10 hours to about 24 hours, from about 10 hours to about 95 hours, from about 14 hours to about 18 hours, from about 14 hours to about 24 hours, from about 14 hours to about 95 hours, from about 18 hours to about 24 hours, from about 18 hours to about 95 hours, or from about 24 hours to about 95 hours. In some embodiments, administration of hyaluronidase occurs at about 0.1 hours, about 0.5 hours, about 1 hour, about 2 hours, about 4 hours, about 6 hours, about 8 hours, about 10 hours, about 14 hours, about 18 hours, about 24 hours, or about 95 hours after injection of the bioabsorbable viscoelastic medium.In some embodiments, administration of hyaluronidase occurs at least about 0.1 hours, about 0.5 hours, about 1 hour, about 2 hours, about 4 hours, about 6 hours, about 8 hours, about 10 hours, about 14 hours, about 18 hours, or about 24 hours after injection of the bioabsorbable viscoelastic medium. In some embodiments, administration of hyaluronidase occurs at most about 0.5 hours, about 1 hour, about 2 hours, about 4 hours, about 6 hours, about 8 hours, about 10 hours, about 14 hours, about 18 hours, about 24 hours, or about 95 hours after injection of the bioabsorbable viscoelastic medium.

[0027] Another aspect provided herein is a method of reducing a dose of radiation therapy to tissue adjacent to a site of radiation treatment in a subject undergoing radiation therapy, the method comprising injecting a bioabsorbable viscoelastic medium into the site of radiation treatment. In some embodiments, the viscoelastic medium comprises gel particles. In some embodiments, the gel particles comprise hyaluronic acid or a derivative thereof.

[0028] In some embodiments, the injection displaces the tissue a distance of about 0.1 cm to about 10 cm. In some embodiments, the injection displaces the tissue a distance of about 0.1 cm to about 0.2 cm, about 0.1 cm to about 0.5 cm, about 0.1 cm to about 1 cm, about 0.1 cm to about 2 cm, about 0.1 cm to about 3 cm, about 0.1 cm to about 4 cm, about 0.1 cm to about 5 cm, about 0.1 cm to about 6 cm, about 0.1 cm to about 7 cm, about 0.1 cm to about 8 cm, about 0.1 cm to about 10 cm, about 0.2 cm to about 0.5 cm, about 0.2 cm to about 1 cm, about 0.2 cm to about 2 cm, about 0.2cm to 3cm, 0.2cm to 4cm, 0.2cm to 5cm, 0.2cm to 6cm, 0.2cm to 7cm, 0.2cm to 8cm, 0.2cm to 10cm, 0.5cm to 1cm, Approximately 0.5cm to approximately 2cm, approximately 0.5cm to approximately 3cm, approximately 0.5cm to approximately 4cm, approximately 0.5cm to approximately 5cm, approximately 0.5cm to approximately 6cm, approximately 0.5cm to approximately 7cm, approximately 0.5cm to approximately 8cm, approximately 0.5cm to approximately 10cm , about 1cm to about 2cm, about 1cm to about 3cm, about 1cm to about 4cm, about 1cm to about 5cm, about 1cm to about 6cm, about 1cm to about 7cm, about 1cm to about 8cm, about 1cm to about 10cm, about 2cm to about 3cm, about 2cm ~4cm, 2cm~5cm, 2cm~6cm, 2cm~7cm, 2cm~8cm, 2cm~10cm, 3cm~4cm, 3cm~5cm, 3cm~6cm, 3cm~7cm , about 3 cm to about 8 cm, about 3 cm to about 10 cm, about 4 cm to about 5 cm, about 4 cm to about 6 cm, about 4 cm to about 7 cm, about 4 cm to about 8 cm, about 4 cm to about 10 cm, about 5 cm to about 6 cm, about 5 cm to about 7 cm, about 5 cm to about 8 cm, about 5 cm to about 10 cm, about 6 cm to about 7 cm, about 6 cm to about 8 cm, about 6 cm to about 10 cm, about 7 cm to about 8 cm, about 7 cm to about 10 cm, or 8 cm to about 10 cm. In some embodiments, the injection displaces the tissue by a distance of about 0.1 cm, about 0.2 cm, about 0.5 cm, about 1 cm, about 2 cm, about 3 cm, about 4 cm, about 5 cm, about 6 cm, about 7 cm, about 8 cm, or about 10 cm.In some embodiments, the injection displaces the tissue a distance of at least about 0.1 cm, about 0.2 cm, about 0.5 cm, about 1 cm, about 2 cm, about 3 cm, about 4 cm, about 5 cm, about 6 cm, about 7 cm, or about 8 cm. In some embodiments, the injection displaces the tissue a distance of at most about 0.2 cm, about 0.5 cm, about 1 cm, about 2 cm, about 3 cm, about 4 cm, about 5 cm, about 6 cm, about 7 cm, about 8 cm, or about 10 cm. In some embodiments, the injection comprises a volume of about 1 ml to about 50 ml.In some embodiments, the injection is from about 1 ml to about 2 ml, from about 1 ml to about 5 ml, from about 1 ml to about 10 ml, from about 1 ml to about 15 ml, from about 1 ml to about 20 ml, from about 1 ml to about 25 ml, from about 1 ml to about 30 ml, from about 1 ml to about 35 ml, from about 1 ml to about 40 ml, from about 1 ml to about 45 ml, from about 1 ml to about 50 ml, from about 2 ml to about 5 ml, from about 2 ml to about 10 ml, from about 2 ml to about 15 ml, from about 2 ml to about 20 ml, from about 2 ml to about 25 ml, from about 2 ml to about 30 ml, from about 2 ml to about 35 ml, from about 2 ...35 ml, from about 2 ml to about 40 ml, from about 2 ml to about 45 ml, from about 2 ml to about 50 ml, from about 2 ml to about 50 ml, from about 2 ml to about 50 ml, from about 2 ml to about 10 ml, from about 2 ml to about 15 ml, from about 2 ml to about 20 ml, from about 2 ml to about 25 ml, from about 2 ml to about 30 ml, from about 2 ml to about 35 ml, from about 2 ml to about 35 ml, from about 2 ml to about 35 ml, from about 2 0ml, about 2ml to about 35ml, about 2ml to about 40ml, about 2ml to about 45ml, about 2ml to about 50ml, about 5ml to about 10ml, about 5ml to about 15ml, about 5ml to about 20ml, about 5ml to about 25ml, about 5ml to about 30ml, approximately 5ml to approximately 35ml, approximately 5ml to approximately 40ml, approximately 5ml to approximately 45ml, approximately 5ml to approximately 50ml, approximately 10ml to approximately 15ml, approximately 10ml to approximately 20ml, approximately 10ml to approximately 25ml, approximately 10ml to approximately 30ml, approximately 10ml to about 35ml, about 10ml to about 40ml, about 10ml to about 45ml, about 10ml to about 50ml, about 15ml to about 20ml, about 15ml to about 25ml, about 15ml to about 30ml, about 15ml to about 35ml, about 15 ml~about 40ml, about 15ml~about 45ml, about 15ml~about 50ml, about 20ml~about 25ml, about 20ml~about 30ml, about 20ml~about 35ml, about 20ml~about 40ml, about 20ml~about 45ml, about 20ml In some embodiments, the injection comprises a volume of about 1 ml, about 2 ml, about 5 ml, about 10 ml, about 15 ml, about 20 ml, about 25 ml, about 30 ml, about 35 ml, about 40 ml, about 45 ml, about 50 ml, about 45 ml, about 50 ml, about 50 ml, about 4 ... In some embodiments, the injection comprises a volume of at least about 1 ml, about 2 ml, about 5 ml, about 10 ml, about 15 ml, about 20 ml, about 25 ml, about 30 ml, about 35 ml, about 40 ml, or about 45 ml.In some embodiments, the injection comprises a volume of at most about 2 ml, about 5 ml, about 10 ml, about 15 ml, about 20 ml, about 25 ml, about 30 ml, about 35 ml, about 40 ml, about 45 ml, or about 50 ml.

[0029] In some embodiments, the concentration of hyaluronic acid in the spacer material is about 1 mg / ml to about 100 mg / ml. In some embodiments, the concentration of hyaluronic acid in the spacer material is about 1 mg / ml to about 5 mg / ml, about 1 mg / ml to about 10 mg / ml, about 1 mg / ml to about 15 mg / ml, about 1 mg / ml to about 20 mg / ml, about 1 mg / ml to about 25 mg / ml, about 1 mg / ml to about 30 mg / ml, about 1 mg / ml to about 40 mg / ml, about 1 mg / ml to about 50 mg / ml, about 1 mg / ml to about 60 mg / ml, about 1 mg / ml to about 80 mg / ml, about 1 mg / ml to about 100 mg / ml, about 5 mg / ml to about 10 mg / ml. l, about 5mg / ml to about 15mg / ml, about 5mg / ml to about 20mg / ml, about 5mg / ml to about 25mg / ml, about 5mg / ml to about 30mg / ml, about 5mg / ml to about 40mg / ml, about 5mg / ml to about 50mg / ml, about 5mg / ml to about 60m g / ml, about 5 mg / ml to about 80 mg / ml, about 5 mg / ml to about 100 mg / ml, about 10 mg / ml to about 15 mg / ml, about 10 mg / ml to about 20 mg / ml, about 10 mg / ml to about 25 mg / ml, about 10 mg / ml to about 30 mg / ml, about 10 mg / ml~about 40mg / ml, about 10mg / ml~about 50mg / ml, about 10mg / ml~about 60mg / ml, about 10mg / ml~about 80mg / ml, about 10mg / ml~about 100mg / ml, about 15mg / ml~about 20mg / ml, about 15mg / ml~about 25 mg / ml, about 15 mg / ml to about 30 mg / ml, about 15 mg / ml to about 40 mg / ml, about 15 mg / ml to about 50 mg / ml, about 15 mg / ml to about 60 mg / ml, about 15 mg / ml to about 80 mg / ml, about 15 mg / ml to about 100 mg / ml, about 2 0mg / ml to about 25mg / ml, about 20mg / ml to about 30mg / ml, about 20mg / ml to about 40mg / ml, about 20mg / ml to about 50mg / ml, about 20mg / ml to about 60mg / ml, about 20mg / ml to about 80mg / ml, about 20mg / ml to about 1 00mg / ml, about 25mg / ml to about 30mg / ml, about 25mg / ml to about 40mg / ml, about 25mg / ml to about 50mg / ml, about 25mg / ml to about 60mg / ml, about 25mg / ml to about 80mg / ml, about 25mg / ml to about 100mg / ml,about 30 mg / ml to about 40 mg / ml, about 30 mg / ml to about 50 mg / ml, about 30 mg / ml to about 60 mg / ml, about 30 mg / ml to about 80 mg / ml, about 30 mg / ml to about 100 mg / ml, about 40 mg / ml to about 50 mg / ml, about 40 mg / ml to about 60 mg / ml, about 40 mg / ml to about 80 mg / ml, about 40 mg / ml to about 100 mg / ml, about 50 mg / ml to about 60 mg / ml, about 50 mg / ml to about 80 mg / ml, about 50 mg / ml to about 100 mg / ml, about 60 mg / ml to about 80 mg / ml, about 60 mg / ml to about 100 mg / ml, or about 80 mg / ml to about 100 mg / ml. In some embodiments, the concentration of hyaluronic acid in the spacer material is about 1 mg / ml, about 5 mg / ml, about 10 mg / ml, about 15 mg / ml, about 20 mg / ml, about 25 mg / ml, about 30 mg / ml, about 40 mg / ml, about 50 mg / ml, about 60 mg / ml, about 80 mg / ml, or about 100 mg / ml. In some embodiments, the concentration of hyaluronic acid in the spacer material is at least about 1 mg / ml, about 5 mg / ml, about 10 mg / ml, about 15 mg / ml, about 20 mg / ml, about 25 mg / ml, about 30 mg / ml, about 40 mg / ml, about 50 mg / ml, about 60 mg / ml, or about 80 mg / ml. In some embodiments, the concentration of hyaluronic acid in the spacer material is at most about 5 mg / ml, about 10 mg / ml, about 15 mg / ml, about 20 mg / ml, about 25 mg / ml, about 30 mg / ml, about 40 mg / ml, about 50 mg / ml, about 60 mg / ml, about 80 mg / ml, or about 100 mg / ml.

[0030] In some embodiments, the injectable gel particles have a size of about 0.1 mm to about 10 mm. In some embodiments, the particles have a size of about 0.1 mm to about 0.2 mm, about 0.1 mm to about 0.5 mm, about 0.1 mm to about 1 mm, about 0.1 mm to about 1.5 mm, about 0.1 mm to about 2 mm, about 0.1 mm to about 3 mm, about 0.1 mm to about 4 mm, about 0.1 mm to about 5 mm, about 0.1 mm to about 6 mm, about 0.1 mm to about 8 mm, about 0.1 mm to about 10 mm, about 0.2 mm to about 0.5 mm, about 0.2 mm to about 1 mm, about 0.2 mm to about 1.5 mm, about 0.2mm to about 2mm, about 0.2mm to about 3mm, about 0.2mm to about 4mm, about 0.2mm to about 5mm, about 0.2mm to about 6mm, about 0.2mm to about 8mm, about 0.2mm to 10mm, about 0.5mm to about 1mm, about 0. 5mm to about 1.5mm, about 0.5mm to about 2mm, about 0.5mm to about 3mm, about 0.5mm to about 4mm, about 0.5mm to about 5mm, about 0.5mm to about 6mm, about 0.5mm to about 8mm, about 0.5mm to about 10mm, about 1 mm~1.5mm, 1mm~2mm, 1mm~3mm, 1mm~4mm, 1mm~5mm, 1mm~6mm, 1mm~8mm, 1mm~10mm, 1.5mm~2mm, 1.5m m~3mm, 1.5mm~4mm, 1.5mm~5mm, 1.5mm~6mm, 1.5mm~8mm, 1.5mm~10mm, 2mm~3mm, 2mm~4mm, 2mm~5mm, The particles have a size of about 2 mm to about 6 mm, about 2 mm to about 8 mm, about 2 mm to about 10 mm, about 3 mm to about 4 mm, about 3 mm to about 5 mm, about 3 mm to about 6 mm, about 3 mm to about 8 mm, about 3 mm to about 10 mm, about 4 mm to about 5 mm, about 4 mm to about 6 mm, about 4 mm to about 8 mm, about 4 mm to about 10 mm, about 5 mm to about 6 mm, about 5 mm to about 8 mm, about 5 mm to about 10 mm, about 6 mm to about 8 mm, about 6 mm to about 10 mm, or about 8 mm to about 10 mm. In some embodiments, the particles have a size of about 0.1 mm, 0.2 mm, 0.5 mm, about 1 mm, about 1.5 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 8 mm, or about 10 mm.In some embodiments, the gel particles have a size of at least about 0.1 mm, about 0.2 mm, about 0.5 mm, about 1 mm, about 1.5 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, or about 8 mm. In some embodiments, the gel particles have a size of at most about 0.2 mm, about 0.5 mm, about 1 mm, about 1.5 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 8 mm, or about 10 mm.

[0031] In some embodiments, the injection is subcutaneous or subepidermal. In some embodiments, migration of the viscoelastic medium is prevented or reduced. In some embodiments, the viscoelastic medium further comprises nanoparticles. In some embodiments, the nanoparticles comprise a precious metal. In some embodiments, the dose of radiation therapy is reduced by about 10% to about 80%. In some embodiments, the site of radiation therapy is selected from the group consisting of the subject's breast, head and neck, cervix, uterus, ovaries, vagina, base of the spine, skin, pancreas, liver, rectum, or lung. In some embodiments, the method further comprises administration of hyaluronidase at the site of radiation therapy.

[0032] In some embodiments, the volume of the viscoelastic medium at the site of radiation treatment is reduced by about 1% to about 95%. In some embodiments, the volume of the viscoelastic medium at the site of radiation treatment is reduced by about 1% to about 5%, about 1% to about 10%, about 1% to about 15%, about 1% to about 20%, about 1% to about 30%, about 1% to about 40%, about 1% to about 50%, about 1% to about 60%, about 1% to about 70%, about 1% to about 80%, about 1% to about 95%, about 5% to about 10%, about 5% to about 15%, about 5% to about 20%, about 5% to about 30%, about 5% to about 60%, about 5% to about 70%, about 5% to about 80%, about 5 ... % to about 40%, about 5% to about 50%, about 5% to about 60%, about 5% to about 70%, about 5% to about 80%, about 5% to about 95%, about 10% to about 15%, about 10% to about 20%, about 10% to about 30%, about 10% to about 40%, about 10% to about 50%, about 10% to about 60%, about 10% to about 70%, about 10% to about 80%, about 10% to about 95%, about 15% to about 20%, about 15% to about 30%, about 15% to about 40 %, about 15% to about 50%, about 15% to about 60%, about 15% to about 70%, about 15% to about 80%, about 15% to about 95%, about 20% to about 30%, about 20% to about 40%, about 20% to about 50%, about 20% to about 60%, about 20% to about 70%, about 20% to about 80%, about 20% to about 95%, about 30% to about 40%, about 30% to about 50%, about 30% to about 60%, about 30% to about 70%, about 30% to about 80 %, about 30% to about 95%, about 40% to about 50%, about 40% to about 60%, about 40%, about 70%, about 40% to about 80%, about 40% to about 95%, about 50% to about 60%, about 50% to about 70%, about 50% to about 80%, about 50% to about 95%, about 60% to about 70%, about 60% to about 80%, about 60% to about 95%, about 70% to about 80%, about 70% to about 95%, or about 80% to about 95%. In some embodiments, the volume of the viscoelastic medium at the site of radiation treatment is reduced by about 1%, about 5%, about 10%, about 15%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, or about 95%. In some embodiments, the volume of the viscoelastic medium at the site of radiation treatment is reduced by at least about 1%, about 5%, about 10%, about 15%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, or about 80%.In some embodiments, the volume of the viscoelastic medium at the site of radiation treatment is reduced by at most about 5%, about 10%, about 15%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, or about 95%.

[0033] In some embodiments, administration of hyaluronidase occurs at about 0.1 hours to about 95 hours after injection of the bioabsorbable viscoelastic medium. In some embodiments, administration of hyaluronidase occurs at about 0.1 hours to about 0.5 hours, about 0.1 hours to about 1 hour, about 0.1 hours to about 2 hours, about 0.1 hours to about 4 hours, about 0.1 hours to about 6 hours, about 0.1 hours to about 8 hours, about 0.1 hours to about 10 hours, about 0.1 hours to about 14 hours, about 0.1 hours to about 18 hours, about 0.1 hours to about 24 hours, about 0.1 hours to about 95 hours, about 0.5 hours to about 1 hour, or about 0.5 hours to about 2 hours after injection of the bioabsorbable viscoelastic medium. 0.5 hours to about 4 hours, about 0.5 hours to about 6 hours, about 0.5 hours to about 8 hours, about 0.5 hours to about 10 hours, about 0.5 hours to about 14 hours, about 0.5 hours to about 18 hours, about 0.5 hours to about 24 hours, about 0.5 hours to about 95 hours, about 1 hour to about 2 hours, about 1 hour to about 4 hours, about 1 hour to about 6 hours, about 1 hour to about 8 hours, about 1 hour to about 10 hours, about 1 hour to about 14 hours, about 1 hour to about 18 hours, about 1 hour to about 24 hours, about 1 hour to about 95 hours, about 2 hours ~about 4 hours, about 2 hours to about 6 hours, about 2 hours to about 8 hours, about 2 hours to about 10 hours, about 2 hours to about 14 hours, about 2 hours to about 18 hours, about 2 hours to about 24 hours, about 2 hours to about 95 hours, about 4 hours to about 6 hours, about 4 hours to about 8 hours, about 4 hours to about 10 hours, about 4 hours to about 14 hours, about 4 hours to about 18 hours, about 4 hours to about 24 hours, about 4 hours to about 95 hours, about 6 hours to about 8 hours, about 6 hours to about 10 hours, about 6 hours to about 14 hours, about 6 hours to about 18 hours, about 6 hours The incubation period may be from about 1 hour to about 24 hours, from about 6 hours to about 95 hours, from about 8 hours to about 10 hours, from about 8 hours to about 14 hours, from about 8 hours to about 18 hours, from about 8 hours to about 24 hours, from about 8 hours to about 95 hours, from about 10 hours to about 14 hours, from about 10 hours to about 18 hours, from about 10 hours to about 24 hours, from about 10 hours to about 95 hours, from about 14 hours to about 18 hours, from about 14 hours to about 24 hours, from about 14 hours to about 95 hours, from about 18 hours to about 24 hours, from about 18 hours to about 95 hours, or from about 24 hours to about 95 hours. In some embodiments, administration of hyaluronidase occurs at about 0.1 hours, about 0.5 hours, about 1 hour, about 2 hours, about 4 hours, about 6 hours, about 8 hours, about 10 hours, about 14 hours, about 18 hours, about 24 hours, or about 95 hours after injection of the bioabsorbable viscoelastic medium.In some embodiments, administration of hyaluronidase occurs at least about 0.1 hours, about 0.5 hours, about 1 hour, about 2 hours, about 4 hours, about 6 hours, about 8 hours, about 10 hours, about 14 hours, about 18 hours, or about 24 hours after injection of the bioabsorbable viscoelastic medium. In some embodiments, administration of hyaluronidase occurs at most about 0.5 hours, about 1 hour, about 2 hours, about 4 hours, about 6 hours, about 8 hours, about 10 hours, about 14 hours, about 18 hours, about 24 hours, or about 95 hours after injection of the bioabsorbable viscoelastic medium.

[0034] Another aspect provided herein is a method of temporarily superspacing tissue adjacent to a site of radiation treatment, comprising injecting a formulation comprising cross-linked hyaluronic acid or a derivative thereof and an amount of degradable nanoparticles encapsulating hyaluronidase. In some embodiments, the amount of degradable nanoparticles encapsulating hyaluronidase is directly proportional to the desired superspacing distance for the desired superspacing duration.

[0035] Another aspect provided herein is a method of treating cancer in a subject suffering from cancer, the method comprising injecting a bioabsorbable viscoelastic medium into a blood vessel, the blood vessel being directly attached to a tumor. In some embodiments, the viscoelastic medium comprises gel particles. In some embodiments, the gel particles comprise hyaluronic acid or a derivative thereof.

[0036] In some embodiments, the injection comprises a volume of about 1 ml to about 50 ml. In some embodiments, the injection comprises a volume of about 1 ml to about 2 ml, about 1 ml to about 5 ml, about 1 ml to about 10 ml, about 1 ml to about 15 ml, about 1 ml to about 20 ml, about 1 ml to about 25 ml, about 1 ml to about 30 ml, about 1 ml to about 35 ml, about 1 ml to about 40 ml, about 1 ml to about 45 ml, about 1 ml to about 50 ml, about 2 ml to about 5 ml, about 2 ml to about 10 ml, about 2 ml to about 15 ml, about 2 ml to about 20 ml, about 2 ml to about 25 ml, about 2 ml to about 30 ml, about 2 ml to about 35 ml, about 2 ml to about 40 ml, about 2 ...2 ml to about 50 ml, about 2 ml to about 50 ml, about 2 ml to about 50 ml, about 2 ml to about 50 ml, about 2 ml to about 10 ml, about 2 ml to about 15 ml, about 2 ml to about 20 ml, about 2 ml to about 25 ml, about 2 ml to about 30 ml, about 2 ml to about 35 ml, about 2 ml to about 35 ml, about 2 ml to about 35 ml, about 2 ml to about 40 ml, about 2 ml to about 45 ml, 0ml, about 2ml to about 35ml, about 2ml to about 40ml, about 2ml to about 45ml, about 2ml to about 50ml, about 5ml to about 10ml, about 5ml to about 15ml, about 5ml to about 20ml, about 5ml to about 25ml, about 5ml to about 30ml, approximately 5ml to approximately 35ml, approximately 5ml to approximately 40ml, approximately 5ml to approximately 45ml, approximately 5ml to approximately 50ml, approximately 10ml to approximately 15ml, approximately 10ml to approximately 20ml, approximately 10ml to approximately 25ml, approximately 10ml to approximately 30ml, approximately 10ml to about 35ml, about 10ml to about 40ml, about 10ml to about 45ml, about 10ml to about 50ml, about 15ml to about 20ml, about 15ml to about 25ml, about 15ml to about 30ml, about 15ml to about 35ml, about 15 ml~about 40ml, about 15ml~about 45ml, about 15ml~about 50ml, about 20ml~about 25ml, about 20ml~about 30ml, about 20ml~about 35ml, about 20ml~about 40ml, about 20ml~about 45ml, about 20ml In some embodiments, the injection comprises a volume of about 1 ml, about 2 ml, about 5 ml, about 10 ml, about 15 ml, about 20 ml, about 25 ml, about 30 ml, about 35 ml, about 40 ml, about 45 ml, about 50 ml, about 45 ml, about 50 ml, about 50 ml, about 4 ...In some embodiments, the injection comprises a volume of at least about 1 ml, about 2 ml, about 5 ml, about 10 ml, about 15 ml, about 20 ml, about 25 ml, about 30 ml, about 35 ml, about 40 ml, or about 45 ml. In some embodiments, the injection comprises a volume of at most about 2 ml, about 5 ml, about 10 ml, about 15 ml, about 20 ml, about 25 ml, about 30 ml, about 35 ml, about 40 ml, about 45 ml, or about 50 ml.

[0037] In some embodiments, the injection is performed with a needle having a gauge of about 10 to about 26. In some embodiments, the injection is performed with a needle having a gauge of about 10 to about 11, about 10 to about 12, about 10 to about 13, about 10 to about 14, about 10 to about 15, about 10 to about 16, about 10 to about 18, about 10 to about 20, about 10 to about 22, about 10 to about 24, about 10 to about 26, about 11 to about 12, about 11 to about 13, about 11 to about 14, about 11 to about 15, about 1 1 to about 16, about 11 to about 18, about 11 to about 20, about 11 to about 22, about 11 to about 24, about 11 to about 26, about 12 to about 13, about 12 to about 14, about 12 to about 15, about 12 to about 16, about 12 to about 18, about 12 to about 20, about 12 to about 22, about 12 to about 24, about 12 to about 26, about 13 to about 14, about 13 to about 15, about 13 to about 16, about 13 to about 18, about 13 to about 20, about 13 to about 22, about 13 to about 24, about 13 to about 26, about 14 to about 15, about 14 to about 16, about 14 to about 18, about 14 to about 20, about 14 to about 22, about 14 to about 24, about 14 to about 26, about 15 to about 16, about 15 to about 18, about 15 to about 20, about 15 to about 22, about 15 to about 2 In some embodiments, the injection comprises a volume of about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 16, about 18, about 16, about 20, about 16, about 22, about 16, about 24, about 16, about 26, about 18, about 18, about 22, about 18, about 24, about 18, about 26, about 20, about 22, about 20, about 24, about 20, about 26, about 22, about 24, about 22, about 26, or about 24 to about 26. In some embodiments, the injection is performed with a needle having a gauge of about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 18, about 20, about 22, about 24, or about 26. In some embodiments, injection is performed with a needle having a gauge of at least about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 18, about 20, about 22, or about 24. In some embodiments, injection is performed with a needle having a gauge of at most about 11, about 12, about 13, about 14, about 15, about 16, about 18, about 20, about 22, about 24, or about 26.

[0038] In some embodiments, the concentration of hyaluronic acid in the spacer material is about 1 mg / ml to about 100 mg / ml. In some embodiments, the concentration of hyaluronic acid in the spacer material is about 1 mg / ml to about 5 mg / ml, about 1 mg / ml to about 10 mg / ml, about 1 mg / ml to about 15 mg / ml, about 1 mg / ml to about 20 mg / ml, about 1 mg / ml to about 25 mg / ml, about 1 mg / ml to about 30 mg / ml, about 1 mg / ml to about 40 mg / ml, about 1 mg / ml to about 50 mg / ml, about 1 mg / ml to about 60 mg / ml, about 1 mg / ml to about 80 mg / ml, about 1 mg / ml to about 100 mg / ml, about 5 mg / ml to about 10 mg / ml. l, about 5mg / ml to about 15mg / ml, about 5mg / ml to about 20mg / ml, about 5mg / ml to about 25mg / ml, about 5mg / ml to about 30mg / ml, about 5mg / ml to about 40mg / ml, about 5mg / ml to about 50mg / ml, about 5mg / ml to about 60m g / ml, about 5 mg / ml to about 80 mg / ml, about 5 mg / ml to about 100 mg / ml, about 10 mg / ml to about 15 mg / ml, about 10 mg / ml to about 20 mg / ml, about 10 mg / ml to about 25 mg / ml, about 10 mg / ml to about 30 mg / ml, about 10 mg / ml~about 40mg / ml, about 10mg / ml~about 50mg / ml, about 10mg / ml~about 60mg / ml, about 10mg / ml~about 80mg / ml, about 10mg / ml~about 100mg / ml, about 15mg / ml~about 20mg / ml, about 15mg / ml~about 25 mg / ml, about 15 mg / ml to about 30 mg / ml, about 15 mg / ml to about 40 mg / ml, about 15 mg / ml to about 50 mg / ml, about 15 mg / ml to about 60 mg / ml, about 15 mg / ml to about 80 mg / ml, about 15 mg / ml to about 100 mg / ml, about 2 0mg / ml to about 25mg / ml, about 20mg / ml to about 30mg / ml, about 20mg / ml to about 40mg / ml, about 20mg / ml to about 50mg / ml, about 20mg / ml to about 60mg / ml, about 20mg / ml to about 80mg / ml, about 20mg / ml to about 1 00mg / ml, about 25mg / ml to about 30mg / ml, about 25mg / ml to about 40mg / ml, about 25mg / ml to about 50mg / ml, about 25mg / ml to about 60mg / ml, about 25mg / ml to about 80mg / ml, about 25mg / ml to about 100mg / ml,about 30 mg / ml to about 40 mg / ml, about 30 mg / ml to about 50 mg / ml, about 30 mg / ml to about 60 mg / ml, about 30 mg / ml to about 80 mg / ml, about 30 mg / ml to about 100 mg / ml, about 40 mg / ml to about 50 mg / ml, about 40 mg / ml to about 60 mg / ml, about 40 mg / ml to about 80 mg / ml, about 40 mg / ml to about 100 mg / ml, about 50 mg / ml to about 60 mg / ml, about 50 mg / ml to about 80 mg / ml, about 50 mg / ml to about 100 mg / ml, about 60 mg / ml to about 80 mg / ml, about 60 mg / ml to about 100 mg / ml, or about 80 mg / ml to about 100 mg / ml. In some embodiments, the concentration of hyaluronic acid in the spacer material is about 1 mg / ml, about 5 mg / ml, about 10 mg / ml, about 15 mg / ml, about 20 mg / ml, about 25 mg / ml, about 30 mg / ml, about 40 mg / ml, about 50 mg / ml, about 60 mg / ml, about 80 mg / ml, or about 100 mg / ml. In some embodiments, the concentration of hyaluronic acid in the spacer material is at least about 1 mg / ml, about 5 mg / ml, about 10 mg / ml, about 15 mg / ml, about 20 mg / ml, about 25 mg / ml, about 30 mg / ml, about 40 mg / ml, about 50 mg / ml, about 60 mg / ml, or about 80 mg / ml. In some embodiments, the concentration of hyaluronic acid in the spacer material is at most about 5 mg / ml, about 10 mg / ml, about 15 mg / ml, about 20 mg / ml, about 25 mg / ml, about 30 mg / ml, about 40 mg / ml, about 50 mg / ml, about 60 mg / ml, about 80 mg / ml, or about 100 mg / ml.

[0039] In some embodiments, the injectable gel particles have a size of about 0.1 mm to about 10 mm. In some embodiments, the particles have a size of about 0.1 mm to about 0.2 mm, about 0.1 mm to about 0.5 mm, about 0.1 mm to about 1 mm, about 0.1 mm to about 1.5 mm, about 0.1 mm to about 2 mm, about 0.1 mm to about 3 mm, about 0.1 mm to about 4 mm, about 0.1 mm to about 5 mm, about 0.1 mm to about 6 mm, about 0.1 mm to about 8 mm, about 0.1 mm to about 10 mm, about 0.2 mm to about 0.5 mm, about 0.2 mm to about 1 mm, about 0.2 mm to about 1.5 mm, about 0.2mm to about 2mm, about 0.2mm to about 3mm, about 0.2mm to about 4mm, about 0.2mm to about 5mm, about 0.2mm to about 6mm, about 0.2mm to about 8mm, about 0.2mm to about 10mm, about 0.5mm to about 1mm, about 0 .5mm to about 1.5mm, about 0.5mm to about 2mm, about 0.5mm to about 3mm, about 0.5mm to about 4mm, about 0.5mm to about 5mm, about 0.5mm to about 6mm, about 0.5mm to about 8mm, about 0.5mm to about 10mm, about 1mm to about 1.5mm, about 1mm to about 2mm, about 1mm to about 3mm, about 1mm to about 4mm, about 1mm to about 5mm, about 1mm to about 6mm, about 1mm to about 8mm, about 1mm to about 10mm, about 1.5mm to about 2mm, about 1.5 mm~3mm, 1.5mm~4mm, 1.5mm~5mm, 1.5mm~6mm, 1.5mm~8mm, 1.5mm~10mm, 2mm~3mm, 2mm~4mm, 2mm~5mm, The gel particles have a size of about 2 mm to about 6 mm, about 2 mm to about 8 mm, about 2 mm to about 10 mm, about 3 mm to about 4 mm, about 3 mm to about 5 mm, about 3 mm to about 6 mm, about 3 mm to about 8 mm, about 3 mm to about 10 mm, about 4 mm to about 5 mm, about 4 mm to about 6 mm, about 4 mm to about 8 mm, about 4 mm to about 10 mm, about 5 mm to about 6 mm, about 5 mm to about 8 mm, about 5 mm to about 10 mm, about 6 mm to about 8 mm, about 6 mm to about 10 mm, or about 8 mm to about 10 mm. In some embodiments, the gel particles have a size of about 0.1 mm, 0.2 mm, 0.5 mm, about 1 mm, about 1.5 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 8 mm, or about 10 mm.In some embodiments, the gel particles have a size of at least about 0.1 mm, 0.2 mm, about 0.5 mm, about 1 mm, about 1.5 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, or about 8 mm. In some embodiments, the gel particles have a size of at most about 0.2 mm, about 0.5 mm, about 1 mm, about 1.5 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 8 mm, or about 10 mm.

