Fluorescence imaging system and method
First Claim
1. A method of imaging, comprising the steps of:
- (a) exposing a surface of a light scattering material to an excitation light from a light source, the material having a heterogeneous composition under the surface;
(b) detecting a fluorescent emission from the material in response to step (a);
(c) establishing an estimate of spatial variation of a fluorescence characteristic of the material;
(d) determining a calculated emission as a function of the estimate;
(e) comparing the calculated emission to the emission detected in step (b) to determine an error;
(f) providing a modified estimate of spatial variation of the fluorescence characteristic and repeating steps (d) through (f) until the error reaches a desired minimum; and
(g) generating an image of the material from the modified estimate, the image corresponding to the heterogeneous composition of the material.
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Accused Products
Abstract
A system and method non-invasive biomedical optical imaging and spectroscopy with low-level light is described. The technique consists of a modulated light source (120) coupled to tissue (100) of a patient to introduce excitation light. Fluorescent light emitted in response to the excitation light is detected with sensor (148). The AC intensity and phase of the excitation and detected fluorescent light is provided to a processor (160) operatively coupled to sensor (148). Processor (160) employs the measured re-emission kinetics of excitation and fluorescent light to "map" the spatial variation of one or more fluorescence characteristics of the tissue (100). The fluorescence characteristic may be provided by exogenous contract agents, endogenous fluorophores, or both. The variation is determined by solving frequency domain diffusion equations at a number of designated points in the tissue as part of a recursive estimation algorithm. Processor (160) generates an imaging signal in accordance with the spatial variation of the fluorescence characteristic for provision to an output device (164). The output device (164) displays an image corresponding spatial variation of the fluorescence characteristic which corresponds to tissue (100) to aid in the detection and diagnosis of disease.
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Citations
47 Claims
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1. A method of imaging, comprising the steps of:
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(a) exposing a surface of a light scattering material to an excitation light from a light source, the material having a heterogeneous composition under the surface; (b) detecting a fluorescent emission from the material in response to step (a); (c) establishing an estimate of spatial variation of a fluorescence characteristic of the material; (d) determining a calculated emission as a function of the estimate; (e) comparing the calculated emission to the emission detected in step (b) to determine an error; (f) providing a modified estimate of spatial variation of the fluorescence characteristic and repeating steps (d) through (f) until the error reaches a desired minimum; and (g) generating an image of the material from the modified estimate, the image corresponding to the heterogeneous composition of the material. - View Dependent Claims (2, 3, 4, 5, 6, 7)
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8. A system for imaging a light scattering tissue having a heterogeneous composition and containing a fluorophore, comprising:
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(a) a light source with a pre-determined time varying intensity, said source being adapted to excite the fluorophore; (b) a sensor configured to provide a detected light signal corresponding to a multiply scattered light emission from the tissue in response to light from said source; (c) a processor operatively coupled to said sensor and responsive to said detected light signal to provide a number of values representative of a level of a fluorescence characteristic of the tissue as a function of position, the level of the fluorescence characteristic varying with the heterogeneous composition of the tissue and corresponding to at least one of fluorescence lifetime, fluorescence quantum efficiency, fluorescence yield, and fluorophore uptake, said processor being configured to generate an image signal as a function of said values; and (d) an output device responsive to said image signal to provide an image corresponding to the heterogeneous composition of the tissue. - View Dependent Claims (9, 10, 11, 12, 13, 14)
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15. A method of tissue analysis, comprising:
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(a) exposing a biologic tissue to an excitation light with a pre-determined time varying intensity, the tissue multiply scattering the excitation light; (b) detecting a multiply scattered light emission from the tissue in response to said exposing; (c) determining a number of values from the emission with a processor, the values each corresponding to a level of a fluorescence characteristic at a different position within the tissue, the level of the characteristic varying with tissue composition; and (d) generating an image of tissue compositional variation in accordance with the values. - View Dependent Claims (16, 17, 18, 19, 20, 21, 22, 23, 24, 25)
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26. A method of tissue analysis, comprising:
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(a) introducing an fluorescent agent into a light scattering biologic tissue with a heterogeneous composition; (b) exposing the tissue to light from a light source with a pre-determined time varying intensity to excite the agent, the tissue multiply scattering the excitation light; (c) detecting a multiply scattered light emission from the tissue in response to said exposing; (d) quantitizing a fluorescence characteristic throughout the tissue from the emission by establishing a number of values with a processor, the values each corresponding to a level of the fluorescence characteristic at a different position within the tissue, the level of the fluorescence characteristic varying with heterogeneous composition of the tissue; and (e) mapping the heterogeneous composition of the tissue in accordance with the values. - View Dependent Claims (27, 28, 29, 30, 31, 32, 33, 34)
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35. A method of tissue analysis, comprising:
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(a) establishing a first set of values corresponding to adsorption and scattering properties of a light scattering biologic tissue; (b) introducing an fluorescent agent into the tissue after said establishing; (c) establishing a second set of values corresponding to adsorption and scattering properties of the tissue after said introducing; and (d) comparing the first set of values and the second set;
of values to map uptake of the agent into the tissue. - View Dependent Claims (36, 37, 38, 39, 40)
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41. A system for imaging a light scattering tissue having a heterogeneous composition and containing a fluorophore, comprising:
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(a) a means for exciting the fluorophore in the tissue; (b) a means for detecting a light signal corresponding to a fluorescent emission from the tissue in response to said exciting means; (c) a processor operatively coupled to said sensor and responsive to said light signal, said processor including a means for generating an output signal by iteratively estimating spatial distribution of a quantitized fluorescent characteristic of the tissue until a desired minimum error is obtained; and (d) a means for providing an image corresponding to the heterogeneous composition of the tissue in response to said output signal.
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42. A method, comprising:
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(a) exposing a biologic tissue with a hidden heterogeneity to an excitation light with a predetermined time-varying intensity, the tissue multiply scattering the excitation light; (b) detecting a light emission from the tissue in response to said exposing; and (c) imaging the tissue to reveal the hidden heterogeniety by mapping spatial variation of a level of a fluorescence property of the tissue from the light emission in accordance with a mathematical relationship modeling multiple light scattering behavior of the tissue. - View Dependent Claims (43, 44, 45, 46, 47)
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Specification