Abstract: A pathlength corrected spectrophotometer for tissue examination includes an oscillator for generating a carrier waveform of a selected frequency, an LED light source for generating light of a selected wavelength that is intensity modulated at the selected frequency introduced to a subject, and a photodiode detector for detecting light that has migrated in the tissue of the subject. The spectrophotometer also includes a phase detector for measuring a phase shift between the introduced and detected light, a magnitude detector for determination of light attenuation in the examined tissue, and a processor adapted to calculate the photon migration pathlength and determine a physiological property of the examined tissue based on the pathlength and on the attenuation data.

Abstract: A method of breast tissue examination using time-resolved spectroscopy includes the following steps. A support that includes an input port and an output port separated by a selected distance is positioned relative to the examined breast. Locations of the input and output ports are selected to examine a tissue region of the breast. Light pulses of a selected wavelength and duration less than a nanosecond are introduced into the breast tissue at the input port and detected over time at the detection port. Signals corresponding to photons of detected modified pulses are accumulated over time. Values of a scattering coefficient or an absorption coefficient of the examined breast tissue are calculated based on the shape of the modified pulses. The examined breast tissue is characterized based on the values of the scattering coefficient or the absorption coefficient. Absorbing or fluorescing contrast agents may be introduced into the examined tissue.

Abstract: The present invention discloses methods and apparatus for the quantitation and localization of tissue hypoxia by both time and frequency domain spectroscopy. The present invention provides several alternate embodiments of apparatus by which the saturation of a tissue region may be determined. In the time-resolved embodiment, a simplified system provides data which are directly proportional to the tissue saturation. In the phase modulating embodiments of the present invention, a first embodiment provides phase shift data which may be converted into saturation readings. A second embodiment, separates the real and imaginary portions of the signal and uses these data along with the data gathered from the DC portion of the signal to determine saturation. Methods of determining the hemoglobin concentration/oxygenation of a tissue region are also disclosed.

Abstract: A system for examination of a relatively small volume of biological tissue of interest using visible or infra-red radiation includes a spectrophotometer, an optical medium of a relatively large volume having selectable scattering and absorptive properties, and a processor adapted to determine a physiological property of the examined tissue. The spectrophotometer includes a light source for introducing radiation at an optical input port, a detector for detecting radiation that has migrated through a path from the input port to an optical detection port, and a processor for evaluating changes between the introduced and the detected radiation. The biological tissue of interest is positioned into the photon migration path inside the optical medium to create a tissue-medium optical path. The optical medium is adapted to limit substantially escape of photons from the tissue.

Abstract: A system for examination of biological tissue of a subject includes a light source, a light detector, a gated integrator and a integrator timing control adapted to integrate detected photons over at least two selected time intervals. The light source is adapted to introduce into the tissue, at an optical input port, pulses of electromagnetic radiation of a selected wavelength in the visible or infra-red range having duration on the order of a nanosecond or less. The detector detects, at an optical detection port, photons of modified pulses that have migrated in the tissue from the input port. The integrator and the integrator timing control register all photons arriving at the detector port over preselected time intervals of the arrival time of the modified pulses. The time-dependent shape of the modified pulses reflects the scattering and absorptive properties of the examined tissue.

Abstract: A method and system for examination of a subject positioned between input and detection ports of the spectroscopic system applied to the subject. The systems shown include at least one light source for introducing at one or multiple input ports, electromagnetic non-ionizing radiation of a known time-varying pattern of photon density of a wavelength selected to be scattered and absorbed while migrating in the subject, radiation pattern control means for achieving a directional pattern of emitted resulting radiation that possesses substantial gradient of photon density, at least one detector for detecting the radiation that has migrated in the subject at one or multiple detection ports. The systems also include processing means for processing the detected radiation and creating sets of data, and evaluation means for examining the subject using the data sets. The emitted directional radiation pattern utilizes its gradient of photon density to detect a hidden object while scanning across the examined subject.

Abstract: A phase modulated spectroscopy (PMS) system for detecting a pathophysiological condition in a subject includes two laser diodes emitting radiation at wavelengths of about 754-760 nm and 816-840 nm. These two laser diodes are modulated sinusoidally at about 220 MHz. The signals from each laser diode are brought to the subject by a bifurcated plastic optical fiber of 1 mm diameter. After transmission through the subject, the signals are detected by a Hamamatsu R928 photomultiplier (PMT), which generates two experimental signals. The experimental signals are compared to a reference signal in a phase detector. The respective phase shifts experienced by the signals are combined to form sum and difference signals, which are correlated to a pathophysiological condition.

