CA2505677A1 - Method and apparatus for time resolved optical imaging of biological tissues as part of animals - Google Patents

Method and apparatus for time resolved optical imaging of biological tissues as part of animals Download PDF

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Publication number
CA2505677A1
CA2505677A1 CA002505677A CA2505677A CA2505677A1 CA 2505677 A1 CA2505677 A1 CA 2505677A1 CA 002505677 A CA002505677 A CA 002505677A CA 2505677 A CA2505677 A CA 2505677A CA 2505677 A1 CA2505677 A1 CA 2505677A1
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Canada
Prior art keywords
points
illumination
light
animal
detector
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Granted
Application number
CA002505677A
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French (fr)
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CA2505677C (en
Inventor
William F. Long
Yves Berube-Lauziere
David J. Hall
Laura Mcintosh
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Softscan Healthcare Group Ltd
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Individual
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Publication of CA2505677A1 publication Critical patent/CA2505677A1/en
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Publication of CA2505677C publication Critical patent/CA2505677C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64Fluorescence; Phosphorescence
    • G01N21/6428Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0062Arrangements for scanning
    • A61B5/0064Body surface scanning
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0073Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by tomography, i.e. reconstruction of 3D images from 2D projections
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47Scattering, i.e. diffuse reflection
    • G01N21/4795Scattering, i.e. diffuse reflection spatially resolved investigating of object in scattering medium
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47Scattering, i.e. diffuse reflection
    • G01N21/49Scattering, i.e. diffuse reflection within a body or fluid
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64Fluorescence; Phosphorescence
    • G01N21/6408Fluorescence; Phosphorescence with measurement of decay time, time resolved fluorescence
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64Fluorescence; Phosphorescence
    • G01N21/645Specially adapted constructive features of fluorimeters
    • G01N21/6456Spatial resolved fluorescence measurements; Imaging
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N2021/178Methods for obtaining spatial resolution of the property being measured
    • G01N2021/1785Three dimensional
    • G01N2021/1787Tomographic, i.e. computerised reconstruction from projective measurements
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64Fluorescence; Phosphorescence
    • G01N2021/6417Spectrofluorimetric devices
    • G01N2021/6419Excitation at two or more wavelengths
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64Fluorescence; Phosphorescence
    • G01N21/6428Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • G01N2021/6439Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" with indicators, stains, dyes, tags, labels, marks
    • G01N2021/6441Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" with indicators, stains, dyes, tags, labels, marks with two or more labels
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64Fluorescence; Phosphorescence
    • G01N21/645Specially adapted constructive features of fluorimeters
    • G01N2021/6463Optics
    • G01N2021/6471Special filters, filter wheel

Abstract

There is provided a method and system for collecting optical data for use in time resolved optical imaging wherein pulsed light is directionally propagated through free-space optics (24, 26, 28, 29) to impinge on a plurality of illumination at the surface of a biological tissue (14) such as that comprised in small animals. Light re-emitted from the tissue is collected and directionally propagated through free space optics (34, 36, 38) towards a detector (18) to produce time resolved optical signals useful for optical image reconstructions.

Claims (39)

1. A method for collecting optical data for use in time resolved optical imaging of an animal the method comprising:
i) positioning said animal for data acquisition through free-space optics ii) directionally propagating through free-space optics a pulsed light beam of a selected intensity to illuminate at one or more wavelength a plurality of predetermined illumination points in a region of interest of the animal;.
iii) selectively collecting, through free-space optics, light emanating, from a plurality of predetermined collection points;
iv) directionally propagating through free-space optics the collected light towards a detector;
v) measuring, at one or mere wavelength, the collected light at the detector to produce a time resolved optical, signal for one or more illumination points/collection points configuration; and wherein light emanating from points other than the predetermined collection paints is optically excluded from detection.
2. The method as claimed in claim 1, wherein the time resolved optical imaging is time domain (TD) imaging and wherein the time resolved optical signal is detected such as to generate information related to a temporal point spread function.
3, The method as claimed in claim 2, wherein the step of measuring comprises detecting the collected light using time correlated single photon counting approach.
4. The method as claimed in claim 3, wherein each illumination point is illuminated by a plurality of pulses.
5. The method as claimed in claim 4, wherein the step of illuminating comprises adjusting the intensity of the light beam such as to avoid distortions caused by electronics dead-time losses.
6. The method as claimed in claim 5, wherein the intensity is adjusted by varying the source intensity.
7. The method as claimed in claim 6, wherein the intensity is adjusted with filters.
8. The method as claimed in any one of claim 1-7, wherein the optical signal is detected at two or more wavelengths simultaneously.
9. The method as claimed in any one of claim 1-7 wherein the optical signal is detected at two or more wavelengths sequentially.
10. The method as claimed in any one of claim 1-9, wherein the illumination points are illuminated in a raster scan fashion.
11. The method as claimed in any one of claim 1-10, wherein the collection points are located at a fixed distance from the illumination points to provide optical signal for topographic imaging.
12. The method as claimed in claim 11, wherein the distance is 3mm.
13. The method as claimed in any one of claim 1-10, wherein two or more collection points are collected for each illumination point to provide optical data for tomographic imaging.
14. The method as claimed in claim 13, wherein at least two of the 2 or more collection points are collected simultaneously.
15. The method as claimed in any one of claim 1-14, wherein detection is effected at a wavelength different from that of illumination.
16. The method as claimed in any one of claim 1-15, wherein the biological tissue comprises one or more fluorophores and wherein the detection wavelength corresponds to an emission wavelength of the one or more fluorophores and the illumination wavelength corresponds to an excitation wavelength of the one or more fluorophores.
17. The method as claimed in claim 16, wherein both the excitation and emission wavelength are detected.
18. The method as claimed in any one of claim 1-17, wherein the time resolved optical signal is integrated to provide attenuation measurement.
19. The method as claimed in any one of claim 1-18, wherein optical data from a plurality of regions of interest are collected during a single session.
20. The method as claimed in claim 19, wherein the plurality of regions of interest comprises a whole body of an animal.
21. The method as claimed in any one of claim 1-20 wherein said animal is controllably heated.
22. A system for collecting optical data for use in time resolved optical imaging of an animal, the system comprising:
i) one or more pulsed light source of selected intensity for providing a light beam at one or more wavelengths:
ii) illuminating optic components for directionally propagating the beam through free space optics such that a region of interest of the biological tissue is illuminated at a plurality of illumination points thereby injecting light into the animal;

