Determination of a measure of a glycation end-product or disease state using tissue fluorescence
First Claim
1. A method of determining a tissue state of the tissue of an individual, comprising:
- a. Illuminating a portion of the tissue of the individual with excitation light;
b. Detecting light emitted from the tissue by fluorescence of a chemical within the tissue, where the tissue is not the lens of the eye;
c. Determining the tissue state from the detected light and a model relating fluorescence and a tissue state, wherein detecting light emitted from the tissue comprises;
d. Determining a tissue reflectance characteristic at an excitation light wavelength;
e. Detecting light returned from the tissue in response to illumination at the excitation wavelength;
f. Determining a corrected fluorescence measurement from the detected light and the tissue reflectance characteristic;
g. And wherein determining a tissue state comprises determining the tissue state from the corrected fluorescence measurement and a model relating fluorescence and tissue state.
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Accused Products
Abstract
A method of determining a measure of a tissue state (e.g., glycation end-product or disease state) in an individual. A portion of the tissue of the individual is illuminated with excitation light, then light emitted by the tissue due to fluorescence of a chemical with the tissue responsive to the excitation light is detected. The detected light can be combined with a model relating fluorescence with a measure of tissue state to determine a tissue state. The invention can comprise single wavelength excitation light, scanning of excitation light (illuminating the tissue at a plurality of wavelengths), detection at a single wavelength, scanning of detection wavelengths (detecting emitted light at a plurality of wavelengths), and combinations thereof. The invention also can comprise correction techniques that reduce determination errors due to detection of light other than that from fluorescence of a chemical in the tissue. For example, the reflectance of the tissue can lead to errors if appropriate correction is not employed. The invention can also comprise a variety of models relating fluorescence to a measure of tissue state, including a variety of methods for generating such models. Other biologic information can be used in combination with the fluorescence properties to aid in the determination of a measure of tissue state. The invention also comprises apparatuses suitable for carrying out the method, including appropriate light sources, detectors, and models (for example, implemented on computers) used to relate detected fluorescence and a measure of tissue state.
199 Citations
44 Claims
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1. A method of determining a tissue state of the tissue of an individual, comprising:
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a. Illuminating a portion of the tissue of the individual with excitation light; b. Detecting light emitted from the tissue by fluorescence of a chemical within the tissue, where the tissue is not the lens of the eye; c. Determining the tissue state from the detected light and a model relating fluorescence and a tissue state, wherein detecting light emitted from the tissue comprises; d. Determining a tissue reflectance characteristic at an excitation light wavelength; e. Detecting light returned from the tissue in response to illumination at the excitation wavelength; f. Determining a corrected fluorescence measurement from the detected light and the tissue reflectance characteristic; g. And wherein determining a tissue state comprises determining the tissue state from the corrected fluorescence measurement and a model relating fluorescence and tissue state. - View Dependent Claims (2, 3, 4)
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5. A method of determining a tissue state of the tissue of an individual, comprising:
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a. Illuminating a portion of the tissue of the individual with excitation light; b. Detecting light emitted from the tissue by fluorescence of a chemical within the tissue, where the tissue is not the lens of the eye; c. Determining the tissue state from the detected light and a model relating fluorescence and a tissue state wherein detecting light emitted from the tissue comprises; d. Determining a tissue reflectance characteristic at a detection wavelength; e. Detecting light at the detection wavelength returned from the tissue in response to illumination; f. Determining a corrected fluorescence measurement from the detected light and the tissue reflectance characteristic; g. And wherein determining a tissue state comprises determining the tissue state from the corrected fluorescence measurement and a model relating fluorescence and tissue state. - View Dependent Claims (6, 7, 8)
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9. A method of determining a tissue state of the tissue of an individual, comprising:
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a. Illuminating a portion of the tissue of the individual with excitation light; b. Detecting light emitted from the tissue by fluorescence of a chemical within the tissue, where the tissue is not the lens of the eye; c. Determining the tissue state from the detected light and a model relating fluorescence and a tissue state, wherein detecting light emitted from the tissue comprises; d. Determining a first tissue reflectance characteristic at an excitation light wavelength; e. Determining a second tissue reflectance characteristic at a detection wavelength; f. Detecting light at the detection wavelength returned from the skin in response to illumination at the excitation wavelength; g. Determining a corrected fluorescence measurement from the detected light and the first and second tissue reflectance characteristics; h. And wherein determining a tissue state comprises determining the tissue state from the corrected fluorescence measurement and a model relating fluorescence and tissue state.
