CA2158435A1 - Pathlength corrected oximeter and the like - Google Patents
Pathlength corrected oximeter and the likeInfo
- Publication number
- CA2158435A1 CA2158435A1 CA002158435A CA2158435A CA2158435A1 CA 2158435 A1 CA2158435 A1 CA 2158435A1 CA 002158435 A CA002158435 A CA 002158435A CA 2158435 A CA2158435 A CA 2158435A CA 2158435 A1 CA2158435 A1 CA 2158435A1
- Authority
- CA
- Canada
- Prior art keywords
- light
- detector
- spectrophotometer
- tissue
- phase
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
- A61B5/14551—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters for measuring blood gases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
- A61B5/14551—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters for measuring blood gases
- A61B5/14552—Details of sensors specially adapted therefor
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
- A61B5/14551—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters for measuring blood gases
- A61B5/14553—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters for measuring blood gases specially adapted for cerebral tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
- A61B5/1459—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters invasive, e.g. introduced into the body by a catheter
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
- A61B5/6801—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be attached to or worn on the body surface
- A61B5/6813—Specially adapted to be attached to a specific body part
- A61B5/6828—Leg
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/314—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry with comparison of measurements at specific and non-specific wavelengths
- G01N21/3151—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry with comparison of measurements at specific and non-specific wavelengths using two sources of radiation of different wavelengths
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/47—Scattering, i.e. diffuse reflection
- G01N21/4795—Scattering, i.e. diffuse reflection spatially resolved investigating of object in scattering medium
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/47—Scattering, i.e. diffuse reflection
- G01N21/49—Scattering, i.e. diffuse reflection within a body or fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
- A61B2562/02—Details of sensors specially adapted for in-vivo measurements
- A61B2562/0233—Special features of optical sensors or probes classified in A61B5/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
- A61B2562/02—Details of sensors specially adapted for in-vivo measurements
- A61B2562/0233—Special features of optical sensors or probes classified in A61B5/00
- A61B2562/0242—Special features of optical sensors or probes classified in A61B5/00 for varying or adjusting the optical path length in the tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
- A61B2562/04—Arrangements of multiple sensors of the same type
- A61B2562/043—Arrangements of multiple sensors of the same type in a linear array
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N2021/1789—Time resolved
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/314—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry with comparison of measurements at specific and non-specific wavelengths
- G01N2021/3181—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry with comparison of measurements at specific and non-specific wavelengths using LEDs
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/47—Scattering, i.e. diffuse reflection
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2201/00—Features of devices classified in G01N21/00
- G01N2201/06—Illumination; Optics
- G01N2201/069—Supply of sources
- G01N2201/0696—Pulsed
Abstract
A pathlength corrected spectrophotomo-ter for tissue examination includes an oscilla-tor (10) for generating a carrier waveform of a selected frequency, an LED light source (22a-22c) for generating light of a selected wave-length that is intensity modulated at the selected frequency introduced to a subject, and a photo-diode detector (24a-24c) for detecting light that has migrated in the tissue of the subject. The spectrophotometer also includes a phase detec-tor (60a-60c) for measuring a phase shift be-tween the introduced and detected light, a mag-nitude detector (40a-40c) for determination of light attenuation in the examined tissue, and a processor (70) adapted to calculate the photon migration pathlength and determine a physio-logical property of the examined tissue based on the pathlength and on the attenuation data.
Description
WO94/21173 ~ PCT~S94/02764 21~8~3~
PATHLENGTH CORRECTED Ox~ ~ AND THE LIKE
~ackqround of the Invention The present invention relates to a wearable tissue 5 spectrophotometer for in vivo ~ tion of tissue of a specific target region.
Continuous wave (CW) tissue oximeters have been widely used to determine in vivo concentration of an optically absorbing pigment (e.g., hemoglobin, 10 oxyhemoglobin) in biological tissue. The CW oximeters measure attenuation of continuous light in the tissue and evaluate the concentration based on the Beer Lambert equation or modified Beer Lambert absorbance equation.
The Beer Lambert equation (1) describes the relationship 15 between the concentration of an absorbent constituent (C), the extinction coefficient (~), the photon migration pathlength <L>, and the attenuated light intensity o ) -log [I/Io] =~ ~ C ( 1) The CW spectrophotometric t~chniques can not determine , 20 C, and <L> at the same time. If one could assume that the photon pathlength were constant and uniform throughout all subjects, direct quantitation of the constituent concentration (C) using CW oximeters would be possible.
In tissue, the optical migration pathlength varies with the size, structure, and physiology of the internal tissue examined by the CW oximeters. For example, in the brain, the gray and white matter and the structures thereof are different in various individuals. In 30 addition, the photon migration pathlength itself is a function of the relative concentration of absorbing constituents. As a result, the pathlength through an organ with a high blood hemoglobin concentration, for WO94/21173 PCT~S94102764 example, will be different from the same with a low blood hemoglobin concentration. Furthermore, the pathlength is frequently dependent upon the wavelength of the light since the absorption coefficient of many tissue 5 constituents is wavelength dependent. Thus, where possible, it is advantageous to measure the pathlength directly when quantifying the hemoglobin concentration in tissue.
SummarY of the Invention In one aspect, the present invention is a pathlength corrected oximeter that utilizes principles of continuous wave spectroscopy and phase modulation spectroscopy. The oximeter is a compact unit constructed to be worn by a subject on the body over long periods of 15 activity. The oximeter is also suitable for tissue monitoring in critical care facilities, in operating rooms while undergoing surgery or in trauma related situations.
The oximeter is mounted on a body-conformable 20 support structure placed on the skin. The su~po~
structure encapsulates several light emitting diodes (LEDs) generating light of different wavelengths introduced into the examined tissue and several photodiode detectors with interference filters for 25 wavelength specific detection. Since both the LEDs and the photodiodes are placed directly on the skin, there is no need to use optical fibers. The distance between the LEDs and the diode detectors is selected to examine a targeted tissue region. The support structure also 30 includes a conformable barrier, located between the LEDs and the diode detectors, designed to reduce detection of light that migrates subcutaneously from the source to the detector. The support structure may further include !.
means for preventing escape of photons from the skin WO94/21173 PCT~S94/02764 ~ 3~
without being detected; the photon escape preventing means are located around the LEDs and the photodiode detectors.
The LEDs, the diode detectors, and the electronic 5 control circuitry of the oximeter are powered by a battery pack adapted to be worn on the body or by the st~A~d 50/60 Hz supply. The electronic circuitry includes a processor for directing operation of the sources, the detectors and for directing the data 10 acquisition and processing. The data may be displayed on a readout device worn by the user, sent by telemetry to a remote location or accumulated in a memory for later use.
The oximeter is adapted to measure the attenuation of light migrating from the source to the detector and 15 also to determine the average migration pathlength. The migration pathlength and the intensity attenuation data are then used for direct quantitation of a tissue property.
In another aspect, the invention is a 20 spectrophotometer for tissue examination utilizing a measured average pathlength of migrating photons, including an oscillator adapted to generate a carrier waveform of a selected frequency comparable to an average migration time of photons scattered in tissue on paths 25 from an optical input port to an optical detection port;
a light source, operatively connected to the oscillator, adapted to generate light of a selected wavelength that is intensity modulated at the frequency and introduced to a subject at the input port; a photodiode detector 30 adapted to detect, at the detection port, light of the selected wavelength that has migrated in the tissue of the subject between the input and detection ports; a phase detector, operatively connected to receive signals from the oscillator and the diode detector, adapted to 35 measure a phase shift between the introduced and the WO94/21173 PCT~S94102764
PATHLENGTH CORRECTED Ox~ ~ AND THE LIKE
~ackqround of the Invention The present invention relates to a wearable tissue 5 spectrophotometer for in vivo ~ tion of tissue of a specific target region.
Continuous wave (CW) tissue oximeters have been widely used to determine in vivo concentration of an optically absorbing pigment (e.g., hemoglobin, 10 oxyhemoglobin) in biological tissue. The CW oximeters measure attenuation of continuous light in the tissue and evaluate the concentration based on the Beer Lambert equation or modified Beer Lambert absorbance equation.
The Beer Lambert equation (1) describes the relationship 15 between the concentration of an absorbent constituent (C), the extinction coefficient (~), the photon migration pathlength <L>, and the attenuated light intensity o ) -log [I/Io] =~ ~ C ( 1) The CW spectrophotometric t~chniques can not determine , 20 C, and <L> at the same time. If one could assume that the photon pathlength were constant and uniform throughout all subjects, direct quantitation of the constituent concentration (C) using CW oximeters would be possible.
In tissue, the optical migration pathlength varies with the size, structure, and physiology of the internal tissue examined by the CW oximeters. For example, in the brain, the gray and white matter and the structures thereof are different in various individuals. In 30 addition, the photon migration pathlength itself is a function of the relative concentration of absorbing constituents. As a result, the pathlength through an organ with a high blood hemoglobin concentration, for WO94/21173 PCT~S94102764 example, will be different from the same with a low blood hemoglobin concentration. Furthermore, the pathlength is frequently dependent upon the wavelength of the light since the absorption coefficient of many tissue 5 constituents is wavelength dependent. Thus, where possible, it is advantageous to measure the pathlength directly when quantifying the hemoglobin concentration in tissue.
SummarY of the Invention In one aspect, the present invention is a pathlength corrected oximeter that utilizes principles of continuous wave spectroscopy and phase modulation spectroscopy. The oximeter is a compact unit constructed to be worn by a subject on the body over long periods of 15 activity. The oximeter is also suitable for tissue monitoring in critical care facilities, in operating rooms while undergoing surgery or in trauma related situations.
The oximeter is mounted on a body-conformable 20 support structure placed on the skin. The su~po~
structure encapsulates several light emitting diodes (LEDs) generating light of different wavelengths introduced into the examined tissue and several photodiode detectors with interference filters for 25 wavelength specific detection. Since both the LEDs and the photodiodes are placed directly on the skin, there is no need to use optical fibers. The distance between the LEDs and the diode detectors is selected to examine a targeted tissue region. The support structure also 30 includes a conformable barrier, located between the LEDs and the diode detectors, designed to reduce detection of light that migrates subcutaneously from the source to the detector. The support structure may further include !.
means for preventing escape of photons from the skin WO94/21173 PCT~S94/02764 ~ 3~
without being detected; the photon escape preventing means are located around the LEDs and the photodiode detectors.
The LEDs, the diode detectors, and the electronic 5 control circuitry of the oximeter are powered by a battery pack adapted to be worn on the body or by the st~A~d 50/60 Hz supply. The electronic circuitry includes a processor for directing operation of the sources, the detectors and for directing the data 10 acquisition and processing. The data may be displayed on a readout device worn by the user, sent by telemetry to a remote location or accumulated in a memory for later use.
The oximeter is adapted to measure the attenuation of light migrating from the source to the detector and 15 also to determine the average migration pathlength. The migration pathlength and the intensity attenuation data are then used for direct quantitation of a tissue property.
In another aspect, the invention is a 20 spectrophotometer for tissue examination utilizing a measured average pathlength of migrating photons, including an oscillator adapted to generate a carrier waveform of a selected frequency comparable to an average migration time of photons scattered in tissue on paths 25 from an optical input port to an optical detection port;
a light source, operatively connected to the oscillator, adapted to generate light of a selected wavelength that is intensity modulated at the frequency and introduced to a subject at the input port; a photodiode detector 30 adapted to detect, at the detection port, light of the selected wavelength that has migrated in the tissue of the subject between the input and detection ports; a phase detector, operatively connected to receive signals from the oscillator and the diode detector, adapted to 35 measure a phase shift between the introduced and the WO94/21173 PCT~S94102764
2 ~g ~ _ 4 _ detected light; and a processor adapted to calculate pathlength based on the phase shift, and determine a physiological property of the examined tissue based on the pathlength.
In another aspect, the invention is a spectrophotometer for tissue examination utilizing a measured average pathlength of migrating photons, including an oscillator adapted to generate a carrier waveform of a selected frequency comparable to an average lO migration time of photons scattered in tissue on paths from an optical input port to an optical detection port;
a light source, operatively connected to the oscillator, adapted to generate light of a selected wavelength that is intensity modulated at the frequency and introduced to l~ a subject at the input port; a photodiode detector adapted to detect, at the detection port, light of the selected wavelength that has migrated in the tissue of the subject between the input and detection ports; a phase splitter adapted to produce, based on the carrier 20 waveform, first and second reference phase signals of predefined substantially different phase; first and second double balanced mixers adapted to correlate the reference phase signals and signals of the detected radiation to produce therefrom a real output signal and 25 an imaginary o~L~ signal, respectively; and a processor adapted to calculate, on the basis of the real o~
signal and the imaginary output signal, a phase shift between the introduced light and the detected light, and determine a physiological property of the examined tissue 30 based on the phase shift.
In another aspect, the invention is a spectrophotometer for tissue ~XA~; ~Ation utilizing a measured average pathlength of migrating photons, comprising a first oscillator adapted to generate a 35 carrier waveform of a first selected frequency comparable WO94121173 2 ~ PCT~S94/02764 to an average migration time of photons scattered in tissue on paths from an optical input port to an optical detection port; a light source, operatively connected to the oscillator, adapted to generate light of a selected 5 wavelength, intensity modulated at the first frequency, that is introduced to a subject at the input port; a photodiode detector adapted to detect, at the detection port, light of the wavelength that has migrated in the tissue of the subject between the input and detection 10 ports, the detector producing a detection signal at the first frequency corresponding to the detected light; a second oscillator adapted to generate a carrier waveform of a second frequency that is offset on the order of 104Hz from the first frequency; a reference mixer, 15 connected to the first and second oscillators, adapted to generate a reference signal of a frequency approximately equal to the difference between the first and second frequencies; a mixer connected to receive signals from the second oscillator and the detection signal and 20 adapted to convert the detection signal to the difference frequency; a phase detector, operatively connected to receive signals from the reference mixer and the converted detection signal, adapted to measure a phase shift between the introduced light and the detected 25 light; and a processor adapted to calculate the pathlength based on the phase shift, and to determine a physiological property of the examined tissue based on the pathlength.
