Abstract: Embodiments of the present invention provide an apparatus suitable for determining properties of in vivo tissue from spectral information collected from the tissue. An illumination system provides light at a plurality of broadband ranges, which are communicated to an optical probe. The optical probe receives light from the illumination system and transmits it to in vivo tissue, and receives light diffusely reflected in response to the broadband light, emitted from the in vivo tissue by fluorescence thereof in response to the broadband light, or a combination thereof. The optical probe communicates the light to a spectrograph which produces a signal representative of the spectral properties of the light. An analysis system determines a property of the in vivo tissue from the spectral properties. A calibration device mounts such that it is periodically in optical communication with the optical probe.

Abstract: Methods and apparatuses for the determination of an attribute of the tissue of an individual use non-invasive Raman spectroscopy. For example, the alcohol concentration in the blood or tissue of an individual can be determined. A portion of the tissue is illuminated with light, which propagates into the tissue where it is Raman scattered. The Raman scattered light is detected and can be combined with a model relating Raman spectra to alcohol concentration to determine the alcohol concentration in the blood or tissue. Correction techniques can reduce determination errors due to detection of light other than that from Raman scattering from the alcohol in the tissue. Other biologic information can be used with the Raman spectral properties to aid in the determination of alcohol concentration, for example age, height, weight, medical history and his/her family, ethnicity, skin melanin content, or a combination thereof.

Abstract: The present invention provides methods and apparatuses for determining a measure of a tissue state in an individual. Light emitted by tissue of the individual due to fluorescence of a chemical with the tissue detected. 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, 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.

Abstract: Coronary artery calcification (CAC) occurs at an earlier age in diabetes and is a risk factor for coronary artery disease (CAD) in subjects with or without diabetes. One postulated mechanism for the increased CAC is the accelerated accumulation of advanced glycation end products (AGEs) in the vasculature. As certain collagen AGEs fluoresce, skin intrinsic fluorescence (SIF) can act as a novel maker of collagen AGEs levels. The present invention provides methods and apparatuses for detecting SIF that can be a useful marker of CAD risk and a therapeutic target.

Abstract: Embodiments of the present invention provide an apparatus suitable for determining properties of in vivo tissue. An illumination system communicates light at a plurality of broadband ranges to an optical probe, which can comprise a flexible probe. Light homogenizers and mode scramblers can be employed in some embodiments. The optical probe can physically contact the tissue, or can be maintained separate from the tissue. The optical probe receives light from the illumination system and transmits it to tissue, and receives light diffusely reflected in response to the broadband light, emitted from the in vivo tissue by fluorescence thereof in response to the broadband light, or a combination thereof. The optical probe can communicate the light to a spectrograph which produces a signal representative of the spectral properties of the light. An analysis system determines a property of the in vivo tissue from the spectral properties.

Abstract: The present invention provides a method of determining 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 in the tissue responsive to the excitation light is detected. The HbA1c or FPG measurement of the individual (or other secondary indication of disease state) can also be determined. A model combining the tissue fluorescence and one or more of the secondary indications can be used to determine the disease state of the individual. In some embodiments, the tissue fluorescence can be used as an initial screen, and the combination with secondary indications only made for those individuals for whom the fluorescence screen indicates an increased likelihood of disease.

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 various light excitation and detection configurations. 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. 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.

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.

Abstract: The present invention provides improved methods and apparatuses for accurate measurements using interferometers. A functional relationship between the optical path difference and time is determined from a reference signal from an interferometer. The times at which the interferometer had specific optical path differences can be determined from the functional relationship. Those times can then be used to select times at which the spectroscopic signal from the interferometer was produced at the specific optical path differences. The invention can be applied, as examples, to maintain instrument calibration, and to transfer or compare calibrations or measurements across different interferometers.

Abstract: The present invention relates generally to non-invasive methods and apparatuses for determining analyte properties of a subject and identity characteristics of a subject. Embodiments of the present invention provide analyte property determination and identity determination or verification from the same spectroscopic information, making unauthorized use or misleading results less likely that in systems that include separate analyte and identity determinations. The invention can be used to control and monitor individuals accessing controlled environments.

Abstract: Methods and apparatuses for the determination of an attribute of the tissue of an individual use non-invasive Raman spectroscopy. For example, the alcohol concentration in the blood or tissue of an individual can be determined non-invasively. A portion of the tissue is illuminated with light, the light propagates into the tissue where it is Raman scattered within the tissue. The Raman scattered light is then detected and can be combined with a model relating Raman spectra to alcohol concentration in order to determine the alcohol concentration in the blood or tissue of the individual. Correction techniques can be used to reduce determination errors due to detection of light other than that from Raman scattering from the alcohol in the tissue.

