Raman chemical imaging of breast tissue

Abstract

Apparatus and methods for spatially resolved Raman chemical imaging of breast tissue is disclosed. A region of breast tissue is illuminated with monochromatic light. A spatially organized area of endogenous molecules in the tissue is then detected in the region by detecting a Raman shifted light signal. The Raman shifted light signal is spatially resolved in at least one direction and is thus useful for examining breast tissue, especially to detect malignant tissue.

1 . A method for detecting the distribution of one or more molecular species within a breast lesion which comprises 
 a) illuminating a region of breast tissue with monochromatic light;    b) detecting Raman shifted light from the one or more molecular species in the region with a Raman chemical imaging spectrophotometer; and    c) spatially resolving the Raman shifted light signal in at least one direction to produce a Raman chemical image indicative of the molecular species within said lesion in said at least one direction.    
     
     
         2 . The method of  claim 1 , wherein said one or more molecular species is lipid, carbohydrate and/or protein.  
     
     
         3 . The method of  claim 1 , wherein said breast lesion is a benign tumor.  
     
     
         4 . The method of  claim 1 , wherein said breast lesion is a malignant tumor.  
     
     
         5 . The method of  claim 1 , wherein said breast lesion is a pocket of infection or inflammation.  
     
     
         6 . The method of  claim 1 , wherein a two-dimensional chemical image of the region is produced.  
     
     
         7 . The method of  claim 6 , wherein a series of two-dimensional chemical images are taken as a function of depth of the tissue.  
     
     
         8 . A method for determining the morphology of a lesion in breast tissue which comprises 
 a) illuminating a region of breast tissue containing said lesion with monochromatic light;    b) detecting Raman shifted light from endogenous molecules in the region with a Raman chemical imaging spectrophotometer; and    c) spatially resolving the Raman shifted light signal to produce a Raman chemical image indicative of the morphology of said lesion in said tissue in at least two dimensions.    
     
     
         9 . The method of  claim 8 , wherein a series of two-dimensional chemical images are taken as a function of depth of the tissue.  
     
     
         10 . The method of  claim 9 , wherein said series of images are subject to morphometric analysis to thereby characterize the size and shape of said lesion.  
     
     
         11 . The method of any one of claims  1 - 10  wherein said molecular species or said molecules are selected from the group consisting of indoles, sulforaphanes, carotenoids, proteoglycans and flavonoids.  
     
     
         12 . The method of  claim 11 , where said molecular species or said molecules are carotenoids.  
     
     
         13 . A method for detecting a malignant breast tissue which comprises 
 a) illuminating a region of breast tissue with monochromatic light;    b) detecting Raman shifted light from endogenous molecules in the region with a Raman chemical imaging spectrophotometer; and    c) spatially resolving the Raman shifted light signal in at least one direction to produce a Raman chemical image (RCI) in said at least one direction,    d) ascertaining whether said breast tissue has an RCI characteristic of malignant breast tissue to thereby identify malignant breast tissue.    
     
     
         14 . The method of  claim 13  wherein said RCI discriminates between benign and malignant tumors.  
     
     
         15 . The method of  claim 13 , wherein a two-dimensional chemical image of the region is produced.  
     
     
         16 . The method of  claim 15 , wherein a series of two-dimensional chemical images are taken as a function of depth of the tissue.  
     
     
         17 . The method of any one of claims  13 - 16 , wherein the molecules are carotenoid molecules.  
     
     
         18 . The method of any one of claims  1 ,  8  or  13 , wherein the region is prepared for illumination, in a step previous to step a), by excision of the tissue and by placing a specimen prepared from the tissue in position for illumination and imaging, wherein the tissue is not treated with staining agents.  
     
     
         19 . The method of any one of claims  1 ,  8  or  13 , wherein the region is prepared for illumination, in a step previous to step a), by excision of the tissue and by placing a specimen prepared from the tissue in position for illumination and imaging, wherein the tissue is treated with staining agents.  
     
