WO2007143141B1 - In-vivo optical imaging method including analysis of dynamic images - Google Patents

In-vivo optical imaging method including analysis of dynamic images

Info

Publication number
WO2007143141B1
WO2007143141B1 PCT/US2007/013024 US2007013024W WO2007143141B1 WO 2007143141 B1 WO2007143141 B1 WO 2007143141B1 US 2007013024 W US2007013024 W US 2007013024W WO 2007143141 B1 WO2007143141 B1 WO 2007143141B1
Authority
WO
WIPO (PCT)
Prior art keywords
distinctive
time
pixel
animal
image data
Prior art date
Application number
PCT/US2007/013024
Other languages
French (fr)
Other versions
WO2007143141A3 (en
WO2007143141A2 (en
Inventor
Elizabeth M C Hillman
Original Assignee
Gen Hospital Corp
Elizabeth M C Hillman
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Gen Hospital Corp, Elizabeth M C Hillman filed Critical Gen Hospital Corp
Priority to US12/302,986 priority Critical patent/US9220411B2/en
Priority to EP07795649A priority patent/EP2034890A4/en
Publication of WO2007143141A2 publication Critical patent/WO2007143141A2/en
Publication of WO2007143141A3 publication Critical patent/WO2007143141A3/en
Publication of WO2007143141B1 publication Critical patent/WO2007143141B1/en

Links

Classifications

    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/41—Detecting, measuring or recording for evaluating the immune or lymphatic systems
    • A61B5/414—Evaluating particular organs or parts of the immune or lymphatic systems
    • A61B5/415—Evaluating particular organs or parts of the immune or lymphatic systems the glands, e.g. tonsils, adenoids or thymus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/41—Detecting, measuring or recording for evaluating the immune or lymphatic systems
    • A61B5/414—Evaluating particular organs or parts of the immune or lymphatic systems
    • A61B5/418—Evaluating particular organs or parts of the immune or lymphatic systems lymph vessels, ducts or nodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/0013—Luminescence
    • A61K49/0017—Fluorescence in vivo
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2503/00—Evaluating a particular growth phase or type of persons or animals
    • A61B2503/40—Animals

Abstract

In-vivo optical molecular imaging methods for producing an image of an animal are described. A time series of image data sets of an optical contrast substance in the animal is acquired using an optical detector. Each image data set is obtained at a selected time and has the same plurality of pixels, with each pixel having an associated value. The image data sets are analyzed to identify a plurality of distinctive time courses, and respective pixel sets are determined from the plurality of pixels which correspond to each of the time courses. In one embodiment, each pixel set is associated with an identified anatomical or other structure, and an anatomical image map of the animal can be generated which includes one or more of the anatomical structures.

