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BR-112020015757-B1 - Methods, systems, kits, and devices for tumor visualization and removal.

BR112020015757B1BR 112020015757 B1BR112020015757 B1BR 112020015757B1BR-112020015757-B1

Abstract

A method for evaluating surgical margins is disclosed. The method involves, following the administration of a compound configured to induce emissions between approximately 600 nm and approximately 660 nm in cancerous tissue cells, positioning a distal end of a portable fluorescence- and white light-based imaging device adjacent to a surgical margin. The method also involves, with the portable device, substantially and simultaneously exciting and detecting autofluorescence emissions from tissue cells and fluorescence emissions of the induced wavelength in tissue cells of the surgical margin. And, based on the presence or quantity of induced wavelength fluorescence emissions detected in the tissue cells of the surgical margin, determining whether the surgical margin is substantially free of at least one of the following precancerous cells, cancerous cells, and satellite lesions. The compound may be a non-activated, non-targeted compound, such as ALA.

Inventors

  • Ralph DACOSTA
  • Christopher Gibson
  • Kathryn OTTOLINO-PERRY
  • NAYANA THALANKI ANANTHA
  • SUSAN JANE DONE
  • Wey-Liang LEONG
  • ALEXANDRA M. EASSON

Assignees

  • UNIVERSITY HEALTH NETWORK

Dates

Publication Date
20260317
Application Date
20190201
Priority Date
20180202

Claims (18)

