Cartridge for storing tissue for imaging

Abstract

A cartridge for storing unlabeled tissue to be imaged by an optical imaging system may include a container for storing unlabeled tissue and for interfacing with the optical imaging system; an optical substrate disposed on the bottom surface of the container, the optical imaging system configured to image the unlabeled tissue through the optical substrate to generate a virtually stained histological image of the unlabeled tissue; and a cap disposed on the top surface of the container, the cap comprising a membrane for pressing the unmarked tissue against the optical substrate such that the entire cutting edge of the unmarked tissue is flat against the optical substrate.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to U.S. Provisional Patent Application No. 63 / 368,112 filed on July 11, 2022 and U.S. Provisional Patent Application No. 63 / 483,556 filed on February 7, 2023, the entire contents of each of which are incorporated herein by reference. Technical Field

[0003] The present disclosure relates to a cassette for storing tissue for imaging, and more particularly to a cassette for storing unlabeled tissue to be imaged by an optical imaging system configured to generate a virtually stained histological image of the unlabeled tissue. However, embodiments herein are also applicable to molecular diagnostics. Background Art

[0004] Surgical resection is an integral part of the treatment of most individual cancerous tumors and involves a surgeon who removes the tumor and surrounding tissue. "Surgical margins" (or "margins") may refer to the boundaries of the tissue removed. "Negative surgical margins" may refer to surgical margins that do not overlap with a cancerous tumor or are sufficiently far from a cancerous tumor. "Positive surgical margins" may refer to surgical margins that overlap with a cancerous tumor or are not sufficiently far from a cancerous tumor.

[0005] During surgical resection, it may be difficult for the surgeon to accurately determine the amount of peritumoral tissue to be removed in order to achieve an adequate surgical margin, and it may be difficult to determine whether a negative margin exists. Therefore, many initial resections result in positive margins, which leads to the need for additional surgery.

[0006] After surgical excision of tissue, the excised tissue is subjected to histological evaluation to determine whether the margin is negative or positive. Typically, the histological evaluation of tissue includes chemical stabilization of the excised tissue with a fixative, embedding the excised tissue in paraffin, slicing the excised tissue, mounting the excised tissue on a slide, staining the excised tissue with a dye (e.g., hematoxylin and eosin), and performing a qualitative optical microscopic analysis of the histological images of the stained tissue. The aforementioned techniques are time-sensitive, expensive, error-prone, and cannot be performed during surgery.

[0007] In some cases, frozen section analysis allows intraoperative assessment of surgical margins. Frozen section analysis includes embedding the excised tissue in a special medium, cooling the excised tissue, freezing the excised tissue, slicing the excised tissue, staining the excised tissue, mounting the stained tissue, and analyzing the histological images of the stained tissue. The above-mentioned technology prolongs the operation time and introduces artifacts that deteriorate the cell morphology and affect the pathological diagnosis of the tissue. In this way, frozen section analysis usually includes an unacceptably high false positive rate.

[0008] Therefore, there is a need for techniques to provide intraoperative assessment of surgical margins in an accurate, safe, and time-sensitive manner. Summary of the invention

[0009] Embodiments of the present disclosure relate particularly to a cassette for storing unlabeled tissue to be imaged by an optical imaging system configured to generate a virtually stained histological image of the unlabeled tissue.Each embodiment disclosed herein may include one or more features described in conjunction with any other disclosed embodiment. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate exemplary embodiments of the present disclosure and, together with the description, serve to explain the principles of the present disclosure.

[0011] Figure 1A-1M is a diagram of a cassette for storing unlabeled tissue.

[0012] Figure 2 is a diagram of a box interfaced with an optical imaging system.

[0013] Figure 3A is a diagram of a cassette storing unlabeled tissue including a cut.

[0014] Figure 3B is a diagram of a display including a tissue image and a patient orientation image.

[0015] Figure 4A is a diagram of a paper including orientation marks.

[0016] Figure 4B is a diagram of a box including orientation marks.

[0017] Figure 5A is a diagram of a box including a unique identifier.

[0018] Figure 5B is a diagram of a box including a unique identifier.

[0019] Figure 6A-6G is a diagram of the pressure component.

[0020] Figure 7 is a diagram of a box that includes the reference point.

[0021] Figure 8 is a diagram of components of an optical imaging system.

[0022] Fig. 9 is a flow chart of the process used to prepare unlabeled tissue for imaging.

[0023] Fig.10is a flow chart of a process for preparing a cartridge for imaging.

[0024] Fig.11 is a flow chart of a process for detecting an interlock between a cartridge and an optical imaging system.

[0025] Fig.12 is a flow chart of a process for imaging tissue.

[0026] Fig.13 is a flow chart of a process for adjusting an imaging head of an optical imaging system.

[0027] Fig.14 is a flow chart of a process for storing tissue in a cassette. DETAILED DESCRIPTION

[0028] As mentioned above, various histological imaging techniques are time intensive and prone to error, and in many cases, cannot be performed intraoperatively. Therefore, intraoperative negative margin confirmation may be extremely difficult or impossible with conventional imaging techniques.

[0029] The present disclosure provides a cassette for storing unlabeled tissue to be imaged by an optical imaging system, the optical imaging system being configured to generate a virtually stained histological image of the unlabeled tissue. However, embodiments herein are also applicable to imaging labeled tissue (e.g., molecular imaging using labeled antibodies, molecular imaging using labeled antigens, molecular imaging using labeled oligonucleotides, fluorescence imaging, etc.).

[0030] The box body includes a container for storing unlabeled tissue and for interfacing with an optical imaging system. In addition, the box body includes an optical substrate, and the optical imaging system is configured to image the unlabeled tissue through the optical substrate to generate a virtually stained histological image of the unlabeled tissue. Further, the box body includes a cover, and the cover includes a membrane to press the unlabeled tissue against the optical substrate so that the entire cut edge of the unlabeled tissue is flat against the optical substrate.

[0031] During surgery, tissue can be removed from the patient and the removed and unlabeled tissue can be placed in a cassette. The cassette can then be interfaced with an optical imaging system. The optical imaging system can generate a virtually stained histological image of the true margin of the unlabeled tissue intraoperatively, while the cassette maintains the orientation of the tissue as removed from the patient. In this way, a determination of whether a negative margin exists in a resected tissue sample can be made more accurately, quickly, and intraoperatively, thereby improving the safety and efficacy of surgical resection of cancerous tumors.

[0032] In some embodiments, "unlabeled tissue" refers to tissue that has not been stained with a stain used in histology. For example, unlabeled tissue is not stained with a stain (such as hematoxylin, eosin, acid dyes, basic dyes, periodic acid-Schiff reaction stains, Masson stains, Alcian blue stains, van Gieson stains, reticulin stains, Giemsa stains, toluidine blue stains, silver and gold stains, chrome alum stains, hematoxylin stains, acetyl blue stains, osmium stains, PAS, T-blue, Congo red, crystal violet, etc.). In some embodiments, "virtually stained histological images" refer to images of unlabeled tissues that simulate staining. In other words, virtually stained histological images depict how unlabeled tissues will appear or may appear if stained.

