CA2389177A1 - Multi-modal optical tissue diagnostic system - Google Patents

Multi-modal optical tissue diagnostic system Download PDF

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Publication number
CA2389177A1
CA2389177A1 CA002389177A CA2389177A CA2389177A1 CA 2389177 A1 CA2389177 A1 CA 2389177A1 CA 002389177 A CA002389177 A CA 002389177A CA 2389177 A CA2389177 A CA 2389177A CA 2389177 A1 CA2389177 A1 CA 2389177A1
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Prior art keywords
target tissue
radiation
measurements
fluorescence
scattering
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CA002389177A
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French (fr)
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CA2389177C (en
Inventor
Shabbir B. Bambot
Mark L. Faupel
Tim Harrel
Anant Agrawal
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Spectrx Inc
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Individual
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0075—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0071—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by measuring fluorescence emission
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0082—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes
    • A61B5/0084—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes for introduction into the body, e.g. by catheters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0082—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes
    • A61B5/0091—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes for mammography
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/43—Detecting, measuring or recording for evaluating the reproductive systems
    • A61B5/4306—Detecting, measuring or recording for evaluating the reproductive systems for evaluating the female reproductive systems, e.g. gynaecological evaluations
    • A61B5/4312—Breast evaluation or disorder diagnosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/43—Detecting, measuring or recording for evaluating the reproductive systems
    • A61B5/4306—Detecting, measuring or recording for evaluating the reproductive systems for evaluating the female reproductive systems, e.g. gynaecological evaluations
    • A61B5/4318—Evaluation of the lower reproductive system
    • A61B5/4331—Evaluation of the lower reproductive system of the cervix
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/72—Signal processing specially adapted for physiological signals or for diagnostic purposes
    • A61B5/7235—Details of waveform analysis
    • A61B5/7264—Classification of physiological signals or data, e.g. using neural networks, statistical classifiers, expert systems or fuzzy systems

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Medical Informatics (AREA)
  • Surgery (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Pathology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)

Abstract

An apparatus and method according to the invention utilizes a radiation sour ce (20) and processor (44) to combine more than one optical modality (spectroscopic method), including but not limited to fluorescence, absorptio n, 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 for tissue condition.</SD OAB>

Claims (46)

