Beta and Alpha Emission Tomography for Three-Dimensional Autoradiography

• US 20170010369A1
• Filed: 02/03/2015
• Published: 01/12/2017
• Est. Priority Date: 02/03/2014
• Status: Active Grant

• Current Assignee: InviCRO LLC (Konica Minolta Inc.), Arizona Board of Regents (University of Arizona)
• Original Assignee: InviCRO LLC (Konica Minolta Inc.), Arizona Board of Regents (University of Arizona)
• Inventors: MILLER, Brian, DING, Yijun, CHEN, Liying, HOPPIN, John William, CAUCCI, Luca, BARRETT, Harrison H.
• Granted Patent: US 9,823,364 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61B 6/037 Emission tomography
• CPC Class Codes: A61B 6/4258 for detecting non x-ray radiation, e.g. gamma radiation A61B6/037 takes precedence
• CPC Class Codes: A61B 6/5205 involving processing of raw data to produce diagnostic data
• CPC Class Codes: G01T 1/161 Applications in the field of nuclear medicine, e.g. in vivo counting apparatus for radiation diagnosis A61B6/00
• CPC Class Codes: G01T 1/2942 using autoradiographic methods
• CPC Class Codes: G01T 1/2985 In depth localisation, e.g. using positron emitters; Tomographic imaging (longitudinal and transverse section imaging; apparatus for radiation diagnosis sequentially in different planes, steroscopic radiation diagnosis); using external radiation sources A61B6/02
• CPC Class Codes: G01T 5/08 Scintillation chambers discharge tubes H01J40/00, H01J47/00; semiconductor devices H01L

Abstract

The present invention provides methods and systems for 3D imaging of in vivo and ex vivo tissues. The disclosed systems and methods employ an autoradiographic approach where particles emitted by a radioactive composition within the tissue are detected. Once detected, a 3D representation of the source of particles within the tissue is reconstructed for viewing and analysis.

Claims

1-74. -74. (canceled)

75. A method for reconstructing a 3D distribution of a source of particles, the method comprising the steps of:

providing said source of particles, wherein said particles comprise beta particles, alpha particles, positrons, or conversion electrons;

repeating, for each of a plurality of said particles from said source, the steps of;

recording an image of a particle track with a particle track detector;

determining attributes of said particle track using said particle track image; and

storing said attributes of said particle track;

thereby generating attributes for each of said plurality of particles from said source; and

reconstructing said 3D distribution of said source of particles using said attributes for each of said plurality of particles.

76. The method of claim 75, wherein said particle track detector comprises a scintillator positioned proximate to said source of particles and a two-dimensional optical detector positioned in optical communication with said scintillator;

wherein each particle track corresponds to a particle path within said scintillator.

77. The method of claim 75, wherein said step of recording an image of a particle track with a particle track detector comprises:

interacting a particle with a scintillator positioned proximate to said source, wherein said interaction generates a detectable optical signal along said particle track within said scintillator; and

detecting at least a portion of said optical signal using a two-dimensional optical detector.

78. The method of claim 77, wherein said scintillator has a thickness selected from a range of 3 μ

m to 3 mm.

80. The method of claim 75, wherein said particle track detector comprises a microchannel plate positioned proximate to said source of particles, a light-emitting material positioned proximate to said microchannel plate and a two-dimensional optical detector positioned in optical communication with said light-emitting material;

wherein each particle track corresponds to a particle path within said microchannel plate.

81. The method of claim 75, wherein said step of recording an image of a particle track with a particle track detector comprises:

interacting a particle with a microchannel plate positioned proximate to said source, wherein said interaction generates electrons along said particle track within said microchannel plate, wherein said generated electrons are amplified within said microchannel plate and directed onto a light-emitting material positioned proximate to said microchannel plate, wherein interactions between said electrons and said light-emitting material generate a detectable optical signal; and

detecting at least a portion of said detectable optical signal using a two-dimensional optical detector.

82. The method of claim 81, wherein an amount of amplification of said generated electrons depends on a position of said particle track within said microchannel plate.

83. The method of claim 82, wherein an intensity of said detectable optical signal is proportional to said amount of amplification of said generated electrons, thereby permitting determination of said position of said particle track within said microchannel plate.

84. The method of claim 81, comprising the step of imaging said detectable optical signal from said light-emitting material onto said two-dimensional optical detector using a lens or lens system.

85. The method of claim 75, wherein said particle track detector comprises deep depletion CCD device or deep-deletion CMOS device positioned proximate to said source of particles;

wherein each particle track corresponds to a particle path within a deep depletion region of said deep depletion CCD device or deep-deletion CMOS device.