[0033] Figure 1A is a diagram of a box used to store unlabeled tissue. Figure 1A As shown, the box body 100 may include a container 110, an optical substrate 120, a cover 130, a film 140 and a cap 150. Figure 1A As further shown in FIG. 1 , the cartridge 100 can store unlabeled tissue 160 .

[0034] The container 110 can store the unlabeled tissue 160 and can be used with an optical imaging system 200 ( Figure 2 The container 110 may include a top surface 110-1, a bottom surface 110-2, and a side surface 110-3. The bottom surface 110-2 and the side surface 110-3 of the container 110 may form a cavity in which the unlabeled tissue 160 is placed and stored. The container 110 may be made of any suitable material (e.g., plastic, metal, etc.) and may be any suitable shape (e.g., circular, hexagonal, square, etc.).

[0035] The optical substrate 120 may be disposed on the bottom surface 110-2 of the container 110 and may allow the optical imaging system 200 to image the unlabeled tissue 160 through the optical substrate 120 to generate a virtually stained histological image 240 of the unlabeled tissue 160, such as Figure 2 As shown. The optical substrate 120 can be formed of any suitable material and can be any suitable shape. For example, the optical substrate 120 can include an optically transparent material configured for the wavelength of operation of the optical imaging system 200. As a specific example, based on the excitation wavelength of the optical imaging system 200 being in the range of 250 nanometers to 270 nanometers, the optical substrate 120 can be UV fused silica or quartz. In addition, the optical substrate 120 can be configured to allow photons of a specific wavelength to pass through based on the specific configuration of the optical imaging system 200.

[0036] Additionally or alternatively, the optical substrate 120 may include an anti-reflective coating. In some embodiments, the anti-reflective coating may only be used once and may not be compatible with sterilization or cleaning protocols. In this way, the single-use nature of the optical substrate 120 may prevent the cartridge 100 from being used multiple times, thereby preventing or reducing the risk of contamination and false negatives or false positives.

[0037] Additionally or alternatively, the optical substrate 120 may include a Fabry-Perot etalon 180 (eg, Figure 1B and Figure 1C ) to allow the optical imaging system 200 to capture all photoacoustic data streams. The optical imaging system 200 using the Fabry-Perot etalon 180 can capture ultrasound propagation data that is used in conjunction with photon absorption remote sensing data streams (e.g., radiative, non-radiative, and scattered) to assist in image reconstruction of an image of the unlabeled tissue 160. The Fabry-Perot etalon 180 can be disposed on a top surface 120-1 of the optical substrate 120 that contacts the unlabeled tissue 160. Alternatively, the Fabry-Perot etalon 180 can be disposed on a bottom surface 120-2 of the optical substrate 120. The Fabry-Perot etalon 180 is deposited on a surface of the optical substrate. The Fabry-Perot etalon 180 can be deposited onto a glass surface using thin film deposition techniques. The initial pressure (generated from the absorption of the excitation light from the excitation laser 176) produces an acoustic wave 172 that modulates the thickness of the thin film of the Fabry-Perot etalon 180, which is detected as a modulation on the detection laser 178. The detection laser collector 174 can be set to capture the radiative / non-radiative channels 182 at the focal depth in the tissue and the Fabry-Perot etalon channels 184 at the first and second surfaces of the Fabry-Perot etalon 180.

[0038] Additionally or alternatively, the cassette 100 may include a transducer 186 (e.g. Figure 1D 100 ). The optical imaging system 200 may include a liquid buffer. In this case, the ultrasonic wave 172 may pass through the liquid buffer to reach the transducer 186.

[0039] Additionally or alternatively, the cassette 100 may include an electrical via 188 (eg, Figure 1D), these electrical vias 188 allow current to pass through the transducer 186 of the box body 100 without housing leakage in the box body 100. In addition, the electrical vias 188 can interconnect the box body 100 to the box board 230 of the optical imaging system 200. In this case, the electrical circuit can provide an interlock that prevents operation of the optical imaging system 200 if the box body 100 is not properly interfaced with the optical imaging system 200. Since the transducer 186 can be sensitive to time of flight, the system may be able to reconstruct and collect depth scans. The physical transducer 186 can be integrated into the box body (on the container wall or optical substrate 120). The transducer 186 will have physical electrical contacts that are connected to the connector interface. Figure 1D Three options are shown for the location of the transducer 186 and the corresponding electrical vias 188. The electrical vias 188 can also be integrated into the optical substrate 120 or on the wall of the box to increase the distance from the location of the actual transducer 186. Liquid can be added to the box to allow improved acoustic wave propagation.

[0040] The cover 130 may be disposed on the top surface of the container 110 and may include a film 140 to press the unmarked tissue 160 against the optical substrate 120 so that the entire cut edge 170 of the unmarked tissue 160 is flat against the optical substrate 120. Here, "flat" may refer to that the surface of the unmarked tissue 160 is in contact with the surface (e.g., the top surface 120-1) of the optical substrate 120 so that there is no gap between the surface of the unmarked tissue 160 and the surface of the optical substrate 120. For example, as shown in FIG1 , the film 140 may receive an external pressure 105 (i.e., from outside the box body 100) and transmit an internal pressure 115 (from inside the box body 100) to the unmarked tissue 160 so that the unmarked tissue 160 is pressed against the optical substrate 120. The film 140 may receive the external pressure 105 from an operator, from a pressure assembly 600 (as described in more detail in conjunction with FIG6 ), and the like. Based on the applied pressure, the membrane 140 can conform to the surface of the unlabeled tissue 160 and can press the unlabeled tissue 160 against the optical substrate 120. The cover 130 can be formed of any suitable material and can be any suitable shape. In addition, the membrane 140 can be formed of any suitable material and can be any suitable shape. The external pressure 105 can be used in conjunction with the internal vacuum, for example, to remove air pockets and residual undesirable fluids. The vacuum may not be enough to flatten the tissue, so the external pressure 105 can be used afterwards. Alternatively, the external pressure 105 (like repeated tapping) can be used to dislodge fixed bubbles, and the vacuum can be used to pull these bubbles out.

[0041] Cap 150 can be disposed on the bottom surface of container 110 and can protect optical substrate 120. Cap 150 can be formed of any suitable material and can be any suitable shape. Optical imaging system 200 can automatically remove cap 150 by mechanical action so that during installation of unlabeled tissue 160 into cassette body 100, optical substrate 120 will not be inadvertently damaged. Cap 150 can be referred to as a "bottom cap", such as when a "top cap" (not shown) is disposed on top of cover 130 (e.g., when the membrane is permeable). The "top cap" will seal the unit for proper storage of fresh tissue. If the membrane is completely impermeable to fluid transfer, a top cap may not be required.

[0042] A surgeon, medical professional, or other individual may excise unmarked tissue 160 from a patient and place unmarked tissue 160 on optical substrate 120 in container 110. As examples, unmarked tissue 160 may be cleaned prior to placement in container 110, may be fixed prior to placement in container 110, or may be placed directly in container 110 without any processing (e.g., placed in container 110 immediately after excision without any intermediate processing steps between excision and placement in the container). In some embodiments, unmarked tissue 160 may be placed in the cassette within a threshold time frame of excision from a patient (e.g., within one minute, within five minutes, within ten minutes, etc.).

