System and methods for providing real-time anatomical guidance in a diagnostic or therapeutic procedure

Abstract

According to one aspect, a system for intraoperatively providing anatomical guidance in a diagnostic or therapeutic procedure is disclosed. In one embodiment, the system includes: a first light source configured to emit a beam of visible light; second light source configured to emit a beam of near-infrared light; a handheld probe optically coupled to the second light source; a second imaging device configured to detect visible light; a third imaging device configured to detect near-infrared light having a first predetermined wavelength; a fourth imaging device configured to detect near-infrared light having a second predetermined wavelength; a display for displaying at least one visual representation of data; and, a controller programmed to generate at least one real-time integrated visual representation of an area of interest and to display the real-time visual representation on the display for guidance during the diagnostic or therapeutic procedure.

1 . A system for intraoperatively providing anatomical guidance in a diagnostic or therapeutic procedure, comprising:
 (a) a first light source configured to emit a beam of visible light to an area of interest of a living subject;   (b) a second light source configured to emit a beam of near-infrared light to the area of interest;   (c) a handheld probe optically coupled to the second light source, comprising an optical fiber configured to deliver the emitted beam of near-infrared light to illuminate the area of interest and configured to collect light that is scattered or emitted from a contrast agent introduced into target tissues in the area of interest, in response to illumination by the second light source;   (d) a first imaging device optically coupled to the handheld probe and configured to detect the collected light and to generate a corresponding signal that comprises collected light data, and wherein the handheld probe is further configured to transmit the collected light to the first electronic imaging device through the optical fiber;   (e) a second imaging device configured to detect visible light that is emitted from the area of interest in response to illumination by the first light source and to generate a corresponding signal comprising visible light data;   (f) a third imaging device configured to detect near-infrared light having a first predetermined wavelength that is emitted from the area of interest in response to illumination by the second light source and to generate a corresponding signal comprising a first set of near-infrared light data;   (g) a fourth imaging device configured to detect near-infrared light having a second predetermined wavelength that is different from the first predetermined wavelength and that is emitted from the area of interest in response to illumination by the second light source, and to generate a corresponding signal comprising a second set of near-infrared light data;   (h) a display for displaying at least one visual representation of data; and   (i) a controller in communication with each of the first light source, second light source, first imaging device, second imaging device, third imaging device, fourth imaging device, and display, and programmed to generate at least one real-time integrated visual representation of the area of interest from each of the collected light data, visible light data, first set of near-infrared light data, and second set of near-infrared light data and to display the at least one real-time visual representation on the display, for guidance during the diagnostic or therapeutic procedure.   
     
     
         2 . The system of  claim 1 , wherein the contrast agent comprises at least one of a Raman probe and a fluorescence probe and the collected light data comprises at least one of Raman data and fluorescence data, respectively. 
     
     
         3 . The system of  claim 2 , wherein the at least one integrated visual representation comprises a wide-field image of the area of interest generated from the visible light data, a laser excitation image of a selected area of the area of interest defined within the wide-field image and generated from at least one of the generated first set of near-infrared light data and the generated second set of near-infrared light data, and at least one of a Raman image generated from the Raman data and a fluorescence image generated from the fluorescence data, wherein the at least one of the Raman image and fluorescence image is defined within the wide-field image and the laser excitation image. 
     
     
         4 . The system of  claim 3 , wherein the at least one of the Raman image and the fluorescence image is an overlay image on the laser excitation image. 
     
     
         5 . The system of  claim 1 , wherein the first imaging device comprises a spectrometer and each of the second imaging device, third imaging device, and fourth imaging device comprises a CCD camera. 
     
     
         6 . An imaging system using integrated bright-field imaging, near-infrared imaging, and at least one of Raman imaging and fluorescence imaging for intraoperatively evaluating target tissues in an area of interest of a living subject, comprising:
 (a) a first light source for delivering a beam of visible light to the area of interest and a second light source for delivering a beam of near-infrared light to the area of interest;   (b) a Raman and fluorescence imaging means, comprising:
 (i) a handheld probe optically coupled to the second light source for delivering the near infrared light to illuminate target tissues of the area of interest and for collecting at least one of scattered light and emitted light from a corresponding at least one of a Raman probe and a fluorescence probe that is introduced into the target tissues and illuminated by the second light source; and 
 (ii) a first imaging device in communication with the handheld probe for obtaining at least one of Raman data from the collected scattered light and fluorescence data from the collected emitted light, respectively; and 
   (c) a bright-field imaging means, comprising:
 (i) a second imaging device for obtaining visible light data from visible light emitted from the area of interest in response to illumination by the first light source; 
 (ii) a third imaging device for obtaining a first set of near-infrared data from light having a first predetermined wavelength that is emitted from the area of interest in response to illumination by the second light source; and 
 (iii) a fourth imaging device for obtaining a second set of near infrared data from light having a second predetermined wavelength that is different from the first predetermined wavelength and that is emitted from the area of interest in response to illumination by the second light source. 
   