Claims

AMENDED CLAIMS received by the International Bureau on 07 May 2008 (07.05.2008)
50. The method of claim 1 , further including calculating a quantitative measure of the targeted optical contrast substance.
51. The method of claim 50, wherein the quantitative measure comprises the concentration of targeted optical contrast substance in the targeted region.
52. The method of claim 51 , wherein the calculation of the concentration is based on measured boundary fluorescence and measured boundary diffuse reflectance.
53. The method of claim 50, wherein calculation of the quantitative measure is based on information obtained from more than one view of the animal.
54. The method of claim 50, wherein the calculation of the quantitative measure incorporates anatomical image data obtained from the generated image of the animal.
55. The method of claim 1 , wherein tho step of acquiring a time series of image data sets comprises acquiring a time series of image data sets of a plurality of targeted optical contrast substances.
56. The method of claim 55, wherein the step of analysis includes spectral delineation of contrast substances.
57. The method of claim 56, wherein spectral delineation is achieved using spectral un-mixing techniques.
58. The method of claim 1 , wherein the step of analysis further includes spectral delineation of the contrast substance based on acquisition of multi-wavelength data.
59. The method of claim 1 , wherein the step of determining a respective pixel set includes using pixel values from multiple time points within the time series and calculating a single spatial distribution of the pixel values across the time series.
AMENDED SHEET (ARTICLE 19)
28
60. The method of claim 1. wherein the step of generating an image is performed only subsequent to the acquiring, analyzing and determining steps.
61. The method of claim 1 , wherein the step of determining a respective pixel set from the plurality of pixels which corresponds to each of the time courses is performed by a computer.
62. The method of claim 1 , wherein th© step of analyzing the image data sets is achieved using pixel values obtained at a plurality of time points within the time series such that the plurality of distinctive time courses are identified based on calculated spatial and temporal patterns of emission from the optical contrast substance.
63. The method of claim 1 , wherein the step ol determining a respective pixel set from the plurality of pixels which corresponds to each of the time courses is a calculation based on the temporal pattern of emission of the optical contrast substance at each pixel.
64. The method of claim 1 wherein dynamics of the optical contrast substance within the animal are used to identify multiple organs within a single image.
65. The method of claim 1 , wherein the step of analyzing the image data sets is achieved using pixel values obtained at a plurality of time points within the time series, and the step of determining a respective pixel set is based on spatial and temporal patterns of emission from the optical contrast substance; and calculated using pixel values obtained at a plurality of time points within the time series,
66. The method of claim 15, wherein the step of determining a respective pixel set includes using pixel values from multiple time points within the time series and calculating a single spatial distribution of the pixel values across the time series.
AMENDED SHEET (ARTICLE 19)
67. The method of claim 15, wherein the step of generating an image is performed only subsequent to the acquiring, analyzing and determining steps.
68. The method of claim 15, wherein the step of determining a respective pixel set from the plurality of pixels which corresponds to each of the time courses is performed by a computer.
69. The method of claim 15, wherein the step of analyzing the image data sets is achieved using pixel values obtained at a plurality of time points within the time series such that the plurality of distinctive time courses are identified based on calculated spatial and temporal patterns of emission from the optical contrast substance.
70. The method of claim 15, wherein the step of determining a respective pixel set from the plurality of pixels which corresponds to each of the time courses is a calculation based on the temporal pattern of emission of the optical contrast substance at each pixel.
71. The method of claim 15 wherein dynamics of the optical contrast substance within the animal are used to identify multiple organs within a single image.
72. The method of claim 15, wherein the image data sets further include a targeted molecular probe, and the generated anatomical image map further includes a co-registered image of a structure targeted by the molecular probθ.
73. The method of claim 15, wherein the step of analyzing the image data sets is achieved using pixel values obtained at a plurality of lime points within the time series, and the step of determining a respective pixel set is based on spatial and temporal patterns of emission from the optical contrast substance; and calculated using pixel values obtained at a plurality of time points within the time series.
AMENDED SHEET (ARTICLE 19)
74. The method of claim 27, further including calculating a quantitative measure of one of the first optical contrast substance and the second optical contrast substance.
75. The method of claim 74, wherein tho calculation of the quantitative measure incorporates the anatomical image data.
76. The method of claim 74, wherein the quantitative measure is calculated of the first optical contrast substance.
77. The method of claim 74, wherein calculation of the quantitative measure is based on information obtained from more than one view of the animal.
78. The method of claim 74, wherein the quantitative measure comprises the concentration of the optical contrast substance in the targeted region.
79. The rneihod of claim 78, wherein tho calculation of the concentration is based on measured boundary fluorescence and measured boundary diffuse reflectance.
80. The method of claim 27, wherein the step of analyzing the anatomical image data sets includes using pixel values from multiple time points within the time series and calculating spatial distributions of Lhe pixel values across the time series.
81. The method of claim 27, wherein the step of generating an image is performed only subsequent to the acquiring and analyzing steps.
82. The method of claim 27, wherein the step of analyzing the anatomical image data sets is achieved using pixel values obtained at a plurality of time points within the time series such that the plurality of anatomical structures are identified based on calculated spatial and temporal patterns of emission from the second optical contrast substance.