[0040] In some embodiments, blood flow to the tumor is prevented or reduced. In some embodiments, movement of viscoelastic media is prevented or reduced. In some embodiments, the method further comprises administration of hyaluronidase at the site of radiation treatment.

[0041] In some embodiments, administration of hyaluronidase occurs at about 0.1 hours to about 95 hours after injection of the bioabsorbable viscoelastic medium. In some embodiments, administration of hyaluronidase occurs at about 0.1 hours to about 0.5 hours, about 0.1 hours to about 1 hour, about 0.1 hours to about 2 hours, about 0.1 hours to about 4 hours, about 0.1 hours to about 6 hours, about 0.1 hours to about 8 hours, about 0.1 hours to about 10 hours, about 0.1 hours to about 14 hours, about 0.1 hours to about 18 hours, about 0.1 hours to about 24 hours, about 0.1 hours to about 95 hours, about 0.5 hours to about 1 hour, or about 0.5 hours to about 2 hours after injection of the bioabsorbable viscoelastic medium. 0.5 hours to about 4 hours, about 0.5 hours to about 6 hours, about 0.5 hours to about 8 hours, about 0.5 hours to about 10 hours, about 0.5 hours to about 14 hours, about 0.5 hours to about 18 hours, about 0.5 hours to about 24 hours, about 0.5 hours to about 95 hours, about 1 hour to about 2 hours, about 1 hour to about 4 hours, about 1 hour to about 6 hours, about 1 hour to about 8 hours, about 1 hour to about 10 hours, about 1 hour to about 14 hours, about 1 hour to about 18 hours, about 1 hour to about 24 hours, about 1 hour to about 95 hours, about 2 hours ~about 4 hours, about 2 hours to about 6 hours, about 2 hours to about 8 hours, about 2 hours to about 10 hours, about 2 hours to about 14 hours, about 2 hours to about 18 hours, about 2 hours to about 24 hours, about 2 hours to about 95 hours, about 4 hours to about 6 hours, about 4 hours to about 8 hours, about 4 hours to about 10 hours, about 4 hours to about 14 hours, about 4 hours to about 18 hours, about 4 hours to about 24 hours, about 4 hours to about 95 hours, about 6 hours to about 8 hours, about 6 hours to about 10 hours, about 6 hours to about 14 hours, about 6 hours to about 18 hours, about 6 hours The incubation period may be from about 1 hour to about 24 hours, from about 6 hours to about 95 hours, from about 8 hours to about 10 hours, from about 8 hours to about 14 hours, from about 8 hours to about 18 hours, from about 8 hours to about 24 hours, from about 8 hours to about 95 hours, from about 10 hours to about 14 hours, from about 10 hours to about 18 hours, from about 10 hours to about 24 hours, from about 10 hours to about 95 hours, from about 14 hours to about 18 hours, from about 14 hours to about 24 hours, from about 14 hours to about 95 hours, from about 18 hours to about 24 hours, from about 18 hours to about 95 hours, or from about 24 hours to about 95 hours. In some embodiments, administration of hyaluronidase occurs at about 0.1 hours, about 0.5 hours, about 1 hour, about 2 hours, about 4 hours, about 6 hours, about 8 hours, about 10 hours, about 14 hours, about 18 hours, about 24 hours, or about 95 hours after injection of the bioabsorbable viscoelastic medium.In some embodiments, administration of hyaluronidase occurs at least about 0.1 hours, about 0.5 hours, about 1 hour, about 2 hours, about 4 hours, about 6 hours, about 8 hours, about 10 hours, about 14 hours, about 18 hours, or about 24 hours after injection of the bioabsorbable viscoelastic medium. In some embodiments, administration of hyaluronidase occurs at most about 0.5 hours, about 1 hour, about 2 hours, about 4 hours, about 6 hours, about 8 hours, about 10 hours, about 14 hours, about 18 hours, about 24 hours, or about 95 hours after injection of the bioabsorbable viscoelastic medium.

[0042] In some embodiments, the method further comprises the step of excising residual tumor cells from the subject.

[0043] Another aspect provided herein is a formulation comprising cross-linked hyaluronic acid and a radiopaque compound selected from the group consisting of iohexol, metrizamide, iopamidol, 3,5-bis(acetylamino)-2,4,6-triiodobenzoic acid, meglumine diatrizoate, iopentol, iopromide, triiodobenzoic acid, erythrosine, and ioversol. In some embodiments, the formulation is used as a fiducial marker.

[0044] Another aspect provided herein is a method of preventing or reducing damage to tissue adjacent to a site of radiation treatment in a subject undergoing radiation therapy, the method comprising injecting a bioabsorbable viscoelastic medium into the site of radiation treatment. In some embodiments, the viscoelastic medium comprises gel particles. In some embodiments, the gel particles comprise polyethylene glycol or a derivative thereof.

[0045] In some embodiments, the injection displaces the tissue a distance of about 0.1 cm to about 10 cm. In some embodiments, the injection displaces the tissue a distance of about 0.1 cm to about 0.2 cm, about 0.1 cm to about 0.5 cm, about 0.1 cm to about 1 cm, about 0.1 cm to about 2 cm, about 0.1 cm to about 3 cm, about 0.1 cm to about 4 cm, about 0.1 cm to about 5 cm, about 0.1 cm to about 6 cm, about 0.1 cm to about 7 cm, about 0.1 cm to about 8 cm, about 0.1 cm to about 10 cm, about 0.2 cm to about 0.5 cm, about 0.2 cm to about 1 cm, about 0.2 cm to about 2 cm, about 0.2cm to 3cm, 0.2cm to 4cm, 0.2cm to 5cm, 0.2cm to 6cm, 0.2cm to 7cm, 0.2cm to 8cm, 0.2cm to 10cm, 0.5cm to 1cm, Approximately 0.5cm to approximately 2cm, approximately 0.5cm to approximately 3cm, approximately 0.5cm to approximately 4cm, approximately 0.5cm to approximately 5cm, approximately 0.5cm to approximately 6cm, approximately 0.5cm to approximately 7cm, approximately 0.5cm to approximately 8cm, approximately 0.5cm to approximately 10cm , about 1cm to about 2cm, about 1cm to about 3cm, about 1cm to about 4cm, about 1cm to about 5cm, about 1cm to about 6cm, about 1cm to about 7cm, about 1cm to about 8cm, about 1cm to about 10cm, about 2cm to about 3cm, about 2cm ~4cm, 2cm~5cm, 2cm~6cm, 2cm~7cm, 2cm~8cm, 2cm~10cm, 3cm~4cm, 3cm~5cm, 3cm~6cm, 3cm~7cm , about 3 cm to about 8 cm, about 3 cm to about 10 cm, about 4 cm to about 5 cm, about 4 cm to about 6 cm, about 4 cm to about 7 cm, about 4 cm to about 8 cm, about 4 cm to about 10 cm, about 5 cm to about 6 cm, about 5 cm to about 7 cm, about 5 cm to about 8 cm, about 5 cm to about 10 cm, about 6 cm to about 7 cm, about 6 cm to about 8 cm, about 6 cm to about 10 cm, about 7 cm to about 8 cm, about 7 cm to about 10 cm, or 8 cm to about 10 cm. In some embodiments, the injection displaces the tissue by a distance of about 0.1 cm, about 0.2 cm, about 0.5 cm, about 1 cm, about 2 cm, about 3 cm, about 4 cm, about 5 cm, about 6 cm, about 7 cm, about 8 cm, or about 10 cm.In some embodiments, the injection displaces the tissue a distance of at least about 0.1 cm, about 0.2 cm, about 0.5 cm, about 1 cm, about 2 cm, about 3 cm, about 4 cm, about 5 cm, about 6 cm, about 7 cm, or about 8 cm. In some embodiments, the injection displaces the tissue a distance of at most about 0.2 cm, about 0.5 cm, about 1 cm, about 2 cm, about 3 cm, about 4 cm, about 5 cm, about 6 cm, about 7 cm, about 8 cm, or about 10 cm. In some embodiments, the injection comprises a volume of about 1 ml to about 50 ml.In some embodiments, the injection is from about 1 ml to about 2 ml, from about 1 ml to about 5 ml, from about 1 ml to about 10 ml, from about 1 ml to about 15 ml, from about 1 ml to about 20 ml, from about 1 ml to about 25 ml, from about 1 ml to about 30 ml, from about 1 ml to about 35 ml, from about 1 ml to about 40 ml, from about 1 ml to about 45 ml, from about 1 ml to about 50 ml, from about 2 ml to about 5 ml, from about 2 ml to about 10 ml, from about 2 ml to about 15 ml, from about 2 ml to about 20 ml, from about 2 ml to about 25 ml, from about 2 ml to about 30 ml, from about 2 ml to about 35 ml, from about 2 ...35 ml, from about 2 ml to about 40 ml, from about 2 ml to about 45 ml, from about 2 ml to about 50 ml, from about 2 ml to about 50 ml, from about 2 ml to about 50 ml, from about 2 ml to about 10 ml, from about 2 ml to about 15 ml, from about 2 ml to about 20 ml, from about 2 ml to about 25 ml, from about 2 ml to about 30 ml, from about 2 ml to about 35 ml, from about 2 ml to about 35 ml, from about 2 ml to about 35 ml, from about 2 0ml, about 2ml to about 35ml, about 2ml to about 40ml, about 2ml to about 45ml, about 2ml to about 50ml, about 5ml to about 10ml, about 5ml to about 15ml, about 5ml to about 20ml, about 5ml to about 25ml, about 5ml to about 30ml, approximately 5ml to approximately 35ml, approximately 5ml to approximately 40ml, approximately 5ml to approximately 45ml, approximately 5ml to approximately 50ml, approximately 10ml to approximately 15ml, approximately 10ml to approximately 20ml, approximately 10ml to approximately 25ml, approximately 10ml to approximately 30ml, approximately 10ml to about 35ml, about 10ml to about 40ml, about 10ml to about 45ml, about 10ml to about 50ml, about 15ml to about 20ml, about 15ml to about 25ml, about 15ml to about 30ml, about 15ml to about 35ml, about 15 ml~about 40ml, about 15ml~about 45ml, about 15ml~about 50ml, about 20ml~about 25ml, about 20ml~about 30ml, about 20ml~about 35ml, about 20ml~about 40ml, about 20ml~about 45ml, about 20ml In some embodiments, the injection comprises a volume of about 1 ml, about 2 ml, about 5 ml, about 10 ml, about 15 ml, about 20 ml, about 25 ml, about 30 ml, about 35 ml, about 40 ml, about 45 ml, about 50 ml, about 45 ml, about 50 ml, about 50 ml, about 4 ... In some embodiments, the injection comprises a volume of at least about 1 ml, about 2 ml, about 5 ml, about 10 ml, about 15 ml, about 20 ml, about 25 ml, about 30 ml, about 35 ml, about 40 ml, about 45 ml.In some embodiments, the injection comprises a volume of at most about 2 ml, about 5 ml, about 10 ml, about 15 ml, about 20 ml, about 25 ml, about 30 ml, about 35 ml, about 40 ml, about 45 ml, or about 50 ml.

[0046] In some embodiments, the injection is performed with a needle having a gauge of about 10 to about 26. In some embodiments, the injection is performed with a needle having a gauge of about 10 to about 11, about 10 to about 12, about 10 to about 13, about 10 to about 14, about 10 to about 15, about 10 to about 16, about 10 to about 18, about 10 to about 20, about 10 to about 22, about 10 to about 24, about 10 to about 26, about 11 to about 12, about 11 to about 13, about 11 to about 14, about 11 to about 15, about 1 1 to about 16, about 11 to about 18, about 11 to about 20, about 11 to about 22, about 11 to about 24, about 11 to about 26, about 12 to about 13, about 12 to about 14, about 12 to about 15, about 12 to about 16, about 12 to about 18, about 12 to about 20, about 12 to about 22, about 12 to about 24, about 12 to about 26, about 13 to about 14, about 13 to about 15, about 13 to about 16, about 13 to about 18, about 13 to about 20, about 13 to about 22, about 13 to about 24, about 13 to about 26, about 14 to about 15, about 14 to about 16, about 14 to about 18, about 14 to about 20, about 14 to about 22, about 14 to about 24, about 14 to about 26, about 15 to about 16, about 15 to about 18, about 15 to about 20, about 15 to about 22, about 15 to about 2 In some embodiments, the injection comprises a volume of about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 16, about 18, about 16, about 20, about 16, about 22, about 16, about 24, about 16, about 26, about 18, about 18, about 22, about 18, about 24, about 18, about 26, about 20, about 22, about 20, about 24, about 20, about 26, about 22, about 24, about 22, about 26, or about 24 to about 26. In some embodiments, the injection is performed with a needle having a gauge of about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 18, about 20, about 22, about 24, or about 26. In some embodiments, injection is performed with a needle having a gauge of at least about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 18, about 20, about 22, or about 24. In some embodiments, injection is performed with a needle having a gauge of at most about 11, about 12, about 13, about 14, about 15, about 16, about 18, about 20, about 22, about 24, or about 26.

[0047] In some embodiments, the concentration of polyethylene glycol in the spacer material is about 1 mg / ml to about 100 mg / ml. In some embodiments, the concentration of polyethylene glycol in the spacer material is about 1 mg / ml to about 5 mg / ml, about 1 mg / ml to about 10 mg / ml, about 1 mg / ml to about 15 mg / ml, about 1 mg / ml to about 20 mg / ml, about 1 mg / ml to about 25 mg / ml, about 1 mg / ml to about 30 mg / ml, about 1 mg / ml to about 40 mg / ml, about 1 mg / ml to about 50 mg / ml, about 1 mg / ml to about 60 mg / ml, about 1 mg / ml to about 80 mg / ml, about 1 mg / ml to about 100 mg / ml, about 5 mg / ml to about 10 mg / ml, approximately 5 mg / ml to approximately 15 mg / ml, approximately 5 mg / ml to approximately 20 mg / ml, approximately 5 mg / ml to approximately 25 mg / ml, approximately 5 mg / ml to approximately 30 mg / ml, approximately 5 mg / ml to approximately 40 mg / ml, approximately 5 mg / ml to approximately 50 mg / ml, approximately 5 mg / ml to approximately 60mg / ml, about 5mg / ml to about 80mg / ml, about 5mg / ml to about 100mg / ml, about 10mg / ml to about 15mg / ml, about 10mg / ml to about 20mg / ml, about 10mg / ml to about 25mg / ml, about 10mg / ml to about 30mg / ml, about 10 mg / ml~about 40mg / ml, about 10mg / ml~about 50mg / ml, about 10mg / ml~about 60mg / ml, about 10mg / ml~about 80mg / ml, about 10mg / ml~about 100mg / ml, about 15mg / ml~about 20mg / ml, about 15mg / ml~about 2 5mg / ml, about 15mg / ml to about 30mg / ml, about 15mg / ml to about 40mg / ml, about 15mg / ml to about 50mg / ml, about 15mg / ml to about 60mg / ml, about 15mg / ml to about 80mg / ml, about 15mg / ml to about 100mg / ml, about 20mg / ml to about 25mg / ml, about 20mg / ml to about 30mg / ml, about 20mg / ml to about 40mg / ml, about 20mg / ml to about 50mg / ml, about 20mg / ml to about 60mg / ml, about 20mg / ml to about 80mg / ml, about 20mg / ml to about 100mg / ml, about 25mg / ml to about 30mg / ml, about 25mg / ml to about 40mg / ml, about 25mg / ml to about 50mg / ml, about 25mg / ml to about 60mg / ml, about 25mg / ml to about 80mg / ml, about 25mg / ml to about 100mg / ml,about 30 mg / ml to about 40 mg / ml, about 30 mg / ml to about 50 mg / ml, about 30 mg / ml to about 60 mg / ml, about 30 mg / ml to about 80 mg / ml, about 30 mg / ml to about 100 mg / ml, about 40 mg / ml to about 50 mg / ml, about 40 mg / ml to about 60 mg / ml, about 40 mg / ml to about 80 mg / ml, about 40 mg / ml to about 100 mg / ml, about 50 mg / ml to about 60 mg / ml, about 50 mg / ml to about 80 mg / ml, about 50 mg / ml to about 100 mg / ml, about 60 mg / ml to about 80 mg / ml, about 60 mg / ml to about 100 mg / ml, or about 80 mg / ml to about 100 mg / ml. In some embodiments, the concentration of polyethylene glycol in the spacer material is about 1 mg / ml, about 5 mg / ml, about 10 mg / ml, about 15 mg / ml, about 20 mg / ml, about 25 mg / ml, about 30 mg / ml, about 40 mg / ml, about 50 mg / ml, about 60 mg / ml, about 80 mg / ml, or about 100 mg / ml. In some embodiments, the concentration of polyethylene glycol in the spacer material is at least about 1 mg / ml, about 5 mg / ml, about 10 mg / ml, about 15 mg / ml, about 20 mg / ml, about 25 mg / ml, about 30 mg / ml, about 40 mg / ml, about 50 mg / ml, about 60 mg / ml, or about 80 mg / ml. In some embodiments, the concentration of polyethylene glycol in the spacer material is at most about 5 mg / ml, about 10 mg / ml, about 15 mg / ml, about 20 mg / ml, about 25 mg / ml, about 30 mg / ml, about 40 mg / ml, about 50 mg / ml, about 60 mg / ml, about 80 mg / ml, or about 100 mg / ml.

[0048] In some embodiments, the injectable gel particles have a size of about 0.1 mm to about 10 mm. In some embodiments, the particles have a size of about 0.1 mm to about 0.2 mm, about 0.1 mm to about 0.5 mm, about 0.1 mm to about 1 mm, about 0.1 mm to about 1.5 mm, about 0.1 mm to about 2 mm, about 0.1 mm to about 3 mm, about 0.1 mm to about 4 mm, about 0.1 mm to about 5 mm, about 0.1 mm to about 6 mm, about 0.1 mm to about 8 mm, about 0.1 mm to about 10 mm, about 0.2 mm to about 0.5 mm, about 0.2 mm to about 1 mm, about 0.2 mm to about 1.5 mm, about 0.2mm to about 2mm, about 0.2mm to about 3mm, about 0.2mm to about 4mm, about 0.2mm to about 5mm, about 0.2mm to about 6mm, about 0.2mm to about 8mm, about 0.2mm to 10mm, about 0.5mm to about 1mm, about 0. 5mm to about 1.5mm, about 0.5mm to about 2mm, about 0.5mm to about 3mm, about 0.5mm to about 4mm, about 0.5mm to about 5mm, about 0.5mm to about 6mm, about 0.5mm to about 8mm, about 0.5mm to about 10mm, about 1 mm~1.5mm, 1mm~2mm, 1mm~3mm, 1mm~4mm, 1mm~5mm, 1mm~6mm, 1mm~8mm, 1mm~10mm, 1.5mm~2mm, 1.5m m~3mm, 1.5mm~4mm, 1.5mm~5mm, 1.5mm~6mm, 1.5mm~8mm, 1.5mm~10mm, 2mm~3mm, 2mm~4mm, 2mm~5mm, The gel particles have a size of about 2 mm to about 6 mm, about 2 mm to about 8 mm, about 2 mm to about 10 mm, about 3 mm to about 4 mm, about 3 mm to about 5 mm, about 3 mm to about 6 mm, about 3 mm to about 8 mm, about 3 mm to about 10 mm, about 4 mm to about 5 mm, about 4 mm to about 6 mm, about 4 mm to about 8 mm, about 4 mm to about 10 mm, about 5 mm to about 6 mm, about 5 mm to about 8 mm, about 5 mm to about 10 mm, about 6 mm to about 8 mm, about 6 mm to about 10 mm, or about 8 mm to about 10 mm. In some embodiments, the gel particles have a size of about 0.1 mm, 0.2 mm, 0.5 mm, about 1 mm, about 1.5 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 8 mm, or about 10 mm.In some embodiments, the injectable gel particles have a size of at least about 0.1 mm, 0.2 mm, about 0.5 mm, about 1 mm, about 1.5 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, or about 8 mm. In some embodiments, the gel particles have a size of at most about 0.2 mm, about 0.5 mm, about 1 mm, about 1.5 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 8 mm, or about 10 mm.

[0049] In some embodiments, the injection is subcutaneous or subepidermal. In some embodiments, migration of the viscoelastic medium is prevented or reduced. In some embodiments, the viscoelastic medium further comprises nanoparticles. In some embodiments, the nanoparticles comprise a precious metal. In some embodiments, the dose of radiation therapy contacting tissue adjacent to the site of radiation treatment is reduced by about 10% to about 80%. In some embodiments, the site of radiation treatment is selected from the group consisting of the subject's breast, head and neck, cervix, vagina, base of the spine, skin, pancreas, liver, or lung. In some embodiments, the method further comprises administration of hyaluronidase at the site of radiation treatment.

[0050] In some embodiments, the volume of the viscoelastic medium at the site of radiation treatment is reduced by about 1% to about 95%. In some embodiments, the volume of the viscoelastic medium at the site of radiation treatment is reduced by about 1% to about 5%, about 1% to about 10%, about 1% to about 15%, about 1% to about 20%, about 1% to about 30%, about 1% to about 40%, about 1% to about 50%, about 1% to about 60%, about 1% to about 70%, about 1% to about 80%, about 1% to about 95%, about 5% to about 10%, about 5% to about 15%, about 5% to about 20%, about 5% to about 30%, about 5% to about 60%, about 5% to about 70%, about 5% to about 80%, about 5 ... % to about 40%, about 5% to about 50%, about 5% to about 60%, about 5% to about 70%, about 5% to about 80%, about 5% to about 95%, about 10% to about 15%, about 10% to about 20%, about 10% to about 30%, about 10% to about 40%, about 10% to about 50%, about 10% to about 60%, about 10% to about 70%, about 10% to about 80%, about 10% to about 95%, about 15% to about 20%, about 15% to about 30%, about 15% to about 40 %, about 15% to about 50%, about 15% to about 60%, about 15% to about 70%, about 15% to about 80%, about 15% to about 95%, about 20% to about 30%, about 20% to about 40%, about 20% to about 50%, about 20% to about 60%, about 20% to about 70%, about 20% to about 80%, about 20% to about 95%, about 30% to about 40%, about 30% to about 50%, about 30% to about 60%, about 30% to about 70%, about 30% to about 80 %, about 30% to about 95%, about 40% to about 50%, about 40% to about 60%, about 40%, about 70%, about 40% to about 80%, about 40% to about 95%, about 50% to about 60%, about 50% to about 70%, about 50% to about 80%, about 50% to about 95%, about 60% to about 70%, about 60% to about 80%, about 60% to about 95%, about 70% to about 80%, about 70% to about 95%, or about 80% to about 95%. In some embodiments, the volume of the viscoelastic medium at the site of radiation treatment is reduced by about 1%, about 5%, about 10%, about 15%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, or about 95%. In some embodiments, the volume of the viscoelastic medium at the site of radiation treatment is reduced by at least about 1%, about 5%, about 10%, about 15%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, or about 80%.In some embodiments, the volume of the viscoelastic medium at the site of radiation treatment is reduced by at most about 5%, about 10%, about 15%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, or about 95%.

[0051] In some embodiments, administration of hyaluronidase occurs at about 0.1 hours to about 95 hours after injection of the bioabsorbable viscoelastic medium. In some embodiments, administration of hyaluronidase occurs at about 0.1 hours to about 0.5 hours, about 0.1 hours to about 1 hour, about 0.1 hours to about 2 hours, about 0.1 hours to about 4 hours, about 0.1 hours to about 6 hours, about 0.1 hours to about 8 hours, about 0.1 hours to about 10 hours, about 0.1 hours to about 14 hours, about 0.1 hours to about 18 hours, about 0.1 hours to about 24 hours, about 0.1 hours to about 95 hours, about 0.5 hours to about 1 hour, or about 0.5 hours to about 2 hours after injection of the bioabsorbable viscoelastic medium. 0.5 hours to about 4 hours, about 0.5 hours to about 6 hours, about 0.5 hours to about 8 hours, about 0.5 hours to about 10 hours, about 0.5 hours to about 14 hours, about 0.5 hours to about 18 hours, about 0.5 hours to about 24 hours, about 0.5 hours to about 95 hours, about 1 hour to about 2 hours, about 1 hour to about 4 hours, about 1 hour to about 6 hours, about 1 hour to about 8 hours, about 1 hour to about 10 hours, about 1 hour to about 14 hours, about 1 hour to about 18 hours, about 1 hour to about 24 hours, about 1 hour to about 95 hours, about 2 hours ~about 4 hours, about 2 hours to about 6 hours, about 2 hours to about 8 hours, about 2 hours to about 10 hours, about 2 hours to about 14 hours, about 2 hours to about 18 hours, about 2 hours to about 24 hours, about 2 hours to about 95 hours, about 4 hours to about 6 hours, about 4 hours to about 8 hours, about 4 hours to about 10 hours, about 4 hours to about 14 hours, about 4 hours to about 18 hours, about 4 hours to about 24 hours, about 4 hours to about 95 hours, about 6 hours to about 8 hours, about 6 hours to about 10 hours, about 6 hours to about 14 hours, about 6 hours to about 18 hours, about 6 hours The incubation period may be from about 1 hour to about 24 hours, from about 6 hours to about 95 hours, from about 8 hours to about 10 hours, from about 8 hours to about 14 hours, from about 8 hours to about 18 hours, from about 8 hours to about 24 hours, from about 8 hours to about 95 hours, from about 10 hours to about 14 hours, from about 10 hours to about 18 hours, from about 10 hours to about 24 hours, from about 10 hours to about 95 hours, from about 14 hours to about 18 hours, from about 14 hours to about 24 hours, from about 14 hours to about 95 hours, from about 18 hours to about 24 hours, from about 18 hours to about 95 hours, or from about 24 hours to about 95 hours. In some embodiments, administration of hyaluronidase occurs at about 0.1 hours, about 0.5 hours, about 1 hour, about 2 hours, about 4 hours, about 6 hours, about 8 hours, about 10 hours, about 14 hours, about 18 hours, about 24 hours, or about 95 hours after injection of the bioabsorbable viscoelastic medium.In some embodiments, administration of hyaluronidase occurs at least about 0.1 hours, about 0.5 hours, about 1 hour, about 2 hours, about 4 hours, about 6 hours, about 8 hours, about 10 hours, about 14 hours, about 18 hours, or about 24 hours after injection of the bioabsorbable viscoelastic medium. In some embodiments, administration of hyaluronidase occurs at most about 0.5 hours, about 1 hour, about 2 hours, about 4 hours, about 6 hours, about 8 hours, about 10 hours, about 14 hours, about 18 hours, about 24 hours, or about 95 hours after injection of the bioabsorbable viscoelastic medium.

[0052] Another aspect provided herein is a method of reducing a dose of radiation therapy to tissue adjacent to a site of radiation treatment in a subject undergoing radiation therapy, the method comprising injecting a bioabsorbable viscoelastic medium into the site of radiation treatment. In some embodiments, the viscoelastic medium comprises gel particles. In some embodiments, the gel particles comprise polyethylene glycol or a derivative thereof.

[0053] In some embodiments, the injection displaces the tissue a distance of about 0.1 cm to about 10 cm. In some embodiments, the injection displaces the tissue a distance of about 0.1 cm to about 0.2 cm, about 0.1 cm to about 0.5 cm, about 0.1 cm to about 1 cm, about 0.1 cm to about 2 cm, about 0.1 cm to about 3 cm, about 0.1 cm to about 4 cm, about 0.1 cm to about 5 cm, about 0.1 cm to about 6 cm, about 0.1 cm to about 7 cm, about 0.1 cm to about 8 cm, about 0.1 cm to about 10 cm, about 0.2 cm to about 0.5 cm, about 0.2 cm to about 1 cm, about 0.2 cm to about 2 cm, about 0.2cm to 3cm, 0.2cm to 4cm, 0.2cm to 5cm, 0.2cm to 6cm, 0.2cm to 7cm, 0.2cm to 8cm, 0.2cm to 10cm, 0.5cm to 1cm, Approximately 0.5cm to approximately 2cm, approximately 0.5cm to approximately 3cm, approximately 0.5cm to approximately 4cm, approximately 0.5cm to approximately 5cm, approximately 0.5cm to approximately 6cm, approximately 0.5cm to approximately 7cm, approximately 0.5cm to approximately 8cm, approximately 0.5cm to approximately 10cm , about 1cm to about 2cm, about 1cm to about 3cm, about 1cm to about 4cm, about 1cm to about 5cm, about 1cm to about 6cm, about 1cm to about 7cm, about 1cm to about 8cm, about 1cm to about 10cm, about 2cm to about 3cm, about 2cm ~4cm, 2cm~5cm, 2cm~6cm, 2cm~7cm, 2cm~8cm, 2cm~10cm, 3cm~4cm, 3cm~5cm, 3cm~6cm, 3cm~7cm , about 3 cm to about 8 cm, about 3 cm to about 10 cm, about 4 cm to about 5 cm, about 4 cm to about 6 cm, about 4 cm to about 7 cm, about 4 cm to about 8 cm, about 4 cm to about 10 cm, about 5 cm to about 6 cm, about 5 cm to about 7 cm, about 5 cm to about 8 cm, about 5 cm to about 10 cm, about 6 cm to about 7 cm, about 6 cm to about 8 cm, about 6 cm to about 10 cm, about 7 cm to about 8 cm, about 7 cm to about 10 cm, or 8 cm to about 10 cm. In some embodiments, the injection displaces the tissue by a distance of about 0.1 cm, about 0.2 cm, about 0.5 cm, about 1 cm, about 2 cm, about 3 cm, about 4 cm, about 5 cm, about 6 cm, about 7 cm, about 8 cm, or about 10 cm.In some embodiments, the injection displaces the tissue a distance of at least about 0.1 cm, about 0.2 cm, about 0.5 cm, about 1 cm, about 2 cm, about 3 cm, about 4 cm, about 5 cm, about 6 cm, about 7 cm, or about 8 cm. In some embodiments, the injection displaces the tissue a distance of at most about 0.2 cm, about 0.5 cm, about 1 cm, about 2 cm, about 3 cm, about 4 cm, about 5 cm, about 6 cm, about 7 cm, about 8 cm, or about 10 cm. In some embodiments, the injection comprises a volume of about 1 ml to about 50 ml.In some embodiments, the injection is from about 1 ml to about 2 ml, from about 1 ml to about 5 ml, from about 1 ml to about 10 ml, from about 1 ml to about 15 ml, from about 1 ml to about 20 ml, from about 1 ml to about 25 ml, from about 1 ml to about 30 ml, from about 1 ml to about 35 ml, from about 1 ml to about 40 ml, from about 1 ml to about 45 ml, from about 1 ml to about 50 ml, from about 2 ml to about 5 ml, from about 2 ml to about 10 ml, from about 2 ml to about 15 ml, from about 2 ml to about 20 ml, from about 2 ml to about 25 ml, from about 2 ml to about 30 ml, from about 2 ml to about 35 ml, from about 2 ...35 ml, from about 2 ml to about 40 ml, from about 2 ml to about 45 ml, from about 2 ml to about 50 ml, from about 2 ml to about 50 ml, from about 2 ml to about 50 ml, from about 2 ml to about 10 ml, from about 2 ml to about 15 ml, from about 2 ml to about 20 ml, from about 2 ml to about 25 ml, from about 2 ml to about 30 ml, from about 2 ml to about 35 ml, from about 2 ml to about 35 ml, from about 2 ml to about 35 ml, from about 2 0ml, about 2ml to about 35ml, about 2ml to about 40ml, about 2ml to about 45ml, about 2ml to about 50ml, about 5ml to about 10ml, about 5ml to about 15ml, about 5ml to about 20ml, about 5ml to about 25ml, about 5ml to about 30ml, approximately 5ml to approximately 35ml, approximately 5ml to approximately 40ml, approximately 5ml to approximately 45ml, approximately 5ml to approximately 50ml, approximately 10ml to approximately 15ml, approximately 10ml to approximately 20ml, approximately 10ml to approximately 25ml, approximately 10ml to approximately 30ml, approximately 10ml to about 35ml, about 10ml to about 40ml, about 10ml to about 45ml, about 10ml to about 50ml, about 15ml to about 20ml, about 15ml to about 25ml, about 15ml to about 30ml, about 15ml to about 35ml, about 15 ml~about 40ml, about 15ml~about 45ml, about 15ml~about 50ml, about 20ml~about 25ml, about 20ml~about 30ml, about 20ml~about 35ml, about 20ml~about 40ml, about 20ml~about 45ml, about 20ml In some embodiments, the injection comprises a volume of about 1 ml, about 2 ml, about 5 ml, about 10 ml, about 15 ml, about 20 ml, about 25 ml, about 30 ml, about 35 ml, about 40 ml, about 45 ml, about 50 ml, about 45 ml, about 50 ml, about 50 ml, about 4 ... In some embodiments, the injection comprises a volume of at least about 1 ml, about 2 ml, about 5 ml, about 10 ml, about 15 ml, about 20 ml, about 25 ml, about 30 ml, about 35 ml, about 40 ml, or about 45 ml.In some embodiments, the injection comprises a volume of at most about 2 ml, about 5 ml, about 10 ml, about 15 ml, about 20 ml, about 25 ml, about 30 ml, about 35 ml, about 40 ml, about 45 ml, or about 50 ml.