     
     
         7 . The imaging system of  claim 6 , wherein the bright-field imaging means further comprises:
 (iv) an optical port;   (v) a system lens comprising a UV-NIR compact lens and a first achromatic correction lens;   (vi) a silver mirror;   (vii) a first dichroic mirror and a second dichroic mirror;   (viii) a first shortpass filter and a second shortpass filter;   (ix) a neutral density filter;   (x) a bandpass filter;   (xi) a longpass filter; and   (xii) a second achromatic lens, a third achromatic lens, and a fourth achromatic lens,
 wherein the optical port and the first imaging device define a first optical path therebetween having the silver mirror, the first dichroic mirror, the second dichroic mirror, and the second achromatic lens, wherein the optical port and the second imaging device define a second optical path therebetween having the silver mirror, first dichroic mirror, second dichroic mirror, neutral density filter, and third achromatic lens, and wherein the optical port and the third imaging device define a third optical path therebetween having the silver mirror, first dichroic mirror, longpass filter, bandpass filter, and fourth achromatic lens. 
   
     
     
         8 . The imaging system of  claim 6 , wherein the first imaging device comprises a spectrometer. 
     
     
         9 . The imaging system of  claim 6 , further comprising:
 (d) a display for displaying at least one visual representation of data; and   (e) a controller in communication with each of the first light source, second light source, first imaging device, second imaging device, third imaging device, fourth imaging device, and display, and programmed for generating in real time at least one integrated visual representation of the area of interest from the visible light data, first set of near-infrared data, second set of near-infrared data, and at least one of the Raman data and fluorescence data and displaying the integrated visual representation on the display, to provide guidance for performing a diagnostic or therapeutic procedure.   
     
     
         10 . The imaging system of  claim 9 , wherein the at least one real-time integrated visual representation of the area of interest comprises a wide-field image of the area of interest generated from the visible light data, a laser excitation image of a predetermined area defined within the wide-field image that is generated from at least one of the first set of near-infrared data and the second set of near-infrared data, and at least one of a Raman image and a fluorescence image that is generated from a corresponding at least one of the Raman data and fluorescence data. 
     
     
         11 . The imaging system of  claim 10 , wherein the laser excitation image is an overlay image on the wide-field image and represents the location of the delivered beam of near-infrared light within the area of interest. 
     
     
         12 . The imaging system of  claim 10 , wherein the at least one of the Raman data and fluorescence data is represented by a signal that, when exceeding a predefined threshold level, signifies disease in the target tissues. 
     
     
         13 . The imaging system of  claim 12 , wherein the at least one of the Raman image and the fluorescence image is a color overlay image on the laser excitation image, having an opacity representative of the level of the signal exceeding the predefined threshold level. 
     
     
         14 . The imaging system of  claim 13 , wherein the opacity of the color overlay image decays over time to be progressively more translucent relative to the laser excitation image. 
     