AMENDED SHEET (ARTICLE 19)
31
83. The method of claim 27 wherein the dynamics of the second optical contrast substance within the animal are used to identify multiple organs within a single image.
84. The method of claim 27, wherein first optical contrast substance is a targeted molecular probe, arid the generated image includes a co-registered image of a structure targeted by the molecular probe.
85. The method of claim 27, wherein the step of analyzing the anatomical image data sets is based on spatial and temporal patterns of emission from the second optical contrast substance; and calculated using pixel values obtained at a plurality of lime points within the time series.
86. An in vivo optical molecular imaging method for producing an image of an animal, comprising: positioning the animal in a desired arrangement in a field of view of an optical detector having a pixel array, acquiring a time series of image data sets of an optical contrast substance in the animal using the optical detector while the animal is in the desired arrangement, each image data set comprising a set of light intensity values as detected by each pixel of the pixel array, analyzing the time series of image data sets to identify a plurality of distinctive time courses, determining a respective pixel set which corresponds to each distinctive time course, and generating an image of the animal which includes at least a subset of respective pixel sets.
67. The imaging method of claim 86 wherein the method further includes; associating at least one respective pixel set with a corresponding anatomical structure of interest.
AMENDED SHEET (ARTICLE 19)
32
88. The imaging method of claim 87 wherein the generated image corresponds to at least one anatomical structure of interest.
89. The imaging method of claim 86 wherein the method further includes; associating al bast one respective pixel set with a physiological process.
90. The imaging method of claim 89 wherein the generated image corresponds to at least one physiological process.
91. The imaging method of claim 86 wherein the method further includes: associating at least one respective pixel set with an organ.
92. The imaging method of claim 91 wherein the generated image corresponds to at least one organ.
93. The imaging method of claim 86, wherein for each image data set, the light intensity valued detected by each pixel corresponds to a sum of the light intensity contributions of one or more distinctive time courses.
94. The imaging method of claim 93, wherein the light intensity value detected by each pixel is decomposed into components associated with respective light intensity contributions of each of the one or more distinctive time courses.
95. The imaging method of claim 94 wherein the generated image is displayed as an associated grayscale value corresponding to the light intensity value detected by each pixel.
96. The imaging method of claim 93 wherein the light intensity value is represented by a grayscale value.
97. The method of claim 86 wherein the generated image includes a subset of respective pixel sels corresponding to anatomical structures of interest, and pixel sets corresponding to confounding phenomena are omitted.
AMENDED SHEET (ARTICLE 19)
33
98. The method of claim 86, wherein the plurality of distinctive time courses comprise a first distinctive time course and a second distinctive time course, the first distinctive time course corresponds to an anatomical structure in which the optical contrast substance is accumulating and the second distinctive time course corresponds to an anatomical structure in which the optical contrast substance is washing out, and the generated image does not include the pixel set associated with the second distinctive time course.
99. The method of claim 86, wherein the plurality of distinctive time courses comprise a first distinctive lime course and a second distinctive time course, the first distinctive time course corresponds to a label that is taken up in the cells of a first anatomical structure and the second distinctive time course corresponds to a second anatomical structure in which the optical contrast substance is accumulating, and the generated image docs not include the pixel set associated with the second distinctive time course.
100. The method of claim 86, wherein the plurality of distinctive time courses comprise a first distinctive time course and a second distinctive time course, the first distinctive time course corresponds to an anatomical structure in which the optical contrast substance is accumulating and the second distinctive lime course corresponds to an anatomical structure which is autofluorescing, and the generated image does not include the pixel set associated with the second distinctive time course.
101. The method of claim 86, wherein the plurality of distinctive time courses comprise a first distinctive time course and a second distinctive time course,
AMENDED SHEET (ARTICLE 19)
34 the first distinctive time course corresponds to an anatomical structure which includes a targeted molecular probe and the second distinctive lime course corresponds to an anatomical structure which is autofluorescing, and the generated image does not include the pixel set associated with the second distinctive time course.
102. The method of claim 86, wherein the plurality of distinctive time courses comprise a first distinctive time course and a second distinctive time course,
Lhe first distinctive time course corresponds to an anatomical structure which includes a targeted molecular probe and the second distinctive time course corresponds lo an anatomical structure in which the optical contrast substance is washing out, and lhe generated image does not include the pixel set associated wilh the second distinctive time course.
103. The method of claim Θ6, wherein the plurality of distinctive lime ct7urses comprise a first distinctive time course and a second distinctive lime course, the first distinctive time course corresponds to an anatomical structure which includes a first activatible probe in an activated state and lhe second distinctive time course corresponds to an anatomical structure which includes a second activatible probe in a non-activated state, and the generated image includes the pixel set associated with the both the first and second distinctive time courses.
104. The method of claim 86, wherein the step of determining a respective pixel set includes using delecled light intensity values from multiple time points within the time series and calculating a single spatial distribution of the detected light intensity values across the time series.
105. The method of claim 86, wherein the step of generating an image is performed only subsequent to the acquiring, analyzing and determining steps.