[0054] In some embodiments, the concentration of polyethylene glycol in the spacer material is about 1 mg / ml to about 100 mg / ml. In some embodiments, the concentration of polyethylene glycol in the spacer material is about 1 mg / ml to about 5 mg / ml, about 1 mg / ml to about 10 mg / ml, about 1 mg / ml to about 15 mg / ml, about 1 mg / ml to about 20 mg / ml, about 1 mg / ml to about 25 mg / ml, about 1 mg / ml to about 30 mg / ml, about 1 mg / ml to about 40 mg / ml, about 1 mg / ml to about 50 mg / ml, about 1 mg / ml to about 60 mg / ml, about 1 mg / ml to about 80 mg / ml, about 1 mg / ml to about 100 mg / ml, about 5 mg / ml to about 10 mg / ml, approximately 5 mg / ml to approximately 15 mg / ml, approximately 5 mg / ml to approximately 20 mg / ml, approximately 5 mg / ml to approximately 25 mg / ml, approximately 5 mg / ml to approximately 30 mg / ml, approximately 5 mg / ml to approximately 40 mg / ml, approximately 5 mg / ml to approximately 50 mg / ml, approximately 5 mg / ml to approximately 60mg / ml, about 5mg / ml to about 80mg / ml, about 5mg / ml to about 100mg / ml, about 10mg / ml to about 15mg / ml, about 10mg / ml to about 20mg / ml, about 10mg / ml to about 25mg / ml, about 10mg / ml to about 30mg / ml, about 10 mg / ml~about 40mg / ml, about 10mg / ml~about 50mg / ml, about 10mg / ml~about 60mg / ml, about 10mg / ml~about 80mg / ml, about 10mg / ml~about 100mg / ml, about 15mg / ml~about 20mg / ml, about 15mg / ml~about 2 5mg / ml, about 15mg / ml to about 30mg / ml, about 15mg / ml to about 40mg / ml, about 15mg / ml to about 50mg / ml, about 15mg / ml to about 60mg / ml, about 15mg / ml to about 80mg / ml, about 15mg / ml to about 100mg / ml, about 20mg / ml to about 25mg / ml, about 20mg / ml to about 30mg / ml, about 20mg / ml to about 40mg / ml, about 20mg / ml to about 50mg / ml, about 20mg / ml to about 60mg / ml, about 20mg / ml to about 80mg / ml, about 20mg / ml to about 100mg / ml, about 25mg / ml to about 30mg / ml, about 25mg / ml to about 40mg / ml, about 25mg / ml to about 50mg / ml, about 25mg / ml to about 60mg / ml, about 25mg / ml to about 80mg / ml, about 25mg / ml to about 100mg / ml,about 30 mg / ml to about 40 mg / ml, about 30 mg / ml to about 50 mg / ml, about 30 mg / ml to about 60 mg / ml, about 30 mg / ml to about 80 mg / ml, about 30 mg / ml to about 100 mg / ml, about 40 mg / ml to about 50 mg / ml, about 40 mg / ml to about 60 mg / ml, about 40 mg / ml to about 80 mg / ml, about 40 mg / ml to about 100 mg / ml, about 50 mg / ml to about 60 mg / ml, about 50 mg / ml to about 80 mg / ml, about 50 mg / ml to about 100 mg / ml, about 60 mg / ml to about 80 mg / ml, about 60 mg / ml to about 100 mg / ml, or about 80 mg / ml to about 100 mg / ml. In some embodiments, the concentration of polyethylene glycol in the spacer material is about 1 mg / ml, about 5 mg / ml, about 10 mg / ml, about 15 mg / ml, about 20 mg / ml, about 25 mg / ml, about 30 mg / ml, about 40 mg / ml, about 50 mg / ml, about 60 mg / ml, about 80 mg / ml, or about 100 mg / ml. In some embodiments, the concentration of polyethylene glycol in the spacer material is at least about 1 mg / ml, about 5 mg / ml, about 10 mg / ml, about 15 mg / ml, about 20 mg / ml, about 25 mg / ml, about 30 mg / ml, about 40 mg / ml, about 50 mg / ml, about 60 mg / ml, or about 80 mg / ml. In some embodiments, the concentration of polyethylene glycol in the spacer material is at most about 5 mg / ml, about 10 mg / ml, about 15 mg / ml, about 20 mg / ml, about 25 mg / ml, about 30 mg / ml, about 40 mg / ml, about 50 mg / ml, about 60 mg / ml, about 80 mg / ml, or about 100 mg / ml.

[0055] In some embodiments, the injectable gel particles have a size of about 0.1 mm to about 10 mm. In some embodiments, the particles have a size of about 0.1 mm to about 0.2 mm, about 0.1 mm to about 0.5 mm, about 0.1 mm to about 1 mm, about 0.1 mm to about 1.5 mm, about 0.1 mm to about 2 mm, about 0.1 mm to about 3 mm, about 0.1 mm to about 4 mm, about 0.1 mm to about 5 mm, about 0.1 mm to about 6 mm, about 0.1 mm to about 8 mm, about 0.1 mm to about 10 mm, about 0.2 mm to about 0.5 mm, about 0.2 mm to about 1 mm, about 0.2 mm to about 1.5 mm, about 0.2mm to about 2mm, about 0.2mm to about 3mm, about 0.2mm to about 4mm, about 0.2mm to about 5mm, about 0.2mm to about 6mm, about 0.2mm to about 8mm, about 0.2mm to 10mm, about 0.5mm to about 1mm, about 0. 5mm to about 1.5mm, about 0.5mm to about 2mm, about 0.5mm to about 3mm, about 0.5mm to about 4mm, about 0.5mm to about 5mm, about 0.5mm to about 6mm, about 0.5mm to about 8mm, about 0.5mm to about 10mm, about 1 mm~1.5mm, 1mm~2mm, 1mm~3mm, 1mm~4mm, 1mm~5mm, 1mm~6mm, 1mm~8mm, 1mm~10mm, 1.5mm~2mm, 1.5m m~3mm, 1.5mm~4mm, 1.5mm~5mm, 1.5mm~6mm, 1.5mm~8mm, 1.5mm~10mm, 2mm~3mm, 2mm~4mm, 2mm~5mm, The gel particles have a size of about 2 mm to about 6 mm, about 2 mm to about 8 mm, about 2 mm to about 10 mm, about 3 mm to about 4 mm, about 3 mm to about 5 mm, about 3 mm to about 6 mm, about 3 mm to about 8 mm, about 3 mm to about 10 mm, about 4 mm to about 5 mm, about 4 mm to about 6 mm, about 4 mm to about 8 mm, about 4 mm to about 10 mm, about 5 mm to about 6 mm, about 5 mm to about 8 mm, about 5 mm to about 10 mm, about 6 mm to about 8 mm, about 6 mm to about 10 mm, or about 8 mm to about 10 mm. In some embodiments, the gel particles have a size of about 0.1 mm, 0.2 mm, 0.5 mm, about 1 mm, about 1.5 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 8 mm, or about 10 mm.In some embodiments, the gel particles have a size of at least about 0.1 mm, 0.2 mm, about 0.5 mm, about 1 mm, about 1.5 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, or about 8 mm. In some embodiments, the gel particles have a size of at most about 0.2 mm, about 0.5 mm, about 1 mm, about 1.5 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 8 mm, or about 10 mm.

[0056] In some embodiments, the injection is subcutaneous or subepidermal. In some embodiments, migration of the viscoelastic medium is prevented or reduced. In some embodiments, the viscoelastic medium further comprises nanoparticles. In some embodiments, the nanoparticles comprise a precious metal. In some embodiments, the dose of radiation therapy is reduced by about 10% to about 80%. In some embodiments, the site of radiation therapy is selected from the group consisting of the subject's breast, head and neck, cervix, vagina, base of the spine, skin, pancreas, liver, rectum, or lung. In some embodiments, the method further comprises administration of hyaluronidase at the site of radiation therapy.

[0057] In some embodiments, the volume of the viscoelastic medium at the site of radiation treatment is reduced by about 1% to about 95%. In some embodiments, the volume of the viscoelastic medium at the site of radiation treatment is reduced by about 1% to about 5%, about 1% to about 10%, about 1% to about 15%, about 1% to about 20%, about 1% to about 30%, about 1% to about 40%, about 1% to about 50%, about 1% to about 60%, about 1% to about 70%, about 1% to about 80%, about 1% to about 95%, about 5% to about 10%, about 5% to about 15%, about 5% to about 20%, about 5% to about 30%, about 5% to about 60%, about 5% to about 70%, about 5% to about 80%, about 5 ... % to about 40%, about 5% to about 50%, about 5% to about 60%, about 5% to about 70%, about 5% to about 80%, about 5% to about 95%, about 10% to about 15%, about 10% to about 20%, about 10% to about 30%, about 10% to about 40%, about 10% to about 50%, about 10% to about 60%, about 10% to about 70%, about 10% to about 80%, about 10% to about 95%, about 15% to about 20%, about 15% to about 30%, about 15% to about 40 %, about 15% to about 50%, about 15% to about 60%, about 15% to about 70%, about 15% to about 80%, about 15% to about 95%, about 20% to about 30%, about 20% to about 40%, about 20% to about 50%, about 20% to about 60%, about 20% to about 70%, about 20% to about 80%, about 20% to about 95%, about 30% to about 40%, about 30% to about 50%, about 30% to about 60%, about 30% to about 70%, about 30% to about 80 %, about 30% to about 95%, about 40% to about 50%, about 40% to about 60%, about 40% to about 70%, about 40% to about 80%, about 40% to about 95%, about 50% to about 60%, about 50% to about 70%, about 50% to about 80%, about 50% to about 95%, about 60% to about 70%, about 60% to about 80%, about 60% to about 95%, about 70% to about 80%, about 70% to about 95%, or about 80% to about 95%. In some embodiments, the volume of the viscoelastic medium at the site of radiation treatment is reduced by about 1%, about 5%, about 10%, about 15%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, or about 95%. In some embodiments, the volume of the viscoelastic medium at the site of radiation treatment is reduced by at least about 1%, about 5%, about 10%, about 15%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, or about 80%.In some embodiments, the volume of the viscoelastic medium at the site of radiation treatment is reduced by at most about 5%, about 10%, about 15%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, or about 95%.

[0058] In some embodiments, administration of hyaluronidase occurs at about 0.1 hours to about 95 hours after injection of the bioabsorbable viscoelastic medium. In some embodiments, administration of hyaluronidase occurs at about 0.1 hours to about 0.5 hours, about 0.1 hours to about 1 hour, about 0.1 hours to about 2 hours, about 0.1 hours to about 4 hours, about 0.1 hours to about 6 hours, about 0.1 hours to about 8 hours, about 0.1 hours to about 10 hours, about 0.1 hours to about 14 hours, about 0.1 hours to about 18 hours, about 0.1 hours to about 24 hours, about 0.1 hours to about 95 hours, about 0.5 hours to about 1 hour, or about 0.5 hours to about 2 hours after injection of the bioabsorbable viscoelastic medium. 0.5 hours to about 4 hours, about 0.5 hours to about 6 hours, about 0.5 hours to about 8 hours, about 0.5 hours to about 10 hours, about 0.5 hours to about 14 hours, about 0.5 hours to about 18 hours, about 0.5 hours to about 24 hours, about 0.5 hours to about 95 hours, about 1 hour to about 2 hours, about 1 hour to about 4 hours, about 1 hour to about 6 hours, about 1 hour to about 8 hours, about 1 hour to about 10 hours, about 1 hour to about 14 hours, about 1 hour to about 18 hours, about 1 hour to about 24 hours, about 1 hour to about 95 hours, about 2 hours ~about 4 hours, about 2 hours to about 6 hours, about 2 hours to about 8 hours, about 2 hours to about 10 hours, about 2 hours to about 14 hours, about 2 hours to about 18 hours, about 2 hours to about 24 hours, about 2 hours to about 95 hours, about 4 hours to about 6 hours, about 4 hours to about 8 hours, about 4 hours to about 10 hours, about 4 hours to about 14 hours, about 4 hours to about 18 hours, about 4 hours to about 24 hours, about 4 hours to about 95 hours, about 6 hours to about 8 hours, about 6 hours to about 10 hours, about 6 hours to about 14 hours, about 6 hours to about 18 hours, about 6 hours The incubation period may be from about 1 hour to about 24 hours, from about 6 hours to about 95 hours, from about 8 hours to about 10 hours, from about 8 hours to about 14 hours, from about 8 hours to about 18 hours, from about 8 hours to about 24 hours, from about 8 hours to about 95 hours, from about 10 hours to about 14 hours, from about 10 hours to about 18 hours, from about 10 hours to about 24 hours, from about 10 hours to about 95 hours, from about 14 hours to about 18 hours, from about 14 hours to about 24 hours, from about 14 hours to about 95 hours, from about 18 hours to about 24 hours, from about 18 hours to about 95 hours, or from about 24 hours to about 95 hours. In some embodiments, administration of hyaluronidase occurs at about 0.1 hours, about 0.5 hours, about 1 hour, about 2 hours, about 4 hours, about 6 hours, about 8 hours, about 10 hours, about 14 hours, about 18 hours, about 24 hours, or about 95 hours after injection of the bioabsorbable viscoelastic medium.In some embodiments, administration of hyaluronidase occurs at least about 0.1 hours, about 0.5 hours, about 1 hour, about 2 hours, about 4 hours, about 6 hours, about 8 hours, about 10 hours, about 14 hours, about 18 hours, or about 24 hours after injection of the bioabsorbable viscoelastic medium. In some embodiments, administration of hyaluronidase occurs at most about 0.5 hours, about 1 hour, about 2 hours, about 4 hours, about 6 hours, about 8 hours, about 10 hours, about 14 hours, about 18 hours, about 24 hours, or about 95 hours after injection of the bioabsorbable viscoelastic medium.

[0059] Another aspect provided herein is a method of temporarily superspacing tissue adjacent to a site of radiation treatment, comprising injecting a formulation comprising cross-linked polyethylene glycol or a derivative thereof and a quantity of degradable nanoparticles encapsulating hyaluronidase. In some embodiments, the amount of degradable nanoparticles encapsulating hyaluronidase is directly proportional to the desired superspacing distance for the desired superspacing duration.

[0060] Another aspect provided herein is a method of treating cancer in a subject suffering from cancer, the method comprising injecting a bioabsorbable viscoelastic medium into a blood vessel, where the blood vessel is directly attached to a tumor. In some embodiments, the viscoelastic medium comprises gel particles. In some embodiments, the gel particles comprise polyethylene glycol or a derivative thereof.

[0061] In some embodiments, the injection comprises a volume of about 1 ml to about 50 ml. In some embodiments, the injection comprises a volume of about 1 ml to about 2 ml, about 1 ml to about 5 ml, about 1 ml to about 10 ml, about 1 ml to about 15 ml, about 1 ml to about 20 ml, about 1 ml to about 25 ml, about 1 ml to about 30 ml, about 1 ml to about 35 ml, about 1 ml to about 40 ml, about 1 ml to about 45 ml, about 1 ml to about 50 ml, about 2 ml to about 5 ml, about 2 ml to about 10 ml, about 2 ml to about 15 ml, about 2 ml to about 20 ml, about 2 ml to about 25 ml, about 2 ml to about 30 ml, about 2 ml to about 35 ml, about 2 ml to about 40 ml, about 2 ...2 ml to about 50 ml, about 2 ml to about 50 ml, about 2 ml to about 50 ml, about 2 ml to about 50 ml, about 2 ml to about 10 ml, about 2 ml to about 15 ml, about 2 ml to about 20 ml, about 2 ml to about 25 ml, about 2 ml to about 30 ml, about 2 ml to about 35 ml, about 2 ml to about 35 ml, about 2 ml to about 35 ml, about 2 ml to about 40 ml, about 2 ml to about 45 ml, 0ml, about 2ml to about 35ml, about 2ml to about 40ml, about 2ml to about 45ml, about 2ml to about 50ml, about 5ml to about 10ml, about 5ml to about 15ml, about 5ml to about 20ml, about 5ml to about 25ml, about 5ml to about 30ml, approximately 5ml to approximately 35ml, approximately 5ml to approximately 40ml, approximately 5ml to approximately 45ml, approximately 5ml to approximately 50ml, approximately 10ml to approximately 15ml, approximately 10ml to approximately 20ml, approximately 10ml to approximately 25ml, approximately 10ml to approximately 30ml, approximately 10ml to about 35ml, about 10ml to about 40ml, about 10ml to about 45ml, about 10ml to about 50ml, about 15ml to about 20ml, about 15ml to about 25ml, about 15ml to about 30ml, about 15ml to about 35ml, about 15 ml~about 40ml, about 15ml~about 45ml, about 15ml~about 50ml, about 20ml~about 25ml, about 20ml~about 30ml, about 20ml~about 35ml, about 20ml~about 40ml, about 20ml~about 45ml, about 20ml In some embodiments, the injection comprises a volume of about 1 ml, about 2 ml, about 5 ml, about 10 ml, about 15 ml, about 20 ml, about 25 ml, about 30 ml, about 35 ml, about 40 ml, about 45 ml, about 50 ml, about 45 ml, about 50 ml, about 50 ml, about 4 ...In some embodiments, the injection comprises a volume of at least about 1 ml, about 2 ml, about 5 ml, about 10 ml, about 15 ml, about 20 ml, about 25 ml, about 30 ml, about 35 ml, about 40 ml, or about 45 ml. In some embodiments, the injection comprises a volume of at most about 2 ml, about 5 ml, about 10 ml, about 15 ml, about 20 ml, about 25 ml, about 30 ml, about 35 ml, about 40 ml, about 45 ml, or about 50 ml.

[0062] In some embodiments, the injection is performed with a needle having a gauge of about 10 to about 26. In some embodiments, the injection is performed with a needle having a gauge of about 10 to about 11, about 10 to about 12, about 10 to about 13, about 10 to about 14, about 10 to about 15, about 10 to about 16, about 10 to about 18, about 10 to about 20, about 10 to about 22, about 10 to about 24, about 10 to about 26, about 11 to about 12, about 11 to about 13, about 11 to about 14, about 11 to about 15, about 1 1 to about 16, about 11 to about 18, about 11 to about 20, about 11 to about 22, about 11 to about 24, about 11 to about 26, about 12 to about 13, about 12 to about 14, about 12 to about 15, about 12 to about 16, about 12 to about 18, about 12 to about 20, about 12 to about 22, about 12 to about 24, about 12 to about 26, about 13 to about 14, about 13 to about 15, about 13 to about 16, about 13 to about 18, about 13 to about 20, about 13 to about 22, about 13 to about 24, about 13 to about 26, about 14 to about 15, about 14 to about 16, about 14 to about 18, about 14 to about 20, about 14 to about 22, about 14 to about 24, about 14 to about 26, about 15 to about 16, about 15 to about 18, about 15 to about 20, about 15 to about 22, about 15 to about 2 In some embodiments, the injection comprises a volume of about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 16, about 18, about 16, about 20, about 16, about 22, about 16, about 24, about 16, about 26, about 18, about 18, about 22, about 18, about 24, about 18, about 26, about 20, about 22, about 20, about 24, about 20, about 26, about 22, about 24, about 22, about 26, or about 24 to about 26. In some embodiments, the injection is performed with a needle having a gauge of about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 18, about 20, about 22, about 24, or about 26. In some embodiments, injection is performed with a needle having a gauge of at least about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 18, about 20, about 22, or about 24. In some embodiments, injection is performed with a needle having a gauge of at most about 11, about 12, about 13, about 14, about 15, about 16, about 18, about 20, about 22, about 24, or about 26.

[0063] In some embodiments, the concentration of polyethylene glycol in the spacer material is about 1 mg / ml to about 100 mg / ml. In some embodiments, the concentration of polyethylene glycol in the spacer material is about 1 mg / ml to about 5 mg / ml, about 1 mg / ml to about 10 mg / ml, about 1 mg / ml to about 15 mg / ml, about 1 mg / ml to about 20 mg / ml, about 1 mg / ml to about 25 mg / ml, about 1 mg / ml to about 30 mg / ml, about 1 mg / ml to about 40 mg / ml, about 1 mg / ml to about 50 mg / ml, about 1 mg / ml to about 60 mg / ml, about 1 mg / ml to about 80 mg / ml, about 1 mg / ml to about 100 mg / ml, about 5 mg / ml to about 10 mg / ml, approximately 5 mg / ml to approximately 15 mg / ml, approximately 5 mg / ml to approximately 20 mg / ml, approximately 5 mg / ml to approximately 25 mg / ml, approximately 5 mg / ml to approximately 30 mg / ml, approximately 5 mg / ml to approximately 40 mg / ml, approximately 5 mg / ml to approximately 50 mg / ml, approximately 5 mg / ml to approximately 60mg / ml, about 5mg / ml to about 80mg / ml, about 5mg / ml to about 100mg / ml, about 10mg / ml to about 15mg / ml, about 10mg / ml to about 20mg / ml, about 10mg / ml to about 25mg / ml, about 10mg / ml to about 30mg / ml, about 10 mg / ml~about 40mg / ml, about 10mg / ml~about 50mg / ml, about 10mg / ml~about 60mg / ml, about 10mg / ml~about 80mg / ml, about 10mg / ml~about 100mg / ml, about 15mg / ml~about 20mg / ml, about 15mg / ml~about 2 5mg / ml, about 15mg / ml to about 30mg / ml, about 15mg / ml to about 40mg / ml, about 15mg / ml to about 50mg / ml, about 15mg / ml to about 60mg / ml, about 15mg / ml to about 80mg / ml, about 15mg / ml to about 100mg / ml, about 20mg / ml to about 25mg / ml, about 20mg / ml to about 30mg / ml, about 20mg / ml to about 40mg / ml, about 20mg / ml to about 50mg / ml, about 20mg / ml to about 60mg / ml, about 20mg / ml to about 80mg / ml, about 20mg / ml to about 100mg / ml, about 25mg / ml to about 30mg / ml, about 25mg / ml to about 40mg / ml, about 25mg / ml to about 50mg / ml, about 25mg / ml to about 60mg / ml, about 25mg / ml to about 80mg / ml, about 25mg / ml to about 100mg / ml,about 30 mg / ml to about 40 mg / ml, about 30 mg / ml to about 50 mg / ml, about 30 mg / ml to about 60 mg / ml, about 30 mg / ml to about 80 mg / ml, about 30 mg / ml to about 100 mg / ml, about 40 mg / ml to about 50 mg / ml, about 40 mg / ml to about 60 mg / ml, about 40 mg / ml to about 80 mg / ml, about 40 mg / ml to about 100 mg / ml, about 50 mg / ml to about 60 mg / ml, about 50 mg / ml to about 80 mg / ml, about 50 mg / ml to about 100 mg / ml, about 60 mg / ml to about 80 mg / ml, about 60 mg / ml to about 100 mg / ml, or about 80 mg / ml to about 100 mg / ml. In some embodiments, the concentration of polyethylene glycol in the spacer material is about 1 mg / ml, about 5 mg / ml, about 10 mg / ml, about 15 mg / ml, about 20 mg / ml, about 25 mg / ml, about 30 mg / ml, about 40 mg / ml, about 50 mg / ml, about 60 mg / ml, about 80 mg / ml, or about 100 mg / ml. In some embodiments, the concentration of polyethylene glycol in the spacer material is at least about 1 mg / ml, about 5 mg / ml, about 10 mg / ml, about 15 mg / ml, about 20 mg / ml, about 25 mg / ml, about 30 mg / ml, about 40 mg / ml, about 50 mg / ml, about 60 mg / ml, or about 80 mg / ml. In some embodiments, the concentration of polyethylene glycol in the spacer material is at most about 5 mg / ml, about 10 mg / ml, about 15 mg / ml, about 20 mg / ml, about 25 mg / ml, about 30 mg / ml, about 40 mg / ml, about 50 mg / ml, about 60 mg / ml, about 80 mg / ml, or about 100 mg / ml.

[0064] In some embodiments, the injectable gel particles have a size of about 0.1 mm to about 10 mm. In some embodiments, the particles have a size of about 0.1 mm to about 0.2 mm, about 0.1 mm to about 0.5 mm, about 0.1 mm to about 1 mm, about 0.1 mm to about 1.5 mm, about 0.1 mm to about 2 mm, about 0.1 mm to about 3 mm, about 0.1 mm to about 4 mm, about 0.1 mm to about 5 mm, about 0.1 mm to about 6 mm, about 0.1 mm to about 8 mm, about 0.1 mm to about 10 mm, about 0.2 mm to about 0.5 mm, about 0.2 mm to about 1 mm, about 0.2 mm to about 1.5 mm, about 0.2mm to about 2mm, about 0.2mm to about 3mm, about 0.2mm to about 4mm, about 0.2mm to about 5mm, about 0.2mm to about 6mm, about 0.2mm to about 8mm, about 0.2mm to 10mm, about 0.5mm to about 1mm, about 0. 5mm to about 1.5mm, about 0.5mm to about 2mm, about 0.5mm to about 3mm, about 0.5mm to about 4mm, about 0.5mm to about 5mm, about 0.5mm to about 6mm, about 0.5mm to about 8mm, about 0.5mm to about 10mm, about 1 mm~1.5mm, 1mm~2mm, 1mm~3mm, 1mm~4mm, 1mm~5mm, 1mm~6mm, 1mm~8mm, 1mm~10mm, 1.5mm~2mm, 1.5m m ~ about 3mm, about 1.5mm - about 4mm, about 1.5mm - about 5mm, about 1.5mm - about 6mm, about 1.5mm - about 8mm, about 1.5mm - about 10mm, about 2mm - about 3mm, about 2mm - about 4mm, about 2mm - about 5mm, The particles have a size of about 2 mm to about 6 mm, about 2 mm to about 8 mm, about 2 mm to about 10 mm, about 3 mm to about 4 mm, about 3 mm to about 5 mm, about 3 mm to about 6 mm, about 3 mm to about 8 mm, about 3 mm to about 10 mm, about 4 mm to about 5 mm, about 4 mm to about 6 mm, about 4 mm to about 8 mm, about 4 mm to about 10 mm, about 5 mm to about 6 mm, about 5 mm to about 8 mm, about 5 mm to about 10 mm, about 6 mm to about 8 mm, about 6 mm to about 10 mm, or about 8 mm to about 10 mm. In some embodiments, the particles have a size of about 0.1 mm, 0.2 mm, 0.5 mm, about 1 mm, about 1.5 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 8 mm, or about 10 mm.In some embodiments, the particles have a size of at least about 0.1 mm, 0.2 mm, 0.5 mm, about 1 mm, about 1.5 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, or about 8 mm. In some embodiments, the particles have a size of at most about 0.2 mm, about 0.5 mm, about 1 mm, about 1.5 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 8 mm, or about 10 mm.

[0065] In some embodiments, blood flow to the tumor is prevented or reduced. In some embodiments, movement of viscoelastic media is prevented or reduced. In some embodiments, the method further comprises administration of hyaluronidase at the site of radiation treatment.

[0066] In some embodiments, administration of hyaluronidase occurs at about 0.1 hours to about 95 hours after injection of the bioabsorbable viscoelastic medium. In some embodiments, administration of hyaluronidase occurs at about 0.1 hours to about 0.5 hours, about 0.1 hours to about 1 hour, about 0.1 hours to about 2 hours, about 0.1 hours to about 4 hours, about 0.1 hours to about 6 hours, about 0.1 hours to about 8 hours, about 0.1 hours to about 10 hours, about 0.1 hours to about 14 hours, about 0.1 hours to about 18 hours, about 0.1 hours to about 24 hours, about 0.1 hours to about 95 hours, about 0.5 hours to about 1 hour, or about 0.5 hours to about 2 hours after injection of the bioabsorbable viscoelastic medium. 0.5 hours to about 4 hours, about 0.5 hours to about 6 hours, about 0.5 hours to about 8 hours, about 0.5 hours to about 10 hours, about 0.5 hours to about 14 hours, about 0.5 hours to about 18 hours, about 0.5 hours to about 24 hours, about 0.5 hours to about 95 hours, about 1 hour to about 2 hours, about 1 hour to about 4 hours, about 1 hour to about 6 hours, about 1 hour to about 8 hours, about 1 hour to about 10 hours, about 1 hour to about 14 hours, about 1 hour to about 18 hours, about 1 hour to about 24 hours, about 1 hour to about 95 hours, about 2 hours ~about 4 hours, about 2 hours to about 6 hours, about 2 hours to about 8 hours, about 2 hours to about 10 hours, about 2 hours to about 14 hours, about 2 hours to about 18 hours, about 2 hours to about 24 hours, about 2 hours to about 95 hours, about 4 hours to about 6 hours, about 4 hours to about 8 hours, about 4 hours to about 10 hours, about 4 hours to about 14 hours, about 4 hours to about 18 hours, about 4 hours to about 24 hours, about 4 hours to about 95 hours, about 6 hours to about 8 hours, about 6 hours to about 10 hours, about 6 hours to about 14 hours, about 6 hours to about 18 hours, about 6 hours The incubation period may be from about 1 hour to about 24 hours, from about 6 hours to about 95 hours, from about 8 hours to about 10 hours, from about 8 hours to about 14 hours, from about 8 hours to about 18 hours, from about 8 hours to about 24 hours, from about 8 hours to about 95 hours, from about 10 hours to about 14 hours, from about 10 hours to about 18 hours, from about 10 hours to about 24 hours, from about 10 hours to about 95 hours, from about 14 hours to about 18 hours, from about 14 hours to about 24 hours, from about 14 hours to about 95 hours, from about 18 hours to about 24 hours, from about 18 hours to about 95 hours, or from about 24 hours to about 95 hours. In some embodiments, administration of hyaluronidase occurs at about 0.1 hours, about 0.5 hours, about 1 hour, about 2 hours, about 4 hours, about 6 hours, about 8 hours, about 10 hours, about 14 hours, about 18 hours, about 24 hours, or about 95 hours after injection of the bioabsorbable viscoelastic medium.In some embodiments, administration of hyaluronidase occurs at least about 0.1 hours, about 0.5 hours, about 1 hour, about 2 hours, about 4 hours, about 6 hours, about 8 hours, about 10 hours, about 14 hours, about 18 hours, or about 24 hours after injection of the bioabsorbable viscoelastic medium. In some embodiments, administration of hyaluronidase occurs at most about 0.5 hours, about 1 hour, about 2 hours, about 4 hours, about 6 hours, about 8 hours, about 10 hours, about 14 hours, about 18 hours, about 24 hours, or about 95 hours after injection of the bioabsorbable viscoelastic medium.

[0067] In some embodiments, the method further comprises the step of excising residual tumor cells from the subject.

[0068] Another aspect provided herein is a formulation comprising cross-linked polyethylene glycol and a radiopaque compound selected from the group consisting of iohexol, metrizamide, iopamidol, 3,5-bis(acetylamino)-2,4,6-triiodobenzoic acid, meglumine diatrizoate, iopentol, iopromide, triiodobenzoic acid, erythrosine, and ioversol. In some embodiments, the formulation is used as a fiducial marker.

[0069] Some embodiments herein disclose a composition comprising a viscoelastic medium and a first visual additive, the first visual additive comprising a metal, the metal having a particle size of 80 micrometers (μm) or more. In some embodiments, the metal is a precious metal. In some embodiments, the metal or the precious metal is selected from the group consisting of gold (Au), iodine (I), gadolinium (Gd), iron (Fe), barium (Ba), calcium (Ca), magnesium (Mg), and combinations thereof. In some embodiments, the metal or the precious metal is an isotope of gold (Au), iodine (I), gadolinium (Gd), iron (Fe), barium (Ba), calcium (Ca), magnesium (Mg), or combinations thereof. In some embodiments, the metal or the precious metal is a powder. In some embodiments, the first visual additive has a radiographic density of about 1.0 g / cm3 to 2.0 g / cm3. In some embodiments, half of the first visual additive is configured to disperse in the tissue within 9 months. In some embodiments, the particle size of the metal or precious metal is between about 80 μm and about 120 μm. In some embodiments, the particle size of the metal or precious metal is about 100 μm. In some embodiments, the first visual additive further comprises one or more microbubbles. In some embodiments, the composition further comprises a second visual additive. In some embodiments, the second visual additive is different from the second visual additive. In some embodiments, the second visual additive comprises one or more microbubbles. In some embodiments, the first visual additive has a concentration in the viscoelastic medium greater than 5 milligrams per milliliter (mg / ml). In some embodiments, the first visual additive has a concentration in the viscoelastic medium less than 90 mg / ml. In some embodiments, the first visual additive has a concentration in the viscoelastic medium between 15 mg / ml and 30 mg / ml. In some embodiments, the metal is about 0.5% to about 9.0% by weight of the composition. In some embodiments, the metal or precious metal is about 0.015% to about 1.5% by weight of the composition.In some embodiments, the viscoelastic medium comprises a volume of about 1 milliliter (ml) to about 50 ml. In some embodiments, the composition is configured to be biodegradable. In some embodiments, the composition is configured to be present on an imaging modality for at least 9 months. In some embodiments, the composition is configured to be substantially immobile before or during imaging. In some embodiments, the first visual additive is configured to be substantially immobile before or during imaging. In some embodiments, the composition is configured to be disposed within a subject. In some embodiments, the subject is in need of radiography. In some embodiments, the composition is configured to be disposed by injection. In some embodiments, the composition is configured to be disposed subcutaneously or subepidermally. In some embodiments, the composition is configured to be disposed within a tissue site. In some embodiments, the tissue site comprises one or more of adipose tissue, muscle tissue, and organ tissue, or a combination thereof. In some embodiments, the composition is configured to be imaged on one or more modalities. In some embodiments, the one or more modalities comprise x-ray, MRI, CT, CBCT, ultrasound, PET, SPECT, or a combination thereof. In some embodiments, the composition configured to be imaged on the one or more modalities comprises the composition configured to be imaged in real time on the one or more modalities. In some embodiments, the composition is configured to be imaged within 30 minutes, 90 minutes, 4 hours, 8 hours, or 4 days of placement. In some embodiments, the viscoelastic medium comprises hyaluronic acid, polyethylene glycol, or dextranoma. In some embodiments, the viscoelastic medium comprises hyaluronic acid, polyethylene glycol, or dextranoma at a concentration of about 5 mg / ml to about 100 mg / ml. In some embodiments, the viscoelastic medium comprises gel particles ranging in size from about 0.08 mm to about 5 mm. In some embodiments, the gel particles comprise the metal particles.In some embodiments, the viscoelastic medium comprises non-animal stabilized hyaluronic acid ("NASHA"). In some embodiments, the viscoelastic medium expands within the tissue site to less than 10% of its original disposition volume. In some embodiments, the viscoelastic medium is injected once every six months. In some embodiments, the viscoelastic medium is completely absorbed within 20 months. In some embodiments, the viscoelastic medium is completely absorbed within 16 months. In some embodiments, the viscoelastic medium is completely absorbed within 12 months.