Preferred embodiments of these aspects may include 30 one or more of the following features.
The spectrophotometer may further include a magnitude detector, connected to the photodiode detector, adapted to measure magnitude of the detected light, and the processor is further adapted to receive the magnitude 35 for determination of the physiological property.
In another aspect, the invention is a spectrophotometer for tissue examination utilizing a measured average pathlength of migrating photons, including an oscillator adapted to generate a carrier waveform of a selected frequency comparable to an average lO migration time of photons scattered in tissue on paths from an optical input port to an optical detection port;
a light source, operatively connected to the oscillator, adapted to generate light of a selected wavelength that is intensity modulated at the frequency and introduced to l~ a subject at the input port; a photodiode detector adapted to detect, at the detection port, light of the selected wavelength that has migrated in the tissue of the subject between the input and detection ports; a phase splitter adapted to produce, based on the carrier 20 waveform, first and second reference phase signals of predefined substantially different phase; first and second double balanced mixers adapted to correlate the reference phase signals and signals of the detected radiation to produce therefrom a real output signal and 25 an imaginary o~L~ signal, respectively; and a processor adapted to calculate, on the basis of the real o~
signal and the imaginary output signal, a phase shift between the introduced light and the detected light, and determine a physiological property of the examined tissue 30 based on the phase shift.
In another aspect, the invention is a spectrophotometer for tissue ~XA~; ~Ation utilizing a measured average pathlength of migrating photons, comprising a first oscillator adapted to generate a 35 carrier waveform of a first selected frequency comparable WO94121173 2 ~ PCT~S94/02764 to an average migration time of photons scattered in tissue on paths from an optical input port to an optical detection port; a light source, operatively connected to the oscillator, adapted to generate light of a selected 5 wavelength, intensity modulated at the first frequency, that is introduced to a subject at the input port; a photodiode detector adapted to detect, at the detection port, light of the wavelength that has migrated in the tissue of the subject between the input and detection 10 ports, the detector producing a detection signal at the first frequency corresponding to the detected light; a second oscillator adapted to generate a carrier waveform of a second frequency that is offset on the order of 104Hz from the first frequency; a reference mixer, 15 connected to the first and second oscillators, adapted to generate a reference signal of a frequency approximately equal to the difference between the first and second frequencies; a mixer connected to receive signals from the second oscillator and the detection signal and 20 adapted to convert the detection signal to the difference frequency; a phase detector, operatively connected to receive signals from the reference mixer and the converted detection signal, adapted to measure a phase shift between the introduced light and the detected 25 light; and a processor adapted to calculate the pathlength based on the phase shift, and to determine a physiological property of the examined tissue based on the pathlength.
Preferred embodiments of these aspects may include 30 one or more of the following features.
The spectrophotometer may further include a magnitude detector, connected to the photodiode detector, adapted to measure magnitude of the detected light, and the processor is further adapted to receive the magnitude 35 for determination of the physiological property.
3 PCT~S94/02764 The spectrophotometer may further include a low frequency oximeter circuit, switchably connected to the source and the photodiode, adapted to determine absorption of light at the wavelength; and the processor 5 is further adapted to receive absorption values from the oximeter circuit for determination of the physiological property.
The spectrophotometer may further include two automatic gain controls adapted to level signals 10 corresponding to the introduced light and the detected light, both the leveled signals being il.L~od~ced to the phase detector.
The photodiode detector may further include a substantially single wavelength filter.
The spectrophotometer may further include a second light source, operatively connected to the oscillator, adapted to generate light of a second selected wavelength that is intensity modulated at the first frequency, the radiation being introduced to a subject at a second input 20 port; the photodiode detector further adapted to detect alternately, at the detection port, light of the first and second wavelengths that have migrated in the tissue of the subject between the first and the second input ports and the detection port, respectively; the phase 25 detector further adapted to receive alternately signals corresponding to the detected first and second wavelengths; and the processor further adapted to receive alternately phase shifts from the phase detector, the phase shifts being subsequently used for determination of 30 the physiological property of the tissue.
The spectrophotometer may further include a second light source, operatively connected to the oscillator, adapted to generate light of a second selected wavelength that is intensity modulated at the first frequency, the 35 radiation being introduced to a subject at a second input WO94121173 215 ~ ~ 3 5 PCT~S94/027~
port; a second photodiode detector adapted to detect, at a second detection port, light of the second wavelength that has migrated in the tissue of the subject between the second input port and the second detection port, 5 respectively; a second phase detector, operatively connected to receive a reference signal and a detection signal from the third diode detector, adapted to measure a phase shift between the introduced and the detected light at the second wavelength; and the processor further 10 adapted to receive a second phase shift at the second wavelength, the first and second phase shifts being subsequently used for determination of the physiological property of the tissue.
The two wavelength spectrophotometer may further 15 include a third light source, operatively connected to the oscillator, adapted to generate light of a third selected wavelength that is intensity modulated at the first frequency, the radiation being introduced to a subject at a third input port; a third photodiode 20 detector adapted to detect, at a third detection port, light of the third wavelength that has migrated in the tissue of the subject between the third input port and the third detection port, respectively; a third phase detector, operatively connected to receive a reference 2s signal and a detection signal from the third diode detector, adapted to measure a phase shift between the introduced and the detected light at the third wavelength; and the processor further adapted to receive phase shifts from the phase detector, the first second 30 and third phase shifts being subsequently used for determination of the physiological property of the tissue.
The two or three wavelength spectrophotometer may further include a first, a second (or a third) magnitude 35 detector connected to the first, second (or third) WO94/21173 PCT~S94/02764 photodiode detectors, respectively, the magnitude detectors being adapted to measure magnitude of the detected light at each of the wavelengths; and the processor further adapted to receive the magnitudes for 5 determination of the physiological property of the tissue.
The light source may be a light emitting diode for generating light of a selected wavelength in the visible or infra-red range.
The photodiode detector may be a PIN diode or an avalanche diode.
The ~m; ned physiological property of the tissue may be hemoglobin oxygenation, myoglobin, cytochrome iron and copper, melanin, glucose or other.
Brief Description of the Drawinq FIG. 1 is a block diagram of a pathlength corrected oximeter in accordance with the present invention.
FIG. 2 is a schematic circuit diagram of a 50.1 20 MHz (50.125 MHz) oscillator used in the oximeter of FIG
1.
FIG. 3 is a schematic circuit diagram of a PIN
diode and a preamplifier used in the oximeter of FIG 1.
FIG. 4 is a schematic circuit diagram of a 25 magnitude detector used in the oximeter of FIG 1.
FIG. 5 is a schematic circuit diagram of a 25 kHz filter used in the oximeter of FIG 1.
FIG. 6 is a schematic diagram of an AGC circuit of the oximeter of FIG 1.
FIG. 7 is a schematic circuit diagram of a phase detector of the oximeter of FIG 1.
FIG. 8A is a plan view of a source-detector probe of the oximeter.
WO94121173 2 ~ PCT~S94/027~
_ g FIG. 8B is a transverse cross-sectional view taken on lines 8B of FIG 8A further showing the photon migration.
Description of the Preferred Embodiments One preferred embodiment of the pathlength corrected oximeter utilizes three LEDs for generation of light at three selected wavelengths intensity modulated at a frequency of 50.1 MHz and coupled directly to the examined tissue. At each wavelength, the introduced 10 light is altered by the tissue and is detected by a wide area photodiode placed against the skin. The introduced and detected radiations are compared to determine their relative phase shift that corresponds to an average pathlength of the migrating photons and, furthermore, the 15 light attenuation is determined.
Referring to FIG. 1, the oximeter includes a master oscillator 10 operating at 50.1 MHz connected to a power amplifier 15 of sufficient output power to drive LEDs 22a, 22b, and 22c (for example HLP 20RG or HLP 40RG
20 made by Hitachi) that emit 760 nm, 840 nm, and 905 nm (or 950 nm) light, respectively. A second local oscillator 14 operating at 50.125 MHz and mixer 12 are used to generate a reference frequency 13 of 25kHz. Each LED
directly positioned on the skin has an appropriate heat 25 sink to eliminate llncomfortable temperature increases that could also alter blood perfusion of the ~ L ounding tissue. Three PIN diode detectors 24a, 24b, and 24c are placed at a distance of approximately 5 cm from the LEDs and have a detection area of about 1 cm2. Photons 30 migrating a few centimeters deep into the tissue are detected by the respective PIN diodes. The source-detector separation can be increased or decreased to capture deeper or shallower migrating photons. The W094121173 PCT~S94/02764 signals from PIN diodes 24a, 24b, and 24c are amplified by preamplifiers 3Oa, 3Ob, and 30c, respectively.
The amplified signaIs (32a, 32b, 32c) are sent to magnitude detectors 36a, 36b, and 36c and to mixers 40a, 5 4Ob, and 40c, respectively. The magnitude detectors are used to determine intensity values of detected signals at each wavelength to be used in Eq. 1. Each mixer, connected to receive a 50.125 MHz reference signal (41a, 41b, 41c) from local oscillator 14, converts the 10 detection signal to a 25 kHz frequency signal (42a, 42b, 42c). The mixers are high dynamic range frequency mixers, model SRA-lH, commercially available from Mini-Circuits (Brooklyn N.Y.). The detection signals (42a, 42b, and 42c) are filtered by filters 45a, 45b, 45c, 15 respectively.
Phase detectors 60a, 60b, and 60c are used to determine phase shift between the input signal and the detected signal at each wavelength. Each phase detector receives the 25 kHz detection signal (54a, 54b, 54c) and 20 the 25 kHz reference signal (56a, 56b, 56c), both of which are automatically leveled by automatic gain controls 50 and 52 to cover the dynamic range of signal changes. Phase detectors 60a, 60b, and 60c generate phase shift signals (62a, 62b, 62c) corresponding to the 25 migration delay of photons at each wavelength. Each phase shift signal is proportional to the migration pathlength used in calculation algorithms performed by processor 70.
FIG. 2 shows a schematic circuit diagram of a 30 precision oscillator used as the 50.1 MHz master oscillator 10 and 50.125 MHz local oscillator 14. The oscillator crystals are neutralized for operation in the fundamental resonance mode; this achieves long-term stability. Both oscillators are thermally coupled so WO94/21173 PCT~S94/02764 ~843~
that their frequency difference is maintained constant at 25 kHz if a frequency drift occurs.
PIN diodes 24a, 24b, and 24c are directly connected to their respective preamplifiers 30a, 30b, and 5 30c, as shown in FIG. 3. The oximeter uses PIN silicon photodiodes S1723-04 with 10mm x 10mm sensitive area and spectral response in the range of 320 nm to 1060 nm. The detection signal is amplified by stages 29 and 31, each providing about 20 dB amplification. The NE5205N
10 operational amplifier is powered at ~8V to operate in a high gain regime. The 8V signal is supplied by a voltage regulator 33. The amplified detection signals (32a, 32b, and 32c) are sent to magnitude detectors 36a, 36b, and 36c, shown in FIG. 4. The magnitude values (37a, 37b, 15 and 37c) are sent to processor 70 that calculates the light attenuation ratio or logarithm thereof as shown E~.
1.
Also referring to FIG. 5, the AGC circuit uses MC
1350 integrated circuit for amplification that maintains 20 the input signal of phase detector 60 at substantially constant levels. The amount of gain is selected to be equal for AGCs, 50 and 52. The signal amplitude is controlled by a feedback network 53. The AGCs provide a substantially constant amplitude of the detected and 25 reference signals to eliminate variations in the detected phase shift due to cross talk between amplitude and phase changes in the phase detector.
Referring to FIG. 6, each phase detector includes a Schmitt trigger that converts the substantially 30 sinusoidal detection signal (54a, 54b, 54c) and reference signal (56a, 56b, 56c) to square waves. The square waves are input to a detector that has complementary MOS
silicon-gate transistors. The phase shift signal is sent - to processor 70.
WO94/21173 PCT~S94/02764 The oximeter is calibrated by measuring the phase shift for a selected distance in a known medium, i.e., using a standard delay unit, and by switching the length of a connector wire to change the electrical delay 5 between master oscillator 10 and local oscillator 14.
Referring to FIGs. 8A and 8B source-detector probe 20 includes several LEDs (22a, 22b, 22c) of selected wavelengths and PIN photodiodes (24a, 24b, 24c) mounted in a body-conformable support structure 21. Structure 21 10 also includes a photon escape barrier 27 made of a material with selected scattering and absorption properties (for example, styrofoam) designed to return escaping photons back to the ~r; ned tissue. The support structure further includes a second conformable 15 barrier 28, located between the LEDs and the diode detectors, designed to absorb photons directly propagating from the source to the detector and thus prevent detection of photons that migrate subcutaneously.
Support structure 21 also includes electronic circuitry 20 29 encapsulated by an electronic shield 21a.
Each PIN diode is provided with an evaporated single wavelength film filter (25a, 25b, 25c). The filters eliminate the cross talk of different wavelength signals and allow continuous operation of the three light 25 sources, i.e., no time sharing is needed.
The use of photodiode detectors has substantial advantages when compared with the photomultiplier tube used in standard phase modulation systems. The photodiodes are placed directly on the skin, i.e., no 30 optical fibers are needed. Furthermore, there is no need to use a high voltage power supply that is necessary for the photomultiplier tube. The photodiodes are much smaller and are easy to place close to the skin.
Advantages of the photomultiplier tube are a huge 35 multiplication gain and a possibility of direct mixing at WO94/21173 ~ 5 ~ 4 ~ 5 PCT~S94/027 the photomultiplier; this cannot be achieved directly by a photodiode. This invention envisions the use of several different photodiodes such as PIN diode, avalanche diode, and other.