iii) collecting optic components for collecting through free space optics light re-emitted at a plurality of predetermined collection points in the region of interest such that light emanating from points other than the predetermined collection points is optically excluded from detection, and for directionally propagating, through free space optics, the collected light; and iv) a time domain detector for detecting the collected light.
23. The system as claimed in claim 22, wherein the one or more light sources are variable intensity light sources.
24. The system as claimed in claim 23, wherein the variable intensity light sources are lasers.
25. The system as claimed in any one of claim 22-24, wherein the illuminating optic components comprise at least one moveable mirror for directing the beam to the plurality of illumination points.
26. The system as claimed in claim 25, wherein the moveable mirror is a mirror galvanometer.
27. The system as claimed in claim 26 further comprising a thin angled mirror located optically downstream of the mirror galvanometer.
28. The system as claimed in claim 27, wherein a lens is positioned between the mirror galvanometer and the thin angled mirror and optically coupled therewith to provide a telecentric imaging configuration.
29. The system as claimed in any one of claim 22-28, wherein the collecting optic components comprise a lens located above the region of interest and having a focal point coincident with the collection point.
30. The system as claimed in claim 29, wherein the collecting optic components further comprise a mirror galvanometer for directing the collected light to the detector.
31. The system as claimed in claim 30, wherein the mirror galvanometers of the illumination optic and collection optic are synchronized so as to provide a fixed distance between the illumination points and respective detection points.
32. The system as claimed in claim 30, wherein the mirror galvanometers of the illumination optic and collection optic are independently adjustable so as to provide a variable distance between the illumination points and respective detection points.
33. The system as claimed in any one of claim 22-32, wherein the illumination optics, the detection optics and the source are part of a gantry that can be rotated around the animal.
34. The system as claimed in any one of claim 22-33, further comprising a translational stage for moving a tray in a plane perpendicular to the illuminating beam wherein the tray is for supporting an animal.
35. The system as claimed in claim 34, wherein the tray is controllably heated to a desired temperature suitable for said animal.
36. The system as claimed in any one of claim 22-35, wherein the detector is a time correlated single photon counting detector.
37. The system as claimed in any one of claim 22-35, wherein the detector is a time gated ICCD.
38. The system as claimed in any one of claim 22-37, wherein the animal, the optical components and the detector are contained in an enclosure.
39. The system as claimed in claim 39, wherein the enclosure is light tight.
CA2505677A 2002-11-11 2003-11-10 Method and apparatus for time resolved optical imaging of biological tissues as part of animals Expired - Fee Related CA2505677C (en)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
IB0204698 2002-11-11
IBPCT/IB02/04698 2002-11-11
US31785602A 2002-12-12 2002-12-12
US10/317,856 2002-12-12
US50535203P 2003-09-22 2003-09-22
US60/505,352 2003-09-22
PCT/CA2003/001705 WO2004044562A1 (en) 2002-11-11 2003-11-10 Method and apparatus for time resolved optical imaging of biological tissues as part of animals

Publications (2)

Publication Number Publication Date
CA2505677A1 true CA2505677A1 (en) 2004-05-27
CA2505677C CA2505677C (en) 2011-11-01

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CA2505677A Expired - Fee Related CA2505677C (en) 2002-11-11 2003-11-10 Method and apparatus for time resolved optical imaging of biological tissues as part of animals

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AU (1) AU2003283106A1 (en)
CA (1) CA2505677C (en)
WO (1) WO2004044562A1 (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2902307B1 (en) * 2006-06-14 2008-08-29 Quidd Sas OPTICAL IMAGING DEVICE
CN102048525B (en) * 2011-01-26 2012-05-30 浙江大学 Organism fluorescent three-dimensional imaging system and application thereof
US10646160B2 (en) 2012-01-19 2020-05-12 Technion Research & Development Foundation Limited Vessel imaging system and method

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5148022A (en) * 1989-02-15 1992-09-15 Hitachi, Ltd. Method for optically inspecting human body and apparatus for the same
JPH0961359A (en) * 1995-08-29 1997-03-07 Hamamatsu Photonics Kk Concentration measuring device
JP3685983B2 (en) * 2000-08-08 2005-08-24 独立行政法人科学技術振興機構 Body temperature holding device for small animals
GB0023619D0 (en) * 2000-09-27 2000-11-08 Amersham Pharm Biotech Uk Ltd Measurement of fluorescence decay times
US6615063B1 (en) * 2000-11-27 2003-09-02 The General Hospital Corporation Fluorescence-mediated molecular tomography
CA2434283A1 (en) * 2001-01-12 2002-07-25 General Hospital Corporation System and method for enabling simultaneous calibration and imaging of a medium
US6856457B2 (en) * 2001-03-27 2005-02-15 Prairie Technologies, Inc. Single and multi-aperture, translationally-coupled confocal microscope

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AU2003283106A1 (en) 2004-06-03
WO2004044562A1 (en) 2004-05-27
CA2505677C (en) 2011-11-01

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