Intraoperative guidance system for tumor surgery

Abstract

The current invention pertains to a system and methods of identifying a site in a tissue of a patient as neoplastic or normal. The system comprises a source of electromagnetic signals; an optical probe which delivers the electromagnetic signals to a working end of the probe; a spectrometer which acquires diffuse reflectance electromagnetic signals returned from the site probed by the optical probe. The spectrometer processes the diffuse reflectance signals to produce a diffuse reflectance spectra which is transmitted to a system controller programmed to analyze the diffuse reflectance spectra to calculate hemoglobin concentration, hemoglobin oxygenation, and/or diffuse reflectance intensity of signals having wavelength of about 700 nm. These parameters are used to identify the site as neoplastic or normal. The system of current invention can be used in identifying neoplastic sites in brain in an intraoperative manner, for example, during a pediatric brain surgery.

1 - 65 . (canceled) 
     
     
         66 . A system for identifying a site in a tissue of a patient as neoplastic or normal, the system comprising:
 a) a source of electromagnetic signals;   b) a probe operably connected to the source of electromagnetic signals, for delivering the electromagnetic signals to a tissue site;   c) a spectrometer which acquires diffuse reflectance electromagnetic signals returned from the tissue site and produces a diffuse reflectance spectra from the returned diffuse reflectance electromagnetic signals; and   d) a system controller operably connected to the spectrometer, wherein the system controller:
 i) analyzes the diffuse reflectance spectra to calculate the relative ratio of absorption coefficient  μa  and reduced scattering cooefficient μ s  between 450 nm and 650 nm (μ a (λ)/μ s (λ)); 
 ii) analyzes μ a (λ)/μ s (λ) with respect to those from normal reference tissue sites to identify the tissue site as neoplastic or normal; and 
 iii) determines the site in the tissue of the patient in the tissue of the patient as neoplastic if:
   μ a (λ)/μ s (λ)>1+ x×μ   a (λ)/μ s (λ) N   _   std  or μ a (λ)/μ s (λ)<1− x×μ   a (λ)/μ s (λ) N   _   std ,
 
 
   wherein x is an adjustable cutoff for μ a (λ)/μ s (λ) and μ a (λ)/μ s (λ) N   _   std  is standard deviation of μ a (λ)/μ s (λ) from a plurality of known noiinal sites.   
     
     
         67 . The system of  claim 66 , wherein the tissue is brain. 
     
     
         68 . The system of  claim 66 , wherein the spectrometer acquires the diffuse reflectance electromagnetic signals returned from the site at a rate of about 33 Hz. 
     
     
         69 . The system of  claim 66 , wherein the the site is smaller than about 5 mm in diameter and thinner than about 2 mm in thickness. 
     
     
         70 . A system for identifying a site in a tissue of a patient as neoplastic or normal, the system comprising:
 a) a source of electromagnetic signals;   b) a probe operably connected to the source of electromagnetic signals, for delivering the electromagnetic signals to a tissue site;   c) a spectrometer which acquires diffuse reflectance electromagnetic signals returned from the tissue site and produces a diffuse reflectance spectra from the returned diffuse reflectance electromagnetic signals; and   d) a system controller operably connected to the spectrometer, wherein the system controller:
 i) analyzes the diffuse reflectance spectra to calculate the absolute hemoglobin oxygenation (SatO 2 ); 
 ii) analyzes SatO 2  with respect to those from normal reference tissue sites to identify the tissue site as neoplastic or normal; and 
 iii) determines the site in the tissue of the patient as neoplastic if:
   SatO 2 >1+ y× SatO 2 N   _   std  or SatO 2 <1− y×SatO   2 N   _   std ,
 
 
   wherein y is an adjustable cutoff for SatO 2  and SatO 2 N   _   std  is standard deviation of SatO 2  from the plurality of known normal sites.   
     
     
         71 . The system of  claim 70 , wherein the tissue is brain. 
     
     
         72 . The system of  claim 70 , wherein the spectrometer acquires the diffuse reflectance electromagnetic signals returned from the site at a rate of about 33 Hz. 
     
