Determination of a measure of a glycation end-product or disease state using tissue fluorescence lifetime
First Claim
1. An apparatus for the determination of 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) an illumination subsystem;
(b) a detection subsystem; and
(c) an input system, configured to accept biologic information comprising one or more of;
gender of the individual, weight of the individual, waist circumference of the individual, history of disease of the individual'"'"'s family, ethnicity, skin melanin content, smoking history of the individual, or a combination thereof;
(d) an analysis subsystem, comprising a model relating fluorescence lifetime of the skin of an individual and the biologic information to 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 measuring the fluorescence lifetime in either time-domain or frequency domain modes. 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. For example, multivariate models can be developed that relate lifetime trends of one or more constituents to increasing propensity to diabetes and pre-diabetes. 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.
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Citations
31 Claims
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1. An apparatus for the determination of 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) an illumination subsystem; (b) a detection subsystem; and (c) an input system, configured to accept biologic information comprising one or more of;
gender of the individual, weight of the individual, waist circumference of the individual, history of disease of the individual'"'"'s family, ethnicity, skin melanin content, smoking history of the individual, or a combination thereof;(d) an analysis subsystem, comprising a model relating fluorescence lifetime of the skin of an individual and the biologic information to tissue state. - View Dependent Claims (2, 3, 4, 5)
- tissue state”
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6. 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 lifetime of a portion of the skin of the individual; (b) acquiring biologic information comprising one of more of;
gender of the individual, weight of the individual, waist circumference of the individual, history of disease of the individual'"'"'s family, ethnicity, skin melanin content, smoking history of the individual, or a combination thereof; and(c) using a multivariate method to determine a tissue state of the individual from the fluorescence lifetime and the biologic information. - View Dependent Claims (7, 8, 9, 10, 11, 12)
- tissue state”
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13. A method of determining a tissue state of the tissue of 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) illuminating a portion of the tissue of the individual with excitation light; (b) detecting light emitted from the tissue by fluorescence lifetime of a chemical within the tissue, where the tissue is not the lens of the eye; (c) determining a tissue reflectance characteristic at an excitation light wavelength; (d) detecting light returned from the tissue in response to illumination at the excitation wavelength; (e) determining a corrected fluorescence lifetime from the detected light and the tissue reflectance characteristic; (f) acquiring biologic information comprising one of more of;
gender of the individual, weight of the individual, waist circumference of the individual, history of disease of the individual'"'"'s family, ethnicity, skin melanin content, smoking history of the individual, or a combination thereof; and(g) determining the tissue state from the biologic information and the corrected fluorescence lifetime and a model relating biologic information, fluorescence lifetime, and tissue state. - View Dependent Claims (14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25)
- tissue state”
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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 lifetime of a portion of the tissue of the subject, where the tissue is not the lens of the eye, by detecting light emitted from the tissue by; (1) determining a tissue reflectance characteristic at an excitation light wavelength; (2) detecting light returned from the tissue in response to illumination at the excitation wavelength; (3) determining a corrected fluorescence lifetime from the detected light and the tissue reflectance characteristic; (ii) determining a tissue state of the subject; (iii) acquiring biologic information comprising one of more of;
gender of the individual, weight of the individual, waist circumference of the individual, history of disease of the individual'"'"'s family, ethnicity, skin melanin content, smoking history of the individual, or a combination thereof; and(b) applying a multivariate method to the plurality of corrected fluorescence lifetime determinations and associated tissue state determinations and associated biologic information to generate a model relating corrected fluorescence lifetime and biologic information to tissue state. - View Dependent Claims (27, 28, 29, 30, 31)
- tissue state”
Specification