Method and apparatus for emission computed tomography using temporal signatures
First Claim
1. An emission computed tomography system comprising:
- means for illuminating a plurality of secondary emitters within an object of interest by using an external non-parallel source beam while the object of interest is moving relative to said external non-parallel source beam;
means, coupled to receive radiation emitted from the plurality of secondary emitters, for providing a localization signal representing the emitted radiation;
means, coupled to receive the localization signal, for, determining a location for each of the plurality of secondary emitters;
means for producing a 3D reconstruction of the object of interest; and
means for combining the location with a computed 3D reconstruction of the object of interest so as to create an image of the plurality of secondary emitters.
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Abstract
An optical tomographic system wherein the localization of secondary emitters within an object of interest is determined using the temporal signatures of secondary emission arising from the object being illuminated by an external primary source beam that is non-parallel, such as a cone beam, while the object is moving relative to said beam in a controlled manner. A unique set of secondary emitter spots is localized within the object and, when combined with a computed 3D reconstruction of the object from its primary cone beam projections, creates an image of the secondary emitters in the object so as to enable quantitative three-dimensional imaging of fluorescent labeled molecular probes in a biological cell, for example.
144 Citations
20 Claims
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1. An emission computed tomography system comprising:
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means for illuminating a plurality of secondary emitters within an object of interest by using an external non-parallel source beam while the object of interest is moving relative to said external non-parallel source beam;
means, coupled to receive radiation emitted from the plurality of secondary emitters, for providing a localization signal representing the emitted radiation;
means, coupled to receive the localization signal, for, determining a location for each of the plurality of secondary emitters;
means for producing a 3D reconstruction of the object of interest; and
means for combining the location with a computed 3D reconstruction of the object of interest so as to create an image of the plurality of secondary emitters. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10)
at least one photomultiplier tube filtered to receive only the secondary fluorescent photons; and
a detector connected to provide a trigger signal to the location determining means and the 3D reconstruction means, where the detector is located at a distant base of the cone beam and the trigger signal is produced when the cone beam is interrupted by the passage of an object of interest between the cone beam and the detector.
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6. The emission computed tomography system of claim 1 wherein the radiation emitted from the plurality of secondary emitters comprises a plurality of temporal signatures;
- and the means for determining a location includes means for analyzing the temporal signals so as to determine the location for each of the plurality of secondary emitters.
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7. The emission computed tomography system of claim 6 wherein the plurality of temporal signatures represent durations proportional to the distance that the plurality of secondary emitters travel through the external non-parallel source beam.
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8. The emission computed tomography system of claim 7 wherein the velocity vector along a Z-axis of the object of interest is known and where the localization signal includes the positions of plurality of secondary emitters mapped along the Z-axis, so that Fourier transforms of the plurality of temporal signatures provide a representation of each duration of each of the plurality of secondary emitters, thereby permitting each of the plurality of secondary emitters to be mapped to its location within the object of interest along the Z-axis.
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9. The emission computed tomography system of claim 8 wherein the localization signal includes location data and the means for combining comprises means for superposition of the location data with a 3D reconstructed image of the object of interest so as to map detected fluorescent structures into a higher resolution absorption image.
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10. The emission computed tomography system of claim 1 wherein the means for combining further includes means for combining temporal signatures with tomographic reconstruction images from projections to localize fluorescent signal spots.
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11. An optical tomography system comprises:
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an emission collection and trigger cylinder that provides a trigger signal indicating the presence of an object;
a 3D optical tomography image reconstruction system;
a sample transport apparatus; and
a computer coupled to control and communicate with the emission collection and trigger cylinder, the 3D optical tomography image reconstruction system, and the sample transport apparatus where the trigger signal clocks the 3D optical tomography image reconstruction system and the computer so as to identify objects of interest. - View Dependent Claims (12)
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13. A method for emission computed tomography using temporal signatures comprising the steps of:
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preparing cells with stains and tagged fluorescent molecular probes;
introducing the cells into an optical tomography system including an emission collection and trigger cylinder and an image reconstruction cylinder;
moving the cells through an emission collection and trigger cylinder, where the emission collection and trigger cylinder produces a trigger signal in response to a cell entering the emission collection and trigger cylinder and wherein the cells are illuminated to produce secondary emissions;
sensing the secondary emissions to produce a set of temporal signatures;
using the trigger signal to start clocking processes for analyzing the set of temporal signatures and determining a first set of 3D data including X, Y coordinate locations as a function of a Z coordinate of detected fluorescence of the molecular probes;
using the trigger signal to activate computer processes for performing 3D reconstruction of the cell structure from projections and determining absorption at X, Y and Z locations so as to generate a second set of 3D data;
combining the first set of 3D data and the second set of 3D data to determine cells of interest;
moving cells through the reconstruction cylinder; and
identifying cells of interest. - View Dependent Claims (14)
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15. An emission computed tomography system comprising:
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a point source for illuminating a plurality of fluorescent molecular probes within a cell, where the cell is moving relative to the point source, and where the plurality of fluorescent molecular probes fluoresce to provide emitted radiation when illuminated;
a set of photomultiplier tubes, coupled to receive radiation emitted from at least one of the plurality of fluorescent molecular probes, for providing a temporal signature responsive to the emitted radiation for at least one of the plurality of fluorescent molecular probes;
a temporal signal analyzer, coupled to receive the temporal signature, for determining a location for at least one of the plurality of fluorescent molecular probes;
an optical tomography system for producing a 3D reconstruction of the cell;
a detector connected to provide a trigger signal to synchronize the temporal signal analyzer and the optical tomography system, where the detector is located at a distant base of the cone beam and the trigger signal is produced when the cone beam is interrupted by the passage of an object of interest between the cone beam and the detector; and
a 3D coordinate computation module for combining the location with a computed 3D reconstruction of the object of interest so as to create an image of the plurality of fluorescent molecular probes. - View Dependent Claims (16, 17, 18, 19, 20)
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Specification