[0070] Certain embodiments disclosed herein are directed to a method of visualizing a tissue, space or location of a radiographic subject, the method comprising disposing an imaging contrast composition, the composition comprising a viscoelastic medium and a first visual additive, the first visual additive being a metal, the metal having a particle size greater than 80 micrometers. In some embodiments, the method further comprises disposing the composition in a first tissue site and imaging, imaging the composition in the first tissue site. In some embodiments, the metal has a particle size greater than 100 micrometers. In some embodiments, the particle size of the metal is large enough that the metal is not absorbed by the tissue of the subject receiving radiotherapy.

[0071] Certain embodiments disclosed herein are directed to a method of spacing a first tissue site of a subject from a second tissue site of the subject, the method comprising disposing a composition in a space between the first tissue site and the second tissue site, the composition comprising a viscoelastic medium and a first visual additive, the first visual additive being a metal, the metal having a particle size greater than 80 micrometers (μm). In some embodiments, the first visual additive has a concentration in the viscoelastic medium that provides a contrast-to-noise ratio of about 0.1 to about 10. In some embodiments, the metal is a noble metal. In some embodiments, the metal or noble metal is selected from the group consisting of gold (Au), iodine (I), gadolinium (Gd), iron (Fe), barium (Ba), calcium (Ca), magnesium (Mg), and combinations thereof. In some embodiments, the metal or precious metal is an isotope of gold (Au), iodine (I), gadolinium (Gd), iron (Fe), barium (Ba), calcium (Ca), magnesium (Mg), or a combination thereof. In some embodiments, the metal or precious metal is a powder. In some embodiments, the first visual additive has a radiographic density of about 1.0 g / cm3 to 2.0 g / cm3. In some embodiments, half of the first visual additive is configured to disperse in tissue within 9 months. In some embodiments, the particle size of the metal or precious metal is between about 80 μm and about 120 μm. In some embodiments, the particle size of the metal or precious metal is about 100 μm. In some embodiments, the first visual additive further comprises one or more microbubbles. In some embodiments, the composition further comprises a second visual additive. In some embodiments, the second visual additive is different from the second visual additive. In some embodiments, the second visual additive comprises one or more microbubbles. In some embodiments, the first visual additive has a concentration in the viscoelastic medium of greater than 5 milligrams per milliliter (mg / ml). In some embodiments, the first visual additive has a concentration in the viscoelastic medium of less than 90 mg / ml. In some embodiments, the first visual additive has a concentration in the viscoelastic medium of between 15 mg / ml and 30 mg / ml. In some embodiments, the metal is about 0.5% to about 9.0% by weight of the composition. In some embodiments, the metal or precious metal is about 0.015% to about 1.5% by weight of the composition. In some embodiments, the viscoelastic medium comprises a volume of between about 1 milliliter (ml) and about 50 ml. In some embodiments, the composition is configured to be biodegradable. In some embodiments, the composition is configured to be detectable on an imaging modality for at least 9 months. In some embodiments, the composition is configured to not move substantially before or during imaging, and imaging is performed about 3 months to about 9 months after the composition is placed. In some embodiments, the first visual additive is configured to not move substantially before or during imaging, and imaging is performed about 3 months to about 9 months after the composition is placed. In some embodiments, the composition is configured to be placed within a subject. The method of claim 70, wherein the subject requires radiography. In some embodiments, the composition is configured to be placed by injection. In some embodiments, the composition is configured to be placed subcutaneously or subepidermally. In some embodiments, the composition is configured to be placed within the first tissue site. In some embodiments, the first tissue site comprises one or more of adipose tissue, muscle tissue, and organ tissue, or a combination thereof. In some embodiments, the composition is configured to be imaged on one or more modalities. In some embodiments, the one or more modalities comprise x-ray, MRI, CT, CBCT, ultrasound, PET, SPECT, or a combination thereof.In some embodiments, the composition configured to be imaged on the one or more modalities comprises the composition configured to be imaged in real time on the one or more modalities. In some embodiments, the composition is configured to be imaged within 30 minutes, 90 minutes, 4 hours, 8 hours, or 4 days of placement. In some embodiments, the viscoelastic medium comprises hyaluronic acid, polyethylene glycol, or dextranoma. In some embodiments, the viscoelastic medium comprises hyaluronic acid, polyethylene glycol, or dextranoma at a concentration of about 5 mg / ml to about 100 mg / ml. In some embodiments, the viscoelastic medium comprises gel particles ranging in size from about 0.08 mm to about 5 mm. In some embodiments, the gel particles comprise the metal particles. In some embodiments, the viscoelastic medium comprises non-animal stabilized hyaluronic acid ("NASHA"). In some embodiments, the viscoelastic medium expands to less than 10% of its original placement volume within the first tissue site. In some embodiments, the viscoelastic medium is injected once every six months. In some embodiments, the viscoelastic medium is completely absorbed within 20 months. In some embodiments, the viscoelastic medium is completely absorbed within 16 months. In some embodiments, the viscoelastic medium is completely absorbed within 12 months.

[0072] Certain embodiments disclosed herein are methods of treating cancer in a subject in need thereof, the method comprising identifying a tumor in the subject, administering a composition adjacent to the tumor, the composition comprising a viscoelastic medium and a first visual additive, the first visual additive being a metal, the metal having a particle size greater than 80 micrometers, and applying a dose of radiation to the tumor. In some embodiments, the first visual additive has a concentration within the viscoelastic medium that provides a contrast-to-noise ratio of about 0.1 to about 40. In some embodiments, the metal is a noble metal. In some embodiments, the metal or noble metal is selected from the group consisting of gold (Au), iodine (I), gadolinium (Gd), iron (Fe), barium (Ba), calcium (Ca), magnesium (Mg), and combinations thereof. In some embodiments, the metal or precious metal is an isotope of gold (Au), iodine (I), gadolinium (Gd), iron (Fe), barium (Ba), calcium (Ca), magnesium (Mg), or a combination thereof. In some embodiments, the metal or precious metal is a powder. In some embodiments, the first visual additive has a radiographic density of about 1.0 g / cm3 to 2.0 g / cm3. In some embodiments, half of the first visual additive is configured to disperse in tissue within 9 months. In some embodiments, the particle size of the metal or precious metal is between about 80 μm and about 120 μm. In some embodiments, the particle size of the metal or precious metal is about 100 μm. In some embodiments, the first visual additive comprises one or more microbubbles. In some embodiments, the composition comprises a second visual additive. In some embodiments, the second visual additive is different from the second visual additive. In some embodiments, the second visual additive comprises one or more microbubbles. In some embodiments, the first visual additive has a concentration in the viscoelastic medium of greater than 5 milligrams per milliliter (mg / ml). In some embodiments, the first visual additive has a concentration in the viscoelastic medium of less than 90 mg / ml.In some embodiments, the first visual additive has a concentration of 15 mg / ml to 30 mg / ml in the viscoelastic medium. In some embodiments, the metal is about 0.5% to about 9.0% by weight of the composition. In some embodiments, the metal or precious metal is about 0.015% to about 1.5% by weight of the composition. In some embodiments, the viscoelastic medium comprises a volume of about 1 milliliter (ml) to about 50 ml. In some embodiments, the composition is configured to be biodegradable. In some embodiments, the composition is configured to be detectable on an imaging modality for at least 9 months. In some embodiments, the composition is configured to be substantially immobile prior to or during imaging, and imaging is performed about 3 months to about 9 months after the composition is placed. In some embodiments, the first visual additive is configured to be substantially immobile prior to or during imaging, and imaging is performed about 3 months to about 9 months after the composition is placed. In some embodiments, the composition is configured to be placed within a subject. In some embodiments, the subject is in need of x-ray imaging. In some embodiments, the composition is configured to be placed by injection. In some embodiments, the composition is configured to be placed subcutaneously or subepidermally. In some embodiments, the composition is configured to be placed within the first tissue site. In some embodiments, the first tissue site comprises one or more of adipose tissue, muscle tissue, and organ tissue, or a combination thereof. In some embodiments, the composition is configured to be imaged on one or more modalities. In some embodiments, the one or more modalities comprise X-ray, MRI, CT, CBCT, ultrasound, PET, SPECT, or a combination thereof. In some embodiments, the composition configured to be imaged on the one or more modalities comprises the composition configured to be imaged in real time on the one or more modalities. In some embodiments, the composition is configured to be imaged within 30 minutes, 90 minutes, 4 hours, 8 hours, or 4 days of placement.In some embodiments, the viscoelastic medium comprises hyaluronic acid, polyethylene glycol, or dextranoma. In some embodiments, the viscoelastic medium comprises hyaluronic acid, polyethylene glycol, or dextranoma at a concentration of about 5 mg / ml to about 100 mg / ml. In some embodiments, the viscoelastic medium comprises gel particles ranging in size from about 0.08 mm to about 5 mm. In some embodiments, the gel particles comprise the metal particles. In some embodiments, the viscoelastic medium comprises non-animal stabilized hyaluronic acid ("NASHA"). In some embodiments, the viscoelastic medium expands to less than 10% of its original placement volume within the first tissue site. In some embodiments, the viscoelastic medium is injected once every six months. In some embodiments, the viscoelastic medium is completely absorbed within 20 months. In some embodiments, the viscoelastic medium is completely absorbed within 16 months, hi some embodiments, the viscoelastic medium is completely absorbed within 12 months. [Brief description of the drawings]

[0073] This patent application contains at least one color drawing. Copies of this patent or patent application with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.

[0074] A better understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the disclosure are utilized, and the accompanying drawings of which: [Figure 1A] 1 is an exemplary image of an injection area of ​​a mastectomy specimen according to one embodiment described herein. [Figure 1B] 1 is an exemplary image of injecting a spacer into a mastectomy specimen using ultrasound guidance, according to an embodiment described herein. [Figure 2A] 1 is an exemplary ultrasound image of glandular and adipose tissue within a mastectomy specimen, according to one embodiment described herein. [Figure 2B]1 is an exemplary ultrasound image of a spacer, glandular tissue, and adipose tissue within a mastectomy specimen according to one embodiment described herein. [Figure 3A] 1 is an exemplary computed tomography (CT) scan of a hyaluronic acid (HA) spacer in a mastectomy specimen, according to one embodiment described herein. [Figure 3B] 1 is an exemplary ultrasound image of a HA spacer in a mastectomy specimen, according to one embodiment described herein. [Figure 3C] 1 is an exemplary CT scan of a polyethylene glycol (PEG) spacer in a mastectomy specimen according to one embodiment described herein. [Figure 3D] 1 is an exemplary CT scan of a PGA spacer in a mastectomy specimen according to one embodiment described herein. [Figure 4A] 1 is an exemplary image of a simulated permanent breast seed implant (PBSI) brachytherapy planning image of a hyaluronic acid (HA) spacer in a mastectomy specimen, according to one embodiment described herein. [Figure 4B] 1 is an exemplary ultrasound image of a HA spacer in a mastectomy specimen, according to one embodiment described herein. [Figure 5A] 1 is an exemplary image of a computed tomography scan prior to injection of a hydrogel spacer between the head of the pancreas and the duodenum, according to one embodiment described herein. [Figure 5B] 1 is an exemplary image of a computed tomography scan after injection of a hydrogel spacer between the head of the pancreas and the duodenum, according to one embodiment described herein. [Figure 5C] 1 is an exemplary image of a gross histologic specimen following injection of a hydrogel spacer between the head of the pancreas and the duodenum, according to one embodiment described herein. [Figure 5D]1 is an exemplary image of a computed tomography scan prior to injection of a hydrogel spacer between the head of the pancreas and the duodenum in a laparotomy, according to one embodiment described herein. [Figure 5E] 1 is an exemplary image of a computed tomography scan following injection of a hydrogel spacer between the head of the pancreas and the duodenum at a laparotomy, according to one embodiment described herein. [Figure 5F] 1 is an exemplary image of a gross tissue specimen following injection of a hydrogel spacer between the head of the pancreas and the duodenum at a laparotomy, according to one embodiment described herein. [Figure 5G] 1 is an exemplary image of a computed tomography scan prior to endoscopically injecting a hydrogel spacer between the head of the pancreas and the duodenum, according to one embodiment described herein. [Figure 5H] 1 is an exemplary image of a computed tomography scan following endoscopic injection of a hydrogel spacer between the head of the pancreas and the duodenum, according to one embodiment described herein. [Figure 5I] 1 is an exemplary image of a gross tissue specimen following endoscopic injection of a hydrogel spacer between the head of the pancreas and the duodenum, according to one embodiment described herein. [Figure 6A] 1 is a first exemplary image of a formalin-fixed, paraffin-embedded section after staining with hematoxylin and eosin, according to one embodiment described herein. [Figure 6B] 13 is a second exemplary image of a formalin-fixed paraffin-embedded section after staining with hematoxylin and eosin, according to an embodiment described herein. [Figure 6C] 1 is a first exemplary high magnification image of a formalin-fixed paraffin-embedded section after staining with hematoxylin and eosin, according to one embodiment described herein. [Figure 6D]13 is a third exemplary image of a formalin-fixed paraffin-embedded section after staining with hematoxylin and eosin, according to an embodiment described herein. [Figure 6E] 13 is a second exemplary high magnification image of a formalin-fixed paraffin-embedded section after staining with hematoxylin and eosin, according to one embodiment described herein. [Figure 7A] 1 is a first exemplary stereotactic body radiation therapy plan prior to hydrogel spacer placement, according to an embodiment described herein. [Figure 7B] 1 is a first exemplary stereotactic body radiation treatment plan after hydrogel spacer placement according to an embodiment described herein. [Figure 7C] 1 is a second exemplary stereotactic body radiation treatment plan prior to hydrogel spacer placement, according to an embodiment described herein. [Figure 7D] 1 is a second exemplary stereotactic body radiation treatment plan after hydrogel spacer placement according to an embodiment described herein. [Figure 8A] 1 is an exemplary baseline image of a computed tomography scan of the duodenum and stereotactic body radiation therapy planning according to an embodiment described herein. [Figure 8B] 1 is an exemplary image of a computed tomography scan and stereotactic body radiation therapy plan of the duodenum with 2 mm spacing according to one embodiment described herein. [Figure 8C] 1 is an exemplary image of a computed tomography scan and stereotactic body radiation therapy plan of the duodenum with 3 mm spacing according to one embodiment described herein. [Figure 8D] 1 is an exemplary image of a computed tomography scan and stereotactic body radiation therapy plan of the duodenum with 5 mm spacing according to one embodiment described herein. [Figure 8E]1 is an exemplary image of a computed tomography scan and stereotactic body radiation therapy plan of the duodenum with 8 mm spacing according to one embodiment described herein. [Figure 8F] 1 is an exemplary image of a computed tomography scan and stereotactic body radiation therapy plan of the duodenum with 15 mm spacing according to one embodiment described herein. [Figure 9] 1 shows an MRI scan of bladder markings, a CT scan of liver markings, an MRI of liver markings, and an MRI of cervical markings, according to one embodiment described herein. [Figure 10A] 1 shows an MRI scan of a submandibular gland tumor before treatment according to one embodiment described herein. [Figure 10B] 1 shows an MRI scan of a submandibular gland tumor with distance measurements of approximately 1 cm, according to an embodiment described herein. [Figure 10C] 1 shows an MRI six months after the tumor was removed according to one embodiment described herein. [Figure 11A] 1 shows an image of an applicator needle inserted into the left side of the neck according to one embodiment described herein. [Figure 11B] 1 shows an image of a location with a single dose of 20 Gy of radiation according to one embodiment described herein. [Figure 12] 1 shows an MRI image of a paravertebral dosing approach according to one embodiment described herein. [Figure 13A] 1 shows an illustration of a reconstructed rectum and prostate prior to brachytherapy radiation according to one embodiment described herein. [Figure 13B] 1 shows an illustration of a reconstructed rectum and prostate following brachytherapy radiation according to one embodiment described herein. [Figure 14A]1 is an illustration showing radiation levels before brachytherapy radiation where the rectum and prostate are more than 25 mm apart according to an embodiment described herein. [Figure 14B] 1 is an illustration showing radiation levels after brachytherapy radiation where the rectum and prostate are more than 25 mm apart, according to an embodiment described herein. [Figure 14C] 1 shows an MRI scan of the prostate and rectum 4 hours after injection according to one embodiment described herein. [Figure 15A] 1 shows an X-ray computed tomography image before radiation therapy according to one embodiment described herein. [Figure 15B] 1 illustrates an X-ray computed tomography image of an external beam radiotherapy treatment plan before radiotherapy, according to an embodiment described herein. [Figure 16A] 1 shows an ultrasound image and a power Doppler image showing a planned path for needle insertion according to one embodiment described herein. [Figure 16B] 1 shows ultrasound and power Doppler images showing a brachytherapy dose distribution and an inserted brachytherapy needle, according to one embodiment described herein. [Figure 16C] 1 shows an ultrasound image after the skin has been lifted 7 mm according to one embodiment described herein. [Figure 17A] 1 shows an X-ray computed tomography and brachytherapy dose distribution according to an embodiment described herein. [Figure 17B] 13 shows an X-ray computed tomography scan and an image of a second lesion according to one embodiment described herein. [Figure 17C]1 shows an X-ray computed tomography scan one year after treatment with no tumor recurrence according to one embodiment described herein. [Figure 18A] 1 shows the initial release of visualization additive from the viscoelastic medium. [Figure 18B] Figure 2 shows the release profile of visualization additive from viscoelastic medium after 7 and 24 hours. [Figure 19A] A CT scan of fat injected with 3 ml of viscoelastic gel containing 90 mg of gold particles is shown. [Figure 19B] CT scan of a muscle injected with 3 ml of viscoelastic gel containing 45 mg of gold particles. [Figure 19C] C shows a CT scan of a muscle injected with 3 ml of viscoelastic gel containing 45 mg of gold particles. [Figure 19D] CT scan of a muscle injected with 3 ml of viscoelastic gel containing 90 mg of gold particles. [Figure 20A] Shown is a CBCT scan of fat injected with 3 ml of viscoelastic gel containing 90 mg of gold particles. [Figure 20B] A CBCT scan of a muscle injected with 3 ml of viscoelastic gel containing 45 mg of gold particles is shown. [Figure 20C] A CBCT scan of a muscle injected with 3 ml of viscoelastic gel containing 45 mg of gold particles is shown. [Figure 20D] A CBCT scan of a muscle injected with 3 ml of viscoelastic gel containing 90 mg of gold particles is shown. [Figure 21] 1 shows the location of a viscoelastic gel within tissue over a period of time.

[0075] Provided herein are methods for reducing the toxicity of advanced ablative cancer therapies to adjacent organs. The methods herein provide spacing between single or multiple tumor sites and surrounding healthy organs while maintaining or improving the patient's quality of life. Such toxicity isolation can be achieved by inserting spacers around one or more tumor sites.

[0076] Also provided herein are compositions and methods for use in conjunction with the spacers described herein to enhance the visual characteristics of the spacers described herein across a variety of imaging modalities (e.g., x-ray, ultrasound, CT, etc.) In addition to aiding the practitioner in visualizing some or all of the interior regions of the spacer that is injected into the patient, the compositions and methods described herein allow the practitioner to visualize the contours of the spacer that is injected into the patient under a variety of imaging modalities.

[0077] Subcutaneous Spacer Materials The subcutaneous spacer material herein is configured to form a cavity adjacent to prevent radiation or toxic damage to organs in proximity or in contact with the treatment organ. The subcutaneous spacer material may be injected into tissue sites, which may be separate locations on a single piece of tissue. The tissue sites may include tissue of the subject's breast, head and neck, cervix, vagina, spinal base, skin, pancreas, liver, lung, rectum, or another tissue site into which the subcutaneous spacer material is injected. The subcutaneous spacer material herein may include a viscoelastic medium including hyaluronic acid particles. The particle size and concentration of hyaluronic acid within the spacer material may be adjusted to exhibit a hardness, density, or both that allows for consistent and uniform injection and cavity formation. In some embodiments, the viscoelastic medium further includes visual additive particles. A type of visual additive particle (e.g., precious metal particles) may increase its effectiveness as a visual additive by increasing visibility and blocking radiation, and may further prevent migration and accumulation of at least a subset of the precious metal particles in organs not at or around the injection site. In some embodiments, prevention of migration and accumulation of at least a subset of the visual additive particles at the injection site or in organs not surrounding the injection site may be related to the particle size of the subset of visual additive particles.

[0078] In some embodiments, the implant comprises one or more particles of a viscoelastic medium dispersed in a physiological salt buffer, a suitable physiological salt solvent, or both. In some embodiments, the implant further comprises other additives such as local anesthetics, anti-inflammatory drugs, antibiotics, and supportive medications (e.g., bone growth factors or cells). In some embodiments, a viscoelastic medium may also be included that may be formed of the same material as the particles or a different material than the particles. In some embodiments, the viscoelastic medium is not present as particles.

[0079] The viscoelastic medium according to the embodiment herein can include gels, dispersions, solutions, suspensions, slurries, and mixtures thereof. In some embodiments, the medium exists as a gel or a dispersion of gel-like particles. The viscoelastic medium provided herein can be more resistant to biodegradation in vivo than natural hyaluronic acid. The long-term presence of a stable viscoelastic material is advantageous for patients, as it allows for longer intervals between treatments. The viscoelastic medium described herein can be biocompatible, can be sterile, and can exist as particles. The viscoelastic medium can further include visual additive particles.

[0080] Advantageously, the viscoelastic medium described herein is stable under physiological conditions, but may be non-permanent. In some embodiments, about 70% to about 90% of the viscoelastic medium remains in vivo for at least 2 weeks. In some embodiments, at least 70% of the viscoelastic medium remains in vivo for about 2 weeks and 2 years. In some embodiments, at least 90% of the viscoelastic medium remains in vivo for about 2 weeks and 2 years. The viscoelastic medium may automatically degrade in vivo after 5 years or more. In some embodiments, when visual additive particles are added to the viscoelastic medium, about 50% to about 90% of the visual additive particles of the viscoelastic medium remain in vivo for at least 9 months. In some embodiments, at least 50% of the visual additive particles remain in vivo for about 9 months and 2 years. In some embodiments, at least 90% of the visual additive particles remain in vivo for about 9 months and 2 years. In some embodiments, at least 10% of the visual additive particles remain in vivo indefinitely.

[0081] Viscoelastic medium includes, but is not limited to, polysaccharides and their derivatives. Suitable viscoelastic medium includes stabilized starch and its derivatives. Suitable viscoelastic medium can also be selected from stabilized glycosaminoglycans and their derivatives, such as stabilized hyaluronic acid, stabilized chondroitin sulfate, stabilized heparin and their derivatives. One example of a viscoelastic medium is non-animal stabilized hyaluronic acid ("NASHA"). NASHA is produced from non-animal sources (bacteria). The residence time of the viscoelastic medium depends on the particle size of the viscoelastic medium.

[0082] In some embodiments, the particles of the viscoelastic medium have a specifically tailored size. The particle size can be achieved by producing a gel made from the viscoelastic medium at a desired concentration and subjecting the gel to physical disruption. The physical disruption can include mincing, mashing filtering, or any combination thereof. The resulting gel particles can be dispersed in a physiological salt solution to obtain a gel dispersion or slurry having particles of a desired size. The particle size can be determined by any suitable method, such as, for example, laser diffraction, microscopy, or filtration. In some embodiments, the particular shape of the gel particles is not important. A spherical particle size can be defined by its diameter. The size can be measured as an average size, a median size, a maximum size, or a minimum size.

[0083] In some embodiments, the viscoelastic medium gel particles have a size in the range of 1-2.5 mm, such as 1.5-2 mm, in the presence of saline. In some embodiments, the viscoelastic medium particles have a size in the range of 2.5-5 mm, such as 3-4 mm, in the presence of saline. At least 50% (v / v) of the particles may have a size of at least about 1 mm. At least 50% (v / v) of the viscoelastic medium particles may have a size of about 1-5 mm in the presence of physiological salt solution. In some embodiments, more than 70% (v / v) of the viscoelastic medium particles are within a given size limit under physiological conditions. In some embodiments, more than 90% (v / v) of the viscoelastic medium particles are within a given size limit under physiological conditions relevant to humans. Administration of an implant using methods according to embodiments herein prevents or reduces migration and / or displacement of the implant, the implant comprising or consisting of larger particles of 1-5 mm under physiological conditions. Larger particles exhibit less mobility in vitro and can be more easily removed, hi some embodiments, the viscoelastic medium is present as particles smaller than 0.1 mm in size.

[0084] In some embodiments, the viscoelastic medium gel particles have a size of about 0.05 mm to about 0.1 mm. In some embodiments, the particles have a size of about 0.05 mm to about 0.06 mm, about 0.05 mm to about 0.07 mm, about 0.05 mm to about 0.08 mm, about 0.05 mm to about 0.09 mm, about 0.05 mm to about 0.1 mm, about 0.06 mm to about 0.07 mm, about 0.06 mm to about 0.08 mm, about 0.06 mm to about 0.09 mm, about 0.06 mm to about 0.1 mm, about 0.07 mm to about 0.08 mm, about 0.07 mm to about 0.09 mm, about 0.07 mm to about 0.1 mm, about 0.08 mm to about 0.09 mm, about 0.08 mm to about 0.1 mm, about 0.09 mm to about 0.1 mm. In some embodiments, the particles have a size of about 0.05 mm, about 0.06 mm, about 0.07 mm, about 0.08 mm, about 0.09 mm, or about 0.1 mm. In some embodiments, the particles have a size of at least about 0.05 mm, about 0.06 mm, about 0.07 mm, about 0.08 mm, or about 0.09 mm. In some embodiments, the particles have a size of at most about 0.06 mm, about 0.07 mm, about 0.08 mm, about 0.09 mm, or about 0.1 mm.

[0085] In some embodiments, the viscoelastic medium gel particles have a size of about 0.1 mm to about 10 mm. In some embodiments, the particles have a size of about 0.1 mm to about 0.2 mm, about 0.1 mm to about 0.5 mm, about 0.1 mm to about 1 mm, about 0.1 mm to about 1.5 mm, about 0.1 mm to about 2 mm, about 0.1 mm to about 3 mm, about 0.1 mm to about 4 mm, about 0.1 mm to about 5 mm, about 0.1 mm to about 6 mm, about 0.1 mm to about 8 mm, about 0.1 mm to about 10 mm, about 0.2 mm to about 0.5 mm, about 0.2 mm to about 1 mm, about 0.2 mm to about 1.5 mm, about 0.2mm to about 2mm, about 0.2mm to about 3mm, about 0.2mm to about 4mm, about 0.2mm to about 5mm, about 0.2mm to about 6mm, about 0.2mm to about 8mm, about 0.2mm to about 10mm, about 0.5mm to about 1mm, about 0 .5mm~about 1.5mm, about 0.5mm~about 2mm, about 0.5mm~about 3mm, about 0.5mm~about 4mm, about 0.5mm~about 5mm, about 0.5mm~about 6mm, about 0.5mm~about 8mm, about 0.5mm~about 10mm, about 1 mm~1.5mm, 1mm~2mm, 1mm~3mm, 1mm~4mm, 1mm~5mm, 1mm~6mm, 1mm~8mm, 1mm~10mm, 1.5mm~2mm, 1.5m m ~ about 3mm, about 1.5mm - about 4mm, about 1.5mm - about 5mm, about 1.5mm - about 6mm, about 1.5mm - about 8mm, about 1.5mm - about 10mm, about 2mm - about 3mm, about 2mm - about 4mm, about 2mm - about 5mm, The particles have a size of about 2 mm to about 6 mm, about 2 mm to about 8 mm, about 2 mm to about 10 mm, about 3 mm to about 4 mm, about 3 mm to about 5 mm, about 3 mm to about 6 mm, about 3 mm to about 8 mm, about 3 mm to about 10 mm, about 4 mm to about 5 mm, about 4 mm to about 6 mm, about 4 mm to about 8 mm, about 4 mm to about 10 mm, about 5 mm to about 6 mm, about 5 mm to about 8 mm, about 5 mm to about 10 mm, about 6 mm to about 8 mm, about 6 mm to about 10 mm, or about 8 mm to about 10 mm. In some embodiments, the particles have a size of about 0.1 mm, 0.2 mm, 0.5 mm, about 1 mm, about 1.5 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 8 mm, or about 10 mm.In some embodiments, the particles have a size of at least about 0.1 mm, about 0.2 mm, about 0.5 mm, about 1 mm, about 1.5 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, or about 8 mm. In some embodiments, the particles have a size of at most 0.2 mm, 0.5 mm, about 1 mm, about 1.5 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 8 mm, or about 10 mm.

[0086] Suitable viscoelastic media also include stabilized dextran and its derivatives, such as dextranomers (Dx). Dx is a macromolecule composed of many cross-linked dextran polymers. The molecular structure of dextran contains glucose units linked by linear α-1,6-glycosidic bonds with a low degree of small branching. When water is added, it forms a gel. For most medical purposes, dextran polymers with molecular weights of 70 kDa and 40 kDa are used. When synthesizing Dx, these polymers are linked together by adding a cross-linking agent. The manufacturing process cross-links the dextran polymers together into small beads known as microspheres. The degree of cross-linking affects the properties of Dx, as does the size of the individual microspheres. Dx microspheres can be made in a variety of sizes, with those used in Q-Med's products ranging from 80 to 250 μm.

[0087] In some embodiments, DX has a molecular weight of about 40 kDa to 70 kDa. In some embodiments, DX has a molecular weight of at most about 70 kDa. In some embodiments, DX has a molecular weight of at least about 40 kDa.

[0088] In some embodiments, the viscoelastic medium is cross-linked hyaluronic acid or a derivative thereof.

[0089] One type of suitable cross-linked hyaluronic acid can be obtained by cross-linking hyaluronic acid.The viscoelastic medium can also be a combination of two or more of the suitable viscoelastic mediums listed herein or otherwise known in the art.The viscoelastic medium can be of non-animal origin.

[0090] In some embodiments, the viscoelastic medium comprises a hydrogel. In some embodiments, the hydrogel is formed from natural, synthetic, or biosynthetic polymers. In some embodiments, the natural polymer comprises a glycosaminoglycan, a polysaccharide, a protein, or any combination thereof. In some embodiments, the glycosaminoglycan is dermatan sulfate, hyaluronic acid, chondroitin sulfate, chitin, heparin, keratan sulfate, keratosulfate, or any combination thereof. In some embodiments, the hydrogel comprises an acid carboxy polymer, an acrylic acid-based polymer, a polyacrylamide, a starch graft copolymer, an acrylate polymer, or any combination thereof. In some embodiments, the hydrogel comprises allyl pentaerythritol, polyacrylic acid, an ester cross-linked polyglucan, or any combination thereof.

[0091] In some embodiments, the viscoelastic medium is hydrophilic.

[0092] In some embodiments, the viscoelastic medium comprises a combination of the disclosed compounds. In one example, the viscoelastic medium comprises hyaluronic acid and Dx. In another example, the viscoelastic medium comprises NASHA / Dx gel. In some embodiments, the NASHA / Dx gel has a low enough viscosity so that it can be injected through the syringe with only finger pressure. In some embodiments, the NASHA / Dx gel has a high enough viscosity to avoid leakage from the injection site. In some embodiments, the NASHA / Dx gel has a long degradation time to allow for and stabilize the natural formation of connective tissue at the site of the implant. In some embodiments, the viscoelastic medium further comprises carbon coated zirconium beads, calcium hydroxyapatite, or both.

[0093] Gel particle size may depend on the ionic strength of the buffer, solution, carrier, or combination thereof contained in and / or surrounding the gel particle. Thus, a given particle size may assume physiological conditions, particularly isotonic conditions. In some embodiments, the gel particles include or are dispersed in a physiological salt solution. In some embodiments, the gel particles are temporarily sized differently by exposing the gel particles to a solution of a different tonicity. Particle size within a given range under physiological conditions when implanted under the epidermis in the body or when subjected to a physiological or isotonic salt solution (i.e., a solution with the same tonicity as the relevant biological fluid, e.g., an isotonic agent including serum).