     
         73 . The system of  claim 70 , wherein the the site is smaller than about 5 mm in diameter and thinner than about 2 mm in thickness. 
     
     
         74 . A system for identifying a site in a tissue of a patient as neoplastic or normal, the system comprising:
 a) a source of electromagnetic signals;   b) a probe operably connected to the source of electromagnetic signals, for delivering the electromagnetic signals to a tissue site;   c) a spectrometer which acquires diffuse reflectance electromagnetic signals returned from the tissue site and produces a diffuse reflectance spectra from the returned diffuse reflectance electromagnetic signals; and   d) a system controller operably connected to the spectrometer, wherein the system controller:
 i) analyzes the diffuse reflectance spectra to calculate the absolute diffuse reflectance intensity of signals having wavelength of about 700 nm (Rd(700)); 
 ii) analyzes Rd(700) with respect to those from normal reference tissue sites to identify the tissue site as neoplastic or normal; and 
 iii) determines the site in the tissue of the patient as neoplastic if:
     Rd (700)>1+ z×Rd (700) N   _   std  or  Rd (700)<1− z×Rd (700) N   _   std  
 
 
   wherein z is an adjustable cutoff and Rd(700) and Rd(700) N   _   Std  is standard deviation for diffuse reflectance intensity of signals having wavelength of about 700 nm from the plurality of known normal sites.   
     
     
         75 . The system of  claim 74 , wherein the tissue is brain. 
     
     
         76 . The system of  claim 74 , wherein the spectrometer acquires the diffuse reflectance electromagnetic signals returned from the site at a rate of about 33 Hz. 
     
     
         77 . The system of  claim 74 , wherein the the site is smaller than about 5 mm in diameter and thinner than about 2 mm in thickness. 
     
     
         78 . A system for identifying a site in a tissue of a patient as neoplastic or normal, the system comprising:
 a) a source of electromagnetic signals;   b) a probe operably connected to the source of electromagnetic signals, for delivering the electromagnetic signals to a tissue site;   c) a spectrometer which acquires diffuse reflectance electromagnetic signals returned from the tissue site and produces a diffuse reflectance spectra from the returned diffuse reflectance electromagnetic signals; and   d) a system controller operably connected to the spectrometer, wherein the system controller:
 i) analyzes the diffuse reflectance spectra to calculate one or more of:
 a) absolute hemoglobin concentration ([Hb]), 
 b) absolute hemoglobin oxygenation (SatO 2 ), 
 c) absolute diffuse reflectance intensity of signals having wavelength of about 700 nm (Rd(700)), and 
 d) relative ratio of absorption coefficient μ a  and reduced scattering cooefficient μ s  between 450 nm and 650 nm (μ a (λ)/μ s (λ)); 
 
 ii) analyzes [Hb], SatO 2 , Rd(700), and/or μ a (λ)/μ s (λ) with respect to those from normal reference tissue sites to identify the tissue site as neoplastic or normal; and 
 iii) determines the site in the tissue of the patient as neoplastic if: 
   a) any one of [Hb], SatO 2 , Rd(700), and μ a (λ)/μ s (λ) was >1±u×(stand_deviation), or   b) any one of [Hb], SatO 2 , Rd(700), and μ a (λ)/μ s (λ) was <1±u×(stand_deviation), wherein u is an adjustable cutoff value for [Hb], SatO 2 , and Rd(700) and (stand_deviation) is the standard deviation for the selected parameter from the plurality of known normal sites.   
     
     
         79 . The system of  claim 78 , wherein the tissue is brain. 
     
     
         80 . The system of  claim 78 , wherein the spectrometer acquires the diffuse reflectance electromagnetic signals returned from the site at a rate of about 33 Hz. 
     
     
         81 . The system of  claim 78 , wherein the the site is smaller than about 5 mm in diameter and thinner than about 2 mm in thickness. 
     