[0043] In some implementations, a fluid can be added to the cartridge 100 to aid in imaging. As examples, the fluid can be saline, water, methanol, ethanol, acetic acid, acetic acid and ethanol, formaldehyde, paraformaldehyde, picrate, organic solvents mediated by hepes-glutamate buffer, aluminum chloride, etc. Additionally or alternatively, a fixative medium (e.g., formalin, paraffin, etc.) can be added (e.g., pumped via the fluid port 185) to the cartridge 100 to preserve the unlabeled tissue 160 during storage of the unlabeled tissue 160 after imaging of the unlabeled tissue 160.

[0044] like Figure 1E As shown, fluid ports 185 can be disposed on top location 190. Fluid can be added or removed via one or more fluid ports 185. When a vacuum is applied to the fluid ports 185, the flexible membrane 140 will be compressed and will conform to the tissue 160, and the tissue 160 will be compressed. In some implementations, a fluid channel 188 can fluidly connect the fluid ports 185 to the container 110.

[0045] like Figure 1FAs shown, the fluid port 185 can be provided at the bottom position. In this case, the fluid port 185 is on the bottom side 192. The port 185 can be engaged with a quick disconnect connection on the machine side. In this way, vacuum can be drawn and / or liquid can be added from the bottom / machine side, which keeps the user side clean (no fluid or plumbing obstructions for the user). A check valve can be added to allow only desired one-way flow.

[0046] like Figure 1G As shown, the fluid port 185 can be disposed at the top location 190. When no vacuum is applied, the membrane 140 does not deform. When a vacuum is applied to the port, the membrane 140 deforms to the tissue 160. The membrane can deform plastically or elastically.

[0047] like Figure 1H As shown, external pressure 105 can be applied to the back / top side of the tissue (through the membrane 140), which plays two roles: 1) adding additional pressure to promote contact of the tissue / optical substrate 120, and 2) adding pressure in a way that promotes the bubble 194 to leave the tissue / glass interface. The combination of vacuum also helps the bubble 194 to escape. The pressure can be static or alternating ("repeated tapping") to promote the bubble 194 to leave. In both cases, the panoramic camera (210) can be used to identify where pressure needs to be added in order to move the bubble 194 from the optical substrate-tissue interface 120. Instead of the panoramic camera, the optical imaging head (220) can be activated to see the bubble 194. For example, a scattering image using the detection wavelength will clearly show the presence of the bubble 194.

[0048] like Fig. 1I As shown, the external pressure array 107 can also be used in conjunction with a vacuum. For example, the external pressure array 107 can be a spring-loaded actuator, a pogo pin array, etc. In the case of a pogo pin array, the pins can be activated individually to expel bubbles 194 from the optical substrate-tissue interface 120 or to increase pressure / force only on certain areas.

[0049] like Figure 1J As shown, in the uncompressed state, the deep cutting edge 163 of the excised tissue 196 is against the optical substrate 120 and the peripheral cutting edge 164 is high. The complete cutting edge can be mapped based on the standard anatomical position. The excised tissue 196 can be displayed from the top view, the side view and the bottom view (such as Figure 1J , Figure 1K and Figure 1L The resected tissue may include visible cancer 197.

[0050] like Figure 1KAs shown, pressure is first applied to the left side so that the cutting edge section 1 161 is completely flat against the optical substrate and focused. The cutting edge section 1 161 is the first scanning area.

[0051] like Figure 1L As shown in , when the first scan is completed, pressure is then applied to the right side so that the cutting edge segment 2 162 is completely flat against the optical substrate and in focus. The cutting edge segment 2 162 is the second scan area.

[0052] like Figure 1M As shown, it is desirable that the optical substrate 120 is flat along the z=0 plane so that the tissue interface remains in focus on the beam for ideal imaging. When pressure is applied or when vacuum is applied, the optical substrate 120 (and the tissue interface) deforms so that the image will be out of focus. By knowing the discrete values ​​of the applied pressure or vacuum, we can predetermine the "bend" profile 198 of the optical substrate 120, and during scanning, we can move the tissue sample up / down along the curved profile 198 so that the image remains in focus. Alternatively, a combination of pressure and vacuum can be "offset" from one another so that the optical substrate and tissue remain flat.

[0053] Figure 2 is a diagram of a box body connected to the optical imaging system interface. Figure 2 As shown, the box body 100 can be interfaced with the optical imaging system 200. For example, as shown, the box body 100 can be interfaced with the box plate 230 of the optical imaging system 200. Among other things, the optical imaging system 200 can include a camera head 210, an imaging head 220, and a box plate 230. The optical imaging system 200 can be configured to move the box plate 230 so that the box body 100 is arranged above the camera head 210 or the imaging head 220 to allow imaging of the unlabeled tissue 160. Figure 2 As further shown, the optical imaging system 200 may be configured to generate a virtually stained histology image 240 of the unlabeled tissue 160. Additionally or alternatively, the optical imaging system 200 may be configured to generate other types of images of the unlabeled tissue 160.

[0054] In some implementations, the optical imaging system 200 may be a photoacoustic remote sensing imaging system, such as a photon absorption remote sensing imaging system. In this case, the optical imaging system 200 may use a picosecond pulse excitation laser 176 (e.g., Figure 1B), which is focused into the unlabeled tissue 160 to produce radiative effects (e.g., light emission), non-radiative effects (e.g., heat and pressure), and scattering effects in the unlabeled tissue 160. Further, the optical imaging system 200 can capture photons and convert them into different forms of emission (e.g., non-radiative and radiative) from the unlabeled tissue 160, while the scattered photons continue to move through other parts of the unlabeled tissue 160 and interact with other parts. Still further, the optical imaging system 200 can be a photoacoustic remote sensing imaging system, such as a photothermal imaging system. In this case, the optical imaging system 200 can use a secondary confocal detection beam to record non-radiative effects, thereby being able to detect temperature or pressure changes. The optical imaging system 200 can record these changes as modulations of the backscattering intensity and directly relate these modulations to the local non-radiative absorption contrast. Unperturbed backscattering (pre-excitation events) simultaneously captures the optical scattering contrast. In this way, the optical imaging system 200 can combine the captured contrast or visualize the captured contrast separately. The optical imaging system 200 may be configured to implement, for example, U.S. Patent No. 10,117,583, published on November 6, 2018; U.S. Patent No. 10,327,646, published on June 25, 2019; U.S. Patent No. 10,627,338, published on April 21, 2020; U.S. Publication No. 2020 / 0359903, published on November 19, 2020; U.S. Publication No. 2021 / 0199566, published on July 1, 2021; U.S. Publication No. 2021 / 0404948, published on December 30, 2021; U.S. Patent No. 11,122,978, published on September 21, 2021; International PCT Publication No. WO 2021 / 0359903, published on November 19, 2020; No. 2021 / 255695; and one or more technologies described in PCT application No. PCT / IB2022 / 054433 filed on May 12, 2011, the entire contents of which are incorporated herein by reference.