The processor uses algorithms that are based on equations described by E.M. Sevick et al. in "Quantitation of Time- and Frequency-Resolved Optical Spectra for the Determination of Tissue Oxygenation"
published in Analytical Biochemistry 195, 330 April 15, 10 1991 which is incorporated by reference as if fully set forth herein.
At each wavelength, the phase shift (e~) (62a, 62b, 62c) is used to calculate the pathlength as follows:
~A = tan~1~c f (tA) = tan-l 2~f(LA) s~ 2~ f (LA) ~2) C C
wherein f is modulation frequency of the illL~ ced light 15 which is in the range of 10 MHz to 100 MHz; t~ is the photon migration delay time; c is the speed of photons in the scattering medium; and L~ is the migration pathlength.
Equation (2) is valid at low modulation 20 frequencies, i.e., 2~f << ~a c. The modulation frequency of 50 MHz was selected due to the frequency limitation of the LEDs and photodiodes. However, for faster LEDs and photodiodes it may be desirable to use higher modulation frequencies that increase the phase shift. At high 25 modulation frequencies, i.e., 2~f >> ~a c, the phase shift is no longer proportional to the mean time of flight <t>.
WO94/21173 PCT~S94102764 ~A = ap~-g) ~6 f~1 - 4 f} (3) wherein p is the source-detector separation; (1-g) ~ is effective scattering coefficient; f is modulation frequency and ~a~ is absorption coefficient at wavelength ~.
5 At two wavelength, the ratio of absorption coefficients is determined as follows:
~11 a~ o1 (4) ~ 2 ~Az ~l2 wherein ~0~ represents background scattering and absorption.
The wavelengths are in the visible and infra-red 10 range and are selected to have absorbance sensitive (or insensitive) to various tissue components such as water, cytochrome iron and copper, oxy- and deoxygenated forms of hemoglobin, myoglobin, melanin, glucose and other.
For oxygenated and deoxygenated hemoblogin, the 15 absorption coefficient written in terms of Beer Lambert relationship is as follows:
~b [Hb] + ~bO [HbO2] + 1 ~5) wherein ~Hb~1 and ~HbO~l are extinction coefficients for hemoglobin and deoxyhemoglobin that can be stored in a look up table; tHb], [HbO2] are the tissue concentration 20 of hemoglobin and oxyhemoglobin, respectively; ~1 is background absorbance. The hemoglobin saturation is conventionally defined as follows:
WO94/21173 ~ 1~ g~ ~ PCT~S94/02764 y [HbO2] (6) For a three wavelength measurement, the hemoglobin saturation can be calculated using Eqs. (5) and (6) as follows:
y _ a(~-~) _ (~A _ ~A2) [(~ ~ -~ ~ )-(~-~)]-a[(~ ~)]
where ~,~Al _ ~A~
a - A~ A~
l~n ~ 1~
5 Thus, processor 70 determines Y based on Eq. (7) using Eq. (2) to determine the average migration pathlength L
that is then used in Eq. (1) and to determine ~a~ for each wavelength Al, ~2~ A3.
In another embodiment, the spectrophotometer's 10 electronics includes a low fre~uency module suitably and a high frequency module switchably coupled to the same source-detector probe 20. The low frequency module and the arrangement of the source-detector probe are substantially similar to the hemoglobinometer described 15 in a copending U.S. Patent Application Ser. No. 701,127 filed May 16, 1991 which is incorporated by reference as if fully set forth herein. The low frequency module corresponds to a st~n~rd oximeter with modulation frequencies in the range of a few hertz to 104 hertz and 20 is adapted to provide intensity attenuation data at two or three wavelengths. Then, the LEDs are switched to the high frequency phase modulation unit, similar to the unit of FIG. 1, which determines the average pathlength at each wavelength. The attenuation and pathlength data are WO94/21173 PCT~S94102764 sent to processor 70 for determination of a physiological property of the ~ ;ned tissue.
In another embodiment, the pathlength corrected oximeter utilizes the same LED sources (22a, 22b, 22c) 5 sinusoidally modulated at a selected frequency comparable to the average migration time of photons scattered in the ~ ;ned tissue on paths from the optical input port of the LED's to the optical detection part of the photodiode detectors (24a, 24b, 24c), but the electronic circuitry 10 is different. The detector output is put through two wide band double balance mixers (DBM) which are coupled through a 90 phase splitter so that real (R) and imaginary (I) portions of the signal are obtained. The double balance mixers preferably operate at the 15 modulation frequency. The phase (~) is the angle whose tangent is the imaginary over the real part.
~A = tan~ ( 8 ) The amplitude is the square root of the sum of the squares of these values, providing the phase shift has been taken out as the residual phase shift ~ set to zero.
AA = ~/(RA)2 + (I~)2 (9~
This embodiment uses summing and dividing circuits to calculate the modulation index, which is the quotient of the amplitude over the amplitude plus the DC component obtained from a narrow band detector.
wo 94~21173 2 ~ ~ 8 ~ 3 ~ PCT~S94/02764 A A ( 1 0 ) A + DC
- The phase processor receives the phase shifts for the phase and amplitude values for two or three wavelengths and calculates the ratio of the phase shifts.
For each wavelength, the phase shift and the DC
5 amplitude are used to determine a selected tissue property, e.g., hemoglobin oxygenation.
Additional embodiments are within the following claims:
The spectrophotometer may further include two automatic gain controls adapted to level signals 10 corresponding to the introduced light and the detected light, both the leveled signals being il.L~od~ced to the phase detector.
The photodiode detector may further include a substantially single wavelength filter.
The spectrophotometer may further include a second light source, operatively connected to the oscillator, adapted to generate light of a second selected wavelength that is intensity modulated at the first frequency, the radiation being introduced to a subject at a second input 20 port; the photodiode detector further adapted to detect alternately, at the detection port, light of the first and second wavelengths that have migrated in the tissue of the subject between the first and the second input ports and the detection port, respectively; the phase 25 detector further adapted to receive alternately signals corresponding to the detected first and second wavelengths; and the processor further adapted to receive alternately phase shifts from the phase detector, the phase shifts being subsequently used for determination of 30 the physiological property of the tissue.
The spectrophotometer may further include a second light source, operatively connected to the oscillator, adapted to generate light of a second selected wavelength that is intensity modulated at the first frequency, the 35 radiation being introduced to a subject at a second input WO94121173 215 ~ ~ 3 5 PCT~S94/027~
port; a second photodiode detector adapted to detect, at a second detection port, light of the second wavelength that has migrated in the tissue of the subject between the second input port and the second detection port, 5 respectively; a second phase detector, operatively connected to receive a reference signal and a detection signal from the third diode detector, adapted to measure a phase shift between the introduced and the detected light at the second wavelength; and the processor further 10 adapted to receive a second phase shift at the second wavelength, the first and second phase shifts being subsequently used for determination of the physiological property of the tissue.
The two wavelength spectrophotometer may further 15 include a third light source, operatively connected to the oscillator, adapted to generate light of a third selected wavelength that is intensity modulated at the first frequency, the radiation being introduced to a subject at a third input port; a third photodiode 20 detector adapted to detect, at a third detection port, light of the third wavelength that has migrated in the tissue of the subject between the third input port and the third detection port, respectively; a third phase detector, operatively connected to receive a reference 2s signal and a detection signal from the third diode detector, adapted to measure a phase shift between the introduced and the detected light at the third wavelength; and the processor further adapted to receive phase shifts from the phase detector, the first second 30 and third phase shifts being subsequently used for determination of the physiological property of the tissue.
The two or three wavelength spectrophotometer may further include a first, a second (or a third) magnitude 35 detector connected to the first, second (or third) WO94/21173 PCT~S94/02764 photodiode detectors, respectively, the magnitude detectors being adapted to measure magnitude of the detected light at each of the wavelengths; and the processor further adapted to receive the magnitudes for 5 determination of the physiological property of the tissue.
The light source may be a light emitting diode for generating light of a selected wavelength in the visible or infra-red range.
The photodiode detector may be a PIN diode or an avalanche diode.
The ~m; ned physiological property of the tissue may be hemoglobin oxygenation, myoglobin, cytochrome iron and copper, melanin, glucose or other.
Brief Description of the Drawinq FIG. 1 is a block diagram of a pathlength corrected oximeter in accordance with the present invention.
FIG. 2 is a schematic circuit diagram of a 50.1 20 MHz (50.125 MHz) oscillator used in the oximeter of FIG
1.
FIG. 3 is a schematic circuit diagram of a PIN
diode and a preamplifier used in the oximeter of FIG 1.
FIG. 4 is a schematic circuit diagram of a 25 magnitude detector used in the oximeter of FIG 1.
FIG. 5 is a schematic circuit diagram of a 25 kHz filter used in the oximeter of FIG 1.
FIG. 6 is a schematic diagram of an AGC circuit of the oximeter of FIG 1.
FIG. 7 is a schematic circuit diagram of a phase detector of the oximeter of FIG 1.
FIG. 8A is a plan view of a source-detector probe of the oximeter.
WO94121173 2 ~ PCT~S94/027~
_ g FIG. 8B is a transverse cross-sectional view taken on lines 8B of FIG 8A further showing the photon migration.
Description of the Preferred Embodiments One preferred embodiment of the pathlength corrected oximeter utilizes three LEDs for generation of light at three selected wavelengths intensity modulated at a frequency of 50.1 MHz and coupled directly to the examined tissue. At each wavelength, the introduced 10 light is altered by the tissue and is detected by a wide area photodiode placed against the skin. The introduced and detected radiations are compared to determine their relative phase shift that corresponds to an average pathlength of the migrating photons and, furthermore, the 15 light attenuation is determined.
Referring to FIG. 1, the oximeter includes a master oscillator 10 operating at 50.1 MHz connected to a power amplifier 15 of sufficient output power to drive LEDs 22a, 22b, and 22c (for example HLP 20RG or HLP 40RG
20 made by Hitachi) that emit 760 nm, 840 nm, and 905 nm (or 950 nm) light, respectively. A second local oscillator 14 operating at 50.125 MHz and mixer 12 are used to generate a reference frequency 13 of 25kHz. Each LED
directly positioned on the skin has an appropriate heat 25 sink to eliminate llncomfortable temperature increases that could also alter blood perfusion of the ~ L ounding tissue. Three PIN diode detectors 24a, 24b, and 24c are placed at a distance of approximately 5 cm from the LEDs and have a detection area of about 1 cm2. Photons 30 migrating a few centimeters deep into the tissue are detected by the respective PIN diodes. The source-detector separation can be increased or decreased to capture deeper or shallower migrating photons. The W094121173 PCT~S94/02764 signals from PIN diodes 24a, 24b, and 24c are amplified by preamplifiers 3Oa, 3Ob, and 30c, respectively.
The amplified signaIs (32a, 32b, 32c) are sent to magnitude detectors 36a, 36b, and 36c and to mixers 40a, 5 4Ob, and 40c, respectively. The magnitude detectors are used to determine intensity values of detected signals at each wavelength to be used in Eq. 1. Each mixer, connected to receive a 50.125 MHz reference signal (41a, 41b, 41c) from local oscillator 14, converts the 10 detection signal to a 25 kHz frequency signal (42a, 42b, 42c). The mixers are high dynamic range frequency mixers, model SRA-lH, commercially available from Mini-Circuits (Brooklyn N.Y.). The detection signals (42a, 42b, and 42c) are filtered by filters 45a, 45b, 45c, 15 respectively.
Phase detectors 60a, 60b, and 60c are used to determine phase shift between the input signal and the detected signal at each wavelength. Each phase detector receives the 25 kHz detection signal (54a, 54b, 54c) and 20 the 25 kHz reference signal (56a, 56b, 56c), both of which are automatically leveled by automatic gain controls 50 and 52 to cover the dynamic range of signal changes. Phase detectors 60a, 60b, and 60c generate phase shift signals (62a, 62b, 62c) corresponding to the 25 migration delay of photons at each wavelength. Each phase shift signal is proportional to the migration pathlength used in calculation algorithms performed by processor 70.
FIG. 2 shows a schematic circuit diagram of a 30 precision oscillator used as the 50.1 MHz master oscillator 10 and 50.125 MHz local oscillator 14. The oscillator crystals are neutralized for operation in the fundamental resonance mode; this achieves long-term stability. Both oscillators are thermally coupled so WO94/21173 PCT~S94/02764 ~843~
that their frequency difference is maintained constant at 25 kHz if a frequency drift occurs.
PIN diodes 24a, 24b, and 24c are directly connected to their respective preamplifiers 30a, 30b, and 5 30c, as shown in FIG. 3. The oximeter uses PIN silicon photodiodes S1723-04 with 10mm x 10mm sensitive area and spectral response in the range of 320 nm to 1060 nm. The detection signal is amplified by stages 29 and 31, each providing about 20 dB amplification. The NE5205N
10 operational amplifier is powered at ~8V to operate in a high gain regime. The 8V signal is supplied by a voltage regulator 33. The amplified detection signals (32a, 32b, and 32c) are sent to magnitude detectors 36a, 36b, and 36c, shown in FIG. 4. The magnitude values (37a, 37b, 15 and 37c) are sent to processor 70 that calculates the light attenuation ratio or logarithm thereof as shown E~.
1.
Also referring to FIG. 5, the AGC circuit uses MC
1350 integrated circuit for amplification that maintains 20 the input signal of phase detector 60 at substantially constant levels. The amount of gain is selected to be equal for AGCs, 50 and 52. The signal amplitude is controlled by a feedback network 53. The AGCs provide a substantially constant amplitude of the detected and 25 reference signals to eliminate variations in the detected phase shift due to cross talk between amplitude and phase changes in the phase detector.