AMENDED SHEET (ARTICLE 19)
35
106. Thθ method of claim 86, wherein the step of determining a respective pixel set from the plurality of pixels which corresponds TO each of the time courses is performed by a computer.
107. The method of claim 86, wherein the siep of analyzing the image data sets is achieved using detected light intensity values obtained at a plurality of time points wiLhin the time series such that the plurality of distinctive time courses are identified based on calculated spatial and temporal patterns of emission from the optical contrast substance.
108. The method of claim 86, wherein the step of determining a respective pixel set which corresponds Io each distinctive time course is a calculation based on the temporal pattern of emission of the oplical contrast substance at each pixel.
109. The method of claim 86 wherein the dynamics of the optical contrast substance within the animal are used to identify multiple organs within a single image.
110. The method of claim 86, wherein the step of analyzing the image data sets is achieved using detected light inieπsity values obtained at a plurality of time points within the lirπe series, and the step of determining a respective pixel set is based on spatial and temporal patterns of emission from Lhe optical contrast substance; and calculated using detected light intensity values obtained at a plurality of time points within the lime series.
111. An in vivo optical molecular imaging method for evaluating organ function in an animal, comprising: positioning the animal in a desired arrangement in a field of view of an optical detector having a pixel array, acquiring a time series of image data sets of an optical contrast substance in the animal using the optical detector while the animal is in the desired arrangement, each image data set comprising a set of light intensity values as detected by each pixel of the pixel array,
AMENDED SHEET (ARTICLE 19)
36 analyzing the time series of image data sets to identify a time course, determining a respective pixel set which corresponds to the time course, associating the respective pixel set with an organ of intβresi, assessing funcLion of the organ of interest based on the corresponding time course.
112. The method of 111 , wherein the function of the organ of interest is assessed by comparison of the delected time course with a known basis time course for the organ of interest
113. The method of 111 , wherein the organ of interest is the liver.
114. The method of 111 , wherein the optical contrast substance is indocyanine green optical contrast substance.
115. The method of 111 , wherein the animal is a human infant.
116. The method of 111 further comprising acquiring a time series of anatomical image data sets of a second optical contrast substance in the animal using the optical detector while The animal is in the same desired arrangement, each anatomical image data set obtained at a selected time and having a same plurality of pixels as the others, each pixel having an associated value, analyzing the anatomical image data sets to generate an anatomical map of the animal which includes a plurality of anatomical structures, and wherein the anatomical map is combined with the at least one signal component to generate an image of the animal showing the location of the organ of interest with respect to the plurality of anatomical structures.
117. An in vivo optical molecular imaging method for producing an image of an animal, comprising: positioning the animal in a desired arrangement in a field of view of an optical detector having a pixel array,
AMENDED SHEET (ARTICLE 19)
37 acquiring a time series of image data sets of a first optica! contrast substance in the animal using the optical detector while the animal is in the desired arrangement, each image data set comprising a set of light intensity values as detected by each pixel of the pixel array, analyzing the time series Of image data sets to identify a plurality of distinctive time courses, resolving the spatial distribution of pixels corresponding to each time course into a sum of contributions for each time course at each pixel, and generating an image of the animal based on the spalial distribution of pixels for the contribution ai at least ono time course.
118. The method of claim 40, wherein the step of determining a respective pixel set includes using pixel values from multiple time points within the lime series and calculating a single spatial distribution of the pixel values across the time series.
119. The method of claim 40, wherein the step of generating an anatomical image map is performed only subsequent to the acquiring, analyzing and determining steps.
120. The method of claim 40, wherein the step of determining a respective pixel set from the plurality of pixels which corresponds to each of the time courses is performed by a computer.
121. The meLhod of claim 40, wherein the step of analyzing the anatomical image data sets is achieved using pixel values obtained at a plurality of time points within the time series such that the plurality of distinctive time courses are identified based on calculated spalial and temporal patterns of emission from the second dye.
122. The method of claim 40, wherein the step of determining a respective pixel set from the plurality of pixels which corresponds to each of the time courses is a calculation based on the temporal pattern of emission of Lhe second dye at each pixel.
123. The method of claim 40 wherein the dynamics of the second dye within the animal are used to identify multiple organs within a single image.
AMENDED SHEET (ARTICLE 19)
38 124, The method υl claim 40, wherein the step of analyzing the image daia sets is achieved using pixel values obtained at a plurality ot time points within the time series, and the step of determining a respective pixel set is based on spatial and temporal patterns of emission from the second dye; and calculated using pixel values obtained at a plurality of time points within the time series.
AMENDED SHEET (ARTICLE 19)
39
PCT/US2007/013024 2006-06-01 2007-05-31 In-vivo optical imaging method including analysis of dynamic images WO2007143141A2 (en)

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US12/302,986 US9220411B2 (en) 2006-06-01 2007-05-31 In-vivo optical imaging method including analysis of dynamic images
EP07795649A EP2034890A4 (en) 2006-06-01 2007-05-31 In-vivo optical imaging method including analysis of dynamic images

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US80986106P 2006-06-01 2006-06-01
US80986006P 2006-06-01 2006-06-01
US60/809,860 2006-06-01
US60/809,861 2006-06-01
US89725907P 2007-01-24 2007-01-24
US60/897,259 2007-01-24

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