[0094] In some embodiments, the gel particles have a specifically tailored size. The size of the gel particles can be achieved by producing a gel made from a viscoelastic medium of a desired concentration and subjecting the gel to physical disruption. The physical disruption can include mincing, mashing, or any combination thereof. The resulting gel particles can be dispersed in a physiological salt solution to obtain a gel dispersion or slurry having particles of a desired size. The particle size can be determined by any suitable method, such as, for example, laser diffraction, microscopy, or filtration. In some embodiments, the particular shape of the gel particles is not important. The size of a spherical particle can be defined as its diameter. The size can be measured as an average size, a median size, a maximum size, or a minimum size.

[0095] In some embodiments, the gel particles have a size in the range of 1-2.5 mm, such as 1.5-2 mm, in the presence of saline. In some embodiments, the gel particles have a size in the range of 2.5-5 mm, such as 3-4 mm, in the presence of saline. At least 50% (v / v) of the particles may have a size of at least about 1 mm. At least 50% (v / v) of the particles may have a size of about 1-5 mm in the presence of physiological salt solution. In some embodiments, more than 70% (v / v) of the gel particles are within a given size limit under physiological conditions. In some embodiments, more than 90% (v / v) of the particles are within a given size limit under physiological conditions. Administration of an implant using a method according to an embodiment herein prevents or reduces migration and / or displacement of the implant, the implant comprising or consisting of larger gel particles of 1-5 mm under physiological conditions. Larger gel particles exhibit less migration in vitro and can be more easily removed. In some embodiments, the viscoelastic medium is not present as particles smaller than 0.1 mm in size. In some embodiments, Dx is comprised of microspheres. In some embodiments, the microspheres have a diameter of about 80 μm to 250 μm. In some embodiments, the microspheres have a diameter of at least about 80 μm. In some embodiments, the microspheres have a diameter of at most about 250 μm. In some embodiments, Dx is comprised of microspheres. In some embodiments, the microspheres have a diameter of about 80 μm to 250 μm. In some embodiments, the microspheres have a diameter of at least about 80 μm. In some embodiments, the microspheres have a diameter of at most about 250 μm.

[0096] In some embodiments, the particles have a specifically tailored density, hardness, or both. Gel particle density can be adjusted by adjusting the concentration of the viscoelastic medium, the amount and type of crosslinker, or both. Harder particles can be achieved by increasing the concentration of the viscoelastic medium in the gel. Harder particles are less viscoelastic than softer particles and may exhibit a longer half-life in vivo. The particles described herein should retain sufficient viscoelastic properties to be safely injected. In some embodiments, the implant includes both soft and harder gel particles. The soft and hard gel particles can be made from the same or different viscoelastic medium. The resulting gel particle mixture combines the desired properties of softness / hardness for use in radiation protection with long durability in vivo.

[0097] Method for forming spacer material - Patent application The subcutaneous spacer material herein is configured to form a cavity adjacent to the treatment organ to prevent radiation or toxic damage to the treatment organ or to organs in contact with the treatment organ. The subcutaneous spacer material herein may include a viscoelastic medium containing hyaluronic acid particles. The particle size and concentration of hyaluronic acid within the spacer material may be adjusted to exhibit a hardness, density, or both that allows for consistent and uniform injection and cavity formation.

[0098] Provided herein is a method of forming a spacer material comprising forming an aqueous solution, the method comprising initiating cross-linking of a water soluble cross-linkable polysaccharide in the presence of a polyfunctional cross-linking agent, sterically hindering the cross-linking reaction from terminating before gelation occurs to produce an activated polysaccharide, mechanically mixing about 45 mg to about 90 mg of visual additive particles, and reintroducing sterically unhindered conditions to allow the activated polysaccharide to continue its cross-linking into a viscoelastic gel. In some embodiments, the individual visual additive particles have a diameter of about 80 micrometers to about 120 micrometers. In some embodiments, the visual additive particles are gold particles. In some embodiments, the initial cross-linking reaction in the presence of the polyfunctional cross-linking agent can be carried out at a variety of pH values, depending primarily on whether an ether or ester reaction is to be promoted.

[0099] The crosslinker may be any previously known crosslinker useful in connection with biocompatible polysaccharides. However, crosslinkers include aldehydes, epoxides, polyaziridyl compounds, glycidyl ethers, divinyl sulfones, or any combination thereof. Glycidyl ethers represent a group in which 1,4-butanediol diglycidyl ether may be advantageous. In some embodiments, the spacer material comprises a hydrogel comprising glycosaminoglycans extracted from purified and derivatized natural sources. In some embodiments, the glycosaminoglycans are synthetically produced or synthesized by modified microorganisms such as bacteria. In some embodiments, the glycosaminoglycans are synthetically modified from a naturally soluble state to a partially soluble or water swellable or hydrogel state.

[0100] Suitable methods for obtaining the desired particle size include producing a gel made from a crosslinked hyaluronic acid of a desired concentration and subjecting the gel to physical disruption, such as mincing or mashing, or passing the gel through a filter with a suitable particle size. The resulting gel particles can be dispersed in a physiological salt solution to obtain a gel dispersion or slurry with particles of a desired size. The particle size can be achieved by producing a gel made from a viscoelastic medium of a desired concentration and subjecting the gel to physical disruption. The physical disruption can include mincing, mashing filters, or any combination thereof. The resulting gel particles can be dispersed in a physiological salt solution to obtain a gel dispersion or slurry with particles of a desired size.

[0101] In some embodiments, the gel particles have a specifically tailored density, hardness, or both. Gel particle density can be adjusted by adjusting the concentration of viscoelastic medium, the amount and type of crosslinker, or both. Harder particles can be achieved by increasing the concentration of viscoelastic medium in the gel. Gel particles of various hardness can be obtained by varying the hyaluronic acid concentration, for example, to 20, 25, 40, 50, and 100 mg / ml. Harder particles are less viscoelastic than softer particles and may exhibit a longer half-life in vivo. The particles described herein should retain sufficient viscoelastic properties to be safe for injection.

[0102] In some embodiments, the implant comprises both soft and harder gel particles. The soft and hard gel particles may be made from the same or different viscoelastic media. The resulting mixture of gel particles combines the desired properties of softness / hardness for use in radiation protection with long durability in vivo. In one embodiment, the soft gel particles comprise 15-22 mg / ml cross-linked hyaluronic acid and the hard gel particles comprise 22-30 mg / ml cross-linked hyaluronic acid.

[0103] When the injection medium is a hyaluronic acid medium, the hyaluronic acid concentration can be at least about 5 mg / ml. In some embodiments, the hyaluronic acid concentration is about 5 mg / ml to about 100 mg / ml. In some embodiments, the hyaluronic acid concentration is about 10 to about 50 mg / ml. In some embodiments, the hyaluronic acid concentration is about 20 mg / ml. The crosslinked hyaluronic acid can be present as any form of particles or beads.

[0104] In some embodiments, the method further comprises adding an image enhancing agent as described herein to the spacer material.In some embodiments, the method further comprises mixing an image enhancing agent as described herein into the spacer material.

[0105] Method for injecting spacer material The subcutaneous spacer material herein is configured to form a cavity adjacent to the treatment organ to prevent radiation or toxic damage to the nearby or contacting organs. The subcutaneous spacer material herein may include a viscoelastic medium containing hyaluronic acid particles. The particle size and concentration of hyaluronic acid in the spacer material can be adjusted to exhibit a hardness, density, or both that allows for consistent and uniform injection and cavity formation. Furthermore, a specific needle size can be used to deliver the spacer material to its intended in vivo location based on the particle size, hardness, density, and concentration of hyaluronic acid.

[0106] Provided herein is a method of injecting a spacing material. The spacing material may include a viscoelastic medium for therapeutic radiation protection in mammals, including humans. The spacing material may be suitable for subcutaneous administration in mammalian sites where therapeutic soft tissue protection from radiation or other toxic sources is required. In particular, the particles are configured to provide maximum contrast and visibility, making them suitable for administration to tissues covered by publicly hidden skin or darker skin, such as rectal tissue. The particles herein are suitable for administration to deep subcutaneous or submuscular / supraperiosteal tissues, optionally administered in multiple layers. Deep subcutaneous or submuscular / supraperitonal administration may further prevent or reduce migration of the particles from the desired site.

[0107] The spacing material can be administered by injection beneath the epidermis in any suitable manner, for example, a skin incision can be made with a scalpel or sharpened needle to facilitate percutaneous insertion of a larger cannula for administration of the implant at the desired site.

[0108] The implant, consisting of particles of viscoelastic medium and optionally other suitable components, may be administered as a single aliquot or as layers of multiple aliquots. Optionally, the viscoelastic medium may be replaced, refilled, or replenished by subsequent injections of the same or another viscoelastic medium. The volume injected is determined by the size of the desired cavity.

[0109] In some embodiments, the volume of the spacer material injected is about 1 ml to about 500 ml. In some embodiments, the volume of the spacer material injected is about 1 ml to about 5 ml, about 1 ml to about 10 ml, about 1 ml to about 25 ml, about 1 ml to about 50 ml, about 1 ml to about 100 ml, about 1 ml to about 150 ml, about 1 ml to about 200 ml, about 1 ml to about 250 ml, about 1 ml to about 300 ml, about 1 ml to about 400 ml, about 1 ml to about 500 ml, about 5 ml to about 10 ml, about 5 ml to about 25 ml, about 5 ml to about 50 ml, about 5 ml to about 100 ml, about 5 ml to about 150 ml, about 5 ml to about 20 0ml, about 5ml to about 250ml, about 5ml to about 300ml, about 5ml to about 400ml, about 5ml to about 500ml, about 10ml to about 25ml, about 10ml to about 50ml, about 10ml to about 100ml, about 10ml to about 150ml, about 10ml to about 2 00ml, about 10ml to about 250ml, about 10ml to about 300ml, about 10ml to about 400ml, about 10ml to about 500ml, about 25ml to about 50ml, about 25ml to about 100ml, about 25ml to about 150ml, about 25ml to about 200ml, about 25 ml~about 250ml, about 25ml~about 300ml, about 25ml~about 400ml, about 25ml~about 500ml, about 50ml~about 100ml, about 50ml~about 150ml, about 50ml~about 200ml, about 50ml~about 250ml, about 50ml~about 30 0ml, about 50ml to about 400ml, about 50ml to about 500ml, about 100ml to about 150ml, about 100ml to about 200ml, about 100ml to about 250ml, about 100ml to about 300ml, about 100ml to about 400ml, about 100ml to about 50 0 ml, about 150 ml to about 200 ml, about 150 ml to about 250 ml, about 150 ml to about 300 ml, about 150 ml to about 400 ml, about 150 ml to about 500 ml, about 200 ml to about 250 ml, about 200 ml to about 300 ml, about 200 ml to about 400 ml, about 200 ml to about 500 ml, about 250 ml to about 300 ml, about 250 ml to about 400 ml, about 250 ml to about 500 ml, about 300 ml to about 400 ml, about 300 ml to about 500 ml, or about 400 ml to about 500 ml.In some embodiments, the volume of spacer material injected is about 1 ml, about 5 ml, about 10 ml, about 25 ml, about 50 ml, about 100 ml, about 150 ml, about 200 ml, about 250 ml, about 300 ml, about 400 ml, or about 500 ml. In some embodiments, the volume of spacer material injected is at least about 1 ml, about 5 ml, about 10 ml, about 25 ml, about 50 ml, about 100 ml, about 150 ml, about 200 ml, about 250 ml, about 300 ml, or about 400 ml. In some embodiments, the volume of spacer material injected is at most about 5 ml, about 10 ml, about 25 ml, about 50 ml, about 100 ml, about 150 ml, about 200 ml, about 250 ml, about 300 ml, about 400 ml, or about 500 ml.

[0110] Administration is performed in any suitable manner, such as by injection through a standard cannula and an appropriately sized needle, where administration is desired, for example, the chin, cheek, or other location on the face or body.

[0111] The spacing material herein can be injected through standard needles used in medicine, such as 20 gauge needles or larger, or the spacing material containing hyaluronic acid can be injected using any of the following sizes of needles:

[0112] [Table 1]

[0113] In some embodiments, the inner surface of the needle includes a protrusion, a mesh, a constriction, or any combination thereof. In some embodiments, injecting the spacing material past the protrusion, mesh, constriction, or any combination thereof generates gas bubbles in the spacing material. In some embodiments, the gas bubbles are microbubbles. In some embodiments, the mesh has a mesh spacing of about 20 μm to 300 μm. In some embodiments, the size of the mesh spacing determines the size of the microbubbles generated thereby.

[0114] Visual Additives Enhanced developments in CT imaging can be used to exploit the stability and visibility of viscoelastic media when visual additives are added to the viscoelastic medium. For example, the addition of precious metals (e.g., gold) or other visual additives (e.g., iodine, gadolinium, iron, barium, calcium, or magnesium) can increase the contrast and reflectivity of the viscoelastic medium. Thus, the addition of precious metals allows for increased effectiveness of viscoelastic media with visual additives by increasing visibility and reducing the negative effects of radiation.

[0115] In some embodiments, the effectiveness of the viscoelastic medium with visual additives may be measured. In those embodiments, the measurement method may include the contrast-to-noise ratio ("CNR") of the associated scanning. The contrast may be measured based on the ratio of the brightness between the injected tissue and the brightness of the surrounding tissue in the associated scanning. In some embodiments, the contrast is measured as the difference between the grayscale signal of the tissue at the injection site and the grayscale signal of the tissue surrounding the injection site. The noise may be measured based on the signal-to-noise ratio of the associated scanning, where the signal is a measure of the true signal and the noise is a random amount of mottle.

[0116] In particular, in some embodiments, the viscoelastic medium containing a visual additive (e.g., gold particles) may provide enhanced features compared to other viscoelastic media. For example, the viscoelastic medium containing a visual additive may have a slower absorption rate, improving visibility and increasing residence time in the body. For example, the viscoelastic medium containing a visual additive may take up to about 1 year to about 3 years to be fully absorbed into the tissue. In another example, the viscoelastic medium containing a visual additive may remain in the tissue indefinitely without being absorbed. Furthermore, the viscoelastic medium containing a visual additive may exhibit an increased ability to retain its shape once injected. For example, a viscoelastic medium containing a visual additive of a particular shape may be compressed for a period of time such that it is no longer in that particular shape, and when compression ceases, the viscoelastic medium may return to that particular shape.

[0117] FIG. 21 shows the amount of viscoelastic medium with visual additive in a body compartment over time. Three exemplary viscoelastic media (2104, 2114, and 2124) were placed in each compartment. The shape and volume of the viscoelastic medium (2104) are shown in graphs (2102a, 2102b, and 2102c). Graph (2102a) shows the shape and volume within 7 days of being injected into each compartment, where the volume of the viscoelastic medium (2104) is 16.51 cubic centimeters. Graph (2102b) shows the shape and volume approximately 3 months after being injected into each compartment, where the volume of the viscoelastic medium (2104) is 4.65 cubic centimeters. Graph (2102c) shows the shape and volume approximately 3 months after being injected into each compartment, where the viscoelastic medium (2104) is no longer present in the compartment. Graph (2112a) shows the shape and volume within seven days of being injected into each compartment, where the volume of the viscoelastic medium (2114) is 9.34 cubic centimeters. Graph (2112b) shows the shape and volume approximately three months after being injected into each compartment, where the volume of the viscoelastic medium (2114) is 7.54 cubic centimeters. Graph (2112c) shows the shape and volume approximately three months after being injected into each compartment, where the viscoelastic medium (2114) is no longer present in the compartment.

[0118] In some embodiments, the visual additive particles have a size of about 15 micrometers (μm) to about 215 μm. In some embodiments, the visual additive particles have a size of about 15 μm to about 35 μm, about 15 μm to about 55 μm, about 15 μm to about 75 μm, about 15 μm to about 95 μm, about 15 μm to about 115 μm, about 15 μm to about 135 μm, about 15 μm to about 155 μm, about 15 μm to about 175 μm, about 15 μm to about 195 μm, about 15 μm to about 215 μm, about 35 μm to about 55 μm, about 35 μm to about 75 μm, about 35 μm to about 95 μm, about 35 μm to about 55 μm, about 35 μm to about 75 μm, about 35 μm to about 95 μm, about 35 μm to about 55 μm, about 35 μm to about 55 μm, about 35 μm to about 75 μm, about 35 μm to about 9 ... ~ approx. 115 μm, approx. 35 μm ~ approx. 135 μm, approx. 35 μm ~ approx. 155 μm, approx. 35 μm ~ approx. 175 μm, approx. 35 μm ~ approx. 195 μm, approx. μm, approximately 55 μm to approximately 115 μm, approximately 55 μm to approximately 135 μm, approximately 55 μm to approximately 155 μm, approximately 55 μm to approximately 175 μm, approximately 55 μm to approximately 195 μm, approximately 55 μm to approximately 215 μm, approximately 75 μm to approximately 95 μm, approximately 75μm to about 115μm, about 75μm to about 135μm, about 75μm to about 155μm, about 75μm to about 175μm, about 75μm to about 195μm, about 75μm to about 215μm, about 95μm to about 115μm, about 95μm m ~ about 135 μm, about 95 μm to about 155 μm, about 95 μm to about 175 μm, about 95 μm to about 195 μm, about 95 μm to about 215 μm, about 115 μm to about 135 μm, about 115 μm to about 155 μm, about 115 μm In some embodiments, the size of the nanoparticles may be from about 175 μm to about 195 μm, from about 115 μm to about 215 μm, from about 135 μm to about 155 μm, from about 135 μm to about 175 μm, from about 135 μm to about 195 μm, from about 135 μm to about 215 μm, from about 155 μm to about 175 μm, from about 155 μm to about 195 μm, from about 155 μm to about 215 μm, from about 175 μm to about 195 μm, from about 175 μm to about 215 μm, or from about 195 μm to about 215 μm. In some embodiments, the visual additive particles have a size of about 15 μm, about 35 μm, about 55 μm, about 75 μm, about 95 μm, about 115 μm, about 135 μm, about 155 μm, about 175 μm, about 195 μm, or about 215 μm.In some embodiments, the visual additive particles have a size of at least about 15 μm, about 35 μm, about 55 μm, about 75 μm, about 95 μm, about 115 μm, about 135 μm, about 155 μm, about 175 μm, or about 195 μm. In some embodiments, the visual additive particles have a size of at most about 35 μm, about 55 μm, about 75 μm, about 95 μm, about 115 μm, about 135 μm, about 155 μm, about 175 μm, about 195 μm, or about 215 μm.

[0119] In some embodiments, the visual additive particles have a size of about 80 μm to about 120 μm. In some embodiments, the visual additive particles have a size of about 80 μm to about 85 μm, about 80 μm to about 90 μm, about 85 μm to about 95 μm, about 80 μm to about 100 μm, about 80 μm to about 105 μm, about 80 μm to about 110 μm, about 80 μm to about 115 μm, about 80 μm to about 120 μm, about 85 μm to about 90 μm, about 85 μm to about 95 μm, about 85 μm to about 100 μm, about 85 μm to about 105 μm, about 85 μm to about 110 μm, about 85 μm to about 115 μm, about 85 μm to about 120 μm, about 90 μm to about 95 μm, about 90 μm to about The size is about 100 μm, about 90 μm to about 105 μm, about 90 μm to about 110 μm, about 90 μm to about 115 μm, about 90 μm to about 120 μm, about 95 μm to about 100 μm, about 95 μm to about 105 μm, about 95 μm to about 110 μm, about 95 μm to about 115 μm, about 95 μm to about 120 μm, about 100 μm to about 105 μm, about 100 μm to about 110 μm, about 100 μm to about 115 μm, about 100 μm to about 120 μm, about 105 μm to about 110 μm, 105 μm to about 115 μm, and about 105 μm to about 120 μm. In some embodiments, the visual additive particles have a size of about 80 μm, about 85 μm, about 90 μm, about 95 μm, about 100 μm, about 105 μm, about 110 μm, about 115 μm, or about 120 μm. In some embodiments, the visual additive particles have a size of at least about 80 μm, about 85 μm, about 90 μm, about 95 μm, about 100 μm, about 105 μm, about 110 μm, or about 115 μm. In some embodiments, the visual additive particles have a size of at most about 85 μm, about 90 μm, about 95 μm, about 100 μm, about 105 μm, about 110 μm, about 115 μm, or about 120 μm.

[0120] In some embodiments, the viscoelastic medium with visual additives can be made using NASHA technology. In these embodiments, the viscoelastic medium can be forced through a mesh. In some embodiments, the mesh is made of metal. In some embodiments, the metal is stainless steel. In some embodiments, forcing the viscoelastic medium through the mesh results in viscoelastic particles of diameter and / or size as described herein. In some embodiments, the viscoelastic particles have a diameter of 0.1 mm to 5.0 mm.

[0121] In some embodiments, the viscoelastic medium including the visual additive may have an increased CNR in the resulting scan (such as CT scans and CBCT scans). In some embodiments, the viscoelastic medium including the visual additive may result in an increased CNR in the resulting scan compared to the CNR in the scan obtained for the viscoelastic medium without the visual additive. In some embodiments, the viscoelastic medium includes a plurality of visual additive particles as described herein. In some embodiments, the plurality of visual additive particles are present in the viscoelastic medium in an amount that produces an increased CNR in the resulting scan compared to the CNR in the scan obtained for the viscoelastic medium without the visual additive. In some embodiments, the CNR may be from about 0.1 to about 1. In some embodiments, the CNR is about 0.1 to about 0.2, about 0.1 to about 0.3, about 0.1 to about 0.4, about 0.1 to about 0.5, about 0.1 to about 0.6, about 0.1 to about 0.7, about 0.1 to about 0.8, about 0.1 to about 0.9, about 0.1 to about 1, about 0.2 to about 0.3, about 0.2 to about 0.4, about 0.2 to about 0.5, about 0.2 to about 0.6, about 0.2 to about 0.7, about 0.2 to about 0.8, about 0.2 to about 0.9, about 0.2 to about 1, about 0.3 to about 0.4, about 0.3 to about 0.5, about 0.3 to about 0.6, about 0.3 to about 0.7, about 0.3 to about 0. It may be about 0.8, about 0.3 to about 0.9, about 0.3 to about 1, about 0.4 to about 0.5, about 0.4 to about 0.6, about 0.4 to about 0.7, about 0.4 to about 0.8, about 0.4 to about 0.9, about 0.4 to about 1, about 0.5 to about 0.6, about 0.5 to about 0.7, about 0.5 to about 0.8, about 0.5 to about 0.9, about 0.5 to about 1, about 0.6 to about 0.7, about 0.6 to about 0.8, about 0.6 to about 0.9, about 0.6 to about 1, about 0.7 to about 0.8, about 0.7 to about 0.9, about 0.7 to about 1, about 0.8 to about 0.9, about 0.8 to about 1, or about 0.9 to about 1. In some embodiments, the CNR can be about 0.1, about 0.2, about 0.3, about 0.4, about 0.5, about 0.6, about 0.7, about 0.8, about 0.9, or about 1. In some embodiments, the CNR can be at least about 0.1, about 0.2, about 0.3, about 0.4, about 0.5, about 0.6, about 0.7, about 0.8, about 0.9.In some embodiments, the CNR can be at most about 0.2, about 0.3, about 0.4, about 0.5, about 0.6, about 0.7, about 0.8, about 0.9, or about 1. In some embodiments, the CNR can be from about 1 to about 5.2. In some embodiments, the CNR can be from about 1 to about 1.6, from about 1 to about 2.2, from about 1 to about 2.8, from about 1 to about 3.4, from about 1 to about 4, from about 1 to about 4.6, from about 1 to about 5.2, from about 1.6 to about 2.2, from about 1.6 to about 2.8, from about 1.6 to about 3.4, from about 1.6 to about 4, from about 1.6 to about 4.6, from about 1.6 to about 5.2, from about 2.2 to about 2. 8, about 2.2 to about 3.4, about 2.2 to about 4, about 2.2 to about 4.6, about 2.2 to about 5.2, about 2.8 to about 3.4, about 2.8 to about 4, about 2.8 to about 4.6, about 2.8 to about 5.2, about 3.4 to about 4, about 3.4 to about 4.6, about 3.4 to about 5.2, about 4 to about 4.6, about 4 to about 5.2, or about 4.6 to about 5.2. In some embodiments, the CNR can be about 1.6, about 2.2, about 2.8, about 3.4, about 4, about 4.6, or about 5.2. In some embodiments, the CNR can be at least about 1, about 1.6, about 2.2, about 2.8, about 3.4, about 4, or about 4.6. In some embodiments, the CNR can be at most about 1.6, about 2.2, about 2.8, about 3.4, about 4, about 4.6, or about 5.2. In some embodiments, the CNR can be at least 5.2, e.g., from about 5.2 to about 15.In some embodiments, the CNR is at least 5.2, about 5.2 to about 6, about 5.2 to about 6.8, about 5.2 to about 7.6, about 5.2 to about 8.4, about 5.2 to about 9.2, about 5.2 to about 10, about 5.2 to about 11, about 5.2 to about 12, about 5.2 to about 13, about 5.2 to about 14, about 5.2 to about 15, about 6 to about 6.8, about 6 to about 7.6, about 6 to about 8.4 , about 6 to about 9.2, about 6 to about 10, about 6 to about 11, about 6 to about 12, about 6 to about 13, about 6 to about 14, about 6 to about 15, about 6.8 to about 7.6, about 6.8 to about 8.4, about 6.8 to about 9.2, about 6.8 to about 10, about 6.8 to about 11, about 6.8 to about 12, about 6.8 to about 13, about 6.8 to about 14, about 6.8 to about 15, about 7.6 to about 8.4, about 7.6 to about 9 .2, about 7.6 to about 10, about 7.6 to about 11, about 7.6 to about 12, about 7.6 to about 13, about 7.6 to about 14, about 7.6 to about 15, about 8.4 to about 9.2, about 8.4 to about 10, about 8.4 to about 11, about 8.4 to about 12, about 8.4 to about 13, about 8.4 to about 14, about 8.4 to about 15, about 9.2 to about 10, about 9.2 to about 11, about 9.2 to about 12, about 9. It can be 2 to about 13, about 9.2 to about 14, about 9.2 to about 15, about 10 to about 11, about 10 to about 12, about 10 to about 13, about 10 to about 14, about 10 to about 15, about 11 to about 12, about 11 to about 13, about 11 to about 14, about 11 to about 15, about 12 to about 13, about 12 to about 14, about 12 to about 15, about 13 to about 14, about 13 to about 15, or about 14 to about 15. In some embodiments, the CNR can be at least 5.2, e.g., about 5.2, about 6, about 6.8, about 7.6, about 8.4, about 9.2, about 10, about 11, about 12, about 13, about 14, or about 15. In some embodiments, the CNR can be at least 5.2, e.g., at least about 5.2, about 6, about 6.8, 7.6, about 8.4, about 9.2, about 10, about 11, about 12, about 13, or about 14. In some embodiments, the CNR can be at least 5.2, e.g., at most about 6, about 6.8, about 7.6, about 8.4, about 9.2, about 10, about 11, about 12, about 13, about 14, or about 15. In some embodiments, the CNR can be at least 14.3, e.g., from about 14.3 to about 23.1.In some embodiments, the CNR is at least 14.3, e.g., from about 14.3 to about 15.1, from about 14.3 to about 15.9, from about 14.3 to about 16.7, from about 14.3 to about 17.5, from about 14.3 to about 18.3, from about 14.3 to about 19.1, from about 14.3 to about 19.9, from about 14.3 to about 20.7, from about 14.3 to about 21.5, from about 14.3 to about 22.3, from about 14.3 to about 23.1, from about 15.1 to about 15.9, from about 15.1 to about 16.7, from about 15.1 to about 17.5, from about 15.1 to about 1 8.3, about 15.1 to about 19.1, about 15.1 to about 19.9, about 15.1 to about 20.7, about 15.1 to about 21.5, about 15.1 to about 22.3, about 15.1 to about 23.1, about 15.9 to about 16.7, about 15.9 to about 17.5, about 15.9 to about 18.3, about 15.9 to about 19.1, about 15.9 to about 19.9, about 15.9 to about 20.7, about 15.9 to about 21.5, about 15.9 to about 22.3, about 15.9 to about 23.1, about 16.7 to about 17.5, about 16.7 to about 18.3, About 16.7 to about 19.1, about 16.7 to about 19.9, about 16.7 to about 20.7, about 16.7 to about 21.5, about 16.7 to about 22.3, about 16.7 to about 23.1, about 17.5 to about 18.3, about 17.5 to about 19.1, about 17.5 to about 19.9, about 17.5 to about 20.7, about 17.5 to about 21.5, about 17.5 to about 22.3, about 17.5 to about 23.1, about 18.3 to about 19.1, about 18.3 to about 19.9, about 18.3 to about 20.7, about 18.3 to about 21.5, about 18. 3 to about 22.3, about 18.3 to about 23.1, about 19.1 to about 19.9, about 19.1 to about 20.7, about 19.1 to about 21.5, about 19.1 to about 22.3, about 19.1 to about 23.1, about 19.9 to about 20.7, about 19.9 to about 21.5, about 19.9 to about 22.3, about 19.9 to about 23.1, about 20.7 to about 21.5, about 20.7 to about 22.3, about 20.7 to about 23.1, about 21.5 to about 22.3, about 21.5 to about 23.1, or about 22.3 to about 23.1. In some embodiments, the CNR can be at least 14.3, e.g., about 14.3, about 15.1, about 15.9, about 16.7, about 17.5, about 18.3, about 19.1, about 19.9, about 20.7, about 21.5, about 22.3, or about 23.1.In some embodiments, the CNR can be at least 14.3, e.g., at least about 14.3, about 15.1, about 15.9, 16.7, about 17.5, about 18.3, about 19.1, about 19.9, about 20.7, about 21.5, or about 22.3. In some embodiments, the CNR can be at least 14.3, e.g., at most about 15.1, about 15.9, about 16.7, about 17.5, about 18.3, about 19.1, about 19.9, about 20.7, about 21.5, about 22.3, or about 23.1. In some embodiments, the CNR can be at least 15.9, e.g., from about 16.9 to about 27.9.In some embodiments, the CNR is at least 15.9, e.g., about 16.9 to about 17.9, about 16.9 to about 18.9, about 16.9 to about 19.9, about 16.9 to about 20.9, about 16.9 to about 21.9, about 16.9 to about 22.9, about 16.9 to about 23.9, about 16.9 to about 24.9, about 16.9 to about 25.9, about 16.9 to about 26.9, about 16.9 to about 27.9, about 17.9 to about 18.9, about 17.9 to about 19.9, about 17.9 to about 20.9, about 17.9 to about 2 1.9, about 17.9 to about 22.9, about 17.9 to about 23.9, about 17.9 to about 24.9, about 17.9 to about 25.9, about 17.9 to about 26.9, about 17.9 to about 27.9, about 18.9 to about 19.9, about 18.9 to about 20.9, about 18.9 to about 21.9, about 18.9 to about 22.9, about 18.9 to about 23.9, about 18.9 to about 24.9, about 18.9 to about 25.9, about 18.9 to about 26.9, about 18.9 to about 27.9, about 19.9 to about 20.9, about 19.9 to about 21.9, About 19.9 to about 22.9, about 19.9 to about 23.9, about 19.9 to about 24.9, about 19.9 to about 25.9, about 19.9 to about 26.9, about 19.9 to about 27.9, about 20.9 to about 21.9, about 20.9 to about 22.9, about 20.9 to about 23.9, about 20.9 to about 24.9, about 20.9 to about 25.9, about 20.9 to about 26.9, about 20.9 to about 27.9, about 21.9 to about 22.9, about 21.9 to about 23.9, about 21.9 to about 24.9, about 21.9 to about 25.9, about 21. 23.9 to about 26.9, about 21.9 to about 27.9, about 22.9 to about 23.9, about 22.9 to about 24.9, about 22.9 to about 25.9, about 22.9 to about 26.9, about 22.9 to about 27.9, about 23.9 to about 24.9, about 23.9 to about 25.9, about 23.9 to about 26.9, about 23.9 to about 27.9, about 24.9 to about 25.9, about 24.9 to about 26.9, about 24.9 to about 27.9, about 25.9 to about 26.9, about 25.9 to about 27.9, or about 26.9 to about 27.9. In some embodiments, the CNR can be at least 15.9, e.g., about 16.9, about 17.9, about 18.9, about 19.9, about 20.9, about 21.9, about 22.9, about 23.9, about 24.9, about 25.9, about 26.9, or about 27.9.In some embodiments, the CNR can be at least 15.9, e.g., at least about 16.9, about 17.9, about 18.9, 19.9, about 20.9, about 21.9, about 22.9, about 23.9, about 24.9, about 25.9, or about 26.9. In some embodiments, the CNR can be at least 15.9, e.g., at most about 17.9, about 18.9, about 19.9, about 20.9, about 21.9, about 22.9, about 23.9, about 24.9, about 25.9, about 26.9, or about 27.9. In some embodiments, the CNR can be at least 20.2, e.g., from about 20.2 to about 40. In some embodiments, the CNR is at least 20.2, e.g., about 20.2 to about 21.1, about 20.2 to about 22, about 20.2 to about 24, about 20.2 to about 26, about 20.2 to about 28, about 20.2 to about 30, about 20.2 to about 32, about 20.2 to about 34, about 20.2 to about 36, about 20.2 to about 38, about 20.2 to about 40, about 21.1 to about 22, about 21.1 to about 24, about 21.1 to about 26, about 21.1 to about 28, about 21.1 to about 30, about 21.1 to about 32, about 21.1 to about 34, about 21.1 to about 36, about 21. 1 to about 38, about 21.1 to about 40, about 22 to about 24, about 22 to about 26, about 22 to about 28, about 22 to about 30, about 22 to about 32, about 22 to about 34, about 22 to about 36, about 22 to about 38, about 22 to about 40, about 24 to about 26, about 24 to about 28, about 24 to about 30, about 24 to about 32, about 24 to about 34, about 24 to about 36, about 24 to about 38, about 24 to about 40, about 26 to about 28, about 26 to about 30, about 26 to about 32, about 26 to about 34, about 26 to about 36, It can be about 26 to about 38, about 26 to about 40, about 28 to about 30, about 28 to about 32, about 28 to about 34, about 28 to about 36, about 28 to about 38, about 28 to about 40, about 30 to about 32, about 30 to about 34, about 30 to about 36, about 30 to about 38, about 30 to about 40, about 32 to about 34, about 32 to about 36, about 32 to about 38, about 32 to about 40, about 34 to about 36, about 34 to about 38, about 34 to about 40, about 36 to about 38, about 36 to about 40, or about 38 to about 40. In some embodiments, the CNR can be at least 20.2, e.g., about 20.2, about 21.1, about 22, about 24, about 26, about 28, about 30, about 32, about 34, about 36, about 38, or about 40. In some embodiments, the CNR can be at least 20.2, e.g., at least about 20.2, about 21.1, about 22, 24, about 26, about 28, about 30, about 32, about 34, about 36, or about 38. In some embodiments, the CNR can be at least 20.2, e.g., at most about 21.1, about 22, about 24, about 26, about 28, about 30, about 32, about 34, about 36, about 38, or about 40.