     
         20 . The method of any one of claims  1 ,  8  or  13 , wherein said region is illuminated in vivo with monochromatic light introduced via an endoscope or a fiberscope.  
     
     
         21 . The method of  claim 20 , wherein a two-dimensional chemical image of the region is produced.  
     
     
         22 . The method of  claim 20 , where said molecular species or said molecules are selected from the group consisting of indoles, sulforaphanes, carotenoids, proteoglycans and flavonoids.  
     
     
         23 . The method of  claim 22 , where said molecular species or said molecules are carotenoids.  
     
     
         24 . The method of  claim 20 , where a non-imaging endoscope or fiberscope is moved through the tissue in vivo, and the Raman shifted light signal is spatially resolved as the endoscope or fiberscope is moved through the tissue.  
     
     
         25 . The method of  claim 20 , where the Raman shifted light from the region passes through an Evan's split element liquid crystal tunable filter.  
     
     
         26 . The method of  claim 20 , wherein the endoscope or fiberscope is moved through the tissue to obtain a Raman chemical image from more than one region of said tissue.  
     
     
         27 . The method of  claim 26 , wherein a two-dimensional chemical image is produced for each region of said tissue.  
     
     
         28 . The method of  claim 27 , wherein said two-dimensional chemical images represent a series of images taken as a function of depth of the tissue.  
     
     
         29 . The method of  claim 28 , wherein said method is for determining the morphology of a lesion and said series of images are subject to morphometric analysis to thereby characterize the size and shape of said lesion.  
     
     
         30 . A method of performing an optical biopsy which comprises 
 a) illuminating multiple regions of breast tissue in vivo with monochromatic light introduced via an endoscope or a fiberscope;    b) detecting Raman shifted light from one or more molecular species in the region with a Raman chemical imaging spectrophotometer;    c) spatially resolving the Raman shifted light signal in two dimensions for each region to produce a Raman chemical image of said tissue in two dimensions; and    d) determining the location of any lesion in said tissue.    
     
     
         31 . The method of  claim 30 , wherein said multiple regions are in series as a function of depth of the tissue.  
     
     
         32 . A biopsy method which comprises 
 a) obtaining the Raman chemical image of breast tissue according to the method of  claim 31;  and    b) performing a biopsy of tissue in or around said lesion.    
     
     
         33 . The method of  claim 32 , wherein said biopsy is a non-surgical biopsy.  
     
     
         34 . The method of  claim 33 , wherein said non-surgical biopsy is a needle core biopsy or a fine needle biopsy.  
     
     
         35 . The method of  claim 32 , wherein said biopsy is an excisional biopsy.  
     
     
         36 . The method of any one of claims  32 - 35  which further comprises examining said biopsied tissue for signs of cancer.  
     
     
         37 . The method of any one of claims  30 - 32 , wherein said one or more molecular species is an endogenous molecule indicative of a border between normal tissue and a lesion.  
     
     
         38 . The method of any one of claims  30 - 32 , wherein said one or more molecular species is hydroxyapatite.  
     
     
         39 . The method of any one of claims  30 - 32 , wherein said Raman chemical image is of calcification in said tissue.  
     
     
         40 . The method of any one of claims  1 ,  8  or  13 , wherein the Raman shifted light from the region passes through a FAST fiber array spectral translator.  
     
     
         41 . The method of any one of claims  1 ,  8  or  13 , wherein the Raman shifted light from the region passes through a filter selected from the group consisting of a Fabry Perot tunable filter, an acousto-optic tunable filter, a liquid crystal tunable filter, a Lyot filter and an Evan's split element liquid crystal tunable filter.  
     
     
         42 . The method of any one of claims  1 ,  8  or  13 , wherein the Raman shifted light from the region passes through a polarization-independent imaging interferometer.  
     
     
         43 . The method of  claim 42 , wherein the Raman shifted light from the region passes through an interferometer selected from the group consisting of a Michelson interferometer, a Sagnac interferometer, a Twynam-Green interferometer and a Mach-Zelmder interferometer.