Abstract: A system for non-invasively determining the oxygenation state of tissue located beneath the surface of the skin, such as muscle tissue, of an exercising person or other subject is disclosed. In a preferred embodiment, a user-wearable detector array and related circuitry which use near-infrared radiation to collect oxygenation data are provided. The apparatus also includes displays for displaying information regarding the oxygenation state in several ways. In one embodiment a user wearable wristband indicator connected to the detector array which is located at another location, such as on the leg, and provides information directly to the user. In another embodiment, a telemetry device allows remote monitoring of a subject during an activity, the oxygenation information being displayed to a coach or other observer. A separate, user-wearable battery pack, which is preferably designed to provide power for the duration of the activity being monitored, is also provided.

Abstract: The present invention to provides methods and apparatus for studying photon migration using signal modulation techniques such as time, frequency and phase modulation. The photon migration data may then be converted, using the principles of time-resolved spectroscopy, to determine the concentration of an absorptive constituent in a scattering medium, such as the concentration of hemoglobin in a brain of other tissue. The methods and apparatus disclosed provide as a specific embodiment, a dual wavelength phase modulation system which allows the clinical application of the advantages of time resolved spectroscopy in an economical and commercially feasible embodiment.

Abstract: Methods and apparatus using the principles of time-resolved spectroscopy are disclosed. The present invention employs incident light pulses of sufficiently short duration to permit the rate of the rise and decay of such pulses to be measured. Consequently, the rate of decay, u, permits a determination of the concentration of an absorptive pigment, such as hemoglobin. The present invention also allows the precise path length the photons travel to be determined. Using this path length information and by measuring changes in optical density using known continuous light (CW) spectrophotometry systems, the methods and apparatus disclosed allow changes in the concentration of an absorptive pigment to be correctly be measured. From these data, the oxygenation state of a tissue region, such as the brain, can be accurately determined in real time.

Abstract: The muscle efficiency of a subject is evaluated with apparatus comprising a nuclear magnetic resonance (NMR) analytical device which comprises a hollow electromagnet having a bore of sufficient size to receive the subject. Any type of animal can be evaluated, in a preferred embodiment a horse or a human is analyzed. A treadmill within the bore and beneath the subject is utilized to produce locmotion of the subject at different rates of work. The NMR analytical device is used to measure at different rates of work the following ratio within a locomotion-producing muscle mass of the subject:Pi/PCrwhere Pi is the concentration within the muscle mass of inorganic phosphate and PCr is the concentration within the muscle mass of phosphocreatine. Methods and apparatus are provided for relating the measured Pi/PCr values to the rates of work then being performed by the subject to provide an efficiency profile for the muscle mass.

Abstract: A sensitive photon detector can be used for external detection in vivo of emission from a body organ, for instance of singlet oxygen emission in the near infrared at 1280 nm, for various purposes such as control of oxygenation of a patient. At such a wavelength bone and overlying tissue are sufficiently transparent to allow detection exteriorly of the body. Stray light and thermal emissions at this wavelength in a lit room are sufficiently low, or can otherwise be controlled, to allow detection of this singlet radiation by for instance a cooled Ge detector, to determine a rate of detected photons. Detection of this radiation can be taken for instance as indicating damage in process from over-oxygenation of a patient, allowing preventing and remedial measures to be taken in oxygen treatment.

Abstract: The muscle efficiency of a living animal is evaluated with apparatus comprising a nuclear magnetic resonance (NMR) analytical device that comprises a hollow electromagnet having a bore of sufficient size to receive the animal. A treadmill within the bore and beneath the animal is utilized to produce locomotion of the animal at different rates of work. The NMR analytical device is used to measure at different rates of work the following ratio within a locomotion-producing muscle mass of the animal: ##EQU1## where Pi is the concentration within the muscle mass of inorganic phosphate and PCr is the concentration within the muscle mass of phosphocreatine. Means is provided for relating the measured ##EQU2## values to the rates of work then being performed by the animal to provide an efficiency profile for the muscle mass.