     
         15 . A method for intraoperatively providing anatomical guidance in a diagnostic or therapeutic procedure, comprising the steps of:
 (a) introducing at least one contrast agent into target tissues in an area of interest of a living subject;   (b) emitting a beam of visible light to the area of interest, using a first light source;   (c) emitting a beam of near-infrared light to the area of interest, using a second light source;   (d) delivering the emitted beam of near-infrared light to illuminate the area of interest, using an optical fiber of a handheld probe that is optically coupled to the second light source;   (e) collecting at least one of scattered light and emitted light from the contrast agent in response to illumination by the second light source, using the optical fiber of the handheld probe, wherein the contrast agent comprises at least one of a Raman probe and a fluorescence probe;   (f) detecting the collected light and generating a corresponding signal that comprises collected light data, using a first imaging device that is optically coupled to the optical fiber, and wherein the optical fiber is further configured to deliver the collected light to the first imaging device;   (g) detecting visible light that is emitted from the area of interest in response to illumination by the first light source and generating a corresponding signal comprising visible light data, using a second imaging device;   (h) detecting near-infrared light having a first predetermined wavelength that is emitted from the area of interest in response to illumination by the second light source and generating a corresponding signal comprising a first set of near-infrared light data, using a third imaging device;   (i) detecting near-infrared light having a second predetermined wavelength that is different from the first predetermined wavelength and that is emitted from the area of interest in response to illumination by the second light source and generating a corresponding signal comprising a second set of near-infrared light data, using a fourth imaging device;   (j) generating at least one real-time integrated visual representation of the area of interest from the collected light data, visible light data, first set of near-infrared data, and second set of near-infrared data, using a controller in communication with each of the first imaging device, second imaging device, third imaging device, and fourth imaging device; and   (k) displaying the at least one real-time integrated visual representation generated by the controller, for guidance during a diagnostic or therapeutic procedure, using a display in communication with the controller.   
     
     
         16 . The method of  claim 15 , wherein the step of generating the at least one real-time integrated visual representation of the area of interest comprises the steps of generating a wide-field image of the area of interest from the visible light data, generating a laser excitation image of a selected area of the area of interest defined within the wide-field image from at least one of the first set near-infrared light data and the second set of near-infrared light data, and generating at least one of a Raman image and a fluorescence image, from the collected light data, that is defined within the wide-field image and the laser excitation image. 
     
     
         17 . The method of  claim 15 , wherein the first imaging device comprises a spectrometer. 
     
     
         18 . The method of  claim 15 , wherein each of the second imaging device, third imaging device, and fourth imaging device comprises a CCD camera. 
     
     
         19 . A computer-readable medium having stored thereon computer-executable instructions which, when executed by a controller, cause a computer to perform functions for intraoperatively providing anatomical guidance in a surgical procedure, the functions comprising:
 (a) causing a first light source in communication with the controller to emit a beam of visible light to an area of interest of a living subject;   (b) causing a second light source optically coupled to an optical fiber and in communication with the controller to emit a beam of near-infrared light to the area of interest through the optical fiber;   (c) causing the optical fiber of the handheld probe to collect at least one of light scattered from a Raman probe introduced into the target tissues in response to illumination by the second light source and light emitted from fluorescence probe introduced into the target tissues in response to illumination by the second light source;   (d) causing a first imaging device in communication with the controller and the optical fiber to detect at least one of light that is scattered from the Raman probe and light that is emitted from the fluorescence probe, and collected through the optical fiber, in response to illumination from the second light source;   (e) causing the first imaging device to generate at least one of a signal from the detected scattered light that comprises Raman data and a signal from the detected emitted light that comprises fluorescence data, respectively;   (f) causing a second imaging device that is in communication with the controller to detect visible light that is emitted from the area of interest in response to illumination by the first light source, and causing the second imaging device to generate a corresponding signal comprising visible light data;   (g) causing a third imaging device that is in communication with the controller to detect near-infrared light having a first predetermined wavelength that is emitted from the area of interest in response to illumination by the second light source and causing the third imaging device to generate a corresponding signal comprising a first set of near-infrared light data;   (h) causing a fourth imaging device that is in communication with the controller to detect near-infrared light having a second predetermined wavelength that is different from the first predetermined wavelength and that is emitted from the area of interest in response to illumination by the second light source, and causing the fourth imaging device to generate a corresponding signal comprising a second set of near-infrared light data;   (i) generating at least one real-time integrated visual representation of the area of interest from the visible light data, first set of near-infrared data, second set of near-infrared data, and at least one of the Raman data and fluorescence data; and   (j) causing a display in communication with the controller to display the generated at least one real-time integrated visual representation for guidance during a diagnostic or therapeutic procedure.   
     
     
         20 . The computer-readable medium of  claim 19 , wherein the step of generating the at least one real-time integrated visual representation of the area of interest comprises the steps of generating a wide-field image of the area of interest from the visible light data, generating a laser excitation image of a selected area of the area of interest defined within the wide-field image from at least one of the first set near-infrared light data and the second set of near-infrared light data, and generating at least one of a Raman image from the Raman data and a fluorescence image from the fluorescence data that is defined within the wide-field image and the laser excitation image. 
     
     
         21 . The computer-readable medium of  claim 20 , wherein the at least one of the Raman image and the fluorescence image is an overlay image on the laser excitation image. 
     
