Methods of diagnosing disease

Abstract

The invention provides methods and systems for diagnosing disease in a sample by monitoring optical signals produced by samples in response to the chemical agents. Preferred methods comprise application of multiple chemical agents that interact to alter an optical signal from the sample. Methods and systems of the invention also comprise monitoring an optical signal from an endogenous chromophore upon application of a chemical agent to a sample. Methods and systems of the invention also comprise the use of triggers, atomizers and image alignment to enhance the results of methods described herein.

What is claimed is:  
     
         1 . A method of diagnosing disease in a patient, the method comprising the steps of: 
 dispensing a plurality of chemical agents on a tissue, wherein the chemical agents interact to alter an optical signal produced by the tissue,    measuring said altered optical signal, and    providing a diagnosis based upon said altered optical signal.    
     
     
         2 . A method of diagnosing disease in a patient, the method comprising the steps of: 
 dispensing a plurality of chemical agents on a tissue;    determining whether said chemical agents alter an optical signal produced by the tissue; and    providing a diagnosis based upon whether said optical signal is altered.    
     
     
         3 . The method of  claim 1 , wherein said chemical agents interact to produce an additive effect on said optical signal.  
     
     
         4 . The method of  claim 1 , wherein said chemical agents interact to reduce an intensity of said optical signal.  
     
     
         5 . The method of  claim 1 , wherein said optical signal is a light spectrum.  
     
     
         6 . The method of  claim 5 , wherein said light spectrum is a fluorescent spectrum.  
     
     
         7 . The method of  claim 1 , wherein said optical signal is produced by an endogenous chromophore.  
     
     
         8 . The method of  claim 7 , wherein said endogenous chromophore is a fluorophore.  
     
     
         9 . The method of  claim 1 , wherein said chemical agents are selected from the group consisting of acetic acid, formic acid, propionic acid, butyric acid, Lugol's iodine, Shiller's iodine, methylene blue, toluidine blue, and indigo carmine.  
     
     
         10 . The method of  claim 1 , wherein said plurality of chemical agents are dispensed substantially simultaneously.  
     
     
         11 . The method of  claim 1 , wherein said plurality of chemical agents are dispensed sequentially.  
     
     
         12 . The method of  claim 1 , wherein said optical signal is measured over a predetermined time.  
     
     
         13 . The method of  claim 1 , wherein at least one member of said plurality of chemical agents alters pH of said sample.  
     
     
         14 . The method of  claim 1 , wherein at least one member of said plurality is selected from the group consisting of osmotic agents and ionic agents. 
 dispensing a chemical agent on a tissue,    measuring a change in response to said chemical agent in an optical signal from an    endogenous chromophore in said tissue, and    providing a diagnosis based upon said change.    
     
     
         16 . The method of claim  15 , wherein said chromophore is a fluorophore.  
     
     
         17 . The method of  claim 1 , wherein said tissue is selected from the group consisting of skin, cervical tissue, epithelial tissue, and colorectal tissue.  
     
     
         18 . A method of diagnosing disease in a patient, the method comprising the steps of: 
 dispensing a chemical agent on a tissue,    providing an automated triggering signal to initiate a measurement period relative to said dispensing step,    measuring a temporal evolution of an optical signal observed from said tissue during said measurement period,    providing a diagnosis based upon said temporal evolution.    
     
     
         19 . The method of  claim 18 , wherein said triggering signal is provided substantially simultaneously with said dispensing step.  
     
     
         20 . The method of  claim 18 , wherein said triggering signal is provided after said dispensing step.  
     
     
         20 . The method of  claim 18 , wherein said triggering signal is provided after said dispensing step.  
     
     
         21 . The method of  claim 18 , wherein said measuring step comprises measuring said temporal evolution at at least one predetermined time relative to said triggering signal.  
     
     
         22 . The method of  claim 1  or  18 , wherein said dispensing step comprises dispensing said chemical agent or agents as a mist in a predefined pattern on said tissue.  
     
     
         23 . The method of  claim 22 , wherein said pattern is substantially circular.  
     
     
         24 . The method of  claim 22 , wherein said pattern is substantially annular.  
     
     
         25 . The method of  claim 22 , wherein said mist is a controlled volume.  
     
     
         26 . The method of  claim 22 , wherein said dispensing occurs at a controlled rate.  
     
     
         27 . A method for diagnosing disease in a patient, the method comprising the steps of: 
 dispensing a chemical agent on a tissue,    capturing a plurality of sequential images of said tissue during a measurement period,    aligning a subset of said plurality of images to spatially correlate said subset,    measuring a temporal evolution of an optical signal from said subset of spatially correlated images, and    providing a diagnosis based on said temporal evolution.    
     
     
         28 . The method of  claim 27 , wherein said aligning step comprises aligning said subset to compensate for relative motion between said sample and a spectral observation device.  
     
     
         29 . The method of  claim 27 , wherein said aligning step comprises aligning said subset to compensate for relative motion between a first portion of said sample and a second portion of said sample.  
     
     
         30 . The method of  claim 27 , wherein said measuring step is performed at predetermined times relative to said dispensing step.  
     
     
         31 . The method of  claim 27 , wherein said tissue is selected from the group consisting of cervical tissue, skin, colorectal tissue, and gastric tissue.  
     
     
         32 . The method of  claim 1 , wherein said optical signal is approximated by a decay function.  
     
     
         33 . The method of  claim 7  or  15 , wherein said endogenous molecule is selected from the group consisting of NADH, collagen, elastin, flavins, hemoglobin, and porphyrins.  
     
     
         34 . The method of  claim 5 , wherein said spectrum is produced at least in part by light scattering properties of said tissue.