Referring to FIG. 6, each phase detector includes a Schmitt trigger that converts the substantially 30 sinusoidal detection signal (54a, 54b, 54c) and reference signal (56a, 56b, 56c) to square waves. The square waves are input to a detector that has complementary MOS
silicon-gate transistors. The phase shift signal is sent - to processor 70.
WO94/21173 PCT~S94/02764 The oximeter is calibrated by measuring the phase shift for a selected distance in a known medium, i.e., using a standard delay unit, and by switching the length of a connector wire to change the electrical delay 5 between master oscillator 10 and local oscillator 14.
Referring to FIGs. 8A and 8B source-detector probe 20 includes several LEDs (22a, 22b, 22c) of selected wavelengths and PIN photodiodes (24a, 24b, 24c) mounted in a body-conformable support structure 21. Structure 21 10 also includes a photon escape barrier 27 made of a material with selected scattering and absorption properties (for example, styrofoam) designed to return escaping photons back to the ~r; ned tissue. The support structure further includes a second conformable 15 barrier 28, located between the LEDs and the diode detectors, designed to absorb photons directly propagating from the source to the detector and thus prevent detection of photons that migrate subcutaneously.
Support structure 21 also includes electronic circuitry 20 29 encapsulated by an electronic shield 21a.
Each PIN diode is provided with an evaporated single wavelength film filter (25a, 25b, 25c). The filters eliminate the cross talk of different wavelength signals and allow continuous operation of the three light 25 sources, i.e., no time sharing is needed.
The use of photodiode detectors has substantial advantages when compared with the photomultiplier tube used in standard phase modulation systems. The photodiodes are placed directly on the skin, i.e., no 30 optical fibers are needed. Furthermore, there is no need to use a high voltage power supply that is necessary for the photomultiplier tube. The photodiodes are much smaller and are easy to place close to the skin.
Advantages of the photomultiplier tube are a huge 35 multiplication gain and a possibility of direct mixing at WO94/21173 ~ 5 ~ 4 ~ 5 PCT~S94/027 the photomultiplier; this cannot be achieved directly by a photodiode. This invention envisions the use of several different photodiodes such as PIN diode, avalanche diode, and other.
The processor uses algorithms that are based on equations described by E.M. Sevick et al. in "Quantitation of Time- and Frequency-Resolved Optical Spectra for the Determination of Tissue Oxygenation"
published in Analytical Biochemistry 195, 330 April 15, 10 1991 which is incorporated by reference as if fully set forth herein.
At each wavelength, the phase shift (e~) (62a, 62b, 62c) is used to calculate the pathlength as follows:
~A = tan~1~c f (tA) = tan-l 2~f(LA) s~ 2~ f (LA) ~2) C C
wherein f is modulation frequency of the illL~ ced light 15 which is in the range of 10 MHz to 100 MHz; t~ is the photon migration delay time; c is the speed of photons in the scattering medium; and L~ is the migration pathlength.
Equation (2) is valid at low modulation 20 frequencies, i.e., 2~f << ~a c. The modulation frequency of 50 MHz was selected due to the frequency limitation of the LEDs and photodiodes. However, for faster LEDs and photodiodes it may be desirable to use higher modulation frequencies that increase the phase shift. At high 25 modulation frequencies, i.e., 2~f >> ~a c, the phase shift is no longer proportional to the mean time of flight <t>.
WO94/21173 PCT~S94102764 ~A = ap~-g) ~6 f~1 - 4 f} (3) wherein p is the source-detector separation; (1-g) ~ is effective scattering coefficient; f is modulation frequency and ~a~ is absorption coefficient at wavelength ~.
5 At two wavelength, the ratio of absorption coefficients is determined as follows:
~11 a~ o1 (4) ~ 2 ~Az ~l2 wherein ~0~ represents background scattering and absorption.
The wavelengths are in the visible and infra-red 10 range and are selected to have absorbance sensitive (or insensitive) to various tissue components such as water, cytochrome iron and copper, oxy- and deoxygenated forms of hemoglobin, myoglobin, melanin, glucose and other.
For oxygenated and deoxygenated hemoblogin, the 15 absorption coefficient written in terms of Beer Lambert relationship is as follows:
~b [Hb] + ~bO [HbO2] + 1 ~5) wherein ~Hb~1 and ~HbO~l are extinction coefficients for hemoglobin and deoxyhemoglobin that can be stored in a look up table; tHb], [HbO2] are the tissue concentration 20 of hemoglobin and oxyhemoglobin, respectively; ~1 is background absorbance. The hemoglobin saturation is conventionally defined as follows:
WO94/21173 ~ 1~ g~ ~ PCT~S94/02764 y [HbO2] (6) For a three wavelength measurement, the hemoglobin saturation can be calculated using Eqs. (5) and (6) as follows:
y _ a(~-~) _ (~A _ ~A2) [(~ ~ -~ ~ )-(~-~)]-a[(~ ~)]
where ~,~Al _ ~A~
a - A~ A~
l~n ~ 1~
5 Thus, processor 70 determines Y based on Eq. (7) using Eq. (2) to determine the average migration pathlength L
that is then used in Eq. (1) and to determine ~a~ for each wavelength Al, ~2~ A3.
In another embodiment, the spectrophotometer's 10 electronics includes a low fre~uency module suitably and a high frequency module switchably coupled to the same source-detector probe 20. The low frequency module and the arrangement of the source-detector probe are substantially similar to the hemoglobinometer described 15 in a copending U.S. Patent Application Ser. No. 701,127 filed May 16, 1991 which is incorporated by reference as if fully set forth herein. The low frequency module corresponds to a st~n~rd oximeter with modulation frequencies in the range of a few hertz to 104 hertz and 20 is adapted to provide intensity attenuation data at two or three wavelengths. Then, the LEDs are switched to the high frequency phase modulation unit, similar to the unit of FIG. 1, which determines the average pathlength at each wavelength. The attenuation and pathlength data are WO94/21173 PCT~S94102764 sent to processor 70 for determination of a physiological property of the ~ ;ned tissue.
In another embodiment, the pathlength corrected oximeter utilizes the same LED sources (22a, 22b, 22c) 5 sinusoidally modulated at a selected frequency comparable to the average migration time of photons scattered in the ~ ;ned tissue on paths from the optical input port of the LED's to the optical detection part of the photodiode detectors (24a, 24b, 24c), but the electronic circuitry 10 is different. The detector output is put through two wide band double balance mixers (DBM) which are coupled through a 90 phase splitter so that real (R) and imaginary (I) portions of the signal are obtained. The double balance mixers preferably operate at the 15 modulation frequency. The phase (~) is the angle whose tangent is the imaginary over the real part.
~A = tan~ ( 8 ) The amplitude is the square root of the sum of the squares of these values, providing the phase shift has been taken out as the residual phase shift ~ set to zero.
AA = ~/(RA)2 + (I~)2 (9~
This embodiment uses summing and dividing circuits to calculate the modulation index, which is the quotient of the amplitude over the amplitude plus the DC component obtained from a narrow band detector.
wo 94~21173 2 ~ ~ 8 ~ 3 ~ PCT~S94/02764 A A ( 1 0 ) A + DC
- The phase processor receives the phase shifts for the phase and amplitude values for two or three wavelengths and calculates the ratio of the phase shifts.
For each wavelength, the phase shift and the DC
5 amplitude are used to determine a selected tissue property, e.g., hemoglobin oxygenation.
Additional embodiments are within the following claims:
Claims (21)
- CLAIMS: 1. A spectrophotometer for tissue examination utilizing a measured average pathlength of migrating photons, comprising:
an oscillator adapted to generate a carrier waveform of a selected frequency comparable to an average migration time of photons scattered in tissue on paths from an optical input port to an optical detection port;
a light source, operatively connected to said oscillator, adapted to generate light of a selected wavelength that is intensity modulated at said frequency, said light being introduced to a subject at said input port;
a photodiode detector adapted to detect, at said detection port, light of said wavelength that has migrated in said tissue of the subject between said input and detection ports;
a phase detector, operatively connected to receive signals from said oscillator and said diode detector, adapted to measure a phase shift between said introduced and said detected light;
a processor adapted to determine said pathlength based on said phase shift; and said processor further adapted to determine a physiological property of the examined tissue based on said pathlength. - 2. A spectrophotometer for tissue examination utilizing a measured average pathlength of migrating photons, comprising:
an oscillator adapted to generate a carrier waveform of a selected frequency comparable to an average migration time of photons scattered in tissue on paths from an optical input port to an optical detection port;
a light source, operatively connected to said oscillator, adapted to generate light of a selected wavelength that is intensity modulated at said frequency, said light being introduced to a subject at said input port;
a photodiode detector adapted to detect, at said detection port, light of said wavelength that has migrated in said tissue of the subject between said input and detection ports;
a phase splitter adapted to produce, based on said carrier waveform, first and second reference phase signals of predefined substantially different phase;
first and second double balanced mixers adapted to correlate said reference phase signals and signals of said detected radiation to produce therefrom a real output signal and an imaginary output signal, respectively;
a processor adapted to determine, on the basis of said real output signal and said imaginary output signal, a phase shift between said introduced light and said detected light; and said processor further adapted to determine a physiological property of the examined tissue based on said phase shift. - 3. A spectrophotometer for tissue examination utilizing a measured average pathlength of migrating photons, comprising:
a first oscillator adapted to generate a carrier waveform of a first selected frequency comparable to an average migration time of photons scattered in tissue on paths from an optical input port to an optical detection port;
a light source, operatively connected to said oscillator, adapted to generate light of a selected wavelength that is intensity modulated at said first frequency, said light being introduced to a subject at said input port;
a photodiode detector adapted to detect, at said detection port, light of said wavelength that has migrated in said tissue of the subject between said input and detection ports, said detector producing a detection signal at said first frequency corresponding to said detected light;
a second oscillator adapted to generate a carrier waveform of a second frequency that is offset on the order of 104Hz from said first frequency;
a reference mixer, connected to said first and second oscillators, adapted to generate a reference signal of a frequency approximately equal to the difference between said first and second frequencies;
a mixer connected to receive signals from said second oscillator and said detection signal and adapted to convert said detection signal to said difference frequency;
a phase detector, operatively connected to receive signals from said reference mixer and said converted detection signal, adapted to measure a phase shift between said introduced light and said detected light, a processor adapted to determine said pathlength based on said phase shift; and said processor further adapted to determine a physiological property of the examined tissue based on said pathlength. - 4. The spectrophotometer of claims 1, 2 or 3 further comprising:
a magnitude detector, connected to said photodiode detector, adapted to measure magnitude of said detected light, and said processor further adapted to receive said magnitude for determination of said physiological property. - 5. The spectrophotometer of claims 1, 2 or 3 further comprising:
a low frequency oximeter circuit, switchably connected to said source and said photodiode, adapted to determine absorption of light at said wavelength; and said processor further adapted to receive absorption values from said oximeter circuit for determination of said physiological property. - 6. The spectrophotometer of claims 1 or 3 further comprising two automatic gain controls adapted to level signals corresponding to said introduced light and said detected light, both said leveled signals being introduced to said phase detector.
- 7. The spectrophotometer of claims 1 or 3 further comprising:
a magnitude detector, connected to said photodiode detector, adapted to measure magnitude of said detected light, and two automatic gain controls adapted to level signals corresponding to said introduced light and said detected light, both said leveled signals being introduced to said phase detector. - 8. The spectrophotometer of claims 1, 2 or 3 wherein said light source is a light emitting diode and said selected wavelength is in the visible or infra-red range.
- 9. The spectrophotometer of claims 1, 2 or 3 wherein said photodiode detector is a PIN diode.
- 10. The spectrophotometer of claims 1, 2 or 3 wherein said photodiode detector is an avalanche diode.
- 11. The spectrophotometer of claims 1, 2 or 3 wherein said photodiode detector further comprises a substantially single wavelength filter.
- 12. The spectrophotometer of claims 1, 2 or 3 further comprising:
a second light source, operatively connected to said oscillator, adapted to generate light of a second selected wavelength that is intensity modulated at said first frequency, said radiation being introduced to a subject at a second input port;
said photodiode detector further adapted to detect alternately, at said detection port, light of said first and second wavelengths that have migrated in said tissue of the subject between the first and said second input ports and said detection port, respectively;
said phase detector further adapted to receive alternately signals corresponding to said detected first and second wavelengths; and said processor further adapted to receive alternately phase shifts from said phase detector, said phase shifts being subsequently used for determination of said physiological property. - 13. The spectrophotometer of claim 12 further comprising:
a magnitude detector, connected to said photodiode detector, adapted to measure magnitude of said detected light at each of said wavelengths, and said processor further adapted to receive said magnitudes for determination of said physiological property. - 14. The spectrophotometer of claims 1 or 3 further comprising:
a second light source, operatively connected to said oscillator, adapted to generate light of a second selected wavelength that is intensity modulated at said first frequency, said radiation being introduced to a subject at a second input port;
a second photodiode detector adapted to detect, at a second detection port, light of said second wavelength that has migrated in said tissue of the subject between said second input port and said second detection port, respectively;
a second phase detector, operatively connected to receive a reference signal and a detection signal from said third diode detector, adapted to measure a phase shift between said introduced and said detected light at said second wavelength; and said processor further adapted to receive a second phase shift at said second wavelength, said first and second phase shifts being subsequently used for determination of said physiological property. - 15. The spectrophotometer of claim 14 further comprising:
a first and a second magnitude detector connected to said first and second photodiode detectors, respectively, said magnitude detectors being adapted to measure magnitude of said detected light at each of said wavelengths, and said processor further adapted to receive said magnitudes for determination of said physiological property. - 16. The spectrophotometer of claims 14 further comprising:
a third light source, operatively connected to said oscillator, adapted to generate light of a third selected wavelength that is intensity modulated at said first frequency, said radiation being introduced to a subject at a third input port;
a third photodiode detector adapted to detect, at a third detection port, light of said third wavelength that has migrated in said tissue of the subject between said third input port and said third detection port, respectively;
a third phase detector, operatively connected to receive a reference signal and a detection signal from said third diode detector, adapted to measure a phase shift between said introduced and said detected light at said third wavelength; and said processor further adapted to receive phase shifts from said phase detector, said first second and third phase shifts being subsequently used for determination of said physiological property. - 17. The spectrophotometer of claim 14 further comprising:
a first, a second and a third magnitude detector connected to said first, second and third photodiode detectors, respectively, said magnitude detectors being adapted to measure magnitude of said detected light at each of said wavelengths; and said processor further adapted to receive said magnitudes for determination of said physiological property. - 18. The spectrophotometer of claim 16 wherein each said light source is a light emitting diode and said selected wavelength is in the visible or infra-red range.