[0055] To generate a virtually stained histological image 240 of the unlabeled tissue 160, the optical imaging system 200 can use ultraviolet light to virtually stain the unlabeled tissue 160, and then color match the virtually stained unlabeled tissue 160 with hematoxylin and eosin stains. In this way, the optical imaging system 200 can generate substantially similar histological images intraoperatively compared to the time-intensive and error-prone tissue processing and staining workflow described above. The virtually stained histological image 240 can be an image of the unlabeled tissue 160, including a simulated hematoxylin stain and a simulated eosin stain, wherein the simulated hematoxylin stain stains the nuclei with a dark blue-purple color, and the simulated eosin stain stains the cytoplasm and extracellular matrix with a pink hue.

[0056] Figure 3A is a diagram of a box containing unlabeled tissue including the incision. Figure 3A As shown, the unmarked tissue 160 may include a cutout 310. The cutout 310 may be a feature in the unmarked tissue 160 that allows the orientation of the unmarked tissue 160 to be maintained relative to the patient. Figure 3B As shown, the incision 310 can correspond to the vertical (up to down) direction of the patient. In other examples, the incision can correspond to the horizontal direction within the patient, such as the lateral-medial direction or the anterior-posterior direction. After the unmarked tissue 160 is removed from the patient, the incision 310 can be applied to, cut into, or otherwise formed in the unmarked tissue 160, and then the unmarked tissue 160 can be placed in the cassette 100. Because the unmarked tissue 160 is not processed compared to other technologies, the risk of the incision 310 being lost or damaged is less.

[0057] Figure 3B is a diagram of a display including a tissue image and a patient orientation image. Figure 3B As shown, the display 320 may display a tissue image 330 , a tissue image axis 340 , a patient image 350 , a tissue image 360 ​​, and a direction indicator 370 .

[0058] Tissue image 330 may be an image of unmarked tissue 160 imaged by optical imaging system 200. Optical imaging system 200 may image unmarked tissue 160, detect incision 310, and based on the incision cause display 320 to display unmarked tissue 160 in an orientation corresponding to the orientation of unmarked tissue 160 relative to the patient. Figure 3B As shown, the incision 310 may correspond to the vertical direction of the patient. Therefore, as shown, the display 320 may display the tissue image 330 such that the incision 310 is arranged in the vertical direction.

[0059] The tissue image 330 may include a tissue image axis 340 superimposed on the tissue image 330. The tissue image axis 340 may include a vertical axis (upper-lower axis) and a horizontal axis (outer-inner axis), as shown. The optical imaging system 200 may cause the tissue image axis 340 to correspond to the incision 310. That is, as shown, the vertical axis of the tissue image axis 340 may be in the same plane as the direction indicated by the incision 310. For example, Figure 3B As shown, the incision 310 may correspond to the vertical direction of the patient. Therefore, as shown, the display 320 may display the tissue image axis 340 on the tissue image 330 such that the vertical axis of the tissue image axis 340 is aligned with the incision 310.

[0060] Patient image 350 may be a representation of a body part of a patient and may include tissue images 360 superimposed on the representation of the body part at locations corresponding to where unmarked tissue 160 was removed from the patient. Figure 3B As shown, patient image 350 includes tissue image 360 ​​disposed on the patient's right cheek.

[0061] The optical imaging system 200 may receive information identifying a location where the unmarked tissue 160 was removed from the patient, and generate a patient image 350 and a tissue image 360 ​​based on the information identifying the location. For example, the optical imaging system 200 may receive information based on an image captured by the optical imaging system 200, based on user input, based on information stored on the cartridge 100, based on artificial intelligence (AI) techniques, based on analyzing the unmarked tissue 160, and the like. In addition, the optical imaging system 200 may generate the patient image 350 such that the tissue image 360 ​​is superimposed on the patient image 350 at a location corresponding to the unmarked tissue 160 removed from the patient. Conventional workflows use inks to indicate the orientation of a sample. Nominally, those inks are bad for PARS because the inks absorb our excitation and / or detection wavelengths. In some implementations, inks with absorption spectra outside of the excitation and / or detection wavelengths of the target make those inks not interfere with optical measurements. In some implementations, surgeons may use PARS-specific inks. In this way, surgeons do not need to change their current inking methods.

[0062] Direction indicator 370 may be an indicator that depicts the orientation of unmarked tissue 160 relative to the patient (as determined by incision 310). Figure 3B As shown, the optical imaging system 200 may overlay a direction indicator 370 indicating a vertical direction on the tissue image 360 ​​and the patient image 350 .

[0063] Figure 4A 4, paper 400 may include orientation marks 410. Paper 400 may be the paper on which unmarked tissue 160 is placed after unmarked tissue 160 is removed from the patient and before being placed in cassette 100. Orientation marks 410 may be marks that allow the orientation of unmarked tissue 160 to be maintained relative to the patient. For example, Figure 4AAs shown, the orientation marks 410 depicted as "I" and "III" can correspond to the vertical direction of the patient (e.g., bottom-top), and the orientation marks 410 depicted as "IIII" and "II" can correspond to the horizontal direction of the patient (e.g., front-back or outside-inside). Unmarked tissue 160 is placed on paper 400 and oriented relative to orientation marks 410 so that the orientation of unmarked tissue 160 relative to the patient can be determined.

[0064] Figure 4B is a diagram of a box including orientation marks. Figure 4B As shown, the optical substrate 120 may include orientation marks 420 that allow the orientation of the unmarked tissue 160 to be maintained relative to the patient. For example, the orientation marks 420 depicted as "I" and "III" may correspond to the vertical direction of the patient (e.g., bottom-top), and the orientation marks 420 depicted as "IIII" and "II" may correspond to the horizontal direction of the patient (e.g., front-back or outside-inside). The paper 400 may include orientation marks 410 corresponding to the orientation marks 420 disposed on the optical substrate 120. Specifically, the paper 400 may have exactly the same markings in exactly the same orientation as the orientation marks 420 on the optical substrate 120. The unmarked tissue 160 may then be transferred to the optical substrate 120 by the same person or individual performing the resection or by a different person or individual while maintaining the orientation of the unmarked tissue 160 relative to the orientation marks 420. For example, the resected unmarked tissue 160 can be placed by the surgeon on paper 400 in an intended orientation relative to the orientation mark 410 of paper 400, and then an assistant, technician, nurse, or other physician, for example, can transfer the unmarked tissue 160 to the optical substrate 120 by visually aligning the markings on paper 400 and the orientation marks 420 of the box 100 so as to maintain the surgeon's intended orientation.

[0065] In this way, the optical imaging system 200 can detect the orientation mark 420 and cause the display 320 to display the unmarked tissue 160 in an orientation corresponding to the orientation of the unmarked tissue 160 relative to the patient. In addition, the optical imaging system 200 can superimpose the orientation mark on the image displayed by the display 320. Although the orientation mark 420 is depicted as being disposed on the optical substrate 120, the orientation mark 420 can also be disposed on any other component of the cassette 100, such as the cover 130, the container 110, or the cap 150. For example, the cap 150 can be in place when the unmarked tissue 160 is placed in the cassette 100, and can have an orientation mark 420 that is large and visible to the unaided human eye and matches the orientation mark 420 on the paper 400. If the cap 150 is keyed to the cassette 100, the alignment of the unmarked tissue 160 relative to the cassette 100 can be maintained after the cap 150 is removed.