86. The method of claim 75, wherein said step of recording an image of a particle track with a particle track detector comprises interacting a particle with a depletion region of a deep-depletion CCD detector positioned proximate to said source, wherein said interaction generates electron-hole pairs along said particle track within said depletion region of said deep-depletion CCD detector, wherein generated electrons from the electron-hole pairs are accelerated toward and accumulated within a two-dimensional array of active CCD wells of said deep-depletion CCD detector.

87. The method of claim 75, wherein said attributes of said particle track comprise one or more of a position of a start of said particle track, a direction of travel of a particle at a start of said particle track, and a total energy deposited by a particle along a particle track.

88. The method of claim 87, wherein said direction of travel of a particle at a start of said particle track is characterized by two or more angles.

89. The method of claim 75, further comprising, for each of said particles, storing said attributes of said particle track as entries in an attribute list, up to pairs rid of bins or a database.

90. The method of claim 75, wherein said step of reconstructing said 3D distribution of said source of particles comprises using a list-mode maximum-likelihood expectation-maximization algorithm.

91. The method of claim 75, wherein said step of reconstructing said 3D distribution of said source of particles comprises calculating a probability density function for each of a plurality of locations within said source of particles.

92. The method of claim 75, further comprising a step of administering said source of particles to a patient, subject or tissue, wherein said source of particles comprises a radiopharmaceutical.

93. The method of claim 75, further comprising a step of obtaining a white-light image of an exposed surface of a tissue sample containing said source of particles.

94. The method of claim 93, wherein said following steps are repeated for a plurality of depths within said tissue sample:

a. repeating said recording, determining and storing steps, thereby generating attributes for each of said plurality of depths,

b. obtaining a white-light image of a surface of said tissue sample;

thereby obtaining white-light images of exposed surfaces of said plurality of depths within said tissue sample and wherein said attributes comprises attributes of a plurality of particle tracks for each of said plurality of depths within said tissue sample;

said method further comprising a step of reconstructing a 3D distribution of said source of particles using said attributes of particle tracks for each of said plurality of depths within said tissue sample.

95. The method of claim 75, further comprising providing a visual display of said 3D distribution of said source of particles.

96. A method for imaging a source of particles within a tissue sample, the method comprising the steps of:

recording images of a plurality of particle tracks with a particle track detector;

determining attributes of said plurality of particle tracks from said images;

storing said attributes of each of said plurality of particle tracks;

repeating said detecting, determining and storing steps for a plurality of depths within said tissue sample, wherein said plurality of depths are obtained by removing one or more layers of said tissue sample and wherein removal of each layer of said tissue sample exposes a deeper surface of said tissue sample, thereby generating particle track attributes for a plurality of particles from said source at a plurality of depths within said tissue sample; and

reconstructing a 3D image of said source of particles using said particle track attributes for a plurality of particles from said source at a plurality of depths within said tissue sample and said plurality of depths within said tissue sample.

97. The method of claim 96 comprising a method of in vivo autoradiography.

98. The method of claim 96 comprising a method of imaging a 3D distribution of a radioactive agent in an in vivo or ex vivo tissue.

99. A device for imaging a source of particles comprising:

a particle track detector for recording images of detectable signals generated along particle tracks in an active material, wherein said detectable signals are generated by an interaction of a particle from said source with said active material, wherein said particle comprises a beta particle, alpha particle, a positron or a conversion electron; and

a processor positioned in data communication with said particle track detector, wherein said processor is configured for;

analyzing a plurality of images of detectable signals generated along particle tracks of a plurality of particles in an active material to determine attributes of said plurality particle tracks; and

reconstructing a 3D image of said source of particles using attributes corresponding to all of said plurality of particles.

100. The device of claim 99, wherein said attributes comprise one or more of a position of a start of a particle track, a direction of travel of a particle at a start of a particle track, and a total energy deposited by a particle along particle track.

101. The device of claim 99, wherein said active material comprises a scintillator, a microchannel plate, a depletion region of a deep-depletion CCD device or deep-depletion CMOS.

102. The device of claim 99, wherein said position sensitive detector comprises a two-dimensional optical detector, a two-dimensional electronic detector, a CCD detector, a deep-depletion CCD detector, a CMOS detector or an active pixel sensor.

103. The device of claim 99 further comprising a camera for obtaining a white-light image of a surface of said tissue.

104. The device of claim 99 further comprising a tomographic imaging system.