Fluorescence-mediated molecular tomography

Abstract

This invention relates to a fluorescence-mediated molecular tomographic imaging system, designed to detect near-infrared fluorescence activation in deep tissues. The system can use targeted fluorescent molecular probes or highly sensitive activatable fluorescence molecular probes. Such probes add molecular specificity and yield high fluorescence contrast, to allow early detection and molecular target assessment of diseased tissue, such as cancers, in vivo. The new tomographic imaging system enables three-dimensional localization in deep tissues and quantitation of molecular probes.

1 - 29 . (canceled) 
     
     
         30 . A method of obtaining a three-dimensional, quantitative tomographic image of a target region within a patient or animal body, the method comprising:
 administering a near-infrared fluorescent probe to the patient or animal body, wherein the probe selectively accumulates within a target region in the patient or animal body;   directing near-infrared excitation light into the patient or animal body at multiple locations, thereby transilluminating the patient or animal body;   detecting at multiple points excitation light transmitted through the patient or animal body;   detecting fluorescent light emitted from the patient or animal body; and   processing the detected excitation light and the detected fluorescent light to provide a three-dimensional tomographic image that corresponds to the three-dimensional target region within the patient or animal body and to the quantity of the probe accumulated in the target region.   
     
     
         31 . The method of  claim 30 , wherein the near-infrared light directed into the patient or animal body is at a wavelength of from 550 nm to 950 nm. 
     
     
         32 . The method of  claim 30 , wherein the near-infrared light directed into the patient or animal body is at a wavelength of from 670 nm to 850 nm. 
     
     
         33 . The method of  claim 30 , wherein the excitation light is continuous wave light. 
     
     
         34 . The method of  claim 30 , wherein processing the detected excitation light and the detected fluorescent light to provide the three-dimensional tomographic image comprises iteratively solving for fluorescent probe distribution using a model of excitation light propagation and emission light propagation through the patient or animal body. 
     
     
         35 . The method of  claim 30 , wherein the fluorescent probe comprises a fluorochrome attached to a delivery vehicle, wherein the delivery vehicle comprises any one or more of a polymer, a dendrimer, a protein, a carbohydrate, a lipid sphere, and a nanoparticle. 
     
     
         36 . The method of  claim 30 , wherein the probe comprises a member selected from the group consisting of an activatable fluorescent probe, a targeted fluorescent probe, a receptor-targeted near-infrared fluorochrome, an antibody-targeted near-infrared fluorochrome, a wavelength-shifting beacon, a multi-color fluorescent probe, and a lanthanide metal-ligand probe. 
     
     
         37 . The method of  claim 30 , wherein the probe has at least one of the following properties: the probe becomes activated upon target interaction; the probe becomes deactivated after target interaction; the probe changes its quantum yield upon target interaction; the probe changes its fluorescence lifetime after target interaction; the probe changes its fluorescent spectrum after target interaction; and the probe has high binding affinity to a target in the target region. 
     
     
         38 . The method of  claim 30 , comprising the step of disposing the patient or animal body within an imaging chamber prior to directing the near-infrared excitation light into the patient or animal body. 
     
     
         39 . The method of  claim 30 , further comprising generating a surface representation of the patient or animal body, wherein the surface representation comprises an identification of positions of incident illumination and positions of detection, and using the surface representation in processing the detected excitation light and the detected fluorescent light to provide the three-dimensional tomographic image. 
     
     
         40 . A fluorescence-mediated tomographic imaging system comprising:
 a near-infrared excitation light source;   an imaging chamber configured to direct the near-infrared excitation light into a patient or animal body disposed within the chamber at multiple locations, thereby transilluminating the patient or animal body;   a detector configured to detect at multiple locations excitation light transmitted through the patient or animal body and fluorescent light emitted from a probe within the patient or animal body; and   a processor configured to process data corresponding to the detected excitation light transmitted through the patient or animal body and the detected fluorescent light emitted from the probe within the patient or animal body to provide a three-dimensional tomographic representation of a region within the patient or animal body and of the quantity of the probe accumulated in the target region.   
     
     
         41 . The system of  claim 40 , wherein the near-infrared excitation light source produces light at a wavelength of from 550 nm to 950 nm. 
     
     
         42 . The system of  claim 40 , wherein the near-infrared excitation light source produces light at a wavelength of from 670 nm to 850 nm. 
     
     
         43 . The system of  claim 40 , wherein the near-infrared excitation light source is configured to produce continuous wave light. 
     
     
         44 . The system of  claim 40 , wherein the near-infrared excitation light is a continuous wave laser. 
     
     
         45 . The system of  claim 40 , wherein the processor is configured to process the data corresponding to the detected excitation light and the detected fluorescent light using a forward model of (i) an excitation field from the near-infrared excitation light source to the probe within the patient or animal body and (ii) an emission field from the probe within the patient or animal body to the detector.