     
         82 . A system for identifying a site in a tissue of a patient as neoplastic or normal, the system comprising:
 a) a source of electromagnetic signals;   b) a probe operably connected to the source of electromagnetic signals, for delivering the electromagnetic signals to a tissue site;   c) a spectrometer which acquires diffuse reflectance electromagnetic signals returned from the tissue site and produces a diffuse reflectance spectra from the returned diffuse reflectance electromagnetic signals; and   d) a system controller operably connected to the spectrometer, wherein the system controller:
 i) analyzes the diffuse reflectance spectra to calculate two or more of:
 a) absolute hemoglobin concentration ([Hb]), 
 b) absolute hemoglobin oxygenation (SatO 2 ), 
 c) absolute diffuse reflectance intensity of signals having wavelength of about 700 nm (Rd(700)), and 
 d) relative ratio of absorption coefficient μ a  and reduced scattering cooefficient μ s  between 450 nm and 650 nm (μ a (λ)/μ s (λ)); 
 
 ii) analyzes [Hb], SatO 2 , Rd( 700 ), and/or μ a (X)/μ s (k) with respect to those from normal reference tissue sites to identify the tissue site as neoplastic or normal; and 
 iii) determines the site in the tissue of the patient as neoplastic if: 
   a) any two of [Hb], SatO 2 , Rd(700), and μ a (λ)/μ s (λ) was >1±v×(stand_deviation), or   b) any two of [Hb], SatO 2 , Rd(700), and μ a (λ)/μ s (λ) was <1±v×(stand_deviation), wherein v is an adjustable cutoff value for any two of [Hb], SatO 2 , Rd(700), and μ a (λ)/μ s (λ) and (stand_deviation) is the standard deviation for the selected parameters from the plurality of known normal sites.   
     
     
         83 . The system of  claim 82 , wherein the tissue is brain. 
     
     
         84 . The system of  claim 82 , wherein the spectrometer acquires the diffuse reflectance electromagnetic signals returned from the site at a rate of about 33 Hz. 
     
     
         85 . The system of  claim 82 , wherein the the site is smaller than about 5 mm in diameter and thinner than about 2 mm in thickness. 
     
     
         86 . A system for identifying a site in a tissue of a patient as neoplastic or normal, the system comprising:
 a) a source of electromagnetic signals;   b) a probe operably connected to the source of electromagnetic signals, for delivering the electromagnetic signals to a tissue site;   c) a spectrometer which acquires diffuse reflectance electromagnetic signals returned from the tissue site and produces a diffuse reflectance spectra from the returned diffuse reflectance electromagnetic signals; and   d) a system controller operably connected to the spectrometer, wherein the system controller:
 i) analyzes the diffuse reflectance spectra to calculate:
 a) absolute hemoglobin concentration ([Hb]), 
 b) absolute hemoglobin oxygenation (SatO 2 ), 
 c) absolute diffuse reflectance intensity of signals having wavelength of about 700 nm (Rd(700)), and 
 d) relative ratio of absorption coefficient μ a  and reduced scattering cooefficient μ s  between 450 nm and 650 nm (μ a (λ)/μ s (λ)); 
 
 ii) analyzes [Hb], SatO 2 , Rd(700), and/or μ a (λ)/μ s (λ) with respect to those from normal reference tissue sites to identify the tissue site as neoplastic or normal; and 
 iii) determines the site in the tissue of the patient as neoplastic if: 
   a) all of [Hb], SatO 2 , Rd(700), and μ a (λ)/μ s (λ) were >1±w×(stand_deviation), or   b) all of [Hb], SatO 2 , Rd(700), and μ a (λ)/μ s (λ) were <1±w×(stand_deviation), wherein w is an adjustable cutoff value for all of [Hb], SatO 2 , and Rd(700) and (stand_deviation) is the standard deviation for the selected parameters from the plurality of known normal sites.   
     
     
         87 . The system of  claim 86 , wherein the tissue is brain. 
     
     
         88 . The system of  claim 86 , wherein the spectrometer acquires the diffuse reflectance electromagnetic signals returned from the site at a rate of about 33 Hz. 
     
     
         89 . The system of  claim 86 , wherein the the site is smaller than about 5 mm in diameter and thinner than about 2 mm in thickness.