[0066] Figure 5A and Figure 5B is a diagram of a box including a unique identifier. Figure 5A and Figure 5B As shown, the container 110 may include a unique identifier 500. The unique identifier 500 may be an identifier that can be electronically tracked. For example, the optical imaging system 200 may electronically track the unique identifier 500 via a communication technology (such as via a quick response (QR (two-dimensional)) code, radio frequency identification (RFID), near field communication (NFC), Bluetooth, a barcode, etc.). As an example, based on the container 110 being connected to the optical imaging system 200 interface, the optical imaging system 200 (e.g., the camera head 210) may read the unique identifier 500 set on the bottom surface of the container 110 and obtain the unique identifier 500. It is also possible to use the detection laser as a scattering microscope, which can also image the barcode (2D or 1D). In this case, a visible camera may not be required. Although Figure 5A and Figure 5B The unique identifier 500 is depicted as being provided in the form of a QR code disposed on the bottom surface of the container 110, but the unique identifier 500 may be disposed at any location on any other component of the box body 100, such as the cover 130, the optical substrate 120, or the cap 150. The unique identifier 500 may be associated with a patient name, a patient identifier, an organization identifier, and the like.

[0067] Additionally or alternatively, the unique identifier 500 may be an interlock for the operation of the optical imaging system 200. For example, operation of the imaging head 220 of the optical imaging system 200 may be prevented until the cartridge 100 is interfaced with the optical imaging system 200 and the unique identifier 500 is detected by the optical imaging system 200. Alternatively, the cartridge 100 may include another type of interlock disposed at a different location or on another component of the cartridge 100. For example, the cartridge 100 may include a mechanical feature that engages with the optical imaging system 200 when the cartridge 100 is interfaced with the optical imaging system 200.

[0068] Additionally or alternatively, the unique identifier 500 can be a control mechanism that prevents multiple uses of the cartridge 100. For example, the optical imaging system 200 can detect the unique identifier 500 and determine whether the cartridge 100 has already been used for imaging. Based on determining that the cartridge 100 has already been used for imaging, the optical imaging system 200 can prevent additional imaging of the unlabeled tissue 160 disposed in the cartridge 100. In this manner, the unique identifier 500 can prevent or reduce the number of false positives or false negatives that occur based on cross contamination.

[0069] Additionally or alternatively, the unique identifier 500 may include information that allows the optical imaging system 200 to provide an appropriate amount of pressure or displacement to the cassette 100 to press the unmarked tissue 160 against the optical substrate 120 so that the entire cut edge of the unmarked tissue 160 is flat against the optical substrate 120. For example, the unique identifier 500 may include information identifying the pressure value applied to the cassette 100, the displacement value of the cassette 100, the AI ​​algorithm to be executed by the optical imaging system 200 to apply pressure to the cassette 100, etc. The identifier may also be associated with the country to which it will be sold. The identifier may also associate regulatory approval with an IDE or RUO.

[0070] Fig. 6A is a diagram of a box interfaced with a pressure assembly of an optical imaging system. Figure 6B is a diagram of a pressure assembly of an optical imaging system connected to a membrane interface of a cartridge. Figure 6C is a diagram of the needle and disk of the pressure assembly of the optical imaging system. Figure 6A-6C As shown in , the pressure assembly 600 can be configured to apply pressure to the unmarked tissue 160 to press the unmarked tissue 160 against the optical substrate 120 so that the entire cut edge 170 of the unmarked tissue 160 is flat against the optical substrate 120. In some implementations, the pressure assembly 600 can be outside the box body 100. For example, the optical imaging system 200 can include the pressure assembly 600. Alternatively, the pressure assembly 600 can be inside the box body 100. Independent actuators in the pressure assembly can be independently addressed so that only one actuator is actuated at a time (or a combination of multiple actuators are actuated simultaneously).

[0071] like Figure 6A-6C As shown in, and as an example, the pressure assembly 600 may include an array of needles 610 and corresponding discs 620. By using the needles 610 and the discs 620, the pressure assembly 600 may apply different pressures at different displacements (different positions along the surface of the membrane 140 and / or the cover 130). For example, the discs 620 may collectively cover the entire surface, substantially all, or another portion of the unmarked tissue 160. In addition, each disc 620 may independently cover a local area of ​​the surface of the unmarked tissue 160. In addition, the pressure applied to each disc 620 via the corresponding needles 610 may be adjusted and changed so that the same or different pressures may be applied to each disc 620. In this way, the pressure applied to the surface of the unmarked tissue 160 may be consistent across the entire surface of the unmarked tissue 160 (e.g., in the case where each disc 620 applies the same pressure), or may vary across the surface of the unmarked tissue 160 (e.g., in the case where one or more discs 620 apply different pressures). In this manner, the pressure assembly 600 can compress the unmarked tissue 160 such that the entire cut edge 170 of the unmarked tissue 160 lies flat against the optical substrate 120 .

[0072] In some implementations, and as Figure 1J-1L As shown, the optical imaging system 200 and / or the box body 100 can be configured to apply positive pressure on the bottom surface of the optical substrate 120 to offset the curvature of the optical substrate 120 and maintain the flatness of the entire cut edge 170 of the unmarked tissue 160 against the optical substrate 120.

[0073] The optical imaging system 200 can be configured to control the pressure assembly 600 to modify the applied pressure so that the entire cut edge 170 of the unmarked tissue 160 is flat against the optical substrate 120. In some implementations, the optical imaging system 200 can control the pressure assembly 600 to apply a specific pressure based on information obtained from the unique identifier 500 of the cartridge 100. For example, the unique identifier 500 can include pressure information that identifies a specific pressure to be applied based on a specific type of unmarked tissue 160 to be imaged. The pressure information can include information identifying a specific pressure to be applied by each needle 610 and disk 620 group of the pressure assembly 600. For example, the pressure information can include a pressure matrix to be applied to the unmarked tissue 160, the pressure matrix corresponding to the group of needles 610 and disks 620. In other words, the pressure information can identify a specific pressure to be applied by each disk 620 of the pressure assembly 600, the pressure corresponding to a specific local area of ​​the surface of the unmarked tissue 160. The pressure information can be predetermined, can be determined using AI techniques, etc.

[0074] Additionally or alternatively, the optical imaging system 200 can modify the applied pressure based on the image of the unmarked tissue 160. For example, the optical imaging system 200 (e.g., the camera head 210) can image the unmarked tissue 160, and the optical imaging system 200 can control the pressure assembly 600 to modify the applied pressure so that the entire cut edge 170 of the unmarked tissue 160 is flat against the optical substrate. In some implementations, an AI algorithm executed by the optical imaging system 200 can control the pressure assembly 600 to perform the aforementioned operations.

[0075] like Fig.6D As shown, before the pressure assembly 600 contacts the membrane, the disk array position and orientation may have matched the needle array 610. That is, the needles 610 engage the disks 620 before the membrane is stretched.