Abstract: The present invention provides methods and apparatuses that can improve measurement accuracy in interferometers. The invention provides methods for determining digital compensation filters that measure a frequency response or responses to be compensated, and then determining a filter target response from the inverse of the frequency response or responses. A digital compensation filter can be determined from the filter target response using a discrete sum of cosines with a phase argument. The invention also allows other desired filter responses to be integrated into the filter target response before determining the digital compensation filter.

Abstract: Methods and apparatuses for the determination of an attribute of the tissue of an individual use non-invasive Raman spectroscopy. For example, the alcohol concentration in the blood or tissue of an individual can be determined non-invasively. A portion of the tissue is illuminated with light, the light propagates into the tissue where it is Raman scattered within the tissue. The Raman scattered light is then detected and can be combined with a model relating Raman spectra to alcohol concentration in order to determine the alcohol concentration in the blood or tissue of the individual. Correction techniques can be used to reduce determination errors due to detection of light other than that from Raman scattering from the alcohol in the tissue.

Abstract: An apparatus and method for non-invasive determination of attributes of human tissue by quantitative infrared spectroscopy. The system includes subsystems optimized to contend with the complexities of the tissue spectrum, high signal-to-noise ratio and photometric accuracy requirements, tissue sampling errors, calibration maintenance problems, and calibration transfer problems. The subsystems include an illumination subsystem, a tissue sampling subsystem, a spectrometer subsystem, a data acquisition subsystem, and a processing subsystem. The invention is applicable, as examples, to determining the concentration or change of concentration of alcohol in human tissue.

Abstract: The present invention provides improved methods and apparatuses for accurate measurements using interferometers. A functional relationship between the optical path difference and time is determined from a reference signal from an interferometer. The times at which the interferometer had specific optical path differences can be determined from the functional relationship. Those times can then be used to select times at which the spectroscopic signal from the interferometer was produced at the specific optical path differences. The invention can be applied, as examples, to maintain instrument calibration, and to transfer or compare calibrations or measurements across different interferometers.

Abstract: The present invention provides methods and apparatuses that can improve measurement accuracy in interferometers. The invention provides methods for determining digital compensation filters that measure a frequency response or responses to be compensated, and then determining a filter target response from the inverse of the frequency response or responses. A digital compensation filter can be determined from the filter target response using a discrete sum of cosines with a phase argument. The invention also allows other desired filter responses to be integrated into the filter target response before determining the digital compensation filter.

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.

Abstract: Methods and apparatuses of determining the pH of a sample. A method can comprise determining an infrared spectrum of the sample, and determining the hemoglobin concentration of the sample. The hemoglobin concentration and the infrared spectrum can then be used to determine the pH of the sample. In some embodiments, the hemoglobin concentration can be used to select an model relating infrared spectra to pH that is applicable at the determined hemoglobin concentration. In other embodiments, a model relating hemoglobin concentration and infrared spectra to pH can be used. An apparatus according to the present invention can comprise an illumination system, adapted to supply radiation to a sample; a collection system, adapted to collect radiation expressed from the sample responsive to the incident radiation; and an analysis system, adapted to relate information about the incident radiation, the expressed radiation, and the hemoglobin concentration of the sample to pH.

Abstract: An apparatus and method for non-invasive measurement of glucose in human tissue by quantitative infrared spectroscopy to clinically relevant levels of precision and accuracy. The system includes six subsystems optimized to contend with the complexities of the tissue spectrum, high signal-to-noise ratio and photometric accuracy requirements, tissue sampling errors, calibration maintenance problems, and calibration transfer problems. The six subsystems include an illumination subsystem, a tissue sampling subsystem, a calibration maintenance subsystem, an FTIR spectrometer subsystem, a data acquisition subsystem, and a computing subsystem.

Abstract: The present invention provides methods and devices for using feedback to improve non-invasive tissue measurements by making measurements faster, easier to perform, and less error prone. In some embodiments, a set of metrics is identified as measurable potential sources of measurement error that can be controlled by a user. In some embodiments, the set of metrics can be analyzed to determine which metrics are related to one another, and some possible error metrics can be discarded, and others used as surrogate metrics for measuring and monitoring measurement errors.