- 19. The spectrophotometer of claim 16 wherein each said photodiode detector is a PIN diode.
- 20. The spectrophotometer of claim 16 wherein each said photodiode detector is an avalanche diode.
- 21. The spectrophotometer of claim 16 wherein each said photodiode detector further comprises a substantially single wavelength filter.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/031,945 | 1993-03-16 | ||
US08/031,945 US5564417A (en) | 1991-01-24 | 1993-03-16 | Pathlength corrected oximeter and the like |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2158435A1 true CA2158435A1 (en) | 1994-09-29 |
Family
ID=21862239
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002158435A Abandoned CA2158435A1 (en) | 1993-03-16 | 1994-03-15 | Pathlength corrected oximeter and the like |
Country Status (7)
Country | Link |
---|---|
US (2) | US5564417A (en) |
EP (1) | EP0689398B1 (en) |
JP (1) | JPH08509880A (en) |
CN (1) | CN1089571C (en) |
CA (1) | CA2158435A1 (en) |
DE (1) | DE69433205T2 (en) |
WO (1) | WO1994021173A1 (en) |
Families Citing this family (299)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6671540B1 (en) | 1990-08-10 | 2003-12-30 | Daryl W. Hochman | Methods and systems for detecting abnormal tissue using spectroscopic techniques |
US6246892B1 (en) | 1991-01-24 | 2001-06-12 | Non-Invasive Technology | Phase modulation spectroscopy |
US5492118A (en) | 1993-12-16 | 1996-02-20 | Board Of Trustees Of The University Of Illinois | Determining material concentrations in tissues |
US5758644A (en) * | 1995-06-07 | 1998-06-02 | Masimo Corporation | Manual and automatic probe calibration |
US5797841A (en) * | 1996-03-05 | 1998-08-25 | Nellcor Puritan Bennett Incorporated | Shunt barrier in pulse oximeter sensor |
US7190984B1 (en) * | 1996-03-05 | 2007-03-13 | Nellcor Puritan Bennett Incorporated | Shunt barrier in pulse oximeter sensor |
FI962448A (en) * | 1996-06-12 | 1997-12-13 | Instrumentarium Oy | Method, apparatus and sensor for the determination of fractional oxygen saturation |
US6018673A (en) | 1996-10-10 | 2000-01-25 | Nellcor Puritan Bennett Incorporated | Motion compatible sensor for non-invasive optical blood analysis |
US9042952B2 (en) | 1997-01-27 | 2015-05-26 | Lawrence A. Lynn | System and method for automatic detection of a plurality of SPO2 time series pattern types |
US8932227B2 (en) | 2000-07-28 | 2015-01-13 | Lawrence A. Lynn | System and method for CO2 and oximetry integration |
US20060161071A1 (en) | 1997-01-27 | 2006-07-20 | Lynn Lawrence A | Time series objectification system and method |
US9521971B2 (en) | 1997-07-14 | 2016-12-20 | Lawrence A. Lynn | System and method for automatic detection of a plurality of SPO2 time series pattern types |
US20070191697A1 (en) | 2006-02-10 | 2007-08-16 | Lynn Lawrence A | System and method for SPO2 instability detection and quantification |
US6055451A (en) | 1997-12-12 | 2000-04-25 | Spectrx, Inc. | Apparatus and method for determining tissue characteristics |
EP1054618B1 (en) * | 1998-02-11 | 2006-12-20 | Non-Invasive Technology, Inc. | Detection, imaging and characterization of breast tumors |
EP1054619B1 (en) * | 1998-02-11 | 2007-11-21 | Non-Invasive Technology, Inc. | Imaging and characterization of brain tissue |
JP2002502654A (en) * | 1998-02-13 | 2002-01-29 | ノン−インヴェイシヴ テクノロジイ,インク. | Cross-abdominal examination, monitoring and imaging of tissue |
US20070167704A1 (en) * | 1998-02-13 | 2007-07-19 | Britton Chance | Transabdominal examination, monitoring and imaging of tissue |
US6078833A (en) * | 1998-03-25 | 2000-06-20 | I.S.S. (Usa) Inc. | Self referencing photosensor |
US6949081B1 (en) * | 1998-08-26 | 2005-09-27 | Non-Invasive Technology, Inc. | Sensing and interactive drug delivery |
US6144444A (en) * | 1998-11-06 | 2000-11-07 | Medtronic Avecor Cardiovascular, Inc. | Apparatus and method to determine blood parameters |
WO2000028887A1 (en) * | 1998-11-18 | 2000-05-25 | Alfons Krug | Device for non-invasively detecting the oxygen metabolism in tissues |
US6675031B1 (en) | 1999-04-14 | 2004-01-06 | Mallinckrodt Inc. | Method and circuit for indicating quality and accuracy of physiological measurements |
DE19922772A1 (en) | 1999-05-18 | 2001-02-08 | Phiscience Gmbh Entwicklung Vo | Device for determining various blood flow conditions and oxygen saturation in blood-bearing tissue |
EP1218023B8 (en) | 1999-10-01 | 2006-05-03 | Johnson & Johnson Consumer Companies, Inc. | Method for calming human beings using personal care compositions |
US6736759B1 (en) * | 1999-11-09 | 2004-05-18 | Paragon Solutions, Llc | Exercise monitoring system and methods |
US7006676B1 (en) | 2000-01-21 | 2006-02-28 | Medical Optical Imaging, Inc. | Method and apparatus for detecting an abnormality within a host medium utilizing frequency-swept modulation diffusion tomography |
US6577884B1 (en) | 2000-06-19 | 2003-06-10 | The General Hospital Corporation | Detection of stroke events using diffuse optical tomagraphy |
US8224412B2 (en) | 2000-04-17 | 2012-07-17 | Nellcor Puritan Bennett Llc | Pulse oximeter sensor with piece-wise function |
PT2322085E (en) | 2000-04-17 | 2014-06-23 | Covidien Lp | Pulse oximeter sensor with piece-wise function |
WO2002032335A1 (en) | 2000-07-25 | 2002-04-25 | Rita Medical Systems Inc. | Apparatus for detecting and treating tumors using localized impedance measurement |
US6801648B2 (en) | 2000-08-04 | 2004-10-05 | Xuefeng Cheng | Optical imaging system with symmetric optical probe |
US6597931B1 (en) | 2000-09-18 | 2003-07-22 | Photonify Technologies, Inc. | System and method for absolute oxygen saturation |
US6516209B2 (en) | 2000-08-04 | 2003-02-04 | Photonify Technologies, Inc. | Self-calibrating optical imaging system |
US6587703B2 (en) | 2000-09-18 | 2003-07-01 | Photonify Technologies, Inc. | System and method for measuring absolute oxygen saturation |
US6889153B2 (en) * | 2001-08-09 | 2005-05-03 | Thomas Dietiker | System and method for a self-calibrating non-invasive sensor |
US6719686B2 (en) * | 2000-08-30 | 2004-04-13 | Mallinckrodt, Inc. | Fetal probe having an optical imaging device |
US20020151527A1 (en) * | 2000-12-20 | 2002-10-17 | Benjamin Wiegand | Method for reducing acne or improving skin tone |
US20020146469A1 (en) * | 2000-12-20 | 2002-10-10 | Benjamin Wiegand | Methods for reducing chronic stress in mammals |
US9053222B2 (en) | 2002-05-17 | 2015-06-09 | Lawrence A. Lynn | Patient safety processor |
US20090281838A1 (en) | 2008-05-07 | 2009-11-12 | Lawrence A. Lynn | Medical failure pattern search engine |
US20060195041A1 (en) | 2002-05-17 | 2006-08-31 | Lynn Lawrence A | Centralized hospital monitoring system for automatically detecting upper airway instability and for preventing and aborting adverse drug reactions |
AU2002255568B8 (en) | 2001-02-20 | 2014-01-09 | Adidas Ag | Modular personal network systems and methods |
SE0101004D0 (en) | 2001-03-21 | 2001-03-21 | Astrazeneca Ab | New measuring technique |
DE60219454T2 (en) * | 2001-04-05 | 2007-07-19 | Agilent Technologies Inc., Santa Clara | DETERMINATION OF OPTICAL PROPERTIES USING THE SIGNAL DIFFERENCES CAUSED BY THE MODULATED LASER SIGNALS |
US20070276199A1 (en) * | 2002-04-04 | 2007-11-29 | Ediger Marwood N | Determination of a Measure of a Glycation End-Product or Disease State Using Tissue Fluorescence |
US6659941B2 (en) * | 2001-06-19 | 2003-12-09 | Mallinckrodt, Inc. | Balloon assisted endoscope for viewing a fetus during delivery |
US6754516B2 (en) | 2001-07-19 | 2004-06-22 | Nellcor Puritan Bennett Incorporated | Nuisance alarm reductions in a physiological monitor |
US6994706B2 (en) | 2001-08-13 | 2006-02-07 | Minnesota Medical Physics, Llc | Apparatus and method for treatment of benign prostatic hyperplasia |
US20050203578A1 (en) * | 2001-08-15 | 2005-09-15 | Weiner Michael L. | Process and apparatus for treating biological organisms |
US6748254B2 (en) | 2001-10-12 | 2004-06-08 | Nellcor Puritan Bennett Incorporated | Stacked adhesive optical sensor |
US7022072B2 (en) * | 2001-12-27 | 2006-04-04 | Medtronic Minimed, Inc. | System for monitoring physiological characteristics |
GB2384563A (en) | 2002-01-29 | 2003-07-30 | Johnson & Johnson Consumer | Method of measuring the stress or relaxation level of a mammal |
GB0203045D0 (en) * | 2002-02-08 | 2002-03-27 | Johnson & Johnson Consumer | Method of afefecting sleep and sleep-related behaviours |
US20080009689A1 (en) * | 2002-04-09 | 2008-01-10 | Benaron David A | Difference-weighted somatic spectroscopy |
US20070015981A1 (en) * | 2003-08-29 | 2007-01-18 | Benaron David A | Device and methods for the detection of locally-weighted tissue ischemia |
US6711426B2 (en) * | 2002-04-09 | 2004-03-23 | Spectros Corporation | Spectroscopy illuminator with improved delivery efficiency for high optical density and reduced thermal load |
JP3602111B2 (en) * | 2002-05-07 | 2004-12-15 | 株式会社日立製作所 | Biological light measurement device |
EP1513440A2 (en) * | 2002-05-30 | 2005-03-16 | The Board of Trustees of The Leland Stanford Junior University | Apparatus and method for coronary sinus access |
US8956280B2 (en) | 2002-05-30 | 2015-02-17 | Intuitive Surgical Operations, Inc. | Apparatus and methods for placing leads using direct visualization |
AU2003253669A1 (en) * | 2002-07-17 | 2004-02-09 | Equine Biomechanics And Exercise Physiology, Inc. | Echocardiographic measurements as predictors of racing succes |
US7087075B2 (en) | 2002-09-30 | 2006-08-08 | Medtronic Emergency Response Systems, Inc. | Feedback system for rapid induction of mild hypothermia |
US7179279B2 (en) | 2002-09-30 | 2007-02-20 | Medtronic Physio Control Corp. | Rapid induction of mild hypothermia |
US7289837B2 (en) | 2002-10-01 | 2007-10-30 | Nellcor Puritan Bennett Incorpoated | Forehead sensor placement |
US7698909B2 (en) | 2002-10-01 | 2010-04-20 | Nellcor Puritan Bennett Llc | Headband with tension indicator |
US7190986B1 (en) | 2002-10-18 | 2007-03-13 | Nellcor Puritan Bennett Inc. | Non-adhesive oximeter sensor for sensitive skin |
US7056282B2 (en) | 2002-12-23 | 2006-06-06 | Medtronic Emergency Response Systems, Inc. | Coolant control for rapid induction of mild hypothermia |
US7006856B2 (en) | 2003-01-10 | 2006-02-28 | Nellcor Puritan Bennett Incorporated | Signal quality metrics design for qualifying data for a physiological monitor |
US7016715B2 (en) | 2003-01-13 | 2006-03-21 | Nellcorpuritan Bennett Incorporated | Selection of preset filter parameters based on signal quality |
CA2515439A1 (en) * | 2003-02-07 | 2004-08-26 | Ramez Emile Necola Shehada | Surgical drain with sensors for monitoring internal tissue condition and for monitoring fluid in lumen |
US20040175438A1 (en) * | 2003-03-03 | 2004-09-09 | Benjamin Wiegand | Methods for alleviating symptoms associated with menopause using sensory regimen |
DE10321338A1 (en) * | 2003-05-13 | 2004-12-02 | MCC Gesellschaft für Diagnosesysteme in Medizin und Technik mbH & Co. KG | Method and device for determining blood components using the method of ratiometric absolute pulse spectroscopy |
GB2403148C2 (en) | 2003-06-23 | 2013-02-13 | Microsulis Ltd | Radiation applicator |
US7047056B2 (en) | 2003-06-25 | 2006-05-16 | Nellcor Puritan Bennett Incorporated | Hat-based oximeter sensor |
US8412297B2 (en) | 2003-10-01 | 2013-04-02 | Covidien Lp | Forehead sensor placement |
AU2004277760B2 (en) * | 2003-10-03 | 2011-09-29 | Academisch Medisch Centrum | System and method for imaging the reflectance of a substrate |
ATE556654T1 (en) * | 2003-12-30 | 2012-05-15 | Univ Florida | NEW SPECIALLY CONFIGURED NASAL PULSE OXYMETER |
US7120479B2 (en) | 2004-02-25 | 2006-10-10 | Nellcor Puritan Bennett Inc. | Switch-mode oximeter LED drive with a single inductor |
US7190985B2 (en) | 2004-02-25 | 2007-03-13 | Nellcor Puritan Bennett Inc. | Oximeter ambient light cancellation |