Abstract: The present invention to provides methods and apparatus for studying photon migration using signal modulation techniques such as time, frequency and phase modulation. The photon migration data may then be converted, using the principles of time-resolved spectroscopy, to determine the concentration of an absorptive constituent in a scattering medium, such as the concentration of hemoglobin in a brain of other tissue. The methods and apparatus of the present invention provide as a specific embodiment, a dual wavelength phase modulation system which allows the clinical application of time resolved spectroscopy in a commerically feasible embodiment.

Abstract: A nuclear magnetic resonance analytic apparatus for obtaining tissue metabolism information from a living body member. The apparatus consists of a large high-intensity electromagnet with an inner space having a uniform magnetic field, for receiving the body member. The space has a probe coil mounted therein with which the body member is engageable. For phosphorus-31 metabolite, there is provided a 24.33 MHz RF generator connected through a control logic section and a driver unit to the probe coil via a transmitter/receiver switching unit arranged to in effect switch the probe coil from a normal connection with a demodulation circuit to the driver unit responsive to a burst of RF pulse energy applied to the switching unit by the driver unit via the control logic section by command of a computer. The control logic section controls the system so as to first apply short pulses of the RF signal to the probe coil for a predetermined excitation time period, gating-off the demodulation unit.

Abstract: A NMR apparatus for determining the relationship between work output of an exercising body member and the steady-state capability of oxidative phosphorylation of the muscle tissue as measured by the PCr/P.sub.i ratio in the tissue. The apparatus includes the large hollow magnet of the NMR system, with a radio frequency probe mounted therein, arranged to underlie a human limb, such as an arm, inserted in the magnet from one end. Adjacent to the opposite end a Cybex ergometer is mounted. A hand lever is pivotally mounted in the magnet and is connected by a link bar to the drive arm of the ergometer. The subject inserts his arm in the magnet and grasps the hand lever, performing controlled work strokes at uniformly spaced short intervals over a selected length of time, such as 10 minutes, observing the output trace of the ergometer and maintaining a constant work output intensity with each stroke. The NMR apparatus provides curves of the NMR response at 24.

Abstract: A method and apparatus for measuring the heterogeneity of oxygen delivery to perfused and in situ organs. A laser is employed as a flying spot scanning excitation fluorometer source which provides excitation for either oxidized flavoprotein of the mitochondrial space or reduced nucleotide of mitochondrial and cytosolic spaces. Emission from the two fluorochromes is acquired at 10.sup.4 to 10.sup.5 data points per sec. and histograms of the fluorescence intensity versus the number of occurrences of that intensity are displayed. The histograms show alterations of the intensity and the degree of heterogeneity of the redox states of the organ tissue under study.

Abstract: Method and apparatus for providing flash photolysis of CO-inhibited cytochrome oxidase in a first portion of a sample exposed to an oxygenating agent and optically comparing the result with a non-photolyzed second portion of the sample or with a previously photolyzed portion of the sample. The sample is contained in a tubular transparent chamber located in the optical scanning path of a split-beam spectrophotometer having respective split-beam light guide channels traversing two spaced portions of the tubular sample chamber. Two corresponding photolyzing light guide channel assemblies are provided perpendicular to the scanning light guide channels, coplanar therewith, with a laser adjustably positioned to selectively flash-illuminate either of the two transverse photolyzing light guide channels optically communicating with the sample chamber.

Abstract: A multi-wavelength time-sharing apparatus usable in various different configurations of optical measuring equipment to provide a plurality of time-shared optical channels and including appropriate circuitry. The apparatus employs a turbine-driven filter wheel having a shaft position-encoding arrangement consisting of a hollow shaft portion which is internally illuminated. The hollow shaft portion has two sets of spaced apertures cyclically communicating with respective angularly spaced pairs of externally fixedly mounted phototransistors which are sequentially illuminated as the shaft portion rotates and which produce timing pulses which drive Schmitt triggers, which, in a typical embodiment, in turn produce pulses compatible with a logic circuit employed to decode the phototransistor signals into triggers for driving a 4-channel switched gain equalizer, a dark current clamp, and detector gates. Appropriate selection of the signals enables the instrument to function as a fluorometer or a spectrophotometer.