[0076] like Fig. 6E As shown, the disc array 620 is attached to the membrane rather than the needle. In this way, no tiny permanent ball joint is required on the pressure assembly 600. In addition, the disc array 620 can potentially retain its shape after pressure is applied, which will keep the tissue in the current orientation even after the pressure assembly 600 is disengaged.

[0077] like Fig. 6F As shown, each disk 620 includes a cup-shaped depression and each needle 610 includes a rounded tip that forms a spherical joint when in contact.

[0078] like Figure 6G As shown, the volume within the box body is sealed. A vent hole may be needed to divert air and fluid. Another hole can be used to add a fixative or embedding medium. A port can be built into the pressure assembly 600, which is connected when the pressure assembly 600 is engaged with the cover 130.

[0079] Figure 7 is a diagram of a box that includes the reference point. Figure 7 As shown, the optical substrate 120 may include fiducials 700 that aid in alignment between the camera head 210 and the imaging head 220 of the optical imaging system 200 to ensure that the PARS acquisition is centered on the appropriate interrogation window. The fiducials 700 may be laser etched on the optical substrate 120 or deposited on the optical substrate 120 using a photolithography tool (e.g., a thin metal deposited and etched at the wafer or grain level). The fiducials 700 may be outside the unmarked tissue 160 imaging window (e.g., an outer annular ring of the optical substrate 120) so as not to obstruct PARS imaging of the tissue and to allow high laser densities to be used without damaging the optical substrate 120. The fiducials may be the correct shape / size so that the visible camera has sufficient optical resolution to resolve. In some implementations, at least 3 fiducials are required to establish the x,y orientation. When the fiducials are scanned by the PARS head, the fiducials should be within the optical field of view of the imaging system.

[0080] In some implementations, the fiducials 700 can be optical resolution targets that facilitate both axial automatic alignment (focus direction) and lateral alignment of the detection and excitation beams of the optical imaging system 200. By measuring the fiducials in all four quadrants, the optical imaging system 200 can automatically level the cassette plate 230 relative to the beams to ensure that the focal plane is consistent across the entire field of view of the unlabeled tissue 160 during scan acquisition.

[0081] By using the scatter images from the excitation and detection lasers, the fiducials 700 can be optically resolved, and if done at the start of each new PARS acquisition, the fiducial image quality can serve as a beam health metric to ensure that the excitation and detection beams remain confocal over time to avoid system drift. If the excitation or detected scatter images fall out of focus, the optical imaging system 200 can trigger an alarm indicating that the optical imaging system 200 needs to be realigned.

[0082] In some implementations, if the optical imaging system 200 implements an active alignment system, the scattered image of the fiducial 700 can be used to steer the light beam(s) in order to regain alignment of the optical imaging system 200 .

[0083] In view of the foregoing, during surgery, tissue may be removed from a patient and placed in the cassette 100. The cassette 100 may then be interfaced with the optical imaging system 200. The optical imaging system 200 may intraoperatively generate a virtually stained histological image 240 of the true resection margin 170 of the unmarked tissue 160 while the cassette 100 maintains the orientation of the tissue as removed from the patient. Furthermore, in this manner, the embodiments herein allow for a more precise, rapid, and intraoperative determination of whether a negative resection margin exists, thereby improving the safety and efficacy of surgical resection of cancerous tumors.

[0084] Figure 8 is a diagram of the components of an optical imaging system. Figure 8 As shown, the optical imaging system 200 may include a bus 810, a processor 820, a memory 830, a storage component 840, an input component 850, an output component 860, and a communication interface 870. Figure 2 and Figure 6A-6C In addition to the components described (eg, camera head 210, imaging head 220, and pressure assembly 600), optical imaging system 200 may include the aforementioned components.

[0085] The bus 810 includes components that allow communication between components of the optical imaging system 200. The processor 820 may be implemented in hardware, firmware, or a combination of hardware and software. The processor 820 may be a central processing unit (CPU), a graphics processing unit (GPU), an accelerated processing unit (APU), a microprocessor, a microcontroller, a digital signal processor (DSP), a field programmable gate array (FPGA), an application specific integrated circuit (ASIC), or another type of processing component.

[0086] The processor 820 may include one or more processors that can be programmed to perform functions. The memory 830 may include a random access memory (RAM), a read-only memory (ROM), and / or another type of dynamic or static storage device (e.g., flash memory, magnetic memory, and / or optical memory) that stores information and / or instructions for use by the processor 820. The storage component 840 may store information and / or software related to the operation and use of the optical imaging system 200. For example, the storage component 840 may include a hard disk (e.g., a magnetic disk, an optical disk, a magneto-optical disk, and / or a solid state disk), a compact disk (CD), a digital versatile disk (DVD), a floppy disk, a cassette tape, and / or another type of non-transitory computer-readable medium, and a corresponding drive.

[0087] Input component 850 may include components that allow optical imaging system 200 to receive information, for example, via user input (e.g., a touch screen display, a keyboard, a keypad, a mouse, a button, a switch, and / or a microphone for receiving reference sound input). Additionally or alternatively, input component 850 may include a sensor for sensing information (e.g., a global positioning system (GPS) component, an accelerometer, a gyroscope, and / or an actuator). Output component 860 may include components that provide output information from optical imaging system 200 (e.g., display 320, a speaker for outputting sound of an output sound level, and / or one or more light emitting diodes (LEDs)).

[0088] The communication interface 870 may include transceiver-like components (e.g., a transceiver and / or a separate receiver and transmitter) that enable the optical imaging system 200 to communicate with other devices, such as via a wired connection, a wireless connection, or a combination of wired and wireless connections. The communication interface 870 may allow the optical imaging system 200 to receive information from another device and / or provide information to another device. For example, the communication interface 870 may include an Ethernet interface, an optical interface, a coaxial interface, an infrared interface, a radio frequency (RF) interface, a universal serial bus (USB) interface, a Wi-Fi interface, a cellular network interface, etc.

[0089] The optical imaging system 200 can perform one or more processes described herein. The optical imaging system 200 can perform these processes based on the processor 820 executing software instructions stored by a non-transitory computer-readable medium (such as memory 830 and / or storage component 840). Computer-readable media is defined as a non-transitory memory device. The memory device may include memory space within a single physical storage device or memory space distributed across multiple physical storage devices. The software instructions can be read from another computer-readable medium or from another device into the memory 830 and / or storage component 840 via the communication interface 870. When executed, the software instructions stored in the memory 830 and / or storage component 840 can cause the processor 820 to perform one or more processes described herein.

[0090] Additionally or alternatively, hardwired circuitry may be used in place of or in combination with software instructions to perform one or more of the processes described herein. Therefore, the implementations described herein are not limited to any specific combination of hardware circuitry and software.

[0091] Figure 8 The number and arrangement of components shown in FIG. 2 are provided as examples. In practice, optical imaging system 200 may include additional components, fewer components, different components, or components that are different from those of FIG. Figure 8Additionally or alternatively, one set of components (eg, one or more components) of optical imaging system 200 may perform one or more functions described as being performed by another set of components of optical imaging system 200 .