  1. 1. Portable imaging device based on fluorescence and white light (600; 700; 800; 900; 1000; 1100) for visualization of at least one of the following: precancerous cells, cancerous cells, and satellite lesions at surgical margins, characterized in that it comprises: a body (610; 710; 810; 910; 1010; 1110) having a first end portion (112) configured to be held in a user's hand and a second end portion (114), wherein the second end portion (114) of the body (610; 710; 810; 910; 1010; 1110) is elongated and configured to: be at least partially positioned inside a surgical cavity containing a surgical margin, be inserted through a 3 cm in size surgical incision and into the cavity surgical, directing light onto the surgical margin, wherein the body (610; 710; 810; 910; 1010; 1110) contains: at least one excitation light source configured to excite autofluorescence emissions from tissue cells and fluorescence emissions from porphyrins induced in tissue cells of the surgical margin; a filter (652; 752; 852; 952; 1052; 1152) configured to prevent the passage of reflected excitation light and allow the passage of emissions that have a wavelength corresponding to autofluorescence emissions from tissue cells and fluorescence emissions from porphyrins induced in tissue cells; an imaging lens (662; 762; 862; 962; 1062; 1162); an image sensor (648; 748; 848; 948; 1048; 1148) configured to detect filtered autofluorescence emissions from tissue cells and fluorescence emissions from porphyrins induced in tissue cells from the surgical margin; a processor configured to receive the detected emissions and to output data regarding the detected filtered autofluorescence emissions from tissue cells and fluorescence emissions from porphyrins induced in tissue cells from the surgical margin; and inductive charging coils (640; 740; 840; 940; 1040; 1140) for charging the device.
  2. 2. Device according to claim 1, characterized in that a distal end portion is configured to be positioned adjacent to the surgical margin without coming into contact with the surgical margin.
  3. 3. Device according to claim 1 or 2, characterized in that at least one excitation light source emits light having a wavelength between about 375 nm and about 800 nm.
  4. 4. Device according to any one of claims 1 to 3, characterized in that at least one excitation light source includes a first excitation light source emitting a first excitation light having a wavelength between about 375 nm and about 430 nm and a second excitation light source emitting a second excitation light having a wavelength between about 550 nm and about 600 nm.
  5. 5. Device according to any one of claims 1 to 4, characterized in that: a) at least one excitation light source includes a first light source (120) comprising a plurality of LEDs configured to emit light at a first wavelength; b) at least one excitation light source includes a second light source (124) comprising a second plurality of LEDs configured to emit light at a second wavelength, different from the first wavelength; c) at least one excitation light source further includes a third excitation light source (128) that emits light at a third wavelength, different from the first wavelength and the second wavelength; d) the third excitation light source (128) is positioned adjacent to the first and second excitation light sources (120, 124); and e) the third excitation light source (128) is configured to excite surgical margin tissue cells containing infrared or near-infrared dye.
  6. 6. Device according to claim 5, characterized in that the third wavelength is between about 700 nm and about 750 nm, about 750 nm and about 800 nm, or about 800 nm and about 850 nm.
  7. 7. Device according to any one of claims 1 to 6, characterized in that it further comprises a white light source to facilitate white light imaging of the surgical cavity.
  8. 8. Device according to any one of claims 1 to 7, characterized in that it further comprises controls for at least one of the following: on/off, picture mode/video mode, excitation light/white light, and filter on/filter off.
  9. 9. Device according to any one of claims 1 to 8, characterized in that it further comprises an ambient light sensor configured to indicate when fluorescence imaging conditions are appropriate.
  10. 10. Device according to any one of claims 1 to 9, characterized in that the device is configured to wirelessly transmit data regarding detected filtered autofluorescence emissions from tissue cells and fluorescence emissions from porphyrins induced in tissue cells at the surgical margin.
  11. 11. Device according to any one of claims 1 to 10, characterized in that the device is configured to detect porphyrin-containing cancer cells induced by administering a therapeutic or diagnostic dose of a non-activated, non-targeted compound configured to induce porphyrins in cancerous tissue.
  12. 12. Device according to any one of claims 1 to 11, characterized in that the first end portion (112) of the body (610; 710; 810; 910; 1010; 1110) of the device forms a base of the device, and in which inductive charging coils (640; 740; 840; 940; 1040; 1140) are positioned on the base of the device for wireless charging of the device.
  13. 13. Multispectral system (1300) for visualizing cancerous cells in surgical margins, characterized in that it comprises: a portable device (600; 700; 800; 900; 1000; 1100) defined in any of claims 1 to 12; a display device (1280) configured to display data emitted by the processor of the portable device (600; 700; 800; 900; 1000; 1100); and a wireless real-time data pre-processing and storage device, optionally configured to receive video and/or image data transmitted from the portable device (600; 700; 800; 900; 1000; 1100).
  14. 14. System according to claim 13, characterized in that it further comprises an autoclave case configured to receive the portable device (600; 700; 800; 900; 1000; 1100) and/or a charging point for wireless charging of the portable device (600; 700; 800; 900; 1000; 1100).
  15. 15. Kit for visualization based on white light and fluorescence of cancerous cells in a surgical margin, characterized in that it comprises: a portable device (600; 700; 800; 900; 1000; 1100) defined in any of claims 1 to 12; and a non-targeted, non-activated compound configured to induce porphyrins in cancerous tissue cells, optionally configured to be administered topically, orally, intravenously, via aerosol, via immersion and/or via washing.
  16. 16. Kit according to claim 15, characterized in that the unbleached, unactivated compound is aminolevulinic acid.
  17. 17. Kit according to claim 15, characterized in that it further comprises a sheath to cover the device and provide a sterile barrier, wherein the sheath optionally includes or is coupled to an optical window covering a distal end of the handheld device to ensure accurate transmission of light emitted from the device.
  18. 18. A method for evaluating an excised tissue specimen, characterized in that it comprises: subsequent to the administration to the excised tissue specimen of an unactivated, untargeted compound configured to induce porphyrins in cancerous tissue cells, and with the device defined in any one of claims 1 to 12; illuminating tissue cells of the excised tissue specimen with an excitation light; detecting fluorescence emissions from tissue cells in the excised tissue specimen containing induced porphyrins; and displaying in real time the tissue cells among which fluorescence emissions were detected.