US7194293B2 (en) | 2004-03-08 | 2007-03-20 | Nellcor Puritan Bennett Incorporated | Selection of ensemble averaging weights for a pulse oximeter based on signal quality metrics |
US8611977B2 (en) * | 2004-03-08 | 2013-12-17 | Covidien Lp | Method and apparatus for optical detection of mixed venous and arterial blood pulsation in tissue |
US7534212B2 (en) | 2004-03-08 | 2009-05-19 | Nellcor Puritan Bennett Llc | Pulse oximeter with alternate heart-rate determination |
US7277741B2 (en) | 2004-03-09 | 2007-10-02 | Nellcor Puritan Bennett Incorporated | Pulse oximetry motion artifact rejection using near infrared absorption by water |
US8060172B2 (en) | 2004-03-29 | 2011-11-15 | Olympus Corporation | In-vivo information measurement apparatus |
GB2415630C2 (en) | 2004-07-02 | 2007-03-22 | Microsulis Ltd | Radiation applicator and method of radiating tissue |
US20060241364A1 (en) * | 2004-10-01 | 2006-10-26 | Academisch Medisch Centrum Of The University Van Amsterdam | System and method for imaging the reflectance of a substrate |
US9131861B2 (en) | 2004-11-30 | 2015-09-15 | Academisch Medisch Centrum | Pulsed lighting imaging systems and methods |
US20060181482A1 (en) * | 2005-02-03 | 2006-08-17 | Iaquinto John M | Apparatus for providing visual data during an operation |
US20120209086A1 (en) * | 2005-02-17 | 2012-08-16 | Q Pidt B.V. | Apparatus and methods for measuring blood flow within the gastrointestinal tract |
US7392075B2 (en) | 2005-03-03 | 2008-06-24 | Nellcor Puritan Bennett Incorporated | Method for enhancing pulse oximetry calculations in the presence of correlated artifacts |
GB2424270A (en) * | 2005-03-14 | 2006-09-20 | Spectrum Medical Llp | Optical monitoring of predetermined substances in blood |
WO2006121833A2 (en) * | 2005-05-06 | 2006-11-16 | Infrascan Inc. | System and method for detection of hematoma |
GB2434314B (en) | 2006-01-03 | 2011-06-15 | Microsulis Ltd | Microwave applicator with dipole antenna |
US7813778B2 (en) * | 2005-07-29 | 2010-10-12 | Spectros Corporation | Implantable tissue ischemia sensor |
US7590439B2 (en) | 2005-08-08 | 2009-09-15 | Nellcor Puritan Bennett Llc | Bi-stable medical sensor and technique for using the same |
US7657295B2 (en) | 2005-08-08 | 2010-02-02 | Nellcor Puritan Bennett Llc | Medical sensor and technique for using the same |
US7657294B2 (en) | 2005-08-08 | 2010-02-02 | Nellcor Puritan Bennett Llc | Compliant diaphragm medical sensor and technique for using the same |
US7736382B2 (en) * | 2005-09-09 | 2010-06-15 | Lockheed Martin Corporation | Apparatus for optical stimulation of nerves and other animal tissue |
US20070060808A1 (en) | 2005-09-12 | 2007-03-15 | Carine Hoarau | Medical sensor for reducing motion artifacts and technique for using the same |
US7725146B2 (en) | 2005-09-29 | 2010-05-25 | Nellcor Puritan Bennett Llc | System and method for pre-processing waveforms |
US7899510B2 (en) | 2005-09-29 | 2011-03-01 | Nellcor Puritan Bennett Llc | Medical sensor and technique for using the same |
US8092379B2 (en) | 2005-09-29 | 2012-01-10 | Nellcor Puritan Bennett Llc | Method and system for determining when to reposition a physiological sensor |
US7904130B2 (en) | 2005-09-29 | 2011-03-08 | Nellcor Puritan Bennett Llc | Medical sensor and technique for using the same |
US7725147B2 (en) | 2005-09-29 | 2010-05-25 | Nellcor Puritan Bennett Llc | System and method for removing artifacts from waveforms |
US7869850B2 (en) | 2005-09-29 | 2011-01-11 | Nellcor Puritan Bennett Llc | Medical sensor for reducing motion artifacts and technique for using the same |
US7555327B2 (en) | 2005-09-30 | 2009-06-30 | Nellcor Puritan Bennett Llc | Folding medical sensor and technique for using the same |
US8062221B2 (en) | 2005-09-30 | 2011-11-22 | Nellcor Puritan Bennett Llc | Sensor for tissue gas detection and technique for using the same |
US7881762B2 (en) | 2005-09-30 | 2011-02-01 | Nellcor Puritan Bennett Llc | Clip-style medical sensor and technique for using the same |
US7483731B2 (en) | 2005-09-30 | 2009-01-27 | Nellcor Puritan Bennett Llc | Medical sensor and technique for using the same |
US7486979B2 (en) | 2005-09-30 | 2009-02-03 | Nellcor Puritan Bennett Llc | Optically aligned pulse oximetry sensor and technique for using the same |
US8233954B2 (en) | 2005-09-30 | 2012-07-31 | Nellcor Puritan Bennett Llc | Mucosal sensor for the assessment of tissue and blood constituents and technique for using the same |
US20070106126A1 (en) | 2005-09-30 | 2007-05-10 | Mannheimer Paul D | Patient monitoring alarm escalation system and method |
US20070093717A1 (en) * | 2005-10-20 | 2007-04-26 | Glucon Inc. | Wearable glucometer configurations |
US8929973B1 (en) | 2005-10-24 | 2015-01-06 | Lockheed Martin Corporation | Apparatus and method for characterizing optical sources used with human and animal tissues |
US8956396B1 (en) | 2005-10-24 | 2015-02-17 | Lockheed Martin Corporation | Eye-tracking visual prosthetic and method |
US8012189B1 (en) | 2007-01-11 | 2011-09-06 | Lockheed Martin Corporation | Method and vestibular implant using optical stimulation of nerves |
US20080077200A1 (en) | 2006-09-21 | 2008-03-27 | Aculight Corporation | Apparatus and method for stimulation of nerves and automated control of surgical instruments |
US8792978B2 (en) | 2010-05-28 | 2014-07-29 | Lockheed Martin Corporation | Laser-based nerve stimulators for, E.G., hearing restoration in cochlear prostheses and method |
US8945197B1 (en) | 2005-10-24 | 2015-02-03 | Lockheed Martin Corporation | Sight-restoring visual prosthetic and method using infrared nerve-stimulation light |
US8744570B2 (en) | 2009-01-23 | 2014-06-03 | Lockheed Martin Corporation | Optical stimulation of the brainstem and/or midbrain, including auditory areas |
US8709078B1 (en) | 2011-08-03 | 2014-04-29 | Lockheed Martin Corporation | Ocular implant with substantially constant retinal spacing for transmission of nerve-stimulation light |
US8475506B1 (en) | 2007-08-13 | 2013-07-02 | Lockheed Martin Corporation | VCSEL array stimulator apparatus and method for light stimulation of bodily tissues |
US20070100220A1 (en) | 2005-10-28 | 2007-05-03 | Baker Clark R Jr | Adjusting parameters used in pulse oximetry analysis |
US7606606B2 (en) * | 2005-12-27 | 2009-10-20 | General Electric Company | Patient monitoring device with multiple sensors |
US20070149864A1 (en) * | 2005-12-27 | 2007-06-28 | Marko Laakkonen | Monitoring device for multiple tissue sites |
US7668579B2 (en) | 2006-02-10 | 2010-02-23 | Lynn Lawrence A | System and method for the detection of physiologic response to stimulation |
US8702606B2 (en) | 2006-03-21 | 2014-04-22 | Covidien Lp | Patient monitoring help video system and method |
US8073518B2 (en) | 2006-05-02 | 2011-12-06 | Nellcor Puritan Bennett Llc | Clip-style medical sensor and technique for using the same |
US10188348B2 (en) | 2006-06-05 | 2019-01-29 | Masimo Corporation | Parameter upgrade system |
US8380271B2 (en) | 2006-06-15 | 2013-02-19 | Covidien Lp | System and method for generating customizable audible beep tones and alarms |
WO2008002405A2 (en) * | 2006-06-16 | 2008-01-03 | Medtor Llc | System and method for a non-invasive medical sensor |
US8145288B2 (en) | 2006-08-22 | 2012-03-27 | Nellcor Puritan Bennett Llc | Medical sensor for reducing signal artifacts and technique for using the same |
US8219170B2 (en) | 2006-09-20 | 2012-07-10 | Nellcor Puritan Bennett Llc | System and method for practicing spectrophotometry using light emitting nanostructure devices |
US8064975B2 (en) | 2006-09-20 | 2011-11-22 | Nellcor Puritan Bennett Llc | System and method for probability based determination of estimated oxygen saturation |
US8175671B2 (en) | 2006-09-22 | 2012-05-08 | Nellcor Puritan Bennett Llc | Medical sensor for reducing signal artifacts and technique for using the same |
US8190224B2 (en) | 2006-09-22 | 2012-05-29 | Nellcor Puritan Bennett Llc | Medical sensor for reducing signal artifacts and technique for using the same |
US8396527B2 (en) | 2006-09-22 | 2013-03-12 | Covidien Lp | Medical sensor for reducing signal artifacts and technique for using the same |
US7869849B2 (en) | 2006-09-26 | 2011-01-11 | Nellcor Puritan Bennett Llc | Opaque, electrically nonconductive region on a medical sensor |
US7574245B2 (en) | 2006-09-27 | 2009-08-11 | Nellcor Puritan Bennett Llc | Flexible medical sensor enclosure |
US8696593B2 (en) | 2006-09-27 | 2014-04-15 | Covidien Lp | Method and system for monitoring intracranial pressure |
US7890153B2 (en) | 2006-09-28 | 2011-02-15 | Nellcor Puritan Bennett Llc | System and method for mitigating interference in pulse oximetry |
US7922665B2 (en) | 2006-09-28 | 2011-04-12 | Nellcor Puritan Bennett Llc | System and method for pulse rate calculation using a scheme for alternate weighting |
US8498699B2 (en) * | 2008-10-03 | 2013-07-30 | Lockheed Martin Company | Method and nerve stimulator using simultaneous electrical and optical signals |
US8996131B1 (en) | 2006-09-28 | 2015-03-31 | Lockheed Martin Corporation | Apparatus and method for managing chronic pain with infrared light sources and heat |
US7796403B2 (en) | 2006-09-28 | 2010-09-14 | Nellcor Puritan Bennett Llc | Means for mechanical registration and mechanical-electrical coupling of a faraday shield to a photodetector and an electrical circuit |
US7925511B2 (en) | 2006-09-29 | 2011-04-12 | Nellcor Puritan Bennett Llc | System and method for secure voice identification in a medical device |
US8728059B2 (en) | 2006-09-29 | 2014-05-20 | Covidien Lp | System and method for assuring validity of monitoring parameter in combination with a therapeutic device |
US7848891B2 (en) | 2006-09-29 | 2010-12-07 | Nellcor Puritan Bennett Llc | Modulation ratio determination with accommodation of uncertainty |
US8160668B2 (en) | 2006-09-29 | 2012-04-17 | Nellcor Puritan Bennett Llc | Pathological condition detector using kernel methods and oximeters |
US8068890B2 (en) | 2006-09-29 | 2011-11-29 | Nellcor Puritan Bennett Llc | Pulse oximetry sensor switchover |
US8175667B2 (en) | 2006-09-29 | 2012-05-08 | Nellcor Puritan Bennett Llc | Symmetric LED array for pulse oximetry |
US7706896B2 (en) | 2006-09-29 | 2010-04-27 | Nellcor Puritan Bennett Llc | User interface and identification in a medical device system and method |
US20080081956A1 (en) | 2006-09-29 | 2008-04-03 | Jayesh Shah | System and method for integrating voice with a medical device |
US7698002B2 (en) | 2006-09-29 | 2010-04-13 | Nellcor Puritan Bennett Llc | Systems and methods for user interface and identification in a medical device |
US7680522B2 (en) | 2006-09-29 | 2010-03-16 | Nellcor Puritan Bennett Llc | Method and apparatus for detecting misapplied sensors |
US7684842B2 (en) | 2006-09-29 | 2010-03-23 | Nellcor Puritan Bennett Llc | System and method for preventing sensor misuse |
US8068891B2 (en) | 2006-09-29 | 2011-11-29 | Nellcor Puritan Bennett Llc | Symmetric LED array for pulse oximetry |
US7476131B2 (en) | 2006-09-29 | 2009-01-13 | Nellcor Puritan Bennett Llc | Device for reducing crosstalk |
US7880626B2 (en) | 2006-10-12 | 2011-02-01 | Masimo Corporation | System and method for monitoring the life of a physiological sensor |
US8255026B1 (en) | 2006-10-12 | 2012-08-28 | Masimo Corporation, Inc. | Patient monitor capable of monitoring the quality of attached probes and accessories |
US7883536B1 (en) | 2007-01-19 | 2011-02-08 | Lockheed Martin Corporation | Hybrid optical-electrical probes |
US8265724B2 (en) | 2007-03-09 | 2012-09-11 | Nellcor Puritan Bennett Llc | Cancellation of light shunting |
US7894869B2 (en) | 2007-03-09 | 2011-02-22 | Nellcor Puritan Bennett Llc | Multiple configuration medical sensor and technique for using the same |
US8280469B2 (en) | 2007-03-09 | 2012-10-02 | Nellcor Puritan Bennett Llc | Method for detection of aberrant tissue spectra |
US7854237B2 (en) * | 2007-06-28 | 2010-12-21 | Nancy Beck Irland | Fetal monitoring transducer aligning device |
