Imaging systems and methods for tissue differentiation, e.g., for intraoperative visualization

Patent metadata

Field	Value
Publication number	US-2019090750-A1
Application number	US-201616060463-A
Country	US
Kind code	A1
Filing date	Dec 15, 2016
Priority date	Dec 15, 2015
Publication date	Mar 28, 2019
Grant date	—

Abstract

Described herein is a multiplex platform that uses ultrasmall nanoparticles (e.g., C dots and C′ dots) to graphically differentiate specific nerves (e.g., sensory nerves vs. motor nerves) for nerve transplants and other surgeries. Also described herein is a multiplex platform that uses ultrasmall nanoparticles (e.g., C dots and C′ dots) to graphically differentiate between different types of lymph nodes and/or lymphatic pathways, e.g., to safely and effectively perform vascularized lymph node transplantation in the treatment of lymphedema. Also described herein is a multiplex platform that uses ultrasmall nanoparticles (e.g., C dots and C′ dots) to graphically differentiate parathyroid tissue.

First claim

1 . A method comprising:
administering two or more different probe species each comprising a spectrally differentiable fluorescent reporter to a lymphatic system; and directing excitation light into the lymph nodes, thereby exciting the fluorescent reporters having spectrally distinguishable emission wavelengths.

2 . The method of claim 1 , wherein the administering comprises intravenously administering two or more different probe species.

3 . The method of claim 1 , wherein the two or more different probe species comprise nanoparticles.

4 . The method of claim 1 , wherein at least a first probe is administered to a tumor site and at least a second probe is administered to an extremity that would be potentially affected by lymphedema.

5 . The method of claim 4 , wherein the tumor site comprises a member selected from the group consisting of a breast, a trunk, an abdomen, a pelvis, and a thoracic cavity.

6 . The method of claim 4 , wherein the extremity comprises a member selected from the group consisting of an upper limb and a lower limb.

7 . The method of claim 1 , wherein the excitation light comprises two or more wavelengths, thereby exciting the different fluorescent reporters.

8 . The method of claim 1 , comprising identifying an appropriate lymph node for transplantation in the treatment of lymphedema.

9 . The method of claim 1 , comprising:
simultaneously detecting fluorescent light of spectrally different emission wavelengths, the detected fluorescent light having been emitted by the fluorescent reporters of the respective probe species in the lymph nodes and/or drainage pathways as a result of illumination by excitation light so as to discriminate between signals received from each probe species.

10 . The method of claim 1 , wherein the fluorescent reporter of a first probe species having received the excitation light fluoresces at a spectrally distinguishable wavelength compared to a second fluorescent reporter of another probe species having received the excitation light.

11 . The method of claim 10 , wherein a signal comprising the spectrally distinguishable emission wavelengths is represented on a display to graphically distinguish between two kinds of lymph nodes and/or drainage pathways.

12 . The method of claim 9 , further comprising identifying an appropriate lymph node for excision.

13 . The method of claim 11 , wherein an upper portion of the display shows a first probe species and the bottom portion of the display shows a second probe species.

14 . The method of claim 11 , wherein the display shows a superimposed image of the first and second probe species.

15 . The method of claim 1 , comprising:
displaying a map of lymph nodes and/or lymphatic pathways of the lymphatic system, wherein the map graphically differentiates between specific lymph nodes and/or between specific lymph node types.

16 . The method of claim 15 , wherein at least one lymph node drains the extremities and at least one lymph node drains a tumor site.

17 . The method of claim 15 , wherein the tumor site comprises a member selected from the group consisting of abreast, a trunk, an abdomen, a pelvis, and a thoracic cavity.

18 . The method of claim 15 , wherein the fluorescent reporter of one probe species indicates drainage to the extremities.

19 . The method of claim 15 , wherein the fluorescent reporter of one probe species indicates drainage to the tumor site, thereby avoiding critical lymph nodes that may lead to lymphedema.

20 . A method comprising:
administering two or more different probe species each comprising a spectrally differentiable fluorescent reporter to nerves; and directing excitation light into the nerves, thereby exciting the fluorescent reporters having spectrally distinguishable emission wavelengths.

