System and Method of Chemical Imaging Using Puled Laser Excitation and Time-Gated Detection to Determine Tissue Margins During Surgery

Abstract

System and method for differentiating tissue margins in a biological sample using pulsed laser excitation and time-gated detection. A region containing a biological tissue is irradiated with substantially monochromatic pulsed laser light to thereby produce Raman scattered photons. The Raman scattered photons are detected using time-gated detection to thereby obtain a Raman spectroscopic image from the irradiated region characteristic of either a neoplastic portion or a non-neoplastic portion of the region containing the biological tissue. A boundary between a neoplastic portion and a non-neoplastic portion is differentiated and the boundary location in the Raman spectroscopic image is displayed.

1 . A system comprising:
 a laser light source for irradiating a region of a sample with illuminating photons to thereby produce Raman scattered photons, wherein said laser light source is selected from the group consisting of: a pulsed laser light source and an intensity modulated laser light source;   a first optics to direct said illuminating photons to said region of said sample; a second optics to collect said photons Raman scattered from said region of said sample;   an illumination light rejection filter configured to block light of a first wavelength and allow light of a second wavelength to pass through said illumination light rejection filter wherein said light of a second wavelength comprises said Raman scattered photons;   a tunable filter for receiving said Raman scattered photons and passing ones of said Raman scattered photons having a wavelength in a predetermined wavelength band;   a gating system configured to open at a specified time, allowing said Raman scattered photons to pass through to a detector camera to thereby generate a Raman spectroscopic image of said region of said sample; and   a computer system configured to perform at least one of: control elements of said system, collect data from said system, and store data collected from said system.   
     
     
         2 . The system of  claim 1  further comprising a device operatively coupled to said laser light source, wherein said device is configured so as to introduce said illuminating photons in vivo. 
     
     
         3 . The system of  claim 2  wherein said device comprises an endoscope. 
     
     
         4 . The system of  claim 1  further comprising a video camera. 
     
     
         5 . The system of  claim 1  wherein said tunable filter comprises a liquid crystal tunable filter. 
     
     
         6 . The system of  claim 1  wherein said gating system comprises a microchannel plate image intensifier. 
     
     
         7 . The system of  claim 1  further comprising a means analyzing said Raman spectroscopic image to thereby distinguish between a neoplastic portion of said sample and a non-neoplastic portion of said sample. 
     
     
         8 . The system of  claim 7  further comprising a means for manipulating said neoplastic portion of said sample. 
     
     
         9 . A system comprising:
 a laser light source for irradiating a region of a sample with illuminating photons to thereby produce Raman scattered photons, wherein said laser light source is selected from the group consisting of: a pulsed laser light source and an intensity modulated laser light source;   an endoscope operatively coupled to said laser light source and configured so as to direct said illuminating photons in vivo;   a first optics to direct said illuminating photons to said region of said sample; a second optics to collect said photons Raman scattered from said region of said sample;   an illumination light rejection filter configured to block light of a first wavelength and allow light of a second wavelength to pass through said illumination light rejection filter wherein said light of a second wavelength comprises said Raman scattered photons;   a tunable filter for receiving said Raman scattered photons and passing ones of said Raman scattered photons having a wavelength in a predetermined wavelength band;   a gating system configured to open at a specified time, allowing said Raman scattered photons to pass through to a detector camera to thereby generate a Raman spectroscopic image of said region of said sample; and a computer system configured to perform at least one of: control elements of said system, collect data from said system, and store data collected from said system.   
     
     
         10 . The system of  claim 9  further comprising a video camera. 
     
     
         11 . The system of  claim 9  wherein said tunable filter comprises a liquid crystal tunable filter. 
     
     
         12 . The system of  claim 9  wherein said gating system comprises a microchannel plate image intensifier. 
     
     
         13 . The system of  claim 9  further comprising a means analyzing said Raman spectroscopic image to thereby distinguish between a neoplastic portion of said sample and a non-neoplastic portion of said sample. 
     
     
         14 . The system of  claim 13  further comprising a means for manipulating said neoplastic portion of said sample.