JP4569615B2 (en) * | 2007-09-25 | 2010-10-27 | ブラザー工業株式会社 | Printing device |
US9131847B2 (en) * | 2007-11-08 | 2015-09-15 | Olympus Corporation | Method and apparatus for detecting abnormal living tissue |
US8998914B2 (en) | 2007-11-30 | 2015-04-07 | Lockheed Martin Corporation | Optimized stimulation rate of an optically stimulating cochlear implant |
US8204567B2 (en) | 2007-12-13 | 2012-06-19 | Nellcor Puritan Bennett Llc | Signal demodulation |
US8346328B2 (en) | 2007-12-21 | 2013-01-01 | Covidien Lp | Medical sensor and technique for using the same |
US8352004B2 (en) | 2007-12-21 | 2013-01-08 | Covidien Lp | Medical sensor and technique for using the same |
US8366613B2 (en) | 2007-12-26 | 2013-02-05 | Covidien Lp | LED drive circuit for pulse oximetry and method for using same |
US8577434B2 (en) | 2007-12-27 | 2013-11-05 | Covidien Lp | Coaxial LED light sources |
US8452364B2 (en) | 2007-12-28 | 2013-05-28 | Covidien LLP | System and method for attaching a sensor to a patient's skin |
US8442608B2 (en) | 2007-12-28 | 2013-05-14 | Covidien Lp | System and method for estimating physiological parameters by deconvolving artifacts |
US8897850B2 (en) | 2007-12-31 | 2014-11-25 | Covidien Lp | Sensor with integrated living hinge and spring |
US8199007B2 (en) | 2007-12-31 | 2012-06-12 | Nellcor Puritan Bennett Llc | Flex circuit snap track for a biometric sensor |
US8092993B2 (en) | 2007-12-31 | 2012-01-10 | Nellcor Puritan Bennett Llc | Hydrogel thin film for use as a biosensor |
US8070508B2 (en) | 2007-12-31 | 2011-12-06 | Nellcor Puritan Bennett Llc | Method and apparatus for aligning and securing a cable strain relief |
US8275553B2 (en) | 2008-02-19 | 2012-09-25 | Nellcor Puritan Bennett Llc | System and method for evaluating physiological parameter data |
US8750953B2 (en) | 2008-02-19 | 2014-06-10 | Covidien Lp | Methods and systems for alerting practitioners to physiological conditions |
WO2009120600A2 (en) | 2008-03-25 | 2009-10-01 | The Curators Of The University Of Missouri | Method and system for non-invasive blood glucose detection utilizing spectral data of one or more components other than glucose |
US8140272B2 (en) | 2008-03-27 | 2012-03-20 | Nellcor Puritan Bennett Llc | System and method for unmixing spectroscopic observations with nonnegative matrix factorization |
US8437822B2 (en) | 2008-03-28 | 2013-05-07 | Covidien Lp | System and method for estimating blood analyte concentration |
US8364224B2 (en) | 2008-03-31 | 2013-01-29 | Covidien Lp | System and method for facilitating sensor and monitor communication |
US8112375B2 (en) | 2008-03-31 | 2012-02-07 | Nellcor Puritan Bennett Llc | Wavelength selection and outlier detection in reduced rank linear models |
US8292809B2 (en) | 2008-03-31 | 2012-10-23 | Nellcor Puritan Bennett Llc | Detecting chemical components from spectroscopic observations |
US11272979B2 (en) | 2008-04-29 | 2022-03-15 | Virginia Tech Intellectual Properties, Inc. | System and method for estimating tissue heating of a target ablation zone for electrical-energy based therapies |
US10117707B2 (en) | 2008-04-29 | 2018-11-06 | Virginia Tech Intellectual Properties, Inc. | System and method for estimating tissue heating of a target ablation zone for electrical-energy based therapies |
US9598691B2 (en) | 2008-04-29 | 2017-03-21 | Virginia Tech Intellectual Properties, Inc. | Irreversible electroporation to create tissue scaffolds |
US11254926B2 (en) | 2008-04-29 | 2022-02-22 | Virginia Tech Intellectual Properties, Inc. | Devices and methods for high frequency electroporation |
US10238447B2 (en) | 2008-04-29 | 2019-03-26 | Virginia Tech Intellectual Properties, Inc. | System and method for ablating a tissue site by electroporation with real-time monitoring of treatment progress |
US10245098B2 (en) | 2008-04-29 | 2019-04-02 | Virginia Tech Intellectual Properties, Inc. | Acute blood-brain barrier disruption using electrical energy based therapy |
US9198733B2 (en) | 2008-04-29 | 2015-12-01 | Virginia Tech Intellectual Properties, Inc. | Treatment planning for electroporation-based therapies |
US10272178B2 (en) | 2008-04-29 | 2019-04-30 | Virginia Tech Intellectual Properties Inc. | Methods for blood-brain barrier disruption using electrical energy |
US10702326B2 (en) | 2011-07-15 | 2020-07-07 | Virginia Tech Intellectual Properties, Inc. | Device and method for electroporation based treatment of stenosis of a tubular body part |
US9283051B2 (en) | 2008-04-29 | 2016-03-15 | Virginia Tech Intellectual Properties, Inc. | System and method for estimating a treatment volume for administering electrical-energy based therapies |
US8992517B2 (en) | 2008-04-29 | 2015-03-31 | Virginia Tech Intellectual Properties Inc. | Irreversible electroporation to treat aberrant cell masses |
US9867652B2 (en) | 2008-04-29 | 2018-01-16 | Virginia Tech Intellectual Properties, Inc. | Irreversible electroporation using tissue vasculature to treat aberrant cell masses or create tissue scaffolds |
CN102961146B (en) * | 2008-05-22 | 2015-09-23 | 密苏里大学董事会 | The method and system of noninvasive Optical blood glucose detection is carried out with spectral data analysis |
US8071935B2 (en) | 2008-06-30 | 2011-12-06 | Nellcor Puritan Bennett Llc | Optical detector with an overmolded faraday shield |
US8862194B2 (en) | 2008-06-30 | 2014-10-14 | Covidien Lp | Method for improved oxygen saturation estimation in the presence of noise |
USD626562S1 (en) | 2008-06-30 | 2010-11-02 | Nellcor Puritan Bennett Llc | Triangular saturation pattern detection indicator for a patient monitor display panel |
USD626561S1 (en) | 2008-06-30 | 2010-11-02 | Nellcor Puritan Bennett Llc | Circular satseconds indicator and triangular saturation pattern detection indicator for a patient monitor display panel |
US7887345B2 (en) | 2008-06-30 | 2011-02-15 | Nellcor Puritan Bennett Llc | Single use connector for pulse oximetry sensors |
US9895068B2 (en) | 2008-06-30 | 2018-02-20 | Covidien Lp | Pulse oximeter with wait-time indication |
US7880884B2 (en) | 2008-06-30 | 2011-02-01 | Nellcor Puritan Bennett Llc | System and method for coating and shielding electronic sensor components |
US8577431B2 (en) | 2008-07-03 | 2013-11-05 | Cercacor Laboratories, Inc. | Noise shielding for a noninvasive device |
US8203704B2 (en) | 2008-08-04 | 2012-06-19 | Cercacor Laboratories, Inc. | Multi-stream sensor for noninvasive measurement of blood constituents |
US8364220B2 (en) | 2008-09-25 | 2013-01-29 | Covidien Lp | Medical sensor and technique for using the same |
US8257274B2 (en) | 2008-09-25 | 2012-09-04 | Nellcor Puritan Bennett Llc | Medical sensor and technique for using the same |
US8417309B2 (en) | 2008-09-30 | 2013-04-09 | Covidien Lp | Medical sensor |
US8433382B2 (en) | 2008-09-30 | 2013-04-30 | Covidien Lp | Transmission mode photon density wave system and method |
US8968193B2 (en) | 2008-09-30 | 2015-03-03 | Covidien Lp | System and method for enabling a research mode on physiological monitors |
US20100081904A1 (en) * | 2008-09-30 | 2010-04-01 | Nellcor Puritan Bennett Llc | Device And Method For Securing A Medical Sensor to An Infant's Head |
US8423112B2 (en) | 2008-09-30 | 2013-04-16 | Covidien Lp | Medical sensor and technique for using the same |
US8386000B2 (en) * | 2008-09-30 | 2013-02-26 | Covidien Lp | System and method for photon density wave pulse oximetry and pulse hemometry |
US8914088B2 (en) | 2008-09-30 | 2014-12-16 | Covidien Lp | Medical sensor and technique for using the same |
WO2010040142A1 (en) | 2008-10-03 | 2010-04-08 | Lockheed Martin Corporation | Nerve stimulator and method using simultaneous electrical and optical signals |
WO2010051487A2 (en) * | 2008-10-31 | 2010-05-06 | Nellcor Puritan Bennett Llc | System and method for facilitating observation of monitored physiologic data |
CA2741026C (en) * | 2008-10-31 | 2015-04-14 | Nellcor Puritan Bennett Llc | System and method for facilitating observation of monitored physiologic data |
US8911368B2 (en) * | 2009-01-29 | 2014-12-16 | Given Imaging, Ltd. | Device, system and method for detection of bleeding |
US8130904B2 (en) | 2009-01-29 | 2012-03-06 | The Invention Science Fund I, Llc | Diagnostic delivery service |
US8111809B2 (en) | 2009-01-29 | 2012-02-07 | The Invention Science Fund I, Llc | Diagnostic delivery service |
US8452366B2 (en) | 2009-03-16 | 2013-05-28 | Covidien Lp | Medical monitoring device with flexible circuitry |
US8221319B2 (en) | 2009-03-25 | 2012-07-17 | Nellcor Puritan Bennett Llc | Medical device for assessing intravascular blood volume and technique for using the same |
US8515515B2 (en) | 2009-03-25 | 2013-08-20 | Covidien Lp | Medical sensor with compressible light barrier and technique for using the same |
US8781548B2 (en) | 2009-03-31 | 2014-07-15 | Covidien Lp | Medical sensor with flexible components and technique for using the same |
US11638603B2 (en) | 2009-04-09 | 2023-05-02 | Virginia Tech Intellectual Properties, Inc. | Selective modulation of intracellular effects of cells using pulsed electric fields |
US11382681B2 (en) | 2009-04-09 | 2022-07-12 | Virginia Tech Intellectual Properties, Inc. | Device and methods for delivery of high frequency electrical pulses for non-thermal ablation |
US8509869B2 (en) | 2009-05-15 | 2013-08-13 | Covidien Lp | Method and apparatus for detecting and analyzing variations in a physiologic parameter |
US8571619B2 (en) | 2009-05-20 | 2013-10-29 | Masimo Corporation | Hemoglobin display and patient treatment |
US8634891B2 (en) | 2009-05-20 | 2014-01-21 | Covidien Lp | Method and system for self regulation of sensor component contact pressure |
US8903488B2 (en) | 2009-05-28 | 2014-12-02 | Angiodynamics, Inc. | System and method for synchronizing energy delivery to the cardiac rhythm |
US9895189B2 (en) | 2009-06-19 | 2018-02-20 | Angiodynamics, Inc. | Methods of sterilization and treating infection using irreversible electroporation |
US8505821B2 (en) | 2009-06-30 | 2013-08-13 | Covidien Lp | System and method for providing sensor quality assurance |
US9010634B2 (en) | 2009-06-30 | 2015-04-21 | Covidien Lp | System and method for linking patient data to a patient and providing sensor quality assurance |
US8311601B2 (en) | 2009-06-30 | 2012-11-13 | Nellcor Puritan Bennett Llc | Reflectance and/or transmissive pulse oximeter |
US8391941B2 (en) | 2009-07-17 | 2013-03-05 | Covidien Lp | System and method for memory switching for multiple configuration medical sensor |
US8494786B2 (en) | 2009-07-30 | 2013-07-23 | Covidien Lp | Exponential sampling of red and infrared signals |
US8417310B2 (en) | 2009-08-10 | 2013-04-09 | Covidien Lp | Digital switching in multi-site sensor |
US8428675B2 (en) | 2009-08-19 | 2013-04-23 | Covidien Lp | Nanofiber adhesives used in medical devices |
US8494606B2 (en) | 2009-08-19 | 2013-07-23 | Covidien Lp | Photoplethysmography with controlled application of sensor pressure |
US8788001B2 (en) | 2009-09-21 | 2014-07-22 | Covidien Lp | Time-division multiplexing in a multi-wavelength photon density wave system |
US8494604B2 (en) | 2009-09-21 | 2013-07-23 | Covidien Lp | Wavelength-division multiplexing in a multi-wavelength photon density wave system |
US8704666B2 (en) | 2009-09-21 | 2014-04-22 | Covidien Lp | Medical device interface customization systems and methods |
EP2480997A2 (en) | 2009-09-24 | 2012-08-01 | Nellcor Puritan Bennett LLC | Determination of a physiological parameter |
US8923945B2 (en) | 2009-09-24 | 2014-12-30 | Covidien Lp | Determination of a physiological parameter |
US8798704B2 (en) | 2009-09-24 | 2014-08-05 | Covidien Lp | Photoacoustic spectroscopy method and system to discern sepsis from shock |
US8571621B2 (en) * | 2009-09-24 | 2013-10-29 | Covidien Lp | Minimax filtering for pulse oximetry |
US8376955B2 (en) | 2009-09-29 | 2013-02-19 | Covidien Lp | Spectroscopic method and system for assessing tissue temperature |
