Detecting optical properties of a turbid medium

Abstract

Disclosed herein are methods and devices for evaluating the optical properties of a turbid medium, wherein the medium is one which both absorbs and scatters light. Turbid media of particular interest include fluids such as coolants, paints, etc., and biologically or medically relevant fluids, such as blood, culture media, etc. The methods and devices disclosed herein can also be used to measure changes in optical properties of a tissue (e.g., an epithelial layer) that are associated with a variety of disease states. Changes or differences in the optical properties of tissue can provide indicia of a pathological state or the efficacy of a therapeutic regimen. In general, the change or difference can be a change or difference relative to a standard that is either internal or external. Also disclosed herein are methods for obtaining absolute values for optical properties that are generally obtained as relative values. This absolute value can be compared effectively with an absolute value from another sample with meaningful results.

What is claimed herein is: 
     
         1 . A device for measuring light scattering and absorption properties of a turbid medium of interest, the device comprising:
 a probe having proximal and distal ends, said probe comprising first and second optical fibers;   wherein said first optical fiber is operatively connected to a light source, and said second optical fiber is operatively connected to an optical detector;   wherein said first and said second optical fibers are substantially parallel to each other at said distal end, and are separated at said distal end by a distance of less than 2 mm;   wherein the tips of the optical fibers at the distal end are polished such that they are parallel to the surface of a probed medium; and   a computer-readable medium comprising instructions for obtaining the reduced scattering coefficient or the absorption coefficient of a turbid medium of interest from a measured reflected spectrum of light energy, the computer-readable medium comprising:   a) instructions for receiving a value for measured reflected light energy from a turbid medium of interest;   b) instructions for determining absorption and/or reduced scattering coefficients for said turbid medium of interest by applying the relationship of Equation (2):   
       
         
           
             
               
                 
                   
                     R 
                     = 
                     
                       
                         ( 
                         
                           a 
                            
                           
                               
                           
                            
                           
                             μ 
                             s 
                             ′ 
                           
                         
                         ) 
                       
                        
                       
                         exp 
                          
                         
                           ( 
                           
                             
                               - 
                               
                                 μ 
                                 a 
                               
                             
                              
                             
                               b 
                               
                                 
                                   ( 
                                   
                                     
                                       μ 
                                       a 
                                     
                                      
                                     
                                       μ 
                                       s 
                                       ′ 
                                     
                                   
                                   ) 
                                 
                                 c 
                               
                             
                           
                           ) 
                         
                       
                     
                   
                 
                 
                   
                     Equation 
                      
                     
                         
                     
                      
                     
                       ( 
                       2 
                       ) 
                     
                   
                 
               
             
           
         
         wherein a, b, and c are constants, R is the absolute reflectance value of the turbid medium of interest obtained from the reflected spectrum of light energy, μ s ′ is the reduced scattering coefficient of said turbid medium of interest, and μ a  is the absorption coefficient of said turbid medium of interest; and 
         c) instructions for transmitting a value of R, μ s ′, or μ a  to an output device. 
       
     
     
         2 . The device of  claim 1 , wherein said first and second optical fibers are arranged in said probe at an angle, θ=0° to 45°, to the surface of the medium at the distal end of said probe. 
     
     
         3 . The device of  claim 1 , wherein said first and second optical fibers are arranged in said probe at an angle, θ=10° to 45°, to the surface of the medium at the distal end of said probe. 
     
     
         4 . The device of  claim 1 , wherein said probe comprises an endoscopic probe. 
     
     
         5 . The device of  claim 1 , wherein said first and second optical fibers are separated by less than or equal to 700 μm at the distal end of said probe. 
     
     
         6 . The device of  claim 1 , wherein the turbid medium of interest is a tissue. 
     
     
         7 . A method of obtaining a reduced scattering coefficient and/or an absorption coefficient from spectra reflected from a turbid medium of interest, the method comprising:
 a) irradiating a first reference turbid medium with light energy from a source in contact with a first turbid medium, said first turbid medium having known reduced scattering and absorption coefficients;   b) for said first reference turbid medium, measuring the amount of light energy reflected from said source to a detector by said first reference turbid medium;   c) irradiating a turbid medium of interest with light energy from a source in contact with said turbid medium of interest;   d) measuring the amount of light energy reflected from said source to a detector by said turbid medium of interest,   e) repeating steps a-d at a second, different wavelength of light; and   f) determining a reduced scattering coefficient and/or an absorption coefficient for said turbid medium of interest, wherein said determining comprises applying Equation (2):   
       
         
           
             
               
                 
                   
                     R 
                     = 
                     
                       
                         ( 
                         
                           a 
                            
                           
                               
                           
                            
                           
                             μ 
                             s 
                             ′ 
                           
                         
                         ) 
                       
                        
                       