[0092] Fig. 9 is a flow chart of the process used to prepare unlabeled tissue for imaging. Fig. 9 As shown, a process 900 for preparing unmarked tissue 160 for imaging may include excising unmarked tissue 160 from a patient (operation 910), incising unmarked tissue 160 (operation 920), and transferring unmarked tissue 160 to paper 400, paper 400 including orientation marks 410 corresponding to orientation marks 420 of cassette 100 (operation 930). For example, a surgeon or other medical personnel may excise unmarked tissue 160 from a patient, incise unmarked tissue 160, and place unmarked tissue 160 on paper 400. In some cases, process 900 may be performed within a threshold time frame (e.g., one minute, five minutes, ten minutes, etc.). Alternatively, the incision may also be completed during the actual excision (i.e., the surgeon or medical personnel may make the incision while the tissue is still on / in the patient).

[0093] Fig.10 is a flow chart of the process of preparing a cartridge for imaging. Fig.10 As shown, process 1000 may include obtaining a unique identifier 500 of a cassette 100 including unlabeled tissue 160 (operation 1010). For example, optical imaging system 200 may detect unique identifier 500, such as by reading a serial number via RFID, via QR, etc. Fig.10 As further shown, process 1000 may include determining a pressure or vacuum to be applied to unmarked tissue 160 based on unique identifier 500 (operation 1020). For example, optical imaging system 200 may determine pressure or vacuum information, such as internal pressure, external pressure, compliance compression setting, vacuum setting, pressure assembly 600 pressure, positive pressure, etc. As a specific example, optical imaging system 200 may determine information identifying the pressure or vacuum to be applied by each corresponding needle 610 and disk 620 group of pressure assembly 600. Fig.10 As further shown, process 1000 may include adding a buffer solution to cartridge 100 (operation 1030) and sealing cartridge 100 (operation 1040).

[0094] Fig.11 is a flow chart of the process for detecting the interlock between the cassette and the optical imaging system. Fig.11As shown, the process 1100 may include detecting an interlock between the cartridge 100 and the optical imaging system 200 (operation 1110). For example, the optical imaging system 200 may detect a mechanical feature that engages with the optical imaging system 200 when the cartridge 100 is interfaced with the optical imaging system 200, and detect the interlock based on detecting the mechanical feature. Alternatively, the optical imaging system 200 may optically detect the cartridge 100, such as via the camera head 210, and detect the interlock based on optically detecting the cartridge 100. Additionally or alternatively, the optical imaging system 200 may detect a unique identifier 500 of the cartridge 100, and detect the interlock based on optically detecting the unique identifier 500 of the cartridge 100.

[0095] like Fig.11 As further shown in FIG. 1 , process 1100 may include applying pressure or vacuum to the unmarked tissue in cartridge 100 (operation 1120). For example, optical imaging system 200 may apply pressure or vacuum to the unmarked tissue in cartridge 100. As a specific example, optical imaging system 200 may control pressure assembly 600 to apply pressure or vacuum to unmarked tissue 160. In this case, optical imaging system 200 may determine pressure or vacuum information, and control and apply a specific pressure or vacuum to each needle 610 and disk 620 group of pressure assembly 600, so that a consistent or varying pressure or vacuum may be applied to the surface of unmarked tissue 160.

[0096] Fig.12 is a flow chart of a process for imaging tissue. Fig.12 As shown, the process 1200 may include reading a quick response code of the cassette 100 (operation 1210). For example, the optical imaging system 200 may read a QR code disposed on the cassette 100 and perform operations 1220 to 1260 based on the read QR code.

[0097] like Fig.12As further shown in FIG. 1 , process 1200 may include applying pressure to the unmarked tissue 160 in the cartridge 100 (operation 1220). For example, the optical imaging system 200 may apply pressure to the unmarked tissue 160. As a specific example, the optical imaging system 200 may determine pressure information and control each needle 610 and disk 620 group of the pressure assembly 600 to apply a consistent or varying pressure to the surface of the unmarked tissue 160. Using the visible camera (210), the system can see whether there is air between the optical substrate and the tissue. Alternatively, the scatter image from the imaging head (220) will give a very clear indication (usually a very high signal) that the tissue is not flat against the optical substrate. In this example, when the scatter image in 210 detects cavitation after a full scan, more pressure (or vacuum) may be applied to the area of ​​the cavitation to clear the air and bring the tissue against the sample, and the system may rescan the area. In this case, the newly scanned area may be stitched back to the full scan to create a completely cavitation-free image.

[0098] like Fig.12 As further shown in , process 1200 may include determining whether the unmarked tissue 160 is flat (operation 1230). For example, optical imaging system 200 may determine whether unmarked tissue 160 is flat against optical substrate 120. Again, here, "flat" may refer to the surface of unmarked tissue 160 being in contact with the surface (e.g., top surface 120-1) of optical substrate 120 such that there is no gap between the surface of unmarked tissue 160 and the surface of optical substrate 120. Optical imaging system 200 may determine that unmarked tissue 160 is flat based on an image captured by optical imaging system 200, based on detecting the absence of a gap between the surface of unmarked tissue 160 and the surface of optical substrate 120, based on determining the absence of bubbles between the surface of unmarked tissue 160 and the surface of optical substrate 120, based on applying a particular pressure to unmarked tissue 160, etc.

[0099] like Fig.12 As further shown in FIG. 1 , if the unmarked tissue is not flat (operation 1230 —No), process 1200 may include returning to operation 1220. For example, optical imaging system 200 may iteratively adjust the pressure applied to unmarked tissue 160 until unmarked tissue 160 is flat against optical substrate 120.

[0100] like Fig.12 As further shown in FIG. 1 , process 1200 may include detecting a boundary of unlabeled tissue (operation 1240). For example, optical imaging system 200 may use camera head 210 and / or imaging head 220 to detect a boundary of unlabeled tissue 160. In the case where imaging head 220 is used to detect the boundary, a fast low-resolution scatter image may be used.

[0101] like Fig.12 As further shown in FIG. 1 , process 1200 may include setting a scanning range (operation 1250 ). For example, optical imaging system 200 may set a scanning range of optical imaging system 200 based on the detected boundary of unmarked tissue 160 .

[0102] like Fig.12 As further shown in FIG. 1 , process 1200 may include displaying and orienting the image of the unlabeled tissue relative to the patient (operation 1260). For example, optical imaging system 200 may display the image of the unlabeled tissue relative to the patient via display 320 in combination with the above Figure 3B The tissue image 330 , tissue image axis 340 , patient image 350 , tissue image 360 ​​, and / or direction indicator 370 are displayed in a similar manner as described.

[0103] Fig.13 is a flow chart of a process for adjusting an imaging head of an optical imaging system. Fig.13 As shown, process 1300 may include automatically leveling the cassette plate (operation 1310). For example, optical imaging system 200 may measure fiducials 700 in all four quadrants and automatically level cassette plate 230 relative to the beam to ensure that the focal plane is consistent across the entire field of view of unlabeled tissue 160 during scan acquisition.

[0104] like Fig.13 As further shown in FIG. 1 , process 1300 may include measuring fiducial image quality (operation 1320). For example, using scatter images from the excitation and detection lasers, fiducials 700 may be optically resolved and, if completed at the start of each new PARS acquisition, fiducial image quality may serve as a beam health metric to ensure that the excitation and detection beams remain confocal over time to avoid system drift. If the excitation or detection scatter images fall out of focus, optical imaging system 200 may trigger an alarm indicating that optical imaging system 200 needs to be realigned.