1. A method for diagnosing a condition of a target tissue, comprising the steps of:
a.) irradiating a target tissue;
b.) sensing a returned radiation;
c.) determining characteristics of the returned radiation using at least two spectroscopic methods;
d.) combining the characteristics determined by the at least two spectroscopic methods; and e.) determining a condition of the target tissue based on the combined determined characteristics.
2. The system of claim 1, wherein the at least two spectroscopic methods comprise fluorescence measurements and scattering or reflectance measurements.
3. The method of claim 1, 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.
4. The method of claim 3, 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.
5. The method of claim 1, wherein step a.) comprises illuminating the target tissue with excitation electromagnetic radiation, and 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.
6. The method of claim 5, 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.
7. The method of claim 1, wherein step a.) comprises illuminating the target tissue with excitation electromagnetic radiation, and 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.
8. The method according to claim 7, wherein a critical timing window, which is defined as the time period between sensing electromagnetic radiation emitted from the target tissue in response to the excitation electromagnetic radiation and subsequently sensing excitation electromagnetic radiation that is scattered from the target tissue, is not greater than approximately 0.25 seconds.
9. The method of claim 7, 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.
10. The method of claim 1, wherein step b.) comprises sensing, approximately simultaneously, radiation returned from a plurality of interrogation points distributed over the target tissue.
11. The method according to claim 10, 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 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.
12. The method according to claim 11, further comprising a step of identifying visual characteristics of the target tissue, wherein the field areas are selected based on the identified visual characteristics of the target tissue.
13. The method according to claim 11, wherein the field areas are selected based on previously identified characteristics of the target tissue.
14. The method according to claim 13, wherein the previously identified characteristics of the target tissue comprise characteristics of the target tissue identified through previous testing of the target tissue using at least one of cytology, colposcopy and histopathology.
15. The method of claim 11, 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 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.
16. The method of claim 10, wherein the method is performed using an apparatus comprising an irradiation source, a detector and a processor, wherein the step of sensing radiation returned from a plurality of interrogation points comprises the steps of:
sensing 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 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.
17. The method of claim 1, further comprising a step of generating a map of conditions of different portions of the target tissue based on the combined determined characteristics.
18. The method of claim 1, further comprising a step of conducting a pattern recognition process to determine whether a pattern of conditions exists within the target tissue.
19. A system for determining a condition of a target biological tissue, comprising:
a source for providing excitation radiation;
a device that couples the excitation radiation to a target tissue;
a device that senses radiation returned from the target tissue;
a processor configured to determine characteristics of the returned 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.
20. The system of claim 19, wherein the at least two spectroscopic methods comprise fluorescence measurement methods and scattering or reflectance measurement methods.
21. The system of claim 19, 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.
22. The system of claim 19, wherein the device that senses returned radiation is configured to simultaneously sense fluorescent radiation emitted by endogenous fluorophores in response to the excitation radiation and excitation radiation that is scattered from the target tissue.
23. The system of claim 22, wherein the processor makes intensity based measurements on both said fluorescent radiation emitted by endogenous fluorophores in response to the excitation radiation and said excitation radiation that is scattered from the target tissue.
24. The system of claim 19, wherein the device that senses radiation is configured to first sense fluorescent radiation emitted by fluorophores in response to the excitation radiation and then subsequently sense excitation radiation that is scattered from the target tissue.
25. The system according to claim 24, wherein a critical timing window, which is defined as the time period between sensing radiation emitted from the target tissue in response to the excitation radiation and subsequently sensing excitation radiation that is scattered from the target tissue, is not greater than approximately 0.25 seconds.
26. The system of claim 24, wherein the processor makes intensity based measurements on both said fluorescent radiation emitted by endogenous fluorophores in response to the excitation radiation and said excitation radiation that is scattered from the target tissue.
27. The system of claim 19, wherein the device that senses radiation is configured to sense radiation returned from a plurality of interrogation points distributed over the target tissue.
28. The system according to claim 27, wherein the processor divides the target tissue into a first set of field areas, determines characteristics of the returned 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.
29. The system according to claim 28, wherein the target tissue is divided into field areas according to previously identified characteristics of the target tissue.
30. The system according to claim 29, wherein the previously identified characteristics of the target tissue are visually identified characteristics of the target tissue.
31. The system according to claim 29, wherein the previously identified characteristics of the target tissue are characteristics of the target tissue identified through previous testing of the target tissue using at least one of cytology, colposcopy and histopathology.
32. The system of claim 28, 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.
33. The system of claim 27, wherein the device that senses radiation is movable to a plurality of pre-determined positions and is configured to sense radiation returned from a subset of the plurality of interrogation points at each pre-determined position.
34. The system of claim 19, wherein the processor is also configured to conduct a pattern recognition process to determine whether a pattern of conditions exists within the target tissue.
35. The system of claim 19, wherein the processor is also configured to create a map of determined conditions of different portions of a target tissue.
36. A method for diagnosing dysplastic tissue, comprising:
irradiating a target tissue with radiation;
sensing radiation returned from the target tissue;
determining 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 determining a condition of the target tissue based the determined characteristics.
37. A system for determining a condition of a target biological tissue, comprising:
a radiation source for providing excitation radiation;
a device that couples the excitation radiation to a target tissue;
a device that senses radiation returned from the target tissue; and a processor configured to determine characteristics of the returned 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.
38. The method according to claim 1, wherein step c) comprises taking fluorescence and scattering or reflective measurements at two wavelengths at each of a plurality of interrogation points; step d) comprises determining a fluorescence ratio for the measurements taken at the two wavelengths at each of the plurality of interrogation points and averaging the fluorescence ratios and determining a scattering or reflectance ratio for the measurements taken at the two wavelengths at each of the plurality of interrogated points and averaging the scattering or reflectance ratios; and step e) comprises determining a condition of the target tissue based on the averaged fluorescence and scattering or reflectance ratios.
39. The method of claim 1, wherein step c) comprises taking fluorescence and scattering or reflectance measurements at two wavelengths at each of a plurality of interrogation points; step d) comprises determining a fluorescence ratio for the measurements taken at the two wavelengths at each of the plurality of interrogation points, averaging the fluorescence ratios, determining a coefficient of variation value for the averaged fluorescence ratio, determining a scattering or reflectance ratio for the measurements taken at the two wavelengths at each of the plurality of interrogation points, averaging the scattering or reflectance ratios, determining a coefficient of variation value for the averaged scattering or reflectance ratio; and step e) comprises determining a condition of the target tissue based on the coefficient of variation values.
40. The method of claim 1, further comprising mapping the characteristics determined by the at least two spectroscopic methods using false color mapping, wherein step e) comprises identifying abnormal tissue using the false color map.
41. The method of claim 1, wherein a multi-modal hyperspectral imaging camera is used to implement the method.
42. The system according to claim 19, wherein the processor makes fluorescence and scattering or reflective measurements at two wavelengths at each of a plurality of interrogation points, determines a fluorescence ratio for the fluorescence measurements taken at the two wavelengths at each of the plurality of interrogation points and averages the fluorescence ratios, and determines a scattering or reflectance ratio for the scattering or reflectance measurements taken at the two wavelengths at each of the plurality of interrogation points and averages the scattering or reflectance ratios.
43. The system of claim 19, wherein the processor makes fluorescence and scattering or reflectance measurements at two wavelengths at each of a plurality of interrogation points, determines a fluorescence ratio for the measurements taken at the two wavelengths at each of the plurality of interrogation points, averages the fluorescence ratios, determines a coefficient of variation value for the averaged fluorescence ratio, determines a scattering or reflectance ratio for the measurements taken at the two wavelengths at each of the plurality of interrogation points, averages the scattering or reflectance ratios and determines a coefficient of variation value for the averaged scattering or reflectance ratio.
44. The system of claim 43, wherein the processor determines the condition of the target tissue based upon the coefficient of variation values for the averaged fluorescence and scattering or reflectance ratios.
45. The method according to claim 1, wherein step c) comprises taking fluorescence and scattering or reflective measurements at two wavelengths at each of a plurality of interrogation points; step d) comprises determining a fluorescence to scattering or reflectance ratio for the measurements taken at the two wavelengths at each of the plurality of interrogation points and averaging the fluorescence to scattering or reflectance ratios; and step e) comprises determining a condition of the target tissue based on the averaged fluorescence to scattering or reflectance ratio.
46. The method according to claim 1, wherein step c) comprises taking fluorescence and scattering or reflective measurements at two wavelengths at each of a plurality of interrogation points; step d) comprises using one or more statistical method to analyze the fluorescence and scattering or reflective measurements; and step e) comprises determining a condition of the target tissue based on the results of the statistical analysis.
CA2389177A 1999-11-05 2000-11-03 Multi-modal optical tissue diagnostic system Expired - Lifetime CA2389177C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US43451899A 1999-11-05 1999-11-05
US09/434,518 1999-11-05
PCT/US2000/028879 WO2001034031A1 (en) 1999-11-05 2000-11-03 Multi-modal optical tissue diagnostic system