     
         22 . The computer-readable medium of  claim 19 , wherein the first imaging device comprises a spectrometer. 
     
     
         23 . The computer-readable medium of  claim 19 , wherein each of the second imaging device, third imaging device, and fourth imaging device comprises a CCD camera. 
     
     
         24 . A method for intraoperatively identifying disease in target tissues in an area of interest of a living subject, to be resected in a diagnostic or therapeutic procedure, comprising the steps of:
 (a) introducing at least one of a Raman probe and a fluorescence probe into the area of interest until the at least one probe has accumulated in the target tissues;   (b) preparing the living subject and the area of interest for a diagnostic or therapeutic procedure;   (c) initializing an imaging system for integrated bright-field imaging, near-infrared imaging, and at least one of Raman imaging and fluorescence imaging;   (d) beginning the diagnostic or therapeutic procedure in the area of interest;   (e) using a first real-time integrated visual representation of the area of interest and the target tissues, generated by the imaging system, to identify a boundary of the target tissues that are diseased;   (f) performing a surgical resection of the identified diseased target tissues within the boundary;   (g) after the surgical resection, using a second displayed at least one real-time integrated visual representation of the area of interest and the target tissues, generated by the imaging system, to identify any remaining diseased target tissues within the boundary; and   (h) if any remaining diseased target tissues are identified, performing a series of further surgical resections on identified remaining diseased target tissues corresponding to a respective series of real-time integrated visual representations generated by the imaging system, until the area of interest is free from diseased target tissues.   
     
     
         25 . The method of  claim 24 , wherein the imaging system comprises:
 (a) a first light source configured to emit a beam of visible light to an area of interest of a living subject;   (b) a second light source configured to emit a beam of near-infrared light to the area of interest;   (c) a handheld probe optically coupled to the second light source, comprising an optical fiber configured to deliver the emitted beam of near-infrared light to illuminate the area of interest and configured to collect light that is scattered or emitted from a contrast agent introduced into target tissues in the area of interest, in response to illumination by the second light source;   (d) a first imaging device optically coupled to the handheld probe and configured to detect the collected light and to generate a corresponding signal that comprises collected light data, and wherein the handheld probe is further configured to transmit the collected light to the first imaging device through the optical fiber;   (e) a second imaging device configured to detect visible light that is emitted from the area of interest in response to illumination by the first light source and to generate a corresponding signal comprising visible light data;   (f) a third imaging device configured to detect near-infrared light having a first predetermined wavelength that is emitted from the area of interest in response to illumination by the second light source and to generate a corresponding signal comprising a first set of near-infrared light data;   (g) a fourth imaging device configured to detect near-infrared light having a second predetermined wavelength that is different from the first predetermined wavelength and that is emitted from the area of interest in response to illumination by the second light source, and to generate a corresponding signal comprising a second set of near-infrared light data;   (h) a display for displaying at least one visual representation of data; and   (i) a controller in communication with each of the first light source, second light source, first imaging device, second imaging device, third imaging device, fourth imaging device, and display, and programmed to generate at least one real-time integrated visual representation of the area of interest from each of the collected light data, visible light data, first set of near-infrared light data, and second set of near-infrared light data and to display the at least one real-time visual representation on the display, for guidance during the diagnostic or therapeutic procedure.   
     
     
         26 . The method of  claim 24 , wherein the step of identifying the boundary of the target tissues that are diseased and the step of identifying any remaining diseased target tissues within the boundary comprise identifying visual representations of the first set of near-infrared light data, second set of near-infrared light data, and collected light data that are displayed in a selected area of the integrated visual representation. 
     
     
         27 . The method of  claim 24 , wherein the visual representation of the first set of near-infrared data and second set of near-infrared data is a laser excitation image that represents the location of the delivered beam of near-infrared light within the area of interest, and that is displayed as a color overlay image on the wide-field image. 
     
     
         28 . The method of  claim 27 , wherein the signal representing the collected light data that is generated by the first imaging device, when exceeding a predetermined threshold level, signifies disease in the target tissues. 
     
     
         29 . The method of  claim 28 , wherein the visual representation of the collected light data is a color overlay image on the laser excitation image, having an opacity representative of the level of the signal exceeding the predefined threshold level. 
     
     
         30 . The method of  claim 29 , wherein the opacity of the color overlay image that represents the collected light data decays over time to be progressively more translucent relative to the laser excitation image.