[0105] Fig.14 is a flow chart of a process for storing tissue in a cassette. Fig.14 As shown, process 1400 can include adding a fixative medium to the cartridge (operation 1410), and storing the cartridge (operation 1420). For example, a fixative medium (e.g., formalin, paraffin, etc.) can be added to the cartridge 100, and the cartridge 100 can be stored for subsequent use, additional imaging, etc. In some implementations, the system can automatically detect bubbles, perform an analysis of the bubbles, and provide instructions to the user on how he or she should adapt the mechanical fixation of the sample to better mount the tissue.

[0106] Although the principles of the present disclosure are described herein with reference to illustrative embodiments for specific applications, it should be understood that the present disclosure is not limited thereto. Those of ordinary skill in the art and access to the teachings provided herein will recognize that additional modifications, applications, embodiments, and replacements of equivalents all fall within the scope of the embodiments described herein. Therefore, implementations should not be considered to be limited by the foregoing description.

Claims

1. A system for optical imaging of unlabeled tissue, the system include: an optical imaging system configured to image the unlabeled tissue to generate a virtually stained histological image of the unlabeled tissue or to perform molecular detection or diagnosis; as well as A box body, the box body is used to store the unlabeled tissue to be imaged by the optical imaging system, the box body comprising: a container for storing the unlabeled tissue and for interfacing with the optical imaging system; an optical substrate disposed on a bottom surface of the container, wherein the optical imaging system is configured to image the unlabeled tissue through the optical substrate; and A cover is disposed on the top surface of the container, the cover comprising a film for pressing the unmarked tissue against the optical substrate so that the entire cut edge of the unmarked tissue lies flat against the optical substrate.

2. The system according to claim 1, in, The cassette includes orientation markings that allow the orientation of the unmarked tissue to be maintained relative to a patient from which the unmarked tissue is resected.

3. The system according to claim 2, in, The orientation mark is disposed on the optical substrate.

4. The system according to claim 1, in, The cartridge includes a unique identifier.

5. The system according to claim 4, in, The unique identifier is disposed on the container.

6. The system according to claim 5, in, The unique identifier is a quick response code.

7. The system according to claim 4, in, The unique identifier is an interlock of the optical imaging system.

8. The system according to claim 4, in, The unique identifier prevents the cartridge from being used with another unlabeled tissue.

9. The system according to claim 4, in, The unique identifier includes information identifying the pressure and / or vacuum applied to the cassette to press the unmarked tissue against the optical substrate.

10. The system according to claim 1, in, The box includes reference points for measurement by the optical imaging system.

11. The system according to claim 1, in, The optical substrate includes a Fabry-Perot etalon.

12. The system according to claim 1, in, The optical imaging system is a photon absorption remote sensing imaging system configured to produce radiative, non-radiative and scattering effects in the unlabeled tissue.

13. The system according to claim 1, further comprising: include: A pressure assembly is configured to apply pressure or vacuum to press the tissue against the optical substrate.

14. A system for optical imaging of unlabeled tissue, the system include: an optical imaging system configured to image the unlabeled tissue to generate an image of the unlabeled tissue; as well as A box body, the box body is used to store the unlabeled tissue to be imaged by the optical imaging system, the box body comprising: a container for storing the unlabeled tissue and for interfacing with the optical imaging system; an optical substrate disposed on the first surface of the container, the optical imaging system being configured to image the unlabeled tissue through the optical substrate; and A cover is disposed on the second surface of the container, the cover comprising a membrane for pressing the unmarked tissue against the optical substrate so that the entire cut edge of the unmarked tissue is flat against the optical substrate.

15. The system according to claim 14, in, The image is a virtually stained histological image of the unlabeled tissue.

16. The system according to claim 14, in, The cassette includes orientation markings that allow the orientation of the unmarked tissue to be maintained relative to a patient from which the unmarked tissue is resected.

17. The system according to claim 14, in, The cartridge includes a unique identifier.

18. A system for optical imaging of unlabeled tissue, the system include: a photon absorption remote sensing imaging system configured to image the unlabeled tissue to generate a virtually stained histological image of the unlabeled tissue; as well as A box body, the box body is used to store the unlabeled tissue to be imaged by the imaging system, the box body comprising: a container for storing the unlabeled tissue and for interfacing with the imaging system; an optical substrate disposed on a bottom surface of the container, wherein the imaging system is configured to image the unlabeled tissue through the optical substrate; and A cover is disposed on the top surface of the container, and the cover film is used to press the unmarked tissue against the optical substrate so that the entire cut edge of the unmarked tissue is flat against the optical substrate.

19. The system according to claim 18, in, The virtually stained histology images simulate hematoxylin and eosin stain.

20. The system according to claim 18, in, The virtually stained histological images are generated intraoperatively.

21. A cassette for storing unlabeled tissue to be imaged by an optical imaging system, the cassette include: a container for storing the unlabeled tissue and for interfacing with the optical imaging system, the optical imaging system being configured to image the unlabeled tissue to generate a virtually stained histological image of the unlabeled tissue; an optical substrate, the optical substrate being disposed on the bottom surface of the container, the optical imaging system being configured to image the unlabeled tissue through the optical substrate; as well as A cover is disposed on the top surface of the container, the cover comprising a film for pressing the unmarked tissue against the optical substrate so that the entire cut edge of the unmarked tissue lies flat against the optical substrate.

22. The box body according to claim 21, in, The cassette includes orientation markings that allow the orientation of the unmarked tissue to be maintained relative to a patient from which the unmarked tissue is resected.

23. The box body according to claim 22, in, The orientation mark is disposed on the optical substrate.

24. The box body according to claim 21, in, The cartridge includes a unique identifier.

25. The box body according to claim 24, in, The unique identifier is disposed on the container.

26. The box body according to claim 25, in, The unique identifier is a quick response code.

27. The box body according to claim 24, in, The unique identifier is an interlock of the optical imaging system.

28. The box body according to claim 24, in, The unique identifier prevents the cartridge from being used with another unlabeled tissue.

29. The box body according to claim 24, in, The unique identifier includes information identifying a pressure applied to the cassette to press the unmarked tissue against the optical substrate.

30. The box body according to claim 21, in, The box includes reference points for measurement by the optical imaging system.

31. The box body according to claim 21, in, The optical substrate includes a Fabry-Perot etalon.

32. The box body according to claim 21, in, The optical imaging system is a photon absorption remote sensing imaging system configured to produce radiative, non-radiative and scattering effects in the unlabeled tissue.

33. The box body according to claim 21, in, The virtually stained histology images simulate hematoxylin and eosin stain.

34. An optical imaging system, the optical imaging system being configured to: imaging unlabeled tissue stored in the cartridge; and A virtually stained histological image of the unlabeled tissue is generated.

35. An imaging system, the imaging system being configured to: imaging unlabeled tissue stored in the cartridge; and A virtually stained histological image of the unlabeled tissue is generated.

Images