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CA2389177A1 true CA2389177A1 (en) 2001-05-17
CA2389177C CA2389177C (en) 2012-05-29

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EP (1) EP1229836A4 (en)
AU (1) AU1572401A (en)
BR (1) BR0015285A (en)
CA (1) CA2389177C (en)
WO (1) WO2001034031A1 (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6697652B2 (en) * 2001-01-19 2004-02-24 Massachusetts Institute Of Technology Fluorescence, reflectance and light scattering spectroscopy for measuring tissue
JP2005515473A (en) * 2002-01-18 2005-05-26 ニユートン・ラボラトリーズ・インコーポレーテツド Spectroscopic diagnosis method and system
WO2003062798A1 (en) * 2002-01-18 2003-07-31 Newton Laboratories, Inc. Spectroscopic diagnostic methods and system
FR2839894A1 (en) 2002-05-21 2003-11-28 Chabunda Christophe Mwanza Integrated radiotherapy equipment for obtaining instant diagnostic images, comprises five sources of photon beams on rotating frames and six sources of photon beams on fixed porticos
CN103328953B (en) * 2011-04-21 2015-07-01 奥林巴斯医疗株式会社 Optical measuring system, optical measuring apparatus, calibration member, and calibration method

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* Cited by examiner, † Cited by third party
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US5090415A (en) * 1989-02-14 1992-02-25 Hamamatsu Photonics Kabushiki Kaisha Examination apparatus
US5203328A (en) * 1991-07-17 1993-04-20 Georgia Tech Research Corporation Apparatus and methods for quantitatively measuring molecular changes in the ocular lens
US5762609A (en) * 1992-09-14 1998-06-09 Sextant Medical Corporation Device and method for analysis of surgical tissue interventions
US5596992A (en) * 1993-06-30 1997-01-28 Sandia Corporation Multivariate classification of infrared spectra of cell and tissue samples
US6008889A (en) * 1997-04-16 1999-12-28 Zeng; Haishan Spectrometer system for diagnosis of skin disease
WO2000015101A1 (en) * 1998-09-11 2000-03-23 Spectrx, Inc. Multi-modal optical tissue diagnostic system
US6174291B1 (en) * 1998-03-09 2001-01-16 Spectrascience, Inc. Optical biopsy system and methods for tissue diagnosis
WO1999057529A1 (en) * 1998-05-04 1999-11-11 The Board Of Regents Combined fluorescence and reflectance spectroscopy

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EP1229836A4 (en) 2007-05-02
BR0015285A (en) 2002-06-18
WO2001034031A1 (en) 2001-05-17
AU1572401A (en) 2001-06-06
CA2389177C (en) 2012-05-29
EP1229836A1 (en) 2002-08-14

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