Optical imaging of induced signals in vivo under ambient light conditions

Abstract

A method for detecting and localizing a target tissue within the body in the presence of ambient light in which an optical contrast agent is administered and allowed to become functionally localized within a contrast-labeled target tissue to be diagnosed. A light source is optically coupled to a tissue region potentially containing the contrast-labeled target tissue. A gated light detector is optically coupled to the tissue region and arranged to detect light substantially enriched in target signal as compared to ambient light, where the target signal is light that has passed into the contrast-labeled tissue region and been modified by the contrast agent. A computer receives signals form the detector, and passes these signals to memory for accumulation and storage, and then to image processing engine for determination of the localization and distribution of the contrast agent. The computer also provides an output signal based upon the localization and distribution of the contrast agent, allowing trace amounts of the target tissue to be detected, located, or images. A system for carrying out the method is also described.

1 . A method for targeting a prostate biopsy needle toward potential prostate cancer sites in a patient, comprising:
 (a) administering to the patient an optical contrast agent targeted to cancer-influenced prostate cell surface antigens;   (b) waiting until the contrast agent has achieved adequate distribution and localization within the body;   (c) illuminating the subject with light from a light source;   (d) providing a gated imaging detector;   (e) detecting light with said light detector after passage of the source light through an opaque region of the body and after interaction and modification of the source light by the contrast agent;   (f) determining the present location of the biopsy needle with respect to the prostate cancer, based upon the modified, detected light; and,   (g) positioning the biopsy needle at an identified potential cancer site and collecting a biopsy sample at that site;   (h) repeating steps (d) through (g) until a sufficient number of prostate biopsy samples have been collected.   
     
     
         2 . A method for removing a breast tumor using a minimally invasive medical probe, comprising:
 (a) intravenously administering an optical contrast agent to the subject, said agent selected so as to provide enhanced contrast between normal and cancerous breast tissue;   (b) waiting until the contrast agent has achieved adequate distribution and localization within the body;   (c) providing a minimally invasive tissue removal device or instrument that is optically coupled to a light source, a light detector, or both, and using the device or instrument during an minimally invasive lumpectomy procedure upon the subject;   (d) illuminating the subject with light from the light source such that the contrast agent in vivo may interact with and modify the illuminating light;   (e) detecting modified light with the light detector after passage of source light through an opaque region of the body and interaction and modification of the source light by the contrast agent;   (f) determining a positional estimate of the present location of the medical device or instrument with respect to any remaining breast cancer based upon said modified, detected light; and,   (g) generating an output signal in response to said measurement;   (h) removing tissue identified as breast cancer; and,   (i) repeating steps (d) through (h) until a diagnostic or therapeutic endpoint is reached.   
     
     
         3 . A medical system for determining the location of one or more sentinel nodes in breast cancer during a lymph node biopsy, comprising:
 (a) a contrast solution of isosulfan blue for providing a source of contrast between said sentinel node tissue and other lymph tissues, said agent injected into the periphery of said breast cancer so as to have achieved distribution and localization within the lymph nodes;   (b) a white light source for illuminating a portion of said subject with illuminating radiation;   (c) a light collector for collecting a portion of said illuminating radiation, after having passed through an opaque region of the body of the subject potentially containing said contrast agent and influenced by said contrast solution, said light collection providing a detected signal in response to said collected portion;   (d) a medical probe for use on or within said subject during said node biopsy, said medical probe coupled to said light source, said light collector, or both; and,   (e) means for determining the location of said sentinel nodes, said determination based upon said detected signal; and   (f) means for generating an output signal related to a distribution and localization of said sentinel nodes in response to said determination.   
     
     
         4 . A medical system for determining the presence or absence of recurrent prostate cancer during a rectal diagnostic procedure, comprising:
 (a) a fluorescent contrast agent targeted to cancer-specific surface antigens for providing a source of contrast between prostate cancer cells and normal prostate tissues, said agent ingested orally and systemically absorbed so as to have achieved distribution and localization within the prostate;   (b) a monochromatic intensity modulated light source for illuminating the prostate with illuminating radiation, said distributed contrast agent at least potentially disposed to fluoresce in response to said illuminating radiation;   (c) a multi-element light collector for collecting a portion of said fluorescent radiation after having passed through an opaque region of the prostate and modified by the contrast agent, said multi-element light collector providing a detected signal in response to said collected portion;   (d) a medical ultrasound probe for rectal use during said prostate examination, said medical probe coupled to said light emitter, said light collector, or both; and,   (e) means for determining the presence and location of prostate cancer based upon said detected signal; and   (f) means for generating an output image related to a distribution and localization of said contrast agent in response to said determination.   
     
     
         5 . A method for producing clean margins during prostate surgery, comprising:
 (a) administering to the patient an optical contrast agent targeted to epithelial cells of prostate origin;   (b) waiting until the contrast agent has achieved adequate distribution and localization within the body;   (c) providing a gated imaging detector;   (d) illuminating the subject with light from a light source;   (e) detecting modified light with said light detector after passage of the source light through an opaque region of the body and after interaction and modification of the source light by the contrast agent;   (f) determining the location of residual cells of prostate origin within the surgical prostatectomy site, based upon the modified, detected light;   (g) removing tissue identified as prostate tissue; and   (h) repeating steps (d) through (g) until the amount of residual prostate tissue falls below a predetermined threshold.   
     
     
         6 . The method of  claim 1  wherein said target location comprises a breast tumor; the method further comprising:
 (a) intravenously administering said optical contrast agent to the subject, said agent selected so as to provide enhanced contrast between normal and cancerous breast tissue;   (b) providing said medical or surgical instrument comprised of a minimally invasive tissue removal device or instrument that is optically coupled to said light source, a light detector, or both, and using the device or instrument during an minimally invasive lumpectomy procedure upon the subject;   (c) illuminating the subject with light from the light source such that the contrast agent in vivo may interact with and modify the illuminating light;   (d) detecting modified light with the light detector after passage of source light through an opaque region of the body and interaction and modification of the source light by the contrast agent;   (e) determining a positional estimate of the present location of the medical device or instrument with respect to any remaining breast cancer based upon said modified, detected light; and,   (f) generating an output signal in response to said measurement;   (g) removing tissue identified as breast cancer; and,   (h) repeating steps (c) through (h) until a diagnostic or therapeutic endpoint is reached.   
     
     
         7 . The system of  claim 3 , wherein:
 said contrast agent comprises isosulfan blue for providing a source of contrast between one or more sentinel node tissues in breast cancer and other lymph tissues, said agent injected into the periphery of said breast cancer so as to have achieved distribution and localization within the lymph nodes;   said light emitter comprises a white light source;   said medical instrument comprises a medical probe for use on or within said subject during said node biopsy, said medical probe coupled to said light source, said light collector, or both; and   the system further comprises:
 means for determining the location of said sentinel nodes, said determination based upon said detected signal; and 
 means for generating an output signal related to a distribution and localization of said sentinel nodes in response to said determination.