[0122] Viscoelastic media containing precious metals may improve efficacy at various injection sites due to increased or decreased noise values ​​at various injection sites. For example, noise values ​​may be relatively high at the abdomen but relatively low at the breast or rectum. Thus, in particular, viscoelastic media are effective as fiducial markers at breast and rectal injection sites. Although breast and rectum are described as injection sites where viscoelastic media may be effectively used as fiducial markers, breast and rectum are exemplary and viscoelastic media may be effectively used as fiducial markers at other injection sites as well.

[0123] Furthermore, the viscoelastic medium containing the visual additive may move through or be absorbed into a particular tissue. In some embodiments, the movement or absorption may be measured. In some embodiments, the movement or absorption may be measured by the dispersion of the viscoelastic medium containing the visual additive. Dispersion may be measured as the movement of the viscoelastic medium, and the movement is the change in the location of the viscoelastic medium particles in the tissue. In some cases, the movement may be measured as a decrease in image contrast. The decrease in image contrast may be measured as the difference between the contrast of the image at the beginning point and the contrast of the image at the later point. For example, the decrease in image contrast may be measured as the distance between the difference between the grayscale of the injected tissue and the grayscale of the tissue surrounding the injected tissue at a first time (e.g., the contrast at the beginning point) and the difference between the grayscale of the injected tissue and the grayscale of the tissue surrounding the injected tissue at a second time (e.g., the contrast at the later point).

[0124] In some embodiments, dispersion in the form of movement may not occur over time (e.g., the viscoelastic medium particles do not move within the tissue). In these embodiments, the viscoelastic medium particles may be evenly distributed without clumping. Additionally, the viscoelastic medium may have a volume of about 0.5 ml to about 30 ml.

[0125] In some embodiments, the dispersion in the form of movement can be about 0.001 mm to about 0.01 mm. In some embodiments, the dispersion in the form of movement can be about 0.001 mm to about 0.01 mm. In some embodiments, the dispersion in the form of movement can be about 0.001 mm to about 0.002 mm, about 0.001 mm to about 0.003 mm, about 0.001 mm to about 0.004 mm, about 0.001 mm to about 0.005 mm, about 0.001 mm to about 0.006 mm, about 0.001 mm to about 0.007 mm, about 0.001 mm to about 0.008 mm, about 0.001 mm to about 0.009 mm, about 0.001 mm to about 0.01 mm, about 0.002 mm to about 0.003 ... mm to about 0.004 mm, about 0.002 mm to about 0.005 mm, about 0.002 mm to about 0.006 mm, about 0.002 mm to about 0.007 mm, about 0.002 mm to about 0.008 mm, about 0.002 mm to about 0.009 mm, about 0.002 mm to about 0.01 mm, about 0.003 mm to about 0.004 mm, about 0.003 mm to about 0.005 mm, about 0.003 mm to about 0.006 mm, about 0.003 mm to about 0.007 mm, about 0.003 mm to about 0.008 mm , about 0.003mm to about 0.009mm, about 0.003mm to about 0.01mm, about 0.004mm to about 0.005mm, about 0.004mm to about 0.006mm, about 0.004mm to about 0.007mm, about 0.004mm to about 0.008mm, about 0.004mm to about 0.009mm, about 0.004mm to about 0.01mm, about 0.005mm to about 0.006mm, about 0.005mm to about 0.007mm, about 0.005mm to about 0.008mm, about 0.005mm to about 0 The diameter of the inner diameter of the hollow fiber layer may be about 0.009 mm, about 0.005 mm to about 0.01 mm, about 0.006 mm to about 0.007 mm, about 0.006 mm to about 0.008 mm, about 0.006 mm to about 0.009 mm, about 0.006 mm to about 0.006 ...7 mm to about 0.008 mm, about 0.007 mm to about 0.009 mm, about 0.007 mm to about 0.01 mm, about 0.008 mm to about 0.009 mm, about 0.008 mm to about 0.01 mm, or about 0.009 mm to about 0.01 mm.In some embodiments, the variance in the form of movement can be about 0.001 mm, about 0.002 mm, about 0.003 mm, about 0.004 mm, about 0.005 mm, about 0.006 mm, about 0.007 mm, about 0.008 mm, about 0.009 mm, or about 0.01 mm. In some embodiments, the variance in the form of movement can be at least about 0.001 mm, about 0.002 mm, about 0.003 mm, about 0.004 mm, about 0.005 mm, about 0.006 mm, about 0.007 mm, about 0.008 mm, or about 0.009 mm. In some embodiments, the variance in the form of movement can be at most about 0.002 mm, about 0.003 mm, about 0.004 mm, about 0.005 mm, about 0.006 mm, about 0.007 mm, about 0.008 mm, about 0.009 mm, or about 0.01 mm.

[0126] In some embodiments, the dispersion in the form of movement can be from about 0.01 mm to about 0.1 mm. In some embodiments, the dispersion in the form of movement can be from about 0.01 mm to about 0.02 mm, from about 0.01 mm to about 0.03 mm, from about 0.01 mm to about 0.04 mm, from about 0.01 mm to about 0.05 mm, from about 0.01 mm to about 0.06 mm, from about 0.01 mm to about 0.07 mm, from about 0.01 mm to about 0.08 mm, from about 0.01 mm to about 0.09 mm, from about 0.01 mm to about 0.1 mm, from about 0.02 mm to about 0.03 mm, from about 0. 0.02mm to approx. 0.04mm, approx. 0.02mm to approx. 0.05mm, approx. 0.02mm to approx. 0.06mm, approx. 0.02mm to approx. 0.07mm, approx. 0.02mm to approx. 0.08mm, approx. 0.02mm to approx. 0.09mm, approx. 0.02mm to approx. 0.1mm, approx. 0.03mm to approx. 0.04mm, approx. 0.03mm to approx. 0.05mm, approx. 0.03mm to approx. 0.06mm, approx. 0.03mm to approx. 0.07mm, approx. 0.03mm to approx. 0.08mm m, about 0.03mm to about 0.09mm, about 0.03mm to about 0.1mm, about 0.04mm to about 0.05mm, about 0.04mm to about 0.06mm, about 0.04mm to about 0.07mm, about 0.04mm to about 0.08mm, about 0.04mm to about 0.09mm, about 0.04mm to about 0.1mm, about 0.05mm to about 0.06mm, about 0.05mm to about 0.07mm, about 0.05mm to about 0.08mm, about 0.05mm to about It may be 0.09 mm, about 0.05 mm to about 0.1 mm, about 0.06 mm to about 0.07 mm, about 0.06 mm to about 0.08 mm, about 0.06 mm to about 0.09 mm, about 0.06 mm to about 0.1 mm, about 0.07 mm to about 0.08 mm, about 0.07 mm to about 0.09 mm, about 0.07 mm to about 0.1 mm, about 0.08 mm to about 0.09 mm, about 0.08 mm to about 0.1 mm, or about 0.09 mm to about 0.1 mm. In some embodiments, the dispersion in the form of migration may be about 0.01 mm, about 0.02 mm, about 0.03 mm, about 0.04 mm, about 0.05 mm, about 0.06 mm, about 0.07 mm, about 0.08 mm, about 0.09 mm, or about 0.1 mm.In some embodiments, the dispersion in the form of movement may be at least about 0.01 mm, about 0.02 mm, about 0.03 mm, about 0.04 mm, about 0.05 mm, about 0.06 mm, about 0.07 mm, about 0.08 mm, or about 0.09 mm. In some embodiments, the dispersion in the form of movement may be at most about 0.02 mm, about 0.03 mm, about 0.04 mm, about 0.05 mm, about 0.06 mm, about 0.07 mm, about 0.08 mm, about 0.09 mm, or about 0.1 mm.

[0127] In some embodiments, the dispersion in the form of movement can be from about 0.1 mm to about 1.0 mm. In some embodiments, the dispersion in the form of movement can be from about 0.1 mm to about 1 mm. In some embodiments, the dispersion in the form of movement can be from about 0.1 mm to about 0.2 mm, from about 0.1 mm to about 0.3 mm, from about 0.1 mm to about 0.4 mm, from about 0.1 mm to about 0.5 mm, from about 0.1 mm to about 0.6 mm, from about 0.1 mm to about 0.7 mm, from about 0.1 mm to about 0.8 mm, from about 0.1 mm to about 0.9 mm, from about 0.1 mm to about 1 mm, from about 0.2 mm to about 0.3 mm. , about 0.2mm to about 0.4mm, about 0.2mm to about 0.5mm, about 0.2mm to about 0.6mm, about 0.2mm to about 0.7mm, about 0.2mm to about 0.8mm, about 0.2mm to about 0. 9mm, about 0.2mm to about 1mm, about 0.3mm to about 0.4mm, about 0.3mm to about 0.5mm, about 0.3mm to about 0.6mm, about 0.3mm to about 0.7mm, about 0.3mm to about 0 .8mm, about 0.3mm to about 0.9mm, about 0.3mm to about 1mm, about 0.4mm to about 0.5mm, about 0.4mm to about 0.6mm, about 0.4mm to about 0.7mm, about 0.4mm to about 0.8mm, approximately 0.4mm~approximately 0.9mm, approximately 0.4mm~approximately 1mm, approximately 0.5mm~approximately 0.6mm, approximately 0.5mm~approximately 0.7mm, approximately 0.5mm~approximately 0.8mm, approximately 0.5mm~ The size of the dispersion may be about 0.9 mm, about 0.5 mm to about 1 mm, about 0.6 mm to about 0.7 mm, about 0.6 mm to about 0.8 mm, about 0.6 mm to about 0.9 mm, about 0.6 mm to about 1 mm, about 0.7 mm to about 0.8 mm, about 0.7 mm to about 0.9 mm, about 0.7 mm to about 1 mm, about 0.8 mm to about 0.9 mm, about 0.8 mm to about 1 mm, or about 0.9 mm to about 1 mm. In some embodiments, the dispersion in the form of migration may be about 0.1 mm, about 0.2 mm, about 0.3 mm, about 0.4 mm, about 0.5 mm, about 0.6 mm, about 0.7 mm, about 0.8 mm, about 0.9 mm, or about 1 mm. In some embodiments, the dispersion in the form of movement can be at least about 0.1 mm, about 0.2 mm, about 0.3 mm, about 0.4 mm, about 0.5 mm, about 0.6 mm, about 0.7 mm, about 0.8 mm, or about 0.9 mm.In some embodiments, the dispersion in the form of movement can be at most about 0.2 mm, about 0.3 mm, about 0.4 mm, about 0.5 mm, about 0.6 mm, about 0.7 mm, about 0.8 mm, about 0.9 mm, or about 1 mm.

[0128] In some embodiments, the dispersion in the form of movement can be from about 1.0 mm to about 2.0 mm. In some embodiments, the dispersion in the form of movement can be from about 1 mm to about 2 mm. In some embodiments, the dispersion in the form of movement can be from about 1 mm to about 1.1 mm, from about 1 mm to about 1.2 mm, from about 1 mm to about 1.3 mm, from about 1 mm to about 1.4 mm, from about 1 mm to about 1.5 mm, from about 1 mm to about 1.6 mm, from about 1 mm to about 1.7 mm, from about 1 mm to about 1.8 mm, from about 1 mm to about 1.9 mm, from about 1 mm to about 2 mm, from about 1.1 mm to about 1.2 mm, from about 1.1 mm to about 1.3 mm, from about 1.1 mm to about 1.4 mm, from about 1.1 mm m to about 1.5 mm, about 1.1 mm to about 1.6 mm, about 1.1 mm to about 1.7 mm, about 1.1 mm to about 1.8 mm, about 1.1 mm to about 1.9 mm, about 1.1 mm to about 2 mm, about 1.2 mm to about 1.3 mm, about 1.2 mm to about 1.4 mm, about 1.2 mm to about 1.5 mm, about 1.2 mm to about 1.6 mm, about 1.2 mm to about 1.7 mm, about 1.2 mm to about 1.8 mm, about 1.2 mm to about 1.9 mm, about 1.2 mm to about 2 mm, about 1. 3mm~about 1.4mm, about 1.3mm~about 1.5mm, about 1.3mm~about 1.6mm, about 1.3mm~about 1.7mm, about 1.3mm~about 1.8mm, about 1.3mm~about 1.9mm, about 1.3mm~about 2mm, about 1 .4mm~1.5mm, 1.4mm~1.6mm, 1.4mm~1.7mm, 1.4mm~1.8mm, 1.4mm~1.9mm, 1.4mm~2mm, 1.5mm~1.6mm, approx. It may be 1.5 mm to about 1.7 mm, about 1.5 mm to about 1.8 mm, about 1.5 mm to about 1.9 mm, about 1.5 mm to about 2 mm, about 1.6 mm to about 1.7 mm, about 1.6 mm to about 1.8 mm, about 1.6 mm to about 1.9 mm, about 1.6 mm to about 2 mm, about 1.7 mm to about 1.8 mm, about 1.7 mm to about 1.9 mm, about 1.7 mm to about 2 mm, about 1.8 mm to about 1.9 mm, about 1.8 mm to about 2 mm, about 1.9 mm to about 2 mm. In some embodiments, the dispersion in the form of migration may be about 1 mm, about 1.1 mm, about 1.2 mm, about 1.3 mm, about 1.4 mm, about 1.5 mm, about 1.6 mm, about 1.7 mm, about 1.8 mm, about 1.9 mm, or about 2 mm.In some embodiments, the dispersion in the form of movement may be at least about 1 mm, about 1.1 mm, about 1.2 mm, about 1.3 mm, about 1.4 mm, about 1.5 mm, about 1.6 mm, about 1.7 mm, about 1.8 mm, or about 1.9 mm. In some embodiments, the dispersion in the form of movement may be at most 1.1 mm, about 1.2 mm, about 1.3 mm, about 1.4 mm, about 1.5 mm, about 1.6 mm, about 1.7 mm, about 1.8 mm, about 1.9 mm, or about 2 mm.

[0129] Dispersion can also be measured as the deformation of the viscoelastic medium by the visual additive in the injected tissue. The deformation can be measured as the difference along radial lines between an image at a start time and an image at a later time. For example, the radial lines of a first image of the injected tissue and surrounding tissue taken at a start time and a second image of the injected tissue and surrounding tissue taken at a later time can be determined, and the deformation can be determined as the movement or difference of the corresponding radial lines of the two images. In these embodiments, the deformation can be measured as a percentage (%) difference or a difference in distance (e.g., mm or cm).

[0130] Dispersion can also be measured as the absorption of the viscoelastic medium in the injected tissue and the surrounding tissue. Absorption can be measured as the percentage loss of the volume of the marker. For example, a first image of the injected tissue and the surrounding tissue can be taken at a start time point, and a second image of the injected tissue and the surrounding tissue can be taken at a later time point. The volume of the marker can be determined at the start time point and at a later time point based on the contrast of the two images as described above, and the percentage loss of volume can be determined based on the difference between the volume at the start time point and the volume at the later time point.

[0131] In some embodiments, the viscoelastic medium particles containing the visual additive may be absorbed into tissue after injection without losing the original shape of the particles.

[0132] Additionally, in some embodiments, the viscoelastic medium particles including the visual additive may not be absorbed into the tissue over time.

[0133] In some embodiments, the viscoelastic medium particles may be absorbed into the tissue over a period of about 3 months to about 36 months. In some embodiments, the viscoelastic medium particles may be absorbed into the tissue over a period of about 3 months to about 6 months, about 3 months to about 9 months, about 3 months to about 12 months, about 3 months to about 15 months, about 3 months to about 18 months, about 3 months to about 21 months, about 3 months to about 24 months, about 3 months to about 27 months, about 3 months to about 30 months, about 3 months to about 33 months, about 3 months to about 36 months, about 6 months to about 9 months, about 6 months to about 12 months, about 6 months to about 15 months, about 6 months to about 18 months, about 6 months to about 21 months, about 6 ...24 months, about 3 months to about 24 months, about 3 months to about 24 months, about 3 months to about 24 months, about 3 months to about 24 months, about 3 months to about 24 months, about 3 months to about 24 months, about 3 months to about 24 months, about 3 months to about 24 months, about 3 months to about 24 months, about 3 months to about 24 months, 6 months to 27 months, 6 months to 30 months, 6 months to 33 months, 6 months to 36 months, 9 months to 12 months, 9 months to 15 months, 9 months to 18 months, 9 months to 21 months, 9 months to 24 months, 9 months to 27 months, 9 months to 30 months, 9 months to 33 months, 9 months to 36 months, 12 months to 15 months, 12 months to 18 months, 12 months to 21 months, 12 months to 24 months, 12 months to 24 months, months to 27 months, 12 months to 30 months, 12 months to 33 months, 12 months to 36 months, 15 months to 18 months, 15 months to 21 months, 15 months to 24 months, 15 months to 27 months, 15 months to 30 months, 15 months to 33 months, 15 months to 36 months, 18 months to 21 months, 18 months to 24 months, 18 months to 27 months, 18 months to 30 months, 18 months to 33 months, 18 months to 36 months , about 21 months to about 24 months, about 21 to about 27 months, about 21 months to about 30 months, about 21 months to about 33 months, about 21 months to about 36 months, about 24 months to about 27 months, about 24 months to about 30 months, about 24 months to about 33 months, about 24 months to about 36 months, about 27 months to about 30 months, about 27 months to about 33 months, about 27 months to about 36 months, about 30 months to about 33 months, about 30 months to about 36 months, or about 33 months to about 36 months. In some embodiments, the viscoelastic medium particles may be absorbed into the tissue over a period of about 3 months, about 6 months, about 9 months, about 12 months, about 15 months, about 18 months, about 21 months, about 24 months, about 27 months, about 30 months, about 33 months, or about 36 months.In some embodiments, the viscoelastic medium particles may be absorbed into tissue over a period of at least about 3 months, about 6 months, about 9 months, about 12 months, about 15 months, about 18 months, about 21 months, about 24 months, about 27 months, about 30 months, or about 33 months. In some embodiments, the viscoelastic medium particles may be absorbed into tissue over a period of at most about 6 months, about 9 months, about 12 months, about 15 months, about 18 months, about 21 months, about 24 months, about 27 months, about 30 months, about 33 months, or about 36 months.

[0134] In some embodiments, the viscoelastic medium particles may be absorbed into the tissue over a period of about 12 months to about 16 months. In some embodiments, the viscoelastic medium particles may be shrunk to about 12 months to about 12.5 months, about 12 months to about 13 months, about 12 months to about 13.5 months, about 12 months to about 14 months, about 12 months to about 14.5 months, about 12 months to about 15 months, about 12 months to about 15.5 months, about 12 months to about 16 months, about 12.5 months to about 13 months, about 12.5 months to about 13.5 months, about 12.5 months to about 14 months, about 12.5 months to about 14.5 months, about 12.5 months to about 15 months, about 12.5 months to about 15.5 months, about 12.5 months to about 16 months, about 13 months to about 13.5 months, about 13 months to about 14 months, about 13 months to about 14.5 months, or months, about 13 months to about 15 months, about 13 months to about 15.5 months, about 13 months to about 16 months, about 13.5 months to about 14 months, about 13.5 months to about 14.5 months, about 13.5 months to about 15 months, about 13.5 months to about 15.5 months, about 13.5 months to about 16 months, about 14 months to about 14.5 months, about 14 months to about 15 months, about 14 months to about 15 months, about 14.5 months to about 15 months, about 14.5 months to about 15 months, about 14.5 months to about 15.5 months, about 14.5 months to about 16 months, about 15 months to about 15.5 months, about 15 months to about 16 months, or about 15.5 months to about 16 months. In some embodiments, the viscoelastic medium particles may be absorbed into tissue over a period of about 12 months, about 12.5 months, about 13 months, about 13.5 months, about 14 months, about 14.5 months, about 15 months, 15.5 months, or about 16 months. In some embodiments, the viscoelastic medium particles may be absorbed into tissue over a period of at least about 12 months, about 12.5 months, about 13 months, about 13.5 months, about 14 months, about 14.5 months, about 15 months, or about 15.5 months. In some embodiments, the viscoelastic medium particles may be absorbed into tissue over a period of at most about 12.5 months, about 13 months, about 13.5 months, about 14 months, about 14.5 months, about 15 months, 15.5 months, or about 16 months.

[0135] In some aspects, the length of time that the viscoelastic medium particles containing visual additive particles are absorbed improves the effectiveness of the viscoelastic medium particles because visibility is increased over a longer period of time and re-administration of the viscoelastic medium particles containing visual additive particles is less frequent, if at all, than is required by other products, hi some embodiments, the viscoelastic medium particles containing visual additive particles are injected once every about 3 months to about 36 months. In some embodiments, the viscoelastic medium particles including the visual additive particles have a shelf life of about 3 months to about 6 months, about 3 months to about 9 months, about 3 months to about 12 months, about 3 months to about 15 months, about 3 months to about 18 months, about 3 months to about 21 months, about 3 months to about 24 months, about 3 months to about 27 months, about 3 months to about 30 months, about 3 months to about 33 months, about 3 months to about 36 months, about 6 months to about 9 months, about 6 months to about 12 months, about 6 months to about 15 months, about 6 months to about 18 months, about 6 months to about 2 ... 1 month, 6 months to 24 months, 6 months to 27 months, 6 months to 30 months, 6 months to 33 months, 6 months to 36 months, 9 months to 12 months, 9 months to 15 months, 9 months to 18 months, 9 months to 21 months, 9 months to 24 months, 9 months to 27 months, 9 months to 30 months, 9 months to 33 months, 9 months to 36 months, 12 months to 15 months, 12 months to 18 months, 12 months to 21 months, 12 months to 24 months 24 months, 12 months to 27 months, 12 months to 30 months, 12 months to 33 months, 12 months to 36 months, 15 months to 18 months, 15 months to 21 months, 15 months to 24 months, 15 months to 27 months, 15 months to 30 months, 15 months to 33 months, 15 months to 36 months, 18 months to 21 months, 18 months to 24 months, 18 months to 27 months, 18 months to 30 months, 18 months to 33 months, 18 months to 36 months It is injected once every about 21 months to about 36 months, about 21 months to about 24 months, about 21 months to about 27 months, about 21 months to about 30 months, about 21 months to about 33 months, about 21 months to about 36 months, about 24 months to about 27 months, about 24 months to about 30 months, about 24 months to about 33 months, about 24 months to about 36 months, about 27 months to about 30 months, about 27 months to about 33 months, about 27 months to about 36 months, about 30 months to about 33 months, about 30 months to about 36 months, or about 33 months to about 36 months.In some embodiments, the viscoelastic medium particles including visual additive particles are injected once every about 3 months, about 6 months, about 9 months, about 12 months, about 15 months, about 18 months, about 21 months, about 24 months, about 27 months, about 30 months, about 33 months, or about 36 months. In some embodiments, the viscoelastic medium particles including visual additive particles are injected at least once every about 3 months, about 6 months, about 9 months, about 12 months, about 15 months, about 18 months, about 21 months, about 24 months, about 27 months, about 30 months, or about 33 months. In some embodiments, the viscoelastic medium particles including visual additive particles are injected at most once every about 6 months, about 9 months, about 12 months, about 15 months, about 18 months, about 21 months, about 24 months, about 27 months, about 30 months, about 33 months, or about 36 months.

[0136] In some embodiments, the viscoelastic medium with the visual additive may appear (e.g., be visible) during or immediately after injection of the viscoelastic medium into the tissue, while in other embodiments, the viscoelastic medium with the visual additive may appear after a period of time following injection (e.g., up to 30 minutes following injection).

[0137] In addition, the addition of a visual additive to the viscoelastic medium improves the visibility of the viscoelastic medium, thus allowing the movement of the viscoelastic medium to be more easily determined. For example, the movement of the viscoelastic medium is more easily determined and obtained due to the contrast of the image, which is clearer and more easily obtained due to the improved visibility of the viscoelastic medium. Furthermore, the addition of a visual additive can affect the movement based on the properties (e.g., size or composition) of the visual additive. For example, if the size of the particles of the visual additive is about 80 micrometers to about 120 micrometers in diameter, the viscoelastic medium containing the visual additive may not move through the tissue as much as a viscoelastic medium containing a visual additive having a smaller particle size. Furthermore, a viscoelastic medium containing visual additive particles with a size ranging from about 80 micrometers to about 120 micrometers in diameter shows less accumulation in organs throughout the body (e.g., liver, spleen, lungs, brain, stomach, and / or pancreas) due to the reduced movement. The additive size ranges of visual additive particles (e.g., about 15 micrometers to about 200 micrometers, about 15 micrometers to about 50 micrometers, and / or about 120 micrometers to about 200 micrometers) may be associated with different amounts of accumulation and movement in organs. Although particular size ranges and characteristics of visual additives are described above, these size ranges and characteristics are exemplary and other size ranges and characteristics can be used.

[0138] In some embodiments, the amount of visual additive in the viscoelastic medium can increase the visibility of the viscoelastic medium. In some embodiments, about 15 mg to about 30 mg of visual additive per ml of viscoelastic medium can be added to the viscoelastic medium. In some embodiments, the weight percentage of the visual additive in the viscoelastic medium can be about 0.01% to about 0.25%. In some embodiments, the weight percentage of the visual additive in the viscoelastic medium can be about 0.01% to about 0.04%, about 0.01% to about 0.07%, about 0.01% to about 0.1%, about 0.01% to about 0.13%, about 0.01% to about 0.16%, about 0.01% to about 0.19%, about 0.01% to about 0.22%, about 0. 01% to about 0.25%, about 0.04% to about 0.07%, about 0.04% to about 0.1%, about 0.04% to about 0.13%, about 0.04% to about 0.16%, about 0.04% to about 0.19%, about 0.04% to about 0.22%, about 0.04% to about 0.25%, about 0.07% to about 0.1%, about 0.07% to about 0.13%, About 0.07% to about 0.16%, about 0.07% to about 0.19%, about 0.07% to about 0.22%, about 0.07% to about 0.25%, about 0.1% to about 0.13%, about 0.1% to about 0.16%, about 0.1% to about 0.19%, about 0.1% to about 0.22%, about 0.1% to about 0.25%, about 0.13% to about 0.16% , about 0.13% to about 0.19%, about 0.13% to about 0.22%, about 0.13% to about 0.25%, about 0.16% to about 0.19%, about 0.16% to about 0.22%, about 0.16% to about 0.25%, about 0.19% to about 0.22%, about 0.19% to about 0.25%, or about 0.22% to about 0.25%. In some embodiments, the weight percentage of the visual additive in the viscoelastic medium can be about 0.01%, about 0.04%, about 0.07%, about 0.1%, about 0.13%, about 0.16%, about 0.19%, about 0.22%, or about 0.25%. In some embodiments, the weight percentage of the visual additive in the viscoelastic medium can be at least about 0.01%, about 0.04%, about 0.07%, about 0.1%, about 0.13%, about 0.16%, about 0.19%, or about 0.22%. In some embodiments, the weight percentage of the visual additive in the viscoelastic medium can be at most about 0.04%, about 0.07%, about 0.1%, about 0.13%, about 0.16%, about 0.19%, or about 0.25%.In some embodiments, the weight percentage of the visual additive in the viscoelastic medium can be from about 0.07% (w / w) to about 0.15% (w / w). In some embodiments, the weight percentage of the visual additive in the viscoelastic medium can be from about 0.07% to about 0.08%, from about 0.07% to about 0.09%, from about 0.07% to about 0.1%, from about 0.07% to about 0.11%, from about 0.07% to about 0.12%, from about 0.07% to about 0.13%, from about 0.07% to about 0.14%, from about 0. 07% to about 0.15%, about 0.08% to about 0.09%, about 0.08% to about 0.1%, about 0.08% to about 0.11%, about 0.08% to about 0.12%, about 0.08% to about 0.13%, about 0.08% to about 0.14%, about 0.08% to about 0.15%, about 0.09% to about 0.1%, about 0.09% to about 0.11%, About 0.09% to about 0.12%, about 0.09% to about 0.13%, about 0.09% to about 0.14%, about 0.09% to about 0.15%, about 0.1% to about 0.11%, about 0.1% to about 0.12%, about 0.1% to about 0.13%, about 0.1% to about 0.14%, about 0.1% to about 0.15%, about 0.11% to about 0.12% , about 0.11% to about 0.13%, about 0.11% to about 0.14%, about 0.11% to about 0.15%, about 0.12% to about 0.13%, about 0.12% to about 0.14%, about 0.12% to about 0.15%, about 0.13% to about 0.14%, about 0.13% to about 0.15%, or about 0.14% to about 0.15%. In some embodiments, the weight percentage of the visual additive in the viscoelastic medium can be about 0.07%, about 0.08%, about 0.09%, about 0.1%, about 0.11%, about 0.12%, about 0.13%, about 0.14%, or about 0.15%. In some embodiments, the weight percentage of the visual additive in the viscoelastic medium can be at least about 0.07%, about 0.08%, about 0.09%, about 0.1%, about 0.11%, about 0.12%, about 0.13%, or about 0.14%. In some embodiments, the weight percentage of the visual additive in the viscoelastic medium can be at most about 0.08%, about 0.09%, about 0.1%, about 0.11%, about 0.12%, about 0.13%, about 0.14%, or about 0.15%.

[0139] Image Enhancement Since polyethylene glycol, hyaluronic acid, and NASHA gel are poorly imageable on CT scans, MRI, and TRUS (transrectal ultrasound), additives (e.g., visual additives) and compositions are configured to allow clinicians to inject the organ spacing materials described herein in precise locations through real-time scanning feedback (e.g., CNR). Furthermore, such scans can be used for radiation planning. Enhanced HA CT imaging is a very important feature that eliminates the need for patient MRI, costs, and CT / MRI fusion steps to treatment planning. Furthermore, for boost and Accelerated Partial Breast Irradiation (APBI) planning, it is very important to have a clear identification of the seroma to enable accurate target volume contouring and to initiate cone beam image guided radiotherapy. However, since seromas are not necessarily visible on CT simulation, many surgeries, such as those requiring full thickness closure at the time of surgery, are difficult to plan and may not be suitable for such APBI procedures. Intra-surgical clip placement has been used to aid in such contouring, but they are often unreliable, with high-Z clip materials distorting the contoured image and low-Z clip materials, such as tantalum, being invisible.

[0140] However, the image enhancing agents provided herein exhibit Z values ​​sufficient to allow full visibility on CT and paramagnetic moment for visibility on MRI, but not too high to avoid degradation of seroma imaging. Further optimal visibility and image quality is achieved by varying the volume of image enhancing agent injected while maintaining minimal expansion of the treated volume.

[0141] In one embodiment, the visual additive comprises iodine, which enhances CT imaging but provides no benefit to MRI and TRUS imaging. Additionally, iodine may be an allergen.

