Multi-modal optical tissue diagnostic system

Abstract

An apparatus and method according to the invention combine more than one optical modality (spectroscopic method), including but not limited to fluorescence, absorption, reflectance, polarization anisotropy, and phase modulation, to decouple morphological and biochemical changes associated with tissue changes due to disease, and thus to provide an accurate diagnosis of the tissue condition.

1 - 37 . (canceled)  
   
   
       38 . A method for diagnosing a condition of a target tissue, comprising the steps of: 
 a.) irradiating a target tissue with excitation electromagnetic radiation;    b.) sensing a returned electromagnetic radiation returned from the target tissue;    c.) determining characteristics of the returned electromagnetic radiation using at least two spectroscopic methods;    d.) combining the characteristics determined by the at least two spectroscopic methods, thereby decoupling biochemical changes from morphological changes in the target tissue; and    e.) determining a condition of the target tissue based on the combined determined characteristics.    
   
   
       39 . The method of  claim 38 , wherein the at least two spectroscopic methods are selected from the group consisting of absorption measurements, scattering measurements, reflection measurements, polarization anisotropic measurements, steady state fluorescence measurements, and time resolved fluorescence measurements.  
   
   
       40 . The method of  claim 39 , wherein the time resolved fluorescence measurements comprise at least one of phase modulation techniques, polarization anisotropic techniques and techniques that directly monitor the decay profile of fluorescent emissions.  
   
   
       41 . The method of  claim 38 , wherein step b.) comprises simultaneously sensing electromagnetic radiation emitted from the target tissue in response to the excitation electromagnetic radiation and excitation electromagnetic radiation that is scattered from the target tissue.  
   
   
       42 . The method of  claim 41 , wherein step c.) comprises making intensity based measurements on both said electromagnetic radiation emitted from the target tissue in response to the excitation electromagnetic radiation and said excitation electromagnetic radiation that is scattered from the target tissue.  
   
   
       43 . The method of  claim 38 , wherein step b.) comprises sensing electromagnetic radiation emitted from the target tissue in response to the excitation electromagnetic radiation and then subsequently sensing excitation electromagnetic radiation that is scattered from the target tissue.  
   
   
       44 . The method of  claim 38 , wherein step b.) comprises sensing electromagnetic radiation returned from a plurality of interrogation points distributed over the target tissue.  
   
   
       45 . The method according to  claim 44 , further comprising a step of dividing the target tissue into a first set of field areas, wherein step c.) comprises determining characteristics of the returned electromagnetic radiation in each of said first set of field areas using at least two spectroscopic methods, step d.) comprises combining the characteristics determined by the at least two spectroscopic methods for each of said first set of field areas and step e.) comprises determining a condition of the target tissue by comparing the combined determined characteristics of each of said first set of field areas.  
   
   
       46 . The method of  claim 45 , further comprising, after determining a condition of the target tissue by comparing the combined determined characteristics of each of said first set of field areas, re-dividing the target tissue into a second set of field areas, different from said first set of field areas and the determining characteristics of the returned electromagnetic radiation in each of said second set of field areas using at least two spectroscopic methods, combining the characteristics determined by the at least two spectroscopic methods for each of said second set of field areas and determining a condition of the target tissue by comparing the combined determined characteristics of each of said second set of field areas.  
   
   
       47 . The method of  claim 44 , wherein the method is performed using an apparatus comprising an irradiation source, a detector and a processor, wherein the step of sensing electromagnetic radiation returned from a plurality of interrogation points comprises the steps of: sensing electromagnetic radiation returned from the target tissue from a first subset of the plurality of interrogation points; moving at least one of the apparatus and the tissue; sensing electromagnetic radiation returned from the target tissue from a second subset of the plurality of interrogation points; again moving at least one of the apparatus and the tissue; and continuing this process until sensing has been peformed at all of the plurality of interrogation points.  
   
   
       48 . A system for determining a condition of a target tissue in a human or animal, comprising: a electromagnetic radiation source for providing excitation electromagnetic radiation; a device that couples the excitation electromagnetic radiation to a target tissue; a device that senses electromagnetic radiation returned from the target tissue; a processor configured to determine characteristics of the returned electromagnetic radiation using at least two spectroscopic methods, wherein the processor combines the characteristics determined by each of the at least two spectroscopic methods in order to decouple biochemical changes from morphological changes in the target tissue and determines a condition of the target tissue based on the combined determined characteristics.  
   
   
       49 . The system of  claim 48 , wherein the at least two spectroscopic methods comprise fluorescence measurement methods and scattering or reflectance measurement methods.  
   
   
       50 . The system of  claim 48 , wherein the at least two spectroscopic methods are selected from the group consisting of absorption measurements, scattering measurements, reflectance measurements, polarization anisotropy measurements, steady state fluorescence measurements and time resolved fluorescence measurements.  
   
   
       51 . The system of  claim 48 , wherein the device that senses returned electromagnetic radiation is configured to simultaneously sense fluorescent radiation emitted by endogenous fluorophores in response to the excitation radiation and excitation electromagnetic radiation that is scattered from the target tissue.  
   
   
       52 . The system of  claim 48 , wherein the device that senses electromagnetic radiation is configured to sense electromagnetic radiation returned from a plurality of interrogation points distributed over the target tissue.  
   
   
       53 . The system according to  claim 52 , wherein the processor divides the target tissue into a first set of field areas, determines characteristics of the returned electromagnetic radiation in each of said first set of field areas using said at least two spectroscopic methods, combines the characteristics determined by each of said at least two spectroscopic methods for each of said first set of field areas and determines a condition of the target tissue in each of said first set of field areas based on the combined determined characteristics of the respective field areas.  
   
   
       54 . The system of  claim 53 , wherein the processor is further configured to, after the processor determines a condition of the target tissue in each of the first set of field areas based on the combined determined characteristics of the respective field areas, divide the target tissue into a second set of field areas, different from the first set of field areas; determine characteristics of the returned electromagnetic radiation in each of said second set of field areas using said at least two spectroscopic methods, combine the characteristics determined by each of said at least two spectroscopic methods for each of said second set of field areas and determine a condition of the target tissue in each of the second set of field areas based on the combined determined characteristics of the respective field areas.  
   
   
       55 . A system for determining a condition of a target tissue in a human or animal, comprising: an electromagnetic radiation source for providing excitation electromagnetic radiation; a device that couples the excitation electromagnetic radiation to a target tissue; a device that senses electromagnetic radiation returned from the target tissue; and a processor configured to determine characteristics of the returned electromagnetic radiation using at least two spectroscopic methods, thereby decoupling biochemical changes from morphological changes in the target tissue occurring due to disease and determine a condition of the target tissue based on the determined characteristics.