Wide field raman imaging apparatus and associated methods

Patent metadata

Field	Value
Publication number	US-2016000329-A1
Application number	US-201414768117-A
Country	US
Kind code	A1
Filing date	Feb 20, 2014
Priority date	Feb 20, 2013
Publication date	Jan 7, 2016
Grant date	—

Abstract

Apparatus and methods are presented herein that permit real-time, accurate detection of residual tumor in the operating room. The Raman-based wide-field imaging apparatus and methods described herein permit real-time imaging of tumor-targeted R-MR nanoparticles over a wide field.

First claim

We claim:

1 . A wide field Raman imaging apparatus comprising:
at least one light source for producing excitation light; optics for directing the excitation light onto and/or into a target tissue; a detector for detecting Raman scattered photons emanating from the target tissue following illumination by the excitation light, the Raman scattered photons indicative of the presence of a Raman reporter in and/or upon the target tissue; and a processor configured to process data corresponding to the Raman scattered photons detected from the target tissue and to produce an image depicting a wide field corresponding to the target tissue, the image visually indicating position and/or intensity of the Raman reporter within the wide field.

2 . The apparatus of claim 1 , wherein the at least one light source, the detector, and the processor are configured to produce a substantially real-time series of images visually indicating position and/or intensity of the Raman reporter within the wide field.

3 . The apparatus of claim 2 , wherein the processor is configured to produce each image of the real-time series of images by obtaining one or more monochromatic images within a given short interval of time (e.g., 500 milliseconds or less, e.g., 50 milliseconds or less), each monochromatic image obtained at a wavelength corresponding to a spectral peak characteristic of the Raman reporter, and to use the one or more monochromatic images to produce the image in the real-time series indicating the position and/or intensity of the Raman reporter within the wide field during the given short interval of time.

4 . The apparatus of any one of the preceding claims, wherein the wide field is at least 100 cm 2 in area (e.g., at least 300, 500, 1000, or 1200 cm 2 ).

5 . The apparatus of any one of the preceding claims, wherein the at least one light source comprises a tunable laser source.

6 . The apparatus of any one of the preceding claims, wherein the optics comprise a tunable laser line filter (LLF) and/or a tunable notch filter (NF) (e.g., said filter(s) comprising tandem thick volume Bragg gratings).

7 . The apparatus of any one of the preceding claims, wherein the detector is a hyperspectral imager with a spatial resolution no greater than about 10 mm 2 (e.g., from 0.1 mm 2 to 3 mm 2 , e.g., about 1 mm 2 ).

8 . The apparatus of any one of the preceding claims, wherein the detector comprises an optical pathway configured to allow x-y imaging of the Raman reporter within the wide field regardless of depth (z) of the Raman reporter in relation to the detector.

9 . The apparatus of any one of the preceding claims, further comprising a visual display for viewing the image.

10 . The apparatus of any one of the preceding claims, wherein the processor is configured to produce a substantially real-time series of images and transmit the images for display on a personal image display (e.g., worn by the surgeon), such that the series of images can be displayed on, in, or through a transparent display that superimposes the displayed series of images over a corresponding view of the wide field.

11 . The apparatus of claim 10 , wherein the processor is configured to track the position of the personal image display and compensate the series of images for movement of the display (e.g., movement of the wearer of the display), accordingly (e.g., by tracking the location of markers affixed on or near the patient as they appear within a field of view of the personal image display).

12 . The apparatus of any one of the preceding claims, further comprising a visual display, wherein the visual display is an adjustable tablet-shaped screen positionable in relation to the target tissue of a patient in an operating bed, wherein the optics for directing the excitation light onto and/or into the target tissue are positioned on the side of the tablet-shaped screen facing the operating bed, and the image is displayed on the side of the tablet-shaped screen facing away from the operating bed so as to be viewable by a surgeon.

13 . The apparatus of any one of the preceding claims, wherein the light source for producing excitation light comprises one or more lasers, and wherein the optics for directing the excitation light onto and/or into the target tissue are configured to disperse the excitation light evenly over the wide field corresponding to the target tissue.

14 . A method for performing wide field Raman imaging of target tissue of a patient during a surgical procedure, the method comprising:
administering a first Raman reporter to the patient (e.g., intravenously, topically, intraarterially, intratumorally, intranodally, via lymphatic vessels, etc.); illuminating the target tissue with excitation light; detecting Raman scattered photons emanating from the target tissue following illumination by the excitation light, the Raman scattered photons indicative of the presence of the first Raman reporter in and/or upon the target tissue; obtaining, by the processor of a computing device, an image depicting a wide field corresponding to the target tissue, the image visually indicating position and/or intensity of the first Raman reporter within the wide field; and displaying the image.

15 . The method of claim 14 , wherein the first Raman reporter accumulates within and/or upon cancerous, diseased, and/or otherwise abnormal portions of the target tissue prior to the illuminating and detecting step.

16 . The method of claim 14 or 15 , comprising obtaining, by the processor of the computing device, a substantially real-time series of images visually indicating position and/or intensity of the first Raman reporter within the wide field and displaying the series of images in real-time.

17 . The method of claim 16 , comprising obtaining, for each image of the real-time series of images, by the processor of the computing device, one or more monochromatic images within a given short interval of time (e.g., 500 milliseconds or less, e.g., 50 milliseconds or less), each monochromatic image obtained at a wavelength corresponding to a spectral peak characteristic of the Raman reporter, and using the one or more monochromatic images to produce the image in the real-time series indicating the position and/or intensity of the Raman reporter within the wide field during the given short interval of time.

18 . The method of claim 16 or 17 , comprising displaying the real-time series of images at a frame rate at least 10 frames per second (e.g., 20 to 25 frames per second).

19 . The method of any one of claims 14 to 18 , wherein the first Raman reporter comprises Raman-MRI (R-MR) nanoparticles.

20 . The method of any one of claims 14 to 18 , wherein the first Raman reporter comprises SERRS nanoparticles.

21 . The method of any one of claims 14 to 20 , comprising administering a second Raman reporter to the patient with different Raman signature than the first Raman reporter, wherein the detected Raman scattered photons are indicative of the presence of the first Raman reporter and the second Raman reporter in and/or upon the target tissue, and wherein the image visually indicates position and/or intensity of the first Raman reporter and the second Raman reporter within the wide field in a manner such that the first Raman reporter is distinguishable from the second Raman reporter.

22 . The method of any one of claims 14 to 21 , wherein the wide field is at least 100 cm 2 in area (e.g., at least 300, 500, 10

Assignees

• Sloan Kettering Inst Cancer

Inventors

• Kircher Moritz
• Toledo-Crow Ricardo

Classifications

• G01N21/65

  Raman scattering · CPC title

• A61B18/12

  by passing a current through the tissue to be heated, e.g. high-frequency current · CPC title

• A61B18/02

  by cooling, e.g. cryogenic techniques · CPC title

• A61B2018/00642

  with feedback, i.e. closed loop control · CPC title

• A61M31/005

  for contrast media · CPC title