[0142] In some embodiments, the visual additive (also referred to above as "the visual additive") comprises a radiopaque compound selected from the group consisting of gold, iodine, gadolinium, iron, barium, calcium, magnesium, or any combination thereof. In some embodiments, the gold visualization additive comprises gold particles. In some embodiments, the concentration of the visual additive in the polyethylene glycol, hyaluronic acid, or both is about 15 mg / ml to about 30 mg / ml. In some embodiments, the concentration of the visual additive in the spacer material is about 0.01% to about 1.5% (w / w). In some embodiments, the concentration of the visual additive in the spacer material is at least about 0.01% to about 1.5% (w / w), e.g., about 0.01% to about 1.0%, about 0.01% to about 0.75%, about 0.01% to about 0.5%, about 0.01% to about 0.25%, about 0.01% to about 0.15%, about 0.01% to about 0.05%, about 0.01% to about 0.04%, about 0.01% to about 0.03%, about 0.0 1% to about 0.02%, about 0.02% to about 1.5%, about 0.02% to about 1.0%, about 0.02% to about 0.75%, about 0.02% to about 0.5%, about 0.02% to about 0.25%, about 0.02% to about 0.15%, about 0.02% to about 0.05%, about 0.02% to about 0.04%, about 0.02% to about 0.03%, about 0.03% to about 1.5%, about 0.03% to about 1.0%, about 0.03% to about 0.75 %, about 0.03% to about 0.5%, about 0.03% to about 0.25%, about 0.03% to about 0.15%, about 0.03% to about 0.05%, about 0.03% to about 0.04%, about 0.04% to about 1.5%, about 0.04% to about 1.0%, about 0.04% to about 0.75%, about 0.04% to about 0.5%, about 0.04% to about 0.25%, about 0.04% to about 0.15%, about 0.04% to about 0.05%, about 0.05 % to about 1.5%, about 0.05% to about 1.0%, about 0.05% to about 0.75%, about 0.05% to about 0.5%, about 0.05% to about 0.25%, about 0.05% to about 0.15%, about 0.15% to about 1.5%, about 0.15% to about 1.0%, about 0.15% to about 0.75%, about 0.15% to about 0.5%, about 0.15% to about 0.25%, about 0.25% to about 1.5%, about 0.25% to about 1.0%, about 0.25% to about 0.75%, about 0.25% to about 0.5%, about 0.50% to about 1.5%, about 0.50% to about 1.0%, about 0.50% to about 0.75%, about 0.75% to about 1.5%, about 0.75% to about 1.0%, about 1.0% to about 1.5%, about 0.01%, about 0.02%, about 0.03%, about 0.04%, about 0.05%, about 0.06%, about 0.07%, about 0.08%, about 0.09%, about 0.1%, about 0.15%, about 0.25%, about 0.50%, about 0.75%, about 1.0%, or about 1.5%. In some embodiments, the concentration of the visual additive in the spacer material is about 0.1% to about 15%. In some embodiments, the concentration of the visual additive in the spacer material is at least about 0.1%, the visual additive is at about 0.5 mg / ml gel to about 1 mg / ml gel, about 0.5 mg / ml gel to about 1.5 mg / ml gel, about 0.5 mg / ml gel to about 2 mg / ml gel, about 0.5 mg / ml gel to about 2.5 mg / ml gel, about 0.5 mg / ml gel to about 3 mg / ml gel, about 0.5 mg / ml gel to about 1 ... gel of about 1 mg / ml to about 3.5 mg / ml, gel of about 0.5 mg / ml to about 4 mg / ml, gel of about 0.5 mg / ml to about 4.5 mg / ml, gel of about 0.5 mg / ml to about 5 mg / ml, gel of about 0.5 mg / ml to about 5.5 mg / ml, gel of about 0.5 mg / ml to about 6 mg / ml, gel of about 1 mg / ml to about 1.5 mg / ml, gel of about 1 mg / ml to about 2 mg / ml gel of about 1 mg / ml to about 2.5 mg / ml, gel of about 1 mg / ml to about 3 mg / ml, gel of about 1 mg / ml to about 3.5 mg / ml, gel of about 1 mg / ml to about 4 mg / ml, gel of about 1 mg / ml to about 4.5 mg / ml, gel of about 1 mg / ml to about 5 mg / ml, gel of about 1 mg / ml to about 5.5 mg / ml, gel of about 1 mg / ml to about 6 mg / ml ml gel, about 1.5 mg / ml gel to about 2 mg / ml gel, about 1.5 mg / ml gel to about 2.5 mg / ml gel, about 1.5 mg / ml gel to about 3 mg / ml gel, about 1.5 mg / ml gel to about 3.5 mg / ml gel, about 1.5 mg / ml gel to about 4 mg / ml gel, about 1.5 mg / ml gel to about 4.5 mg / ml gel, about 1.5 mg / ml gel to about 5 mg / ml gel, about 1.5mg / ml gel to about 5.5mg / ml gel, about 1.5mg / ml gel to about 6mg / ml gel, about 2mg / ml gel to about 2.5mg / ml gel, about 2mg / ml gel to about 3mg / ml gel, about 2mg / ml gel to about 3.5mg / ml gel, about 2mg / ml gel to about 4mg / ml gel, about 2mg / ml gel to about 4.5mg / ml gel, about 2mg / ml gel to about 5mg / ml gel, about 2mg / ml gel to about 5.5mg / ml gel, about 2mg / ml gel to about 6mg / ml gel of about 2.5 mg / ml to about 3 mg / ml, gel of about 2.5 mg / ml to about 3.5 mg / ml, gel of about 2.5 mg / ml to about 4 mg / ml, gel of about 2.5 mg / ml to about 4.5 mg / ml, gel of about 2.5 mg / ml to about 5 mg / ml, gel of about 2.5 mg / ml to about 5.5 mg / ml, gel of about 2.5 mg / ml to about 6 mg / ml, gel of about 3 mg / ml to about 3.5 mg / ml, gel of about 3 mg / ml to about 4 ... g / ml gel to about 4.5 mg / ml gel, about 3 mg / ml gel to about 5 mg / ml gel, about 3 mg / ml gel to about 5.5 mg / ml gel, about 3 mg / ml gel to about 6 mg / ml gel, about 3.5 mg / ml gel to about 4 mg / ml gel, about 3.5 mg / ml gel to about 4.5 mg / ml gel, about 3.5 mg / ml gel to about 5 mg / ml gel, about 3.5 mg / ml gel to about 5.5 mg / ml gel, about 3.5 mg / ml gel to about 6 mg / ml gel, about 4 mg / ml gel to about 4. In some embodiments, the visual additive is present in a gel of about 0.5 mg / ml, about 1 mg / ml, about 1.5 mg / ml, about 2 mg / ml, about 3 mg / ml, about 4 mg / ml, about 5 ...In some embodiments, the visual additive is present in at least about 0.5 mg / ml, about 1 mg / ml, about 1.5 mg / ml, about 2 mg / ml, about 2.5 mg / ml, about 3 mg / ml, about 3.5 mg / ml, about 4 mg / ml, about 4.5 mg / ml, about 5 mg / ml, or about 5.5 mg / ml. In some embodiments, the visual additive is present in at most about 1 mg / ml of the gel, about 1.5 mg / ml of the gel, about 2 mg / ml of the gel, about 2.5 mg / ml of the gel, about 3 mg / ml of the gel, about 3.5 mg / ml of the gel, about 4 mg / ml of the gel, about 4.5 mg / ml of the gel, about 5 mg / ml of the gel, about 5.5 mg / ml of the gel, or about 6 mg / ml of the gel. Other examples of viscoelastic media treated to facilitate visualization are taught in WO2011084465, which is incorporated herein by reference in its entirety.

[0143] In some embodiments, an additional visual additive is added to the gel, the additional visual additive comprising a gas. In some embodiments, the gas is air, nitrogen, helium, oxygen, or any combination thereof. In some embodiments, the gas forms a plurality of bubbles within the spacer material. In some embodiments, the concentration of the additional visual additive in the spacer material is between about 0.1% and about 15%. In some embodiments, the size of the microbubbles is between about 1 μm and about 100 μm. In some embodiments, the concentration of the visual additive in the spacer material is at least about 0.1%. In some embodiments, the gas is injected into the spacer material. In some embodiments, the visual additive has an outer width of at least about 20 microns. In some embodiments, the gas is injected into the spacer material while the spacer material is under pressure. In some embodiments, the visual additive has a diameter of at least about 20 microns. In some embodiments, the spacer material is agitated in an environment containing a gas to form microbubbles. In some embodiments, the spacer material is pressurized and agitated in an environment containing a gas to form microbubbles. In some embodiments, the microbubbles are formed prior to injection of the spacer material into the subject. In some embodiments, the microbubbles are formed during injection of the spacer material into a subject. In some embodiments, the microbubbles are formed during injection of the spacer material into a subject, where the shape of the needle forms the microbubbles. In some embodiments, the microbubbles are formed in-situ. In some embodiments, a cross-linked viscoelastic medium entraps and stabilizes the microbubbles. In some embodiments, the gels described herein include an additional visual additive, where the additional visual additive comprises a gas without any other visual additives.

[0144] In some embodiments, the viscoelastic medium is NASHA and the visual additive is a known imaging (e.g., MRI) contrast agent. In some embodiments, the visual additive is any of the compounds disclosed herein. In some embodiments, the visual additive comprises a gadolinium complex. In some embodiments, the gadolinium complex comprises gadopentate dimeglumine. In some embodiments, a gel containing 5 mg / ml of gadopentate dimeglumine was prepared by weighing. In some embodiments, the visual additive was mixed with the gel by manual stirring, and the resulting gel was centrifuged to remove air bubbles one day before use. In some embodiments, the visual additive is superparamagnetic iron oxide.

[0145] Terms and Definitions Unless otherwise defined, all technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

[0146] As used herein, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise. Any reference to "or" herein is intended to include "and / or" unless specifically stated otherwise.

[0147] As used herein, the term "about" refers to an amount to the nearest 10%, 5%, or 1% of the recited amount, including increments thereof.

[0148] As used herein, the term "about" in reference to a percentage refers to an amount that is 10%, 5%, or 1% greater or less than the recited percentage, including increments thereof.

[0149] As used herein, "at least one," "one or more," and "and / or" are open-ended expressions that are both conjunctive and disjunctive in operation. For example, each of the expressions "at least one of A, B and C," "at least one of A, B, or C," "one or more of A, B, and C," "one or more of A, B, or C," and "A, B, and / or C" means A alone, B alone, C alone, A and B together, A and C together, B and C together, or A, B and C together.

[0150] As used herein, the term "radiative protection" refers to any type of soft tissue volume augmentation, including, but not limited to, facial contouring (e.g., more prominent cheeks or chin), correction of concave deformities (e.g., post-trauma, HIV-associated lipoatrophy), and correction of deep age-related facial folds. Radiative protection may therefore be used solely for cosmetic purposes, or for medical purposes, such as after trauma or degenerative disease.

[0151] The term "degraded" means that less than 20%, or less than 10%, of the medium remains in the body.

[0152] As used herein, the term "soft tissue" refers to tissue that connects, supports, or surrounds other structures and organs of the body. Soft tissue includes muscle, fibrous tissue, and fat.

[0153] As used herein, the terms "subepidermal administration" or "subcuticular administration" refer to administration below the epidermis of the skin, and include administration deeper, such as into the dermis, subcutaneous, or submuscular layers, or into the periosteum (in the vicinity of bone tissue), where applicable.

[0154] As used herein, the term "therapeutic" includes any type of preventative, palliative or curative treatment.

[0155] As used herein, the term "super spacing" refers to the dictionary definitions of the terms "super" and "spacing," as well as the definition of extraordinary spacing as compared to conventional texts regarding spacing of similar tissue in the same context of a given subject.

[0156] As used herein, a physiological or isotonic solution is a solution having an osmolality in the range of about 200 to about 400 mOsm / l, about 250 to about 350 mOsm / l, or about 300 mOsm / l. For practical purposes, this osmolality may be achieved by preparation of a 0.9% (0.154 M) NaCl solution.

[0157] As used herein, the term "implant" refers broadly to any type of implanted or implantable foreign object or material. Implants also include objects or materials that are nearly identical to non-foreign objects or materials. Implants are not limited to any particular shape. The final shape of the implant within the body is determined by one of skill in the art based on the purpose of the treatment.

[0158] As used herein, the term "viscoelastic medium" refers to a medium that exhibits a combination of viscous and elastic properties. Specifically, the viscoelastic medium is injectable through a 20 gauge or larger needle, such as a 10-20 gauge needle, by applying a pressure of 15-50 N. In particular, the medium, or an implant or medicament comprising the medium, is suitable for subepidermal injection into a human in need thereof at a desired site.

[0159] As used herein, the term "stabilized" refers to any form of chemical stabilization that renders the stabilized compound more stable to biodegradation than the parent compound under physiological conditions. Stabilized compounds include, but are not limited to, cross-linked and partially cross-linked compounds.

[0160] The term "derivative" of a polysaccharide, as used herein, means any suitable derivative thereof, including cross-linked polysaccharides and substituted polysaccharides, such as sulfated polysaccharides. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0161] Exemplary embodiments Among the exemplary embodiments are the following: Embodiment 1. 1. A composition comprising: A viscoelastic medium; a first visual additive, said first visual additive comprising a metal, said metal having a particle size of 80 micrometers (μm) or greater; A composition comprising: Embodiment 2. The composition of claim 1 , wherein the metal is a precious metal. Embodiment 3. 3. The composition of claim 1 or 2, wherein the metal or precious metal is selected from the group consisting of gold (Au), iodine (I), gadolinium (Gd), iron (Fe), barium (Ba), calcium (Ca), magnesium (Mg), and combinations thereof. Embodiment 4. 4. The composition of claim 1, wherein the metal or precious metal is an isotope of gold (Au), iodine (I), gadolinium (Gd), iron (Fe), barium (Ba), calcium (Ca), magnesium (Mg), or a combination thereof. Embodiment 5. 5. The composition according to claim 1, wherein the metal or the precious metal is in the form of a powder. Embodiment 6. 6. The composition of claim 1, wherein the first visual additive has a radiographic density of about 1.0 g / cm3 to 2.0 g / cm3. Embodiment 7. 7. The composition of claim 1, wherein half of the first visual additive is configured to disperse in tissue within 9 months. Embodiment 8. 8. The composition according to claim 1, wherein the particle size of the metal or the precious metal is from about 80 μm to about 120 μm. EMBODIMENT 9. 9. The composition according to claim 1, wherein the particle size of the metal or precious metal is about 100 μm. Embodiment 10. 10. The composition of claim 1, wherein the first visual additive further comprises one or more microbubbles. Embodiment 11. 11. The composition of claim 1, further comprising a second visual additive. Embodiment 12. 12. The composition of any one of claims 1 to 11, wherein the second visual additive is different from the first visual additive. Embodiment 13. 13. The composition of claim 11 or 12, wherein the second visual additive comprises one or more microbubbles. Embodiment 14. 14. The composition of claim 1, wherein the first visual additive has a concentration in the viscoelastic medium of greater than 5 milligrams per milliliter (mg / ml). EMBODIMENT 15. 15. The composition of claim 1, wherein the first visual additive has a concentration in the viscoelastic medium of less than 90 mg / ml. Embodiment 16. 16. The composition of claim 1, wherein the first visual additive has a concentration in the viscoelastic medium of from 15 mg / ml to 30 mg / ml. EMBODIMENT 17. 17. The composition according to claim 1, wherein the metal is about 0.5% to about 9.0% by weight of the composition. EMBODIMENT 18. 18. The composition according to claim 1, wherein the metal or precious metal is about 0.015% to about 1.5% by weight of the composition. EMBODIMENT 19. 19. The composition of claim 1, wherein the viscoelastic medium comprises a volume of about 1 milliliter (ml) to about 50 ml. EMBODIMENT 20. The composition of any one of claims 1 to 19, wherein the composition is configured to be biodegradable. EMBODIMENT 21. 21. The composition of claim 1, wherein the composition is configured to be detectable on an imaging modality for at least 9 months. EMBODIMENT 22. The composition according to any one of claims 1 to 21, wherein the composition is configured to be substantially immobile before or during imaging. EMBODIMENT 23. 23. The composition of any one of claims 1 to 22, wherein the first visual additive is configured to be substantially immobile prior to or during imaging. EMBODIMENT 24. 24. The composition of claim 1, wherein the composition is configured to be placed within a subject. EMBODIMENT 25. The composition of claim 24, wherein the subject is in need of radiography. 26. 26. The composition of any one of claims 1 to 25, wherein the composition is adapted to be deployed by injection. EMBODIMENT 27. 27. The composition of claim 25 or 26, wherein the composition is configured to be placed subcutaneously or subepidermally. 28. 28. The composition of any one of claims 1 to 27, wherein the composition is configured for placement within a tissue site. 29. 30. The composition of claim 28, wherein the tissue site comprises one or more of adipose tissue, muscle tissue, organ tissue, or a combination thereof. EMBODIMENT 30. 30. The composition of claim 1, wherein the composition is configured to be imaged on one or more modalities. EMBODIMENT 31. 31. The composition of claim 30, wherein the one or more modalities include X-ray, MRI, CT, CBCT, ultrasound, PET, SPECT, or a combination thereof. EMBODIMENT 32. 32. The composition of claim 30 or 31, wherein the composition configured to be imaged on the one or more modalities comprises the composition configured to be imaged in real time on the one or more modalities. EMBODIMENT 33. 33. The composition of any one of claims 1-32, wherein the composition is configured to be imaged within 30 minutes, within 90 minutes, within 4 hours, within 8 hours, or within 4 days of placement. EMBODIMENT 34. 34. The composition according to any one of claims 1 to 33, wherein the viscoelastic medium comprises hyaluronic acid, polyethylene glycol, or dextranomer. EMBODIMENT 35. 35. The composition of claim 1, wherein the viscoelastic medium comprises hyaluronic acid, polyethylene glycol, or dextranoma in a concentration of about 5 mg / ml to about 100 mg / ml. 36. 36. The composition of claim 1, wherein the viscoelastic medium comprises gel particles ranging in size from about 0.08 mm to about 5 mm. 37. 37. The composition of claim 36, wherein the gel particles comprise the metal particles. 38. 38. The composition of claim 1, wherein the viscoelastic medium comprises non-animal stabilized hyaluronic acid ("NASHA"). 39. 39. The composition of any one of claims 1-38, wherein the viscoelastic medium expands within the tissue site to less than 10% of its initial deployment volume. EMBODIMENT 40. 40. The composition according to any one of claims 1 to 39, wherein the viscoelastic medium is injected once every six months. EMBODIMENT 41. 41. The composition according to any one of claims 1 to 40, wherein the viscoelastic medium is completely absorbed within 20 months. EMBODIMENT 42. 42. The composition according to any one of claims 1 to 41, wherein the viscoelastic medium is completely absorbed within 16 months. EMBODIMENT 43. 43. The composition according to any one of claims 1 to 42, wherein the viscoelastic medium is completely absorbed within 12 months. EMBODIMENT 44. 44. The composition of any one of claims 1 to 43, wherein the first visual additive is present in an amount sufficient to produce a contrast-to-noise of about 0.1 to about 40 when the composition is scanned using radiation therapy. EMBODIMENT 45. 1. A method of visualizing a tissue, space or location in a radiographic subject, the method comprising the step of placing an imaging contrast composition, the composition comprising: A viscoelastic medium; a first visual additive, said first visual additive being a metal, said metal having a particle size greater than about 80 micrometers; A method comprising: EMBODIMENT 46. 44. The method of claim 43, further comprising the steps of: (a) placing the composition within a first tissue site; and (b) imaging the composition within the first tissue site. EMBODIMENT 47. 45. The method of claim 44, wherein the metal has a particle size greater than 100 micrometers. 48. 1. A method of spacing a first tissue site of a subject from a second tissue site of the subject, the method comprising: (a) disposing a composition in a space between the first tissue site and the second tissue site, the composition comprising a viscoelastic medium and a first visual additive, the first visual additive being a metal, the first visual additive having a particle size greater than 80 micrometers (μm). 49. 47. The method of any one of claims 43 to 46, wherein the first visual additive has a concentration in the viscoelastic medium that provides a contrast-to-noise ratio of about 0.1 to about 10. EMBODIMENT 50. 48. The method according to any one of claims 43 to 47, wherein the metal is a noble metal. EMBODIMENT 51. 49. The method of any one of claims 43 to 48, wherein the metal or noble metal is selected from the group consisting of gold (Au), iodine (I), gadolinium (Gd), iron (Fe), barium (Ba), calcium (Ca), magnesium (Mg), and combinations thereof. EMBODIMENT 52. 50. The method of any one of claims 43 to 49, wherein the metal or noble metal is an isotope of gold (Au), iodine (I), gadolinium (Gd), iron (Fe), barium (Ba), calcium (Ca), magnesium (Mg), or a combination thereof. EMBODIMENT 53. 51. The method according to any one of claims 43 to 50, wherein the metal or the precious metal is a powder. EMBODIMENT 54. 52. The method of any one of claims 43 to 51, wherein the first visual additive has a radiographic density of about 1.0 g / cm3 to 2.0 g / cm3. EMBODIMENT 55. 53. The method of any one of claims 43 to 52, wherein half of the first visual additive is configured to disperse in the tissue within 9 months. EMBODIMENT 56. 54. The method according to any one of claims 43 to 53, wherein the particle size of the metal or noble metal is from about 80 μm to about 120 μm. EMBODIMENT 57. 55. The method according to any one of claims 43 to 54, wherein the particle size of the metal or noble metal is about 100 μm. EMBODIMENT 58. 56. The method of any one of claims 43 to 55, wherein the first visual additive further comprises one or more microbubbles. EMBODIMENT 59. 57. The method of any one of claims 43 to 56, wherein the composition comprises a second visual additive. 60. 58. The method of claim 57, wherein the second visual additive is different from the first visual additive. 61. 59. The method of claim 57 or 58, wherein the second visual additive comprises one or more microbubbles. 62. 60. The method of any one of claims 43-59, wherein the first visual additive has a concentration in the viscoelastic medium of greater than 5 milligrams per milliliter (mg / ml). 63. 61. The method of any one of claims 43 to 60, wherein the first visual additive has a concentration in the viscoelastic medium of less than 90 mg / ml. 64. 62. The method of any one of claims 43 to 61, wherein the first visual additive has a concentration in the viscoelastic medium of between 15 mg / ml and 30 mg / ml. 65. 63. The method of any one of claims 43 to 62, wherein the metal is about 0.5% to about 9.0% by weight of the composition. 66. 64. The method of any one of claims 43 to 63, wherein the metal or precious metal is about 0.015% to about 1.5% by weight of the composition. 67. 65. The method of any one of claims 43 to 64, wherein the viscoelastic medium comprises a volume of about 1 milliliter (ml) to about 50 ml. 68. 66. The method of any one of claims 43 to 65, wherein the composition is configured to be biodegradable. 69. 67. The method of any one of claims 43 to 66, wherein the composition is configured to be detectable on an imaging modality for at least 9 months. EMBODIMENT 70. 68. The method of any one of claims 43 to 67, wherein the composition is configured to not substantially move prior to or during imaging, and the imaging is performed about 3 months to about 9 months after the composition is placed. EMBODIMENT 71. 69. The method of any one of claims 43 to 68, wherein the first visual additive is configured to be substantially immobile before or during imaging, and the imaging is performed about 3 months to about 9 months after the composition is placed. EMBODIMENT 72. 70. The method of any one of claims 43 to 69, wherein the composition is configured to be placed within a subject. EMBODIMENT 73. 71. The method of claim 70, wherein the subject requires radiography. 74. 72. The method of any one of claims 43 to 71, wherein the composition is configured to be deployed by injection. 75. 73. The method of any one of claims 43 to 72, wherein the composition is configured to be placed subcutaneously or subepidermally. EMBODIMENT 76. 74. The method of any one of claims 44 to 73, wherein the composition is configured to be placed within the first tissue site. 77. 75. The method of any one of claims 44-74, wherein the first tissue site comprises one or more of adipose tissue, muscle tissue, and organ tissue, or a combination thereof. 78. 76. The method of any one of claims 43 to 75, wherein the composition is configured to be imaged on one or more modalities. 79. 77. The method of claim 76, wherein the one or more modalities include X-ray, MRI, CT, CBCT, ultrasound, PET, SPECT, or a combination thereof. 80. 78. The method of claim 76 or 77, wherein the composition configured to be imaged on one or more modalities comprises the composition configured to be imaged in real time on the one or more modalities. 81. 79. The method of any one of claims 43-78, wherein the composition is configured to be imaged within 30 minutes, within 90 minutes, within 4 hours, within 8 hours, or within 4 days of placement. 82. 80. The method of any one of claims 43 to 79, wherein the viscoelastic medium comprises hyaluronic acid, polyethylene glycol, or dextranomer. 83. 81. The method of any one of claims 43 to 80, wherein the viscoelastic medium comprises hyaluronic acid, polyethylene glycol, or dextranoma in a concentration of about 5 mg / ml to about 100 mg / ml. 84. 82. The method of any one of claims 43 to 81, wherein the viscoelastic medium comprises gel particles ranging in size from about 0.08 mm to about 5 mm. 85. 83. The method of claim 82, wherein the gel particles comprise the metal particles. 86. 84. The method of any one of claims 43 to 83, wherein the viscoelastic medium comprises non-animal stabilized hyaluronic acid ("NASHA"). 87. 85. The method of any one of claims 43-84, wherein the viscoelastic medium expands within the first tissue site to less than 10% of its initial deployment volume. 88. 86. The method of any one of claims 43 to 85, wherein the viscoelastic medium is injected once every six months. 89. 87. The method of any one of claims 43 to 86, wherein the viscoelastic medium is completely absorbed within 20 months. EMBODIMENT 90. 88. The method of any one of claims 43 to 87, wherein the viscoelastic medium is completely absorbed within 16 months. EMBODIMENT 91. 89. The method of any one of claims 43 to 88, wherein the viscoelastic medium is completely absorbed within 12 months. EMBODIMENT 92. 1. A method of treating cancer in a subject in need thereof, the method comprising: identifying a tumor in said subject; administering a composition adjacent to the tumor, the composition comprising a viscoelastic medium and a first visual additive, the first visual additive being a metal, the metal having a particle size greater than about 80 micrometers; applying a dose of radiation to the tumor; A method comprising: EMBODIMENT 93. 93. The method of claim 92, wherein the first visual additive has a concentration in the viscoelastic medium that provides a contrast-to-noise ratio of about 0.1 to about 40. EMBODIMENT 94. 94. The method of claim 92 or 93, wherein the metal is a noble metal. EMBODIMENT 95. 95. The method of any one of claims 92 to 94, wherein the metal or noble metal is selected from the group consisting of gold (Au), iodine (I), gadolinium (Gd), iron (Fe), barium (Ba), calcium (Ca), magnesium (Mg), and combinations thereof. EMBODIMENT 96. 96. The method of any one of claims 92 to 95, wherein the metal or noble metal is an isotope of gold (Au), iodine (I), gadolinium (Gd), iron (Fe), barium (Ba), calcium (Ca), magnesium (Mg), or a combination thereof. EMBODIMENT 97. 97. The method according to any one of claims 92 to 96, wherein the metal or the precious metal is a powder. EMBODIMENT 98. 98. The method of any one of claims 92 to 97, wherein the first visual additive has a radiographic density of about 1.0 g / cm3 to 2.0 g / cm3. EMBODIMENT 99. 99. The method of any one of claims 92-98, wherein half of the first visual additive is configured to disperse in the tissue within 9 months. EMBODIMENT 100. 100. The method according to any one of claims 92 to 99, wherein the particle size of the metal or precious metal is from about 80 μm to about 120 μm. EMBODIMENT 101. 101. The method according to any one of claims 92 to 100, wherein the particle size of the metal or precious metal is about 100 μm. EMBODIMENT 102. 102. The method of any one of claims 92-101, wherein the first visual additive further comprises one or more microbubbles. EMBODIMENT 103. 103. The method of any one of claims 92 to 102, wherein the composition comprises a second visual additive. EMBODIMENT 104. 104. The method of claim 103, wherein the second visual additive is different from the first visual additive. EMBODIMENT 105. 105. The method of claim 103 or 104, wherein the second visual additive comprises one or more microbubbles. EMBODIMENT 106. 106. The method of any one of claims 92-105, wherein the first visual additive has a concentration in the viscoelastic medium of greater than 5 milligrams per milliliter (mg / ml). EMBODIMENT 107. 107. The method of any one of claims 92 to 106, wherein the first visual additive has a concentration in the viscoelastic medium of less than 90 mg / ml. EMBODIMENT 108. 108. The method of any one of claims 92 to 107, wherein the first visual additive has a concentration in the viscoelastic medium of from 15 mg / ml to 30 mg / ml. EMBODIMENT 109. 109. The method of any one of claims 92-108, wherein the metal is about 0.5% to about 9.0% by weight of the composition. EMBODIMENT 110. 110. The method of any one of claims 92 to 109, wherein the metal or precious metal is about 0.015% to about 1.5% by weight of the composition. EMBODIMENT 111. 111. The method of any one of claims 92-110, wherein the viscoelastic medium comprises a volume of about 1 milliliter (ml) to about 50 ml. EMBODIMENT 112. The method of any one of claims 92 to 111, wherein the composition is configured to be biodegradable. EMBODIMENT 113. The method of any one of claims 92 to 112, wherein the composition is configured to be detectable on an imaging modality for at least 9 months. EMBODIMENT 114. 114. The method of any one of claims 92 to 113, wherein the composition is configured to not substantially move prior to or during imaging, and the imaging is performed about 3 months to about 9 months after the composition is placed. EMBODIMENT 115. 115. The method of any one of claims 92 to 114, wherein the first visual additive is configured to be substantially immobile before or during imaging, and the imaging is performed about 3 months to about 9 months after the composition is placed. EMBODIMENT 116. 116. The method of any one of claims 92 to 115, wherein the composition is configured to be placed within the subject. EMBODIMENT 117. 117. The method of claim 116, wherein the subject requires radiography. EMBODIMENT 118. 118. The method of any one of claims 92 to 117, wherein the composition is configured to be deployed by injection. EMBODIMENT 119. 119. The method of any one of claims 92 to 118, wherein the composition is configured to be placed subcutaneously or subepidermally. EMBODIMENT 120. 120. The method of any one of claims 93-119, wherein the composition is configured to be placed within the first tissue site. EMBODIMENT 121. 121. The method of any one of claims 93-120, wherein the first tissue site comprises one or more of adipose tissue, muscle tissue, and organ tissue, or a combination thereof. EMBODIMENT 122. 122. The method of any one of claims 92 to 121, wherein the composition is configured to be imaged on one or more modalities. EMBODIMENT 123. 123. The method of claim 122, wherein the one or more modalities include X-ray, MRI, CT, CBCT, ultrasound, PET, SPECT, or a combination thereof. EMBODIMENT 124. 124. The method of claim 122 or 123, wherein the composition configured to be imaged on the one or more modalities comprises the composition configured to be imaged in real time on the one or more modalities. EMBODIMENT 125. 125. The method of any one of claims 92-124, wherein the composition is configured to be imaged within 30 minutes, within 90 minutes, within 4 hours, within 8 hours, or within 4 days of placement. EMBODIMENT 126. 126. The method of any one of claims 92 to 125, wherein the viscoelastic medium comprises hyaluronic acid, polyethylene glycol, or dextranomer. EMBODIMENT 127. 127. The method of any one of claims 92 to 126, wherein the viscoelastic medium comprises hyaluronic acid, polyethylene glycol, or dextranoma in a concentration of about 5 mg / ml to about 100 mg / ml. EMBODIMENT 128. 128. The method of any one of claims 92-127, wherein the viscoelastic medium comprises gel particles ranging in size from about 0.08 mm to about 5 mm. EMBODIMENT 129. 129. The method of claim 128, wherein the gel particles comprise metal particles. EMBODIMENT 130. 130. The method of any one of claims 92-129, wherein the viscoelastic medium comprises non-animal stabilized hyaluronic acid ("NASHA"). EMBODIMENT 131. 131. The method of any one of claims 92-130, wherein the viscoelastic medium expands within the first tissue site to less than 10% of its initial deployment volume. EMBODIMENT 132. 132. The method of any one of claims 92 to 131, wherein the viscoelastic medium is injected once every six months. EMBODIMENT 133. 134. The method of any one of claims 92 to 133, wherein the viscoelastic medium is completely absorbed within 20 months. EMBODIMENT 134. 134. The method of any one of claims 92 to 133, wherein the viscoelastic medium is completely absorbed within 16 months. EMBODIMENT 135. 135. The method of any one of claims 92 to 134, wherein the viscoelastic medium is completely absorbed within 12 months. EXAMPLES

[0162] The following illustrative examples are representative of embodiments of the software applications, systems, and methods described herein, and are not intended to be limiting in any way.

[0163] Example 1 - Spacer injection between the pancreatic head and duodenum In one example, absorbable hydrogel containing hyaluronic acid microparticles was injected into the space between the Head of Pancreas (HOP) and the third part of the duodenal loop using an 18-gauge needle. Endoscopic ultrasound (EUS) linked to an ultrasound workstation was used to identify the duodenal and HOP interface, and hydrogel was subsequently injected into this peripancreatic space using a 19-gauge fine needle aspiration needle in 1 mL increments until the desired space was created. The EUS scope was then adjusted (slightly advanced or retracted) around the target site to shape the peritumoral area and create the desired space, with total injected volumes ranging from 1.0 mL to 27 mL.

[0164] A visible separation between the HOP and duodenum was created to confirm the position of the hydrogel and to allow measurement of the distance created between the duodenum and HOP. The average distance of separation due to hydrogel placement was measured by averaging the measured thickness of the gel on each CT slice where the gel was visualized on the post-injection simulation CT scan acquired at a slice thickness of 2 mm. The average thickness of the spacer was 1.1 cm (0.9 cm to 1.2 cm) and 0.9 cm (0.8 cm to 1.1 cm) for EUS cadaveric specimens 1 and 2, respectively, in the post-injection CT scan.