21 . (canceled)

22 . (canceled)

23 . The method of claim 20 , wherein the nerves comprise a member selected from the group consisting of, motor nerves and sensory nerves.

24 - 36 . (canceled)

37 . The method of claim 1 , wherein the two or more probes species comprise silica.

38 . The method of claim 37 , wherein the two or more probe species comprise nanoparticles that have a silica architecture and a dye-rich core.

39 . The method of claim 38 , wherein the nanoparticles comprise C or C′ dots.

40 . The method of claim 38 , wherein the dye rich core comprises the fluorescent reporter.

41 . The method of claim 1 , wherein the fluorescent reporter is a near infrared or far red dye.

42 . The method of claim 1 , wherein the fluorescent reporter is selected from the group consisting of a fluorophore, fluorochrome, dye, pigment, fluorescent transition metal, and fluorescent protein.

43 . The method of claim 1 , wherein the fluorescent reporter is selected from the group consisting of Cy5, Cy5.5, Cy2, FITC, TRITC, Cy7, FAM, Cy3, Cy3.5, Texas Red, ROX, HEX, JA133, AlexaFluor 488, AlexaFluor 546, AlexaFluor 633, AlexaFluor 555, AlexaFluor 647, DAPI, TMR, R6G, GFP, enhanced GFP, CFP, ECFP, YFP, Citrine, Venus, YPet, CyPet, AMCA, Spectrum Green, Spectrum Orange, Spectrum Aqua, Lissamine, Europium, Dy800 dye, and LiCor 800 dye.

44 . The method of claim 1 , wherein the fluorescent light from the fluorescent reporters are detected and mapped in real-time using a handheld fluorescence camera system.

45 . A kit comprising:
a plurality of containers, wherein each container has a type selected from the group consisting of an ampule, a vial, a cartridge, a reservoir, a lyo-ject, and a pre-filled syringe; a first probe species each comprising a first fluorescent reporter; a second probe species each comprising a second fluorescent reporter, wherein a first container of the plurality of containers holds the first probe species and the second container of the plurality of containers holds the second probe species.

46 . The kit of claim 45 , wherein the kit is for identification of an appropriate lymph node for excision.

47 . The kit of claim 45 , wherein the kit is for use in treating lymphedema.

48 . The kit of claim 45 , wherein the kit is for identification of an appropriate nerve for transplantation.

49 . (canceled)

50 . The kit of claim 45 , wherein the first and second probe species comprise a member selected from the group consisting of nanoparticles, C dots, and C′ dots.

51 . (canceled)

52 . (canceled)

53 . An imaging method comprising:
administering to a subject a plurality of compositions, each composition comprising at least one peptide, and allowing the compositions to selectively bind to tissues of the subject, wherein a first composition of the plurality comprises a first peptide that selectively binds to a first tissue type and wherein a second composition of the plurality comprises a second peptide that selectively binds to a second tissue type; exposing tissue of the subject to excitation light; and detecting light emitted by a first fluorescent agent of the first composition and a second fluorescent agent of the second composition to create an image; and displaying the image.

54 - 56 . (canceled)

Assignees

• Memorial Sloan Kettering Cancer Center
• Univ Cornell

Inventors

• Bradbury Michelle S
• Yoo Barney
• Wiesner Ulrich
• Chen Peiming
• Ma Kai
• Patel Snehal G
• Zanoni Daniella Karassawa
• Dayan Joseph
• Abu-Rustum Nadeem R

Classifications

• A61M5/007

  for contrast media · CPC title

• A61B5/0071 Primary

  by measuring fluorescence emission · CPC title

• A61K49/0093 Primary

  Nanoparticle, nanocapsule, nanobubble, nanosphere, nanobead, i.e. having a size or diameter smaller than 1 micrometer, e.g. polymeric nanoparticle · CPC title

• A61B5/413

  Monitoring transplanted tissue or organ, e.g. for possible rejection reactions after a transplant · CPC title

• A61B5/743

  Displaying an image simultaneously with additional graphical information, e.g. symbols, charts, function plots · CPC title