                         exp 
                          
                         
                           ( 
                           
                             
                               - 
                               
                                 μ 
                                 a 
                               
                             
                              
                             
                               b 
                               
                                 
                                   ( 
                                   
                                     
                                       μ 
                                       a 
                                     
                                      
                                     
                                       μ 
                                       s 
                                       ′ 
                                     
                                   
                                   ) 
                                 
                                 c 
                               
                             
                           
                           ) 
                         
                       
                     
                   
                 
                 
                   
                     Equation 
                      
                     
                         
                     
                      
                     
                       ( 
                       2 
                       ) 
                     
                   
                 
               
             
           
         
         wherein a, b, and c are constants, R is the absolute reflectance value of the turbid medium of interest obtained from the reflected spectrum of light energy, μ s ′ is the reduced scattering coefficient, and μ a  is the absorption coefficient, whereby a reduced scattering coefficient or an absorption coefficient are determined from said turbid medium of interest. 
       
     
     
         8 . The method of  claim 7 , wherein said turbid medium is a tissue. 
     
     
         9 . The method of  claim 8 , wherein said tissue is an epithelial layer. 
     
     
         10 . The method of  claim 8 , wherein said turbid medium of interest and said reference turbid medium are each an epithelial layer, and wherein a difference in said reduced scattering coefficient or said absorption coefficient is indicative of a disease state. 
     
     
         11 . The method of  claim 7 , wherein the amount of light energy from spectra reflected from a turbid medium of interest is obtained using a device comprising:
 a probe having proximal and distal ends, said probe comprising first and second optical fibers,   wherein said first optical fiber is operatively connected to a light source, and said second optical fiber is operatively connected to an optical detector,   wherein said first and said second optical fibers are substantially parallel to each other at said distal end, and are separated at said distal end by a distance of less than 2 mm; and   wherein the tips of the optical fibers at the distal end are polished such that they are parallel to the surface of a probed medium.   
     
     
         12 . The method of  claim 11 , wherein said first and second optical fibers are arranged in said probe at an angle, θ=0° to 45°, to the plane perpendicular to the distal end of said probe. 
     
     
         13 . The method of  claim 11 , wherein said first and second optical fibers are arranged in said probe at an angle, θ=10° to 45°, to the plane perpendicular to the distal end of said probe. 
     
     
         14 . A method of determining a reduced scattering coefficient and/or an absorption coefficient of a turbid medium of interest, the method comprising:
 a) obtaining reflectance spectra from a turbid medium of interest using a probe in contact with said turbid medium of interest, said probe operatively connected to a light energy source which irradiates said turbid medium of interest and an optical detector which detects light energy reflected from said turbid medium of interest;   b) determining a reduced scattering coefficient and/or an absorption coefficient for said turbid medium of interest, wherein said determining comprises applying Equation (2):   
       
         
           
             
               
                 
                   
                     R 
                     = 
                     
                       
                         ( 
                         
                           a 
                            
                           
                               
                           
                            
                           
                             μ 
                             s 
                             ′ 
                           
                         
                         ) 
                       
                        
                       
                         exp 
                          
                         
                           ( 
                           
                             
                               - 
                               
                                 μ 
                                 a 
                               
                             
                              
                             
                               b 
                               
                                 
                                   ( 
                                   
                                     
                                       μ 
                                       a 
                                     
                                      
                                     
                                       μ 
                                       s 
                                       ′ 
                                     
                                   
                                   ) 
                                 
                                 c 
                               
                             
                           
                           ) 
                         
                       
                     
                   
                 
                 
                   
                     Equation 
                      
                     
                         
                     
                      
                     
                       ( 
                       2 
                       ) 
                     
                   
                 
               
             
           
         
         wherein a, b, and c are constants, R is the absolute reflectance value of the turbid medium of interest obtained from the reflected spectrum of light energy, μ s ′ is the reduced scattering coefficient of said turbid medium of interest, and μ a  is the absorption coefficient of said turbid medium of interest, whereby a reduced scattering coefficient or an absorption coefficient is determined for said turbid medium. 
       
     
     
         15 . The method of  claim 14 , further comprising the step of comparing an absolute value for the reduced scattering or absorption coefficient of said turbid medium of interest to a reduced scattering coefficient and/or absorption coefficient obtained from a reference turbid medium, wherein a difference in said absolute value is indicative of a difference between said turbid medium of interest and said reference turbid medium. 
     
     
         16 . The method of  claim 15 , wherein said turbid medium is a tissue. 
     
     
         17 . The method of  claim 16 , wherein said tissue is an epithelial layer. 
     
     
         18 . The method of  claim 17 , wherein said turbid medium of interest and said reference turbid medium are each an epithelial layer, and wherein a difference in said reduced scattering coefficient or said absorption coefficient is indicative of a disease state.