[0165] FIG. 5A is an exemplary image of a computed tomography scan before injecting a hydrogel spacer between the pancreatic head and the duodenum. FIG. 5B is an exemplary image of a computed tomography scan after injecting a hydrogel spacer between the pancreatic head and the duodenum. FIG. 5C is an exemplary image of a gross tissue specimen after injecting a hydrogel spacer between the pancreatic head and the duodenum. FIG. 5D is an exemplary image of a computed tomography scan before injecting a hydrogel spacer (laparotomy hydrogel spacer) between the pancreatic head and the duodenum. FIG. 5E is an exemplary image of a computed tomography scan after injecting a hydrogel spacer between the pancreatic head and the duodenum. FIG. 5F is an exemplary image of a gross tissue specimen after injecting a hydrogel spacer between the pancreatic head and the duodenum. FIG. 5G is an exemplary image of a computed tomography scan before injecting a hydrogel spacer under an endoscope between the pancreatic head and the duodenum. FIG. 5H is an exemplary image of a computed tomography scan after endoscopic injection of a hydrogel spacer between the head of the pancreas and the duodenum. FIG. 5H is an exemplary image of a gross tissue specimen after endoscopic injection of a hydrogel spacer between the head of the pancreas and the duodenum. FIG. 6A is a first exemplary image of a formalin-fixed, paraffin-embedded section after staining with hematoxylin and eosin. FIG. 6B is a second exemplary image of a formalin-fixed, paraffin-embedded section after staining with hematoxylin and eosin. FIG. 6C is a first exemplary high-magnification image of a formalin-fixed, paraffin-embedded section after staining with hematoxylin and eosin. FIG. 6D is a third exemplary image of a formalin-fixed, paraffin-embedded section after staining with hematoxylin and eosin. Figure 6E is a second exemplary high magnification image of a formalin-fixed paraffin-embedded section after staining with hematoxylin and eosin. Figure 7A is a first exemplary stereotactic body radiation treatment plan before hydrogel spacer placement. Figure 7B is a first exemplary stereotactic body radiation treatment plan after hydrogel spacer placement. Figure 7C is a second exemplary stereotactic body radiation treatment plan before hydrogel spacer placement.FIG. 7D is a second exemplary stereotactic body radiation therapy plan after hydrogel spacer placement. FIG. 8A is an exemplary baseline image of a computed tomography scan of the duodenum and a stereotactic body radiation therapy plan. FIG. 8B is an exemplary image of a computed tomography scan of the duodenum and a stereotactic body radiation therapy plan with 2 mm spacing. FIG. 8C is an exemplary image of a computed tomography scan of the duodenum and a stereotactic body radiation therapy plan with 3 mm spacing. FIG. 8D is an exemplary image of a computed tomography scan of the duodenum and a stereotactic body radiation therapy plan with 5 mm spacing. FIG. 8E is an exemplary image of a computed tomography scan of the duodenum and a stereotactic body radiation therapy plan with 8 mm spacing. FIG. 8F is an exemplary image of a computed tomography scan of the duodenum and a stereotactic body radiation therapy plan with 15 mm spacing.

[0166] Example 2 - Subcutaneous Breast Spacer Injection In one case, ultrasound-guided spacer injection of iodine and polyethylene glycol (PEG) was performed to create a spacer with a thickness of more than 5 mm. After defining the clinical target volume, pre- and post-injection CT scans were used. Maximum dose to small skin volume (D 0.2cc ) and the presence of hot spots (≥90% isodose per cm2 of skin) were calculated as indicators of skin toxicity. After removal of the breast, a spacer was injected directly under the skin to create an extra space of 5 mm between the skin and the superficial fascial layer of the breast by hydrodissection.

[0167] The intervention success rate was 90.9%. Hydrodissection was feasible in 63.6% of cases. For PEG, the median system usability scale score was 82.5 (p<0.001). Mean D was 80.8 Gy without spacers and 53.7 Gy with spacers (p<0.001). Skin hot spots were present in 40.9% without spacers but absent with spacers (p<0.001).

[0168] The success rate of spacer injection was high (91%) when the marker was used.

[0169] Example 3 - Subcutaneous Esophageal Spacer Injection In one example, the gel was prepared as a viscous mixture of contrast media consisting of 10 ml of 1 mg / ml hyaluronic acid (HA), 0.8 ml of 300 mg / ml iodine. After local anesthesia of the subcutaneous tissue with lidocaine, under ultrasound and CT guidance, a 21-gauge needle was inserted at the lateral puncture point of the trachea at the level of the upper border of the sternum and advanced to the location of gel injection. The needle penetrated first the skin, second the subcutaneous tissue between both ends of the squamous part in the SCF (superficial cervical fascia, SCF), third the relatively tough covering fascia of the deep cervical fascia (DCF) containing the suprasternal space (space of Burns) filled with fatty connective tissue and the transverse cervical vein, and the adipose tissue beneath this fascia, and fourth the pretracheal layer of the DCF spanning the peritracheal space, which is continuous with the paraesophageal adipose tissue. The trachea was manually moved approximately 5-10 mm to the right or left, as necessary, to safely advance the needle. Using this route, the needle passed medial to the sternothyroid and sternothyroid strap muscles, avoiding the effect of muscle contraction on the needle. When the needle tip reached the predefined injection point, gel was injected to create a space and force the esophagus away from the target. The created space was confirmed by CT.

[0170] Example 4 - Reduction of radiation therapy dose to tissue adjacent to the site of radiation therapy for pancreatic cancer Two patients are treated for pancreatic cancer with radiation therapy. One patient receives a PEG-based spacer injected using the technique described in Example 1. The injection technique of Example 1 is utilized to create a space between the site of radiation treatment and the duodenum ranging from 0.9 cm to 1.2 cm. The dose of radiation in tissues adjacent to the site of radiation treatment is reduced by 40% in patients who received the spacer compared to patients who did not receive the spacer.

[0171] Example 5 - Reduction of radiation therapy dose to tissue adjacent to the radiation treatment site for esophageal cancer Two patients are treated for esophageal cancer with radiation therapy. One patient receives a PEG-based spacer injected using the technique described in Example 1. The injection technique from Example 4 is utilized to create a space between the site of radiation treatment and the duodenum ranging from 0.9 cm to 1.2 cm. The dose of radiation in tissues adjacent to the site of radiation treatment is reduced by 20% in patients who received the spacer compared to patients who did not receive the spacer.

[0172] Example 6 - Erasable Hyaluronic Acid Spacer Utilizing the techniques described in Examples 4 and 5. The patient requires rapid reduction in the size of the spacer following radiation therapy due to pressure exerted by the spacer on the patient's esophagus. The care physician injects hyaluronidase at about 1 U to about 100 U in a volume of about 1 ml to about 10 ml until the desired volume of the spacer is achieved.

[0173] Example 7 - Erasable PEG-based spacers Utilizing the techniques described in Examples 4 and 5. The patient requires rapid reduction in the size of the spacer after radiation therapy due to the pressure exerted by the spacer on the patient's esophagus. The care physician injects a volume of about 1 ml to about 50 ml of water until the desired volume of the spacer is achieved.

[0174] Example 8 - Shrinking Hyaluronic Acid Super Spacer The injection technique of Example 4 is adapted to accommodate a dual syringe. One syringe contains a desired volume of crosslinked hyaluronic acid particles, and the other syringe contains degradable nanoparticles containing hyaluronidase, which are soluble in hyaluronic acid. The concentration of degradable nanoparticles contained in the syringe is determined by the determined length of radiation treatment. A larger spacing distance is achieved compared to the use of a spacer without degradable nanoparticles containing hyaluronidase, because the spacer shrinks before tissue damage due to large displacement of said tissue occurs or before undesirable cosmetic changes occur to the target's anatomical structure. This result is only possible with a shrinking super spacer.

[0175] Example 9 - Use of Shrink Hyaluronic Acid Superspacer on Buffer Solution in Subjects from Melanoma on the Scalp The subject has a melanoma tumor located on the scalp. The tumor measures 0.4 cm x 0.8 cm x 0.2 cm. Radiation therapy is selected as the desired treatment. The treating physician determines that the radiation therapy will take approximately 10 minutes. The treating physician wishes to use a higher dose of radiation therapy than is conventional due to the condition of the tumor. The injection technique described in Examples 4 and 7 is adapted for subcutaneous injection into the scalp. A volume of approximately 3 ml to approximately 6 ml is injected to space the tumor away from the subject's brain. A certain percentage of this volume is made up of degradable nanoparticles containing hyaluronidase. This spaces the brain away from the tumor a distance that damages the connective tissue adjacent to the skull and creates an undesirable cosmetic appearance. However, as soon as the spacer is injected into the space between the brain and the tumor, the spacer begins to shrink. Radiation therapy is administered, exposing the subject's brain to approximately 20% less dose of radiation therapy compared to subjects who did not receive the spacer. The radiation therapy session is completed and the subject's scalp appears like the subject's scalp that did not receive the spacer because the degradable nanoparticles have degraded the spacer.

[0176] Example 10 - Shrinkable PEG-based superspacer The injection technique of Example 4 is adapted to accommodate dual syringes. One syringe contains the desired volume of PEG particles, and the other syringe contains water-containing degradable nanoparticles that are soluble in hyaluronic acid. The concentration of degradable nanoparticles contained in the syringe is determined by the determined length of radiation treatment. A larger spacing distance is achieved compared to the use of a spacer without water-containing degradable nanoparticles, because the spacer shrinks before tissue damage occurs due to large displacement of the tissue or before undesirable cosmetic changes occur to the target's anatomical structure. This result is only possible with a shrinking super spacer.

[0177] Example 11 - Use of a shrink PEG-based superspacer on a buffer solution in a subject from a melanoma on the scalp The subject has a melanoma tumor located on the scalp. The tumor measures 0.4 cm x 0.8 cm x 0.2 cm. Radiation therapy is selected as the desired treatment. The treating physician determines that the radiation therapy will take approximately 10 minutes. The treating physician wishes to use a higher dose of radiation therapy than is conventional due to the condition of the tumor. The injection technique described in Examples 4 and 7 is adapted for subcutaneous injection into the scalp. A volume of approximately 3 ml to approximately 6 ml is injected to space the tumor away from the subject's brain. A certain percentage of this volume is made up of degradable nanoparticles containing water. This spaces the tumor away from the brain a distance that damages the connective tissue adjacent to the skull and creates an undesirable cosmetic appearance. However, as soon as the spacer is injected into the space between the brain and the tumor, the spacer begins to shrink. Radiation therapy is administered, exposing the subject's brain to approximately 20% less dose of radiation therapy compared to subjects who did not receive the spacer. The radiation therapy session is completed and the subject's scalp appears like the subject's scalp that did not receive the spacer because the degradable nanoparticles have degraded the spacer.

[0178] Example 12 - Use of Improved Tissue Spacers for Interventional Oncology 7.4g of Poloxamer 407 and 0.2g of polyethylene glycol modified polylactic acid PLA-PEG are added to 20ml and 10ml of pure water and placed at 25°C for 3 days to completely dissolve the polymer. The two are then mixed and vortexed to obtain a gel dispersion, which is distilled off under reduced pressure and water. The spacer is then dried, sealed, and stored at 4°C.

[0179] The above hydrogel is directly inserted into the blood vessels that are directly connected to the tumor. Cancer is treated by the hydrogel, which cuts off the tumor blood supply, and the tumor becomes ischemic, hypoxic and necrotic. In addition, the cancer tissue necrosis continues to stimulate the body's immune system, which can eliminate distant metastases (preferably melanoma); delivery of embolic agents to the tumor with chemotherapeutic agent mixed target artery feeding, which not only cuts off the blood supply but also delays the release of chemotherapy drugs, plays a role in local chemotherapy, thus resulting in the short-term effectiveness of tumor lytic outcomes.

[0180] Example 13 - Incorporation of iodine into PEG PEG SG containing iodine core (having SG count of 2.3 per molecule) was synthesized. The PEG-1 molecule was 6400 Daltons, of which iodine was 381 Daltons (5.9%). Thus, for example, at this iodine content, the percentage of solids of PEG-I in the hydrogel was 1.68 and 3.36%, resulting in iodine concentrations of 0.1% and 0.2% in the resulting matrix. Table II of WO2011084465, incorporated herein in its entirety, shows how the PEG-1 concentration can be manipulated to obtain the percentage of iodine content, which can be related to the CT number.

[0181] Example 14 - Preparation of Gadopentate Dimeglumine using NASHA Gel A gel containing 5 mg / ml gadopentate dimeglumine was prepared by weighing out gadopentate dimeglumine (Magnevist 469 mg / ml (0.5 mmol Gd / ml, Shering)) and thoroughly mixing it with NASHA-gel (20 mg HA / ml, Q-Med) by manual stirring. The resulting gel was centrifuged to remove air bubbles. The average size of the particles in the resulting gel was 1 mm.

[0182] The release of the gadolinium complex from the gel was measured using a USP-paddle system. The release of the gadolinium complex was followed using NMR and ICP-MS. 2D spin echo (SE) and 3D gradient echo (FEF) sequences were generated, both sequences with and without fat saturation (FS). MRI was also performed on gels that released the gadolinium complex for different periods of time. The initial release of the gadolinium complex was relatively fast, a rate that corresponds very well with the diffusion rate of small drug molecules (Figure 18A). ICP-MS analysis after 7 and 24 hours of release showed that 82 and 85% of the gadolinium was released (Figure 18B), indicating that a small amount of gadolinium interacted and was released at a much slower rate. In the MRI measurements on the gels, at the first time points (30 and 90 min), the NASHA-gel gave a strong contrast compared to water and oil. At later times (from 8 hours to 4 days), the contrast was much weaker compared to the NASHA-gel without the gadolinium complex, but was still visible, indicating that a small amount of gadolinium appears to interact with the NASHA-gel. However, this amount is not sufficient to provide useful contrast for MRI in vivo. The intensity of the signal in the MRI measurements is summarized in Table 1 below.

[0183] [Table 2]

[0184] Example 15 - Making an Omni-Opaque Spacer using any of the materials described herein A viscoelastic medium comprising any one or combination of materials described herein is expanded to a particle size configured to be drawn into a syringe. A fine (20 gauge or greater) needle is attached to the syringe, and a portion of the interior surface of the needle includes a mesh structure. The mesh structure is configured to generate substantially homogenous microbubbles within the viscoelastic medium that is forced through the mesh.

[0185] MRI is performed on gels containing viscoelastic media with microbubbles for different time periods. Initial visualization of gels with microbubbles corresponds relatively well to other gels in combination with radiopaque agents described herein. At 30 and 90 minutes, gels containing microbubbles provide strong contrast compared to water and oil, comparable to gels with radiopaque agents described herein. At later time points (8 hours to 4 days), the contrast of the gels with microbubbles is retained sufficiently to provide useful contrast for in vivo MRI, CT, ultrasound, or any other imaging modality known in the art, including any one of the radiopaque agents described herein with microbubbles, or combinations thereof. These gels retain sufficient contrast for imaging in vivo, in real time, at 30 minutes, 90 minutes, and up to 8 hours and up to 4 days.

[0186] Example 16 - Cavity visualization In another example, a skin incision is made with a scalpel at the desired site and the viscoelastic medium from Example 15 is administered by injection beneath the epidermis, with microbubbles being formed within the space material as it passes through the mesh structure of the needle into the injection site. 2 ~about 1.5mm 2 The mesh structure includes a space of approximately 0.001 mm 2 ~about 0.005mm 2 , about 0.001 mm2 ~ about 0.01 mm 2 、 about 0.001 mm 2 ~ about 0.05 mm 2 、 about 0.001 mm 2 ~ about 0.06 mm 2 、 about 0.001 mm 2 ~ about 0.07 mm 2 、 about 0.001 mm 2 ~ about 0.08 mm 2 、 about 0.001 mm 2 ~ about 0.09 mm 2 、 about 0.001 mm 2 ~ about 0.1 mm 2 、 about 0.001 mm 2 ~ about 0.5 mm 2 、 about 0.001 mm 2 ~ about 1 mm 2 、 about 0.001 mm 2 ~ about 1.5 mm 2 、 about 0.005 mm 2 ~ about 0.01 mm 2 、 about 0.005 mm 2 ~ about 0.05 mm 2 、 about 0.005 mm 2 ~ about 0.06 mm 2 、 about 0.005 mm 2 ~ about 0.07 mm 2 、 about 0.005 mm 2 ~ about 0.08 mm 2 、 about 0.005 mm 2 ~ about 0.09 mm 2 、 about 0.005 mm 2 ~ about 0.1 mm 2 、 about 0.005 mm 2 ~ about 0.5 mm 2 、 about 0.005 mm 2 ~ about 1 mm 2 、 about 0.005 mm 2 ~ about 1.5 mm 2 、 about 0.01 mm 2 ~ about 0.05 mm 2 、 about 0.01 mm 2 ~ about 0.06 mm 2 、 about 0.01 mm 2 ~ about 0.07 mm 2 、 about 0.01 mm 2 ~ about 0.08 mm2 , about 0.01 mm 2 ~ approx. 0.09mm 2 , about 0.01 mm 2 ~about 0.1mm 2 , about 0.01 mm 2 ~about 0.5mm 2 , about 0.01 mm 2 ~about 1mm 2 , about 0.01 mm 2 ~about 1.5mm 2 , about 0.05mm 2 ~ approx. 0.06mm 2 , about 0.05mm 2 ~ approx. 0.07mm 2 , about 0.05mm 2 ~ approx. 0.08 mm 2 , about 0.05mm 2 ~ approx. 0.09mm 2 , about 0.05mm 2 ~about 0.1mm 2 , about 0.05mm 2 ~about 0.5mm 2 , about 0.05mm 2 ~about 1mm 2 , about 0.05mm 2 ~about 1.5mm 2 , about 0.06 mm 2 ~ approx. 0.07mm 2 , about 0.06 mm 2 ~ approx. 0.08 mm 2 , about 0.06 mm 2 ~ approx. 0.09mm 2 , about 0.06 mm 2 ~about 0.1mm 2 , about 0.06 mm 2 ~about 0.5mm 2 , about 0.06 mm 2 ~about 1mm ...

Claims

1. 1. A composition comprising: a viscoelastic medium; a first visual additive, said first visual additive comprising a metal, said metal having a particle size of 80 micrometers (μm) or greater; A composition comprising:

2. The composition of claim 1 wherein the metal is a noble metal.

3. 3. The composition of claim 1 or 2, wherein the metal or noble metal is selected from the group consisting of gold (Au), iodine (I), gadolinium (Gd), iron (Fe), barium (Ba), calcium (Ca), magnesium (Mg), and combinations thereof.

4. 3. The composition of claim 1 or 2, wherein the metal or noble metal is an isotope of gold (Au), iodine (I), gadolinium (Gd), iron (Fe), barium (Ba), calcium (Ca), magnesium (Mg), or a combination thereof.

5. 3. The composition of claim 1 or 2, wherein the metal or precious metal is a powder.

6. 10. The composition of claim 1, wherein the first visual additive has a radiographic density of about 1.0 g / cm3 to 2.0 g / cm3.

7. 10. The composition of claim 1, wherein half of the first visual additive is configured to disperse in tissue within nine months.

8. 3. The composition of claim 1, wherein the particle size of the metal or precious metal is from about 80 μm to about 120 μm.

9. 3. The composition of claim 1 or 2, wherein the particle size of the metal or precious metal is about 100 μm.

10. The composition of claim 1 , wherein the first visual additive further comprises one or more microbubbles.

11. The composition of claim 1 further comprising a second visual additive.

12. 12. The composition of claim 11, wherein the second visual additive is different from the first visual additive.

13. 13. The composition of claim 11 or 12, wherein the second visual additive comprises one or more microbubbles.

14. 10. The composition of claim 1, wherein the first visual additive has a concentration in the viscoelastic medium greater than 5 milligrams per milliliter (mg / ml).

15. 10. The composition of claim 1, wherein the first visual additive has a concentration in the viscoelastic medium of less than 90 mg / ml.

16. 10. The composition of claim 1, wherein the first visual additive has a concentration in the viscoelastic medium of from 15 mg / ml to 30 mg / ml.

17. The composition of claim 1, wherein the metal is from about 0.5% to about 9.0% by weight of the composition.

18. 3. The composition of claim 1, wherein the metal or precious metal is from about 0.015% to about 1.5% by weight of the composition.

19. The composition of claim 1 , wherein the viscoelastic medium comprises a volume of from about 1 milliliter (ml) to about 50 ml.

20. The composition of claim 1 , wherein the composition is configured to be biodegradable.

21. 10. The composition of claim 1, wherein the composition is configured to be detectable on an imaging modality for at least 9 months.

22. The composition of claim 1 , wherein the composition is configured to be substantially immobile before or during imaging.

23. 10. The composition of claim 1, wherein the first visual additive is configured to be substantially immobile before or during imaging.

24. The composition of claim 1 , wherein the composition is configured to be placed within a subject.

25. 25. The composition of claim 24, wherein the subject is in need of radiography.

26. The composition of claim 1 , wherein the composition is configured to be deployed by injection.

27. 27. The composition of claim 25 or 26, wherein the composition is configured to be placed subcutaneously or subepidermally.

28. The composition of claim 1 , wherein the composition is configured to be placed within a tissue site.

29. 30. The composition of claim 28, wherein the tissue site comprises one or more of adipose tissue, muscle tissue, organ tissue, or a combination thereof.

30. The composition of claim 1 , wherein the composition is configured to be imaged on one or more modalities.

31. 31. The composition of claim 30, wherein the one or more modalities include X-ray, MRI, CT, CBCT, ultrasound, PET, SPECT, or a combination thereof.

32. 32. The composition of claim 30 or 31, wherein the composition configured to be imaged on the one or more modalities comprises the composition configured to be imaged in real time on the one or more modalities.

33. 10. The composition of claim 1, wherein the composition is configured to be imaged within 30 minutes, 90 minutes, 4 hours, 8 hours, or 4 days of placement.

34. The composition of claim 1 , wherein the viscoelastic medium comprises hyaluronic acid, polyethylene glycol, or dextranomer.

35. The composition of claim 1, wherein the viscoelastic medium comprises hyaluronic acid, polyethylene glycol, or dextranomer at a concentration of about 5 mg / ml to about 100 mg / ml.

36. The composition of claim 1 , wherein the viscoelastic medium comprises gel particles ranging in size from about 0.08 mm to about 5 mm.

37. 37. The composition of claim 36, wherein the gel particles comprise metal particles.

38. The composition of claim 1 , wherein the viscoelastic medium comprises non-animal stabilized hyaluronic acid ("NASHA").

39. The composition of claim 1 , wherein the viscoelastic medium expands within the tissue site to less than 10% of its initial deployment volume.

40. The composition of claim 1 , wherein the viscoelastic medium is formulated to be injected once every six months.

41. 41. The composition of claim 40, wherein the viscoelastic medium is completely absorbed within 20 months.

42. 41. The composition of claim 40, wherein the viscoelastic medium is completely absorbed within 16 months.

43. 41. The composition of claim 40, wherein the viscoelastic medium is completely absorbed within 12 months.

44. 10. The composition of claim 1, wherein the first visual additive is present in an amount sufficient to produce a contrast to noise of from about 0.1 to about 40 when the composition is scanned using radiation therapy.

45. 1. A method of visualizing a tissue, space, or location in a radiographic subject, the method comprising the step of placing an imaging contrast composition, the composition comprising: a viscoelastic medium; a first visual additive, said first visual additive being a metal, said metal having a particle size greater than about 80 micrometers; A method comprising:

46. (a) placing the composition within a first tissue site; (b) imaging the composition within the first tissue site; 46. ​​The method of claim 45, further comprising:

47. 46. ​​The method of claim 45, wherein the metal has a particle size greater than 100 micrometers.

48. 1. A method of spacing a first tissue site on a subject from a second tissue site on the subject, the method comprising: (a) disposing a composition in a space between the first tissue site and the second tissue site, the composition comprising a viscoelastic medium and a first visual additive, the first visual additive being a metal, the metal having a particle size greater than 80 micrometers (μm).

49. 49. The method of claim 48, wherein the first visual additive has a concentration in the viscoelastic medium that provides a contrast-to-noise ratio of from about 0.1 to about 40.

50. 49. The method of claim 48, wherein the metal is a noble metal.

51. 51. The method of claim 48 or 50, wherein the metal or noble metal is selected from the group consisting of gold (Au), iodine (I), gadolinium (Gd), iron (Fe), barium (Ba), calcium (Ca), magnesium (Mg), and combinations thereof.

52. 51. The method of claim 48 or 50, wherein the metal or noble metal is an isotope of gold (Au), iodine (I), gadolinium (Gd), iron (Fe), barium (Ba), calcium (Ca), magnesium (Mg), or a combination thereof.

53. 51. The method of claim 48 or 50, wherein the metal or precious metal is a powder.

54. 49. The method of claim 48, wherein the first visual additive has a radiographic density of about 1.0 g / cm3 to 2.0 g / cm3.

55. 49. The method of claim 48, wherein half of the first visual additive is configured to disperse in tissue within nine months.

56. 51. The method of claim 48 or 50, wherein the particle size of the metal or precious metal is from about 80 μm to about 120 μm.

57. 51. The method of claim 48 or 50, wherein the particle size of the metal or precious metal is about 100 μm.

58. 49. The method of claim 48, wherein the first visual additive further comprises one or more microbubbles.

59. 49. The method of claim 48, wherein the composition comprises a second visual additive.

60. The method of claim 59, wherein the second visual additive is different from the first visual additive.

61. 61. The method of claim 59 or 60, wherein the second visual additive comprises one or more microbubbles.

62. 49. The method of claim 48, wherein the first visual additive has a concentration in the viscoelastic medium greater than 5 milligrams per milliliter (mg / ml).

63. 49. The method of claim 48, wherein the first visual additive has a concentration in the viscoelastic medium of less than 90 mg / ml.

64. 49. The method of claim 48, wherein the first visual additive has a concentration in the viscoelastic medium of 15 mg / ml to 30 mg / ml.

65. 49. The method of claim 48, wherein the metal is about 0.5% to about 9.0% by weight of the composition.

66. 51. The method of claim 48 or 50, wherein the metal or precious metal is from about 0.015% to about 1.5% by weight of the composition.

67. 49. The method of claim 48, wherein the viscoelastic medium comprises a volume of about 1 milliliter (ml) to about 50 ml.

68. 49. The method of claim 48, wherein the composition is configured to be biodegradable.

69. 49. The method of claim 48, wherein the composition is configured to be detectable on an imaging modality for at least 9 months.

70. 49. The method of claim 48, wherein the composition is configured to not substantially move before or during imaging, and the imaging occurs about 3 months to about 9 months after the composition is deployed.

71. 49. The method of claim 48, wherein the first visual additive is configured to not substantially move before or during imaging, and the imaging occurs from about 3 months to about 9 months after the composition is placed.

72. 49. The method of claim 48, wherein the composition is configured to be placed within a subject.

73. 73. The method of claim 72, wherein the subject requires radiography.

74. 49. The method of claim 48, wherein the composition is configured to be deployed by injection.

75. 75. The method of claim 74, wherein the composition is configured to be placed subcutaneously or subepidermally.

76. 49. The method of claim 48, wherein the composition is configured to be disposed within the first tissue site.

77. 77. The method of claim 76, wherein the first tissue site comprises one or more of adipose tissue, muscle tissue, and organ tissue, or a combination thereof.

78. 49. The method of claim 48, wherein the composition is configured to be imaged on one or more modalities.

79. The method of claim 78, wherein the one or more modalities include X-ray, MRI, CT, CBCT, ultrasound, PET, SPECT, or a combination thereof.

80. The method described in claim 78 or 79, wherein the composition configured to be imaged on the one or more modalities includes the composition configured to be imaged in real time on the one or more modalities.

81. 49. The method of claim 48, wherein the composition is configured to be imaged within 30 minutes, 90 minutes, 4 hours, 8 hours, or 4 days of placement.

82. 49. The method of claim 48, wherein the viscoelastic medium comprises hyaluronic acid, polyethylene glycol, or dextranomer.

83. 49. The method of claim 48, wherein the viscoelastic medium comprises hyaluronic acid, polyethylene glycol, or dextranomer at a concentration of about 5 mg / ml to about 100 mg / ml.

84. 49. The method of claim 48, wherein the viscoelastic medium comprises gel particles ranging in size from about 0.08 mm to about 5 mm.

85. 85. The method of claim 84, wherein the gel particles comprise metal particles.

86. 49. The method of claim 48, wherein the viscoelastic medium comprises non-animal stabilized hyaluronic acid ("NASHA").

87. 49. The method of claim 48, wherein the viscoelastic medium expands within the first tissue site to less than 10% of its initial deployment volume.

88. 49. The method of claim 48, wherein the viscoelastic medium is formulated to be injected once every six months.

89. 49. The method of claim 48, wherein the viscoelastic medium is completely absorbed within 20 months.

90. 49. The method of claim 48, wherein the viscoelastic medium is completely absorbed within 16 months.

91. 49. The method of claim 48, wherein the viscoelastic medium is completely absorbed within 12 months.

92. Use of a composition comprising a viscoelastic medium and a first visual additive in the manufacture of a medicament for treating cancer, comprising: the composition is injectable adjacent to a tumor in a subject; the first visual additive is a metal, the metal having a particle size greater than about 80 micrometers; The composition is formulated to protect tissue adjacent to the tumor from a dose of radiation applied to the tumor.

93. 93. The use of claim 92, wherein the first visual additive has a concentration in the viscoelastic medium that provides a contrast-to-noise ratio of from about 0.1 to about 40.

94. 94. The use according to claim 92 or 93, wherein the metal is a noble metal.

95. 95. The use of claim 94, wherein the metal or noble metal is selected from the group consisting of gold (Au), iodine (I), gadolinium (Gd), iron (Fe), barium (Ba), calcium (Ca), magnesium (Mg), and combinations thereof.

96. 95. The use of claim 94, wherein the metal or noble metal is an isotope of gold (Au), iodine (I), gadolinium (Gd), iron (Fe), barium (Ba), calcium (Ca), magnesium (Mg), or a combination thereof.

97. 95. The use according to claim 94, wherein the metal or the precious metal is a powder.

98. 93. The use of claim 92, wherein the first visual additive has a radiographic density of about 1.0 g / cm3 to 2.0 g / cm3.

99. 93. The use of claim 92, wherein half of the first visual additive is configured to disperse in the tissue within nine months.

100. 95. The use of claim 94, wherein the particle size of the metal or noble metal is from about 80 μm to about 120 μm.

101. 95. The use of claim 94, wherein the particle size of the metal or noble metal is about 100 μm.

102. 93. The use of claim 92, wherein the first visual additive further comprises one or more microbubbles.

103. 93. The use of claim 92, wherein the composition comprises a second visual additive.

104. 104. The use of claim 103, wherein the second visual additive is different from the first visual additive.

105. 104. The use of claim 103, wherein the second visual additive comprises one or more microbubbles.

106. 93. The use of claim 92, wherein the first visual additive has a concentration in the viscoelastic medium greater than 5 milligrams per milliliter (mg / ml).

107. 93. The use of claim 92, wherein the first visual additive has a concentration in the viscoelastic medium of less than 90 mg / ml.

108. 93. The use of claim 92, wherein the first visual additive has a concentration in the viscoelastic medium of 15 mg / ml to 30 mg / ml.

109. 93. The use of claim 92, wherein the metal is from about 0.5% to about 9.0% by weight of the composition.

110. 95. The use of claim 94, wherein the metal or noble metal is from about 0.015% to about 1.5% by weight of the composition.

111. 93. The use of claim 92, wherein the viscoelastic medium comprises a volume of about 1 milliliter (ml) to about 50 ml.

112. 93. The use of claim 92, wherein the composition is configured to be biodegradable.

113. 93. The use of claim 92, wherein the composition is configured to be detectable on an imaging modality for at least 9 months.

114. 93. The use of claim 92, wherein the composition is configured to not substantially move before or during imaging, which occurs about 3 months to about 9 months after the composition is placed.

115. 93. The use of claim 92, wherein the first visual additive is configured to be substantially immobile before or during imaging, which occurs about 3 months to about 9 months after the composition is deployed.

116. The use described in claim 92, wherein the subject requires radiography.

117. The use described in claim 92, wherein the composition is configured to be placed subcutaneously or subepidermally.

118. The use described in claim 92, wherein the composition is configured to be placed within the first tissue site.

119. The use described in claim 92, wherein the first tissue site includes one or more of adipose tissue, muscle tissue, and organ tissue, or combinations thereof.

120. The use described in claim 92, wherein the composition is configured to be imaged on one or more modalities.

121. The use described in claim 120, wherein the one or more modalities include X-ray, MRI, CT, CBCT, ultrasound, PET, SPECT, or a combination thereof.

122. The use described in claim 120 or 121, wherein the composition configured to be imaged on the one or more modalities comprises the composition configured to be imaged in real time on the one or more modalities.

123. The use described in claim 92, wherein the composition is configured to be imaged within 30 minutes, within 90 minutes, within 4 hours, within 8 hours, or within 4 days of placement.

124. The use described in claim 92, wherein the viscoelastic medium comprises hyaluronic acid, polyethylene glycol, or dextran.

125. The use described in claim 92, wherein the viscoelastic medium comprises hyaluronic acid, polyethylene glycol, or dextran at a concentration of about 5 mg / ml to about 100 mg / ml.

126. The use described in claim 92, wherein the viscoelastic medium comprises gel particles in the size range of about 0.08 mm to about 5 mm.

127. The use described in claim 126, wherein the gel particles include metal particles.

128. The use described in claim 92, wherein the viscoelastic medium comprises non-animal stabilized hyaluronic acid ("NASHA").

129. The use described in claim 92, wherein the viscoelastic medium expands within the first tissue region to less than 10% of its initial deployment volume.

130. The use of claim 92, wherein the viscoelastic medium is formulated to be injected once every six months.

131. The use described in claim 92, wherein the viscoelastic medium is completely absorbed within 20 months.

132. The use described in claim 92, wherein the viscoelastic medium is completely absorbed within 16 months.

133. The use described in claim 92, wherein the viscoelastic medium is completely absorbed within 12 months.

Images