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10. A method of determining a tissue state, other than cancer, of the tissue of an individual, comprising:
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a. Illuminating a portion of the tissue of the individual with excitation light; b. Detecting light emitted from the tissue by fluorescence of a chemical within the tissue, where the tissue is not the lens of the eye; c. Determining the tissue state from the detected light and a model relating fluorescence and a tissue state; further comprising acquiring biologic information relating to the individual, and wherein determining a tissue state comprises determining the tissue state from the information, the detected light, and a model relating biologic information, fluorescence and tissue state, wherein the biologic information comprises gender of the individual, height of the individual, weight of the individual, waist circumference of the individual, history of disease in the individuals family, ethnicity, skin melanin content, smoking history of the individual, or a combination thereof. - View Dependent Claims (11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21)
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22. A method of determining a tissue state in an individual, comprising:
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a. Establishing an interface between an optical system and a portion of the skin of the individual; b. Determining a relationship of illumination light at an excitation wavelength and the response of the skin at a detection wavelength for each of a plurality of pairings of excitation wavelength and detection wavelength; c. Determining a tissue reflectance property of the skin at each of the illumination wavelengths and at each of the detection wavelengths; d. Determining a measure of the intrinsic fluorescence of the skin from the relationships of illumination light and detected light and the tissue reflectance properties; e. Determining the tissue state of the individual from the intrinsic fluorescence using a model relating intrinsic fluorescence and tissue state. - View Dependent Claims (23, 24, 25)
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26. A method of determining a model relating fluorescence and tissue state, where “
- tissue state”
is any of (i) a disease state based on long-term changes (greater than one month duration) in tissue, (ii) a measure of chemical change based on long-term (greater than one month duration) glycemic control, (iii) a measure of glycation end-products in tissue, and (iv) a combination of the above, comprising;a. For each of a plurality of subjects; i. Determining a fluorescence property of a portion of the tissue of the subject, where the tissue is not the lens of the eye, by illuminating the portion of the tissue with excitation light;
determining a tissue reflectance characteristic at the excitation light wavelength, detecting light returned from the tissue in response to illumination at the excitation wavelength, determining a corrected fluorescence measurement from the detected light and the tissue reflectance characteristic;ii. Determining a tissue state of the subject; b. Applying a multivariate method to the plurality of corrected fluorescence measurements and associated tissue state determinations to generate a model relating fluorescence property to tissue state. - View Dependent Claims (27, 28, 29, 30, 31, 32, 33, 34)
- tissue state”
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35. A method of determining a model relating fluorescence and tissue state, comprising:
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a. For each of a plurality of subjects; i. Determining a fluorescence property of a portion of the tissue of the subject, where the tissue is not the lens of the eye; ii. Determining a tissue state of the subject; b. Applying a multivariate method to the plurality of fluorescence property determinations and associated tissue state determinations to generate a model relating fluorescence property to tissue state;
wherein determining a fluorescence property of a portion of the tissue of the subject comprises;c. Illuminating the portion of the tissue of the individual with excitation light; d. Detecting light emitted from the tissue by fluorescence of a chemical within the tissue, wherein detecting light emitted from the tissue comprises; e. Determining a tissue reflectance characteristic at an excitation light wavelength; f. Detecting light returned from the tissue in response to illumination at the excitation wavelength; g. Determining a corrected fluorescence measurement from the detected light and the tissue reflectance characteristic.
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36. A method of determining a model relating fluorescence and tissue state, comprising:
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a. For each of a plurality of subjects; i. Determining a fluorescence property of a portion of the tissue of the subject, where the tissue is not the lens of the eye; ii. Determining a tissue state of the subject; b. Applying a multivariate method to the plurality of fluorescence property determinations and associated tissue state determinations to generate a model relating fluorescence properly to tissue state;
wherein determining a fluorescence property of a portion of the tissue of the subject comprises;c. Illuminating the portion of the tissue of the individual with excitation light; d. Detecting light emitted from the tissue by fluorescence of a chemical within the tissue, wherein detecting light emitted from the tissue comprises; e. Determining a tissue reflectance characteristic at a detection wavelength; f. Detecting light at the detection wavelength returned from the tissue in response to illumination; g. Determining a corrected fluorescence measurement from the detected light and the tissue reflectance characteristic.
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37. A method of determining a model relating fluorescence and tissue state, comprising:
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a. For each of a plurality of subjects; i. Determining a fluorescence property of a portion of the tissue of the subject, where the tissue is not the lens of the eye; ii. Determining a tissue state of the subject; b. Applying a multivariate method to the plurality of fluorescence property determinations and associated tissue state determinations to generate a model relating fluorescence property to tissue state;
wherein determining a fluorescence property of a portion of the tissue of the subject comprises;c. Illuminating the portion of the tissue of the individual with excitation light; d. Detecting light emitted from the tissue by fluorescence of a chemical within the tissue, wherein detecting light emitted from the tissue comprises; e. Determining a first tissue reflectance characteristic at an excitation light wavelength; f. Determining a second tissue reflectance characteristic at a detection wavelength; g. Detecting light at the detection wavelength returned from the skin in response to illumination at the excitation wavelength; h. Determining a corrected fluorescence measurement from the detected light and the first and second tissue reflectance characteristics.
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38. An apparatus for the determination of a tissue state, other than cancer, in an individual, where “
- tissue state”
is any of (i) a disease state based on long-term changes (greater than one month duration) in tissue, (ii) a measure of chemical change based on long-term (greater than one month duration) glycemic control, (iii) a measure of glycation end-products in tissue, and (iv) a combination of the above, comprising;a. An illumination subsystem; b. A detection subsystem; c. An analysis subsystem, comprising a model relating fluorescence property of the skin and biologic information an individual to tissue state, wherein biologic information comprises gender of the individual, height of the individual, weight of the individual, waist circumference of the individual, history of disease in the individual'"'"'s family, ethnicity, skin melanin content, smoking history of the individual, or a combination thereof. - View Dependent Claims (39)
- tissue state”
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40. A method of determining a tissue state in an individual, where “
- tissue state”
is any of (i) a disease state based on long-term changes (greater than one month duration) in tissue, (ii) a measure of chemical change based on long-term (greater than one month duration) glycemic control, (iii) a measure of glycation end-products in tissue, and (iv) a combination of the above, comprising;a. Determining a fluorescence property of a portion of the skin of the individual by illuminating the portion of the skin with excitation light;
determining a skin reflectance characteristic at the excitation light wavelength, detecting light returned from the skin in response to illumination at the excitation wavelength, determining a corrected fluorescence measurement from the detected light and the skin reflectance characteristic;b. Using a multivariate method to determine a tissue state of the individual from the corrected fluorescence measurement. - View Dependent Claims (41, 42, 43, 44)
- tissue state”
Specification