Multiple in vivo tissue chromophores
The present device and method can be used to monitor therapeutic treatment of methemoglobinemia using methylene blue. Also, the device and method can be used for cyanide toxicity treatment with therapeutically induced methemoglobin and in neonatal methemoglobinema management during inhaled nitric oxide treatment for hypoxemic respiratory failure. In addition to specific examples described above, this technique is expected to be useful in evaluating dynamics of drug delivery and therapeutic efficacy in blood chemistry, human, and pre-clinical animal models.
The present invention is directed to a method and device that uses broadband diffuse optical spectroscopy to dynamically calculate and monitor the concentrations of multiple chromophores in a sample of biological tissue (e.g., tissue of a subject) in a non-invasive manner. A method for monitoring the concentrations of multiple chromophores in a subject includes the step of providing a broadband diffuse optical spectroscopy device, the device having a first light source emitting light at a plurality of wavelengths and a second light source including a broadband light source. The first light source is optically coupled to a first source optical fiber that terminates in a probe. The second light source is optically coupled to a second source optical fiber that terminates in the probe. The device further includes a first detector optical fiber optically coupled to a detector and a second detector optical fiber optically coupled to a spectrometer, the first and second detector optical fibers also terminating in the probe. The method includes the steps of radiating the subject with light from the first light source, detecting intensity-modulated diffuse reflectance signals using the detector, determining absorption and reduced scattering coefficients at each wavelength of the first light source, radiating the subject with radiation from the second light source, acquiring steady-state broadband reflectance measurements using the spectrometer, determining absolute reflectance spectra based on the steady-state broadband reflectance measurements and the absorption and reduced scattering coefficients, calculating μa spectra from the absolute reflectance spectra, and determining the concentration of the multiple chromophores based on wavelength-dependent extinction coefficient spectra of each chromophore. In another aspect of the invention, a broadband diffuse optical spectroscopy device for monitoring the concentrations of multiple chromophores in vivo includes first and second light sources, the first light source emitting light at a plurality of wavelengths and the second light source including a broadband light source. A first source optical fiber is optically coupled to the first light source at a proximal end and terminates at the probe at the distal end. A second source optical fiber is optically coupled to the second light source at a proximal end and terminates at the probe at the distal end. The device includes a first detector optical fiber optically coupled to a detector at a proximal end and terminating at the probe at the other end. The device also includes a second detector optical fiber optically coupled to a spectrometer at a proximal end and terminating at the probe at the distal end. A computer interfaces with the detector and the spectrometer and calculates the concentrations of the multiple chromophores based on intensity-modulated diffuse reflectance signals detected at the detector and steady-state reflectance measurements made by the spectrometer. In one aspect of the invention, the optical fibers terminate in a probe having a distal face that is oriented generally perpendicular to the long axis of the probe. In another aspect of the invention, the optical fibers terminate in a probe having a exit face that is oriented generally planar to the long axis of the probe. In this latter embodiment, the incoming and outgoing light is bent or turned through an angle of about 90°. The probe may be taped, clamped, wrapped, or adhered to the skin of a patient. In yet another aspect of the invention, a method of monitoring methemoglobinemia in a subject includes the steps of providing a broadband DOS device as described herein. The subject is irradiated with light from the first light source. Intensity-modulated diffuse reflectance signals are detected using the detector. Absorption and reduced scattering coefficients are determined at each wavelength of the first light source. The subject is irradiated with light (e.g., radiation) from the second light source. Broadband reflectance measurements are acquired using the spectrometer. Absolute reflectance spectra is determined based on the broadband reflectance measurements and the absorption and reduced scattering coefficients. μa spectra is then calculated from the absolute reflectance spectra. The concentration of at least two chromophores are detected based on wavelength-dependent extinction coefficient spectra, the chromophores being selected from the group consisting of methemoglobin, deoxyhemoglobin, oxyhemoglobin, water, and methylene blue. It is an object of the invention to provide a broadband diffuse optical spectroscopy device and method that can dynamically monitor multiple in vivo tissue chromophores in a non-invasive manner. It is a further object of the invention to provide a device and method to non-invasively dynamically monitor multiple in vivo tissue chromophores for therapeutic monitoring of a patient. The present invention employs a quantitative method based on broadband diffuse optical spectroscopy (DOS) that combines multi-frequency frequency-domain photon migration (FDPM) methods with NIR spectroscopy. Broadband DOS can be used to dynamically monitor in vivo concentrations of multiple chromophores such as MetHb, MB, Hb-O2, Hb-R, and water in tissue non-invasively. Particular emphasis is placed on DOS sensitivity to dynamic changes in chromophore concentrations and physiological information that can be used to assess the success or failure of therapeutic interventions. Unlike arterial blood gas analysis, pulse oximetry, and co-oximetry, broadband DOS is able to non-invasively quantify real-time changes in MetHb and four additional tissue components (Hb-R, Hb-O2, H2O, and MB) with sub-micromolar sensitivity and significant overlapping spectral features.
7248909
Tech ID/UC Case 27168/2004-505-0 Related Cases 2004-505-0
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