Description

[001] This application claims priority to Provisional Application No. 62/625,967, filed on February 2, 2018, to Provisional Application No. 62/625,983, filed on February 3, 2018, and to Provisional Application No. 62/793,843, filed on January 17, 2019, the entire content of each of which is incorporated by reference into the present invention. FIELD OF TECHNIQUE [002] The present disclosure relates to devices, systems, and methods for visualizing and removing tumors. The disclosed devices, systems, and methods can also be used to stage tumors and evaluate surgical margins and specimens such as tissue margins, excised tissue specimens, and tissue slices from excised tumors and margins in the tissue beds/surgical bed from which a tumor and/or tissue has been removed. The disclosed devices, systems, and methods can also be used to identify one or more residual cancerous cells, precancerous cells, and satellite lesions and provide guidance for their removal and/or treatment. The disclosed devices can be used to obtain materials to be used for diagnostic and planning purposes. INTRODUCTION [003] Surgery is one of the oldest types of cancer therapy and is an effective treatment for many types of cancer. Oncological surgery can take different forms depending on the goals of the surgery. For example, oncological surgery may include biopsies to diagnose or determine a type or stage of cancer, tumor removal to remove some or all of a tumor or cancerous tissue, exploratory surgery to locate or identify a tumor or cancerous tissue, debridement surgery to reduce the size or remove as much as possible of a tumor without adversely affecting other body structures, and palliative surgery to treat conditions caused by a tumor such as pain or pressure on body organs. [004] In surgeries where the goal is to remove the tumor (or tumors or cancerous tissue), surgeons often encounter uncertainty in determining whether all the cancer has been removed. The surgical bed or tissue bed from which a tumor is removed may contain residual cancer cells, that is, cancer cells that remain at the surgical margin of the area from which the tumor is removed. If residual cancer cells remain in the body, the likelihood of recurrence and metastasis increases. Frequently, the suspected presence of residual cancer cells, based on examination of surgical margins of the excised tissue during pathological analysis of the tumor, leads to secondary surgery to remove additional tissue from a surgical margin. [005] For example, breast cancer, the most prevalent cancer in women, is commonly treated by breast-conserving surgery (BCS), for example, a lumpectomy, which removes the tumor while leaving as much healthy breast tissue as possible. The effectiveness of BCS treatment depends on the complete removal of malignant tissue while leaving enough healthy breast tissue to ensure adequate breast reconstruction, which can be poor if too much breast tissue is removed. Visualization of tumor margins under standard operating room conditions with white light (WL) is challenging due to the low contrast of normal tissue to tumor, resulting in reoperation (i.e., secondary surgery) in approximately 23% of patients with early-stage invasive breast cancer and 36% of patients with ductal carcinoma in situ. Re-excision is associated with a higher risk of recurrence, worse patient outcomes including reduced breast cosmesis, and increased healthcare costs. Positive surgical margins (i.e., margins containing cancerous cells) after BCS are also associated with decreased disease-specific survival. [006] Current best practice in BCS involves palpation and/or specimen radiography and, rarely, intraoperative histopathology to guide resection. Specimen radiography assesses excised margins using X-ray images, and intraoperative histopathology (touch-prepared or frozen) assesses small specimen tissue samples for cancerous cells, both of which are limited by the time delay they cause (~20 min) and inaccurate colocalization of a positive margin in the excised tissue to the surgical bed. Thus, there is an urgent clinical need for intraoperative imaging technology to assess the excised specimen and surgical bed margins and provide guidance for visualization and removal of one or more residual cancerous cells, precancerous cells, and satellite lesions. SUMMARY [007] The present disclosure may solve one or more of the problems mentioned above and/or may demonstrate one or more of the desirable characteristics mentioned above. Other characteristics and/or advantages may become evident from the description that follows. [008] According to one aspect of the present disclosure, a method for evaluating surgical margins and/or specimens is disclosed. The method comprises, subsequent to the administration of a compound configured to induce porphyrins in cancerous tissue cells, positioning a distal end of a portable fluorescence- and white light-based imaging device adjacent to a surgical margin.