US8515511B2 (en) | 2009-09-29 | 2013-08-20 | Covidien Lp | Sensor with an optical coupling material to improve plethysmographic measurements and method of using the same |
US9554739B2 (en) | 2009-09-29 | 2017-01-31 | Covidien Lp | Smart cable for coupling a medical sensor to an electronic patient monitor |
US8401608B2 (en) * | 2009-09-30 | 2013-03-19 | Covidien Lp | Method of analyzing photon density waves in a medical monitor |
GB2474233A (en) | 2009-10-06 | 2011-04-13 | Uk Investments Associates Llc | Cooling pump comprising a detachable head portion |
JP5552819B2 (en) * | 2010-01-28 | 2014-07-16 | ソニー株式会社 | Concentration measuring device |
JP5663900B2 (en) | 2010-03-05 | 2015-02-04 | セイコーエプソン株式会社 | Spectroscopic sensor device and electronic device |
US8391943B2 (en) | 2010-03-31 | 2013-03-05 | Covidien Lp | Multi-wavelength photon density wave system using an optical switch |
US8498683B2 (en) | 2010-04-30 | 2013-07-30 | Covidien LLP | Method for respiration rate and blood pressure alarm management |
US9380982B2 (en) | 2010-07-28 | 2016-07-05 | Covidien Lp | Adaptive alarm system and method |
US8930145B2 (en) | 2010-07-28 | 2015-01-06 | Covidien Lp | Light focusing continuous wave photoacoustic spectroscopy and its applications to patient monitoring |
JP5710767B2 (en) | 2010-09-28 | 2015-04-30 | マシモ コーポレイション | Depth of consciousness monitor including oximeter |
US9775545B2 (en) | 2010-09-28 | 2017-10-03 | Masimo Corporation | Magnetic electrical connector for patient monitors |
EP2627274B1 (en) | 2010-10-13 | 2022-12-14 | AngioDynamics, Inc. | System for electrically ablating tissue of a patient |
CN103429153A (en) | 2010-11-03 | 2013-12-04 | 华盛顿大学商业中心 | Determination of tissue oxygenation in vivo |
WO2012088149A2 (en) | 2010-12-20 | 2012-06-28 | Virginia Tech Intellectual Properties, Inc. | High-frequency electroporation for cancer therapy |
US8610769B2 (en) | 2011-02-28 | 2013-12-17 | Covidien Lp | Medical monitor data collection system and method |
US20120310060A1 (en) * | 2011-05-31 | 2012-12-06 | Nellcor Puritan Bennett Llc | Method of analyzing photon density waves in a medical monitor |
CN102846323A (en) * | 2011-07-01 | 2013-01-02 | 中国计量学院 | LED-based noninvasive blood oxygen saturation tester |
US9078665B2 (en) | 2011-09-28 | 2015-07-14 | Angiodynamics, Inc. | Multiple treatment zone ablation probe |
US9833146B2 (en) | 2012-04-17 | 2017-12-05 | Covidien Lp | Surgical system and method of use of the same |
US10610159B2 (en) * | 2012-10-07 | 2020-04-07 | Rhythm Diagnostic Systems, Inc. | Health monitoring systems and methods |
US10413251B2 (en) | 2012-10-07 | 2019-09-17 | Rhythm Diagnostic Systems, Inc. | Wearable cardiac monitor |
DE102013100483A1 (en) | 2013-01-17 | 2014-07-17 | Andreas von Keitz | breakaway coupling |
FR3011170B1 (en) * | 2013-09-30 | 2017-03-31 | Apd Advanced Perfusion Diagnostics | NON-INVASIVE MEASUREMENT DEVICE AND METHOD FOR ESTIMATING LOCAL METABOLIC PARAMETERS |
JP6594901B2 (en) | 2014-05-12 | 2019-10-23 | バージニア テック インテレクチュアル プロパティース インコーポレイテッド | Selective modulation of intracellular effects of cells using pulsed electric fields |
WO2016057553A1 (en) | 2014-10-07 | 2016-04-14 | Masimo Corporation | Modular physiological sensors |
WO2016057042A1 (en) | 2014-10-10 | 2016-04-14 | Medtor Llc | System and method for a non-invasive medical sensor |
WO2016100325A1 (en) | 2014-12-15 | 2016-06-23 | Virginia Tech Intellectual Properties, Inc. | Devices, systems, and methods for real-time monitoring of electrophysical effects during tissue treatment |
US10328202B2 (en) | 2015-02-04 | 2019-06-25 | Covidien Lp | Methods and systems for determining fluid administration |
US10499835B2 (en) | 2015-03-24 | 2019-12-10 | Covidien Lp | Methods and systems for determining fluid responsiveness in the presence of noise |
DE102015117940A1 (en) | 2015-10-21 | 2017-04-27 | Osram Opto Semiconductors Gmbh | Optical sensor |
JP6112190B2 (en) * | 2015-12-25 | 2017-04-12 | セイコーエプソン株式会社 | Spectroscopic sensor and pulse oximeter |
AU2017357747A1 (en) | 2016-11-10 | 2019-05-30 | The Research Foundation For The State University Of New York | System, method and biomarkers for airway obstruction |
US10905492B2 (en) | 2016-11-17 | 2021-02-02 | Angiodynamics, Inc. | Techniques for irreversible electroporation using a single-pole tine-style internal device communicating with an external surface electrode |
US10154813B1 (en) | 2017-07-03 | 2018-12-18 | Spyros Kokolis | Method and apparatus for patient skin color monitoring and drug efficacy measurement |
US11723518B2 (en) * | 2017-10-25 | 2023-08-15 | Boston Scientific Scimed, Inc. | Direct visualization catheter and system |
US11607537B2 (en) | 2017-12-05 | 2023-03-21 | Virginia Tech Intellectual Properties, Inc. | Method for treating neurological disorders, including tumors, with electroporation |
CN111683588A (en) * | 2018-01-22 | 2020-09-18 | 光谱公司 | Optical response measurements from skin and tissue using spectroscopy |
US11311329B2 (en) | 2018-03-13 | 2022-04-26 | Virginia Tech Intellectual Properties, Inc. | Treatment planning for immunotherapy based treatments using non-thermal ablation techniques |
US11925405B2 (en) | 2018-03-13 | 2024-03-12 | Virginia Tech Intellectual Properties, Inc. | Treatment planning system for immunotherapy enhancement via non-thermal ablation |
US11317807B2 (en) * | 2018-10-15 | 2022-05-03 | Hi Llc | Detection of fast-neural signal using depth-resolved spectroscopy via intensity modulated interferometry having tunable pump laser |
US10791286B2 (en) | 2018-12-13 | 2020-09-29 | Facebook Technologies, Llc | Differentiated imaging using camera assembly with augmented pixels |
US10855896B1 (en) * | 2018-12-13 | 2020-12-01 | Facebook Technologies, Llc | Depth determination using time-of-flight and camera assembly with augmented pixels |
US10791282B2 (en) | 2018-12-13 | 2020-09-29 | Fenwick & West LLP | High dynamic range camera assembly with augmented pixels |
US11950835B2 (en) | 2019-06-28 | 2024-04-09 | Virginia Tech Intellectual Properties, Inc. | Cycled pulsing to mitigate thermal damage for multi-electrode irreversible electroporation therapy |
US11903700B2 (en) | 2019-08-28 | 2024-02-20 | Rds | Vital signs monitoring systems and methods |
US10902623B1 (en) | 2019-11-19 | 2021-01-26 | Facebook Technologies, Llc | Three-dimensional imaging with spatial and temporal coding for depth camera assembly |
US11194160B1 (en) | 2020-01-21 | 2021-12-07 | Facebook Technologies, Llc | High frame rate reconstruction with N-tap camera sensor |
Family Cites Families (38)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3229685A (en) * | 1963-04-19 | 1966-01-18 | Emerson Electric Co | Blood pressure measuring |
US3461856A (en) * | 1965-10-23 | 1969-08-19 | American Optical Corp | Oximeters |
US3638640A (en) * | 1967-11-01 | 1972-02-01 | Robert F Shaw | Oximeter and method for in vivo determination of oxygen saturation in blood using three or more different wavelengths |
US3866599A (en) * | 1972-01-21 | 1975-02-18 | Univ Washington | Fiberoptic catheter |
US4029085A (en) * | 1976-03-26 | 1977-06-14 | Purdue Research Foundation | Method for determining bilirubin concentration from skin reflectance |
US4281645A (en) * | 1977-06-28 | 1981-08-04 | Duke University, Inc. | Method and apparatus for monitoring metabolism in body organs |
US4207874A (en) * | 1978-03-27 | 1980-06-17 | Choy Daniel S J | Laser tunnelling device |
US4416285A (en) * | 1978-11-29 | 1983-11-22 | Oximetrix, Inc. | Improved optical catheter and method for making same |
US4700708A (en) * | 1982-09-02 | 1987-10-20 | Nellcor Incorporated | Calibrated optical oximeter probe |
US4714341A (en) * | 1984-02-23 | 1987-12-22 | Minolta Camera Kabushiki Kaisha | Multi-wavelength oximeter having a means for disregarding a poor signal |
JPS60209146A (en) * | 1984-03-31 | 1985-10-21 | Olympus Optical Co Ltd | Fluorescence spectrochemical analysis device |
US4648892A (en) * | 1985-03-22 | 1987-03-10 | Massachusetts Institute Of Technology | Method for making optical shield for a laser catheter |
US4655225A (en) * | 1985-04-18 | 1987-04-07 | Kurabo Industries Ltd. | Spectrophotometric method and apparatus for the non-invasive |
FR2593916B1 (en) * | 1986-01-24 | 1988-05-13 | France Etat Armement | SPECTROPHOTOMETER FOR DETERMINATION WITHIN A LIVING ORGANISM |
EP0305404A4 (en) * | 1986-05-21 | 1989-10-04 | Univ Johns Hopkins | Two-band optical comparator for use with chopped cw singlet oxygen monitor. |
JPS6323645A (en) * | 1986-05-27 | 1988-01-30 | 住友電気工業株式会社 | Reflection heating type oxymeter |
US4895156A (en) * | 1986-07-02 | 1990-01-23 | Schulze John E | Sensor system using fluorometric decay measurements |
US4800495A (en) * | 1986-08-18 | 1989-01-24 | Physio-Control Corporation | Method and apparatus for processing signals used in oximetry |
US4824242A (en) * | 1986-09-26 | 1989-04-25 | Sensormedics Corporation | Non-invasive oximeter and method |
US4773422A (en) * | 1987-04-30 | 1988-09-27 | Nonin Medical, Inc. | Single channel pulse oximeter |
JPS63277039A (en) * | 1987-05-08 | 1988-11-15 | Hamamatsu Photonics Kk | Diagnostic apparatus |
US4805623A (en) * | 1987-09-04 | 1989-02-21 | Vander Corporation | Spectrophotometric method for quantitatively determining the concentration of a dilute component in a light- or other radiation-scattering environment |
US4827934A (en) * | 1987-10-27 | 1989-05-09 | Siemens-Pacesetter, Inc. | Sensing margin detectors for implantable electromedical devices |
US4800885A (en) * | 1987-12-02 | 1989-01-31 | The Boc Group, Inc. | Blood constituent monitoring apparatus and methods with frequency division multiplexing |
US4972331A (en) * | 1989-02-06 | 1990-11-20 | Nim, Inc. | Phase modulated spectrophotometry |
CA1331483C (en) * | 1988-11-02 | 1994-08-16 | Britton Chance | User-wearable hemoglobinometer for measuring the metabolic condition of a subject |
US5122974A (en) * | 1989-02-06 | 1992-06-16 | Nim, Inc. | Phase modulated spectrophotometry |
US5873821A (en) * | 1992-05-18 | 1999-02-23 | Non-Invasive Technology, Inc. | Lateralization spectrophotometer |
US5596987A (en) * | 1988-11-02 | 1997-01-28 | Noninvasive Technology, Inc. | Optical coupler for in vivo examination of biological tissue |
US5119815A (en) * | 1988-12-21 | 1992-06-09 | Nim, Incorporated | Apparatus for determining the concentration of a tissue pigment of known absorbance, in vivo, using the decay characteristics of scintered electromagnetic radiation |
US5187672A (en) * | 1989-02-06 | 1993-02-16 | Nim Incorporated | Phase modulation spectroscopic system |
US5197470A (en) * | 1990-07-16 | 1993-03-30 | Eastman Kodak Company | Near infrared diagnostic method and instrument |
US5127408A (en) * | 1990-09-14 | 1992-07-07 | Duke University | Apparatus for intravascularly measuring oxidative metabolism in body organs and tissues |
US5257991A (en) * | 1990-11-15 | 1993-11-02 | Laserscope | Instrumentation for directing light at an angle |
SG85573A1 (en) * | 1991-01-24 | 2002-01-15 | Non Invasive Technology Inc | Quantitation and localization of tissue hypoxia by time and frequency domain spectroscopy |
US5247932A (en) * | 1991-04-15 | 1993-09-28 | Nellcor Incorporated | Sensor for intrauterine use |
US5242438A (en) * | 1991-04-22 | 1993-09-07 | Trimedyne, Inc. | Method and apparatus for treating a body site with laterally directed laser radiation |
EP0591289B1 (en) * | 1991-05-16 | 1999-07-07 | Non-Invasive Technology, Inc. | Hemoglobinometers and the like for measuring the metabolic condition of a subject |
-
1993
- 1993-03-16 US US08/031,945 patent/US5564417A/en not_active Expired - Lifetime
-
1994
- 1994-03-15 CN CN94191476A patent/CN1089571C/en not_active Expired - Lifetime
- 1994-03-15 JP JP6521168A patent/JPH08509880A/en active Pending
- 1994-03-15 WO PCT/US1994/002764 patent/WO1994021173A1/en active IP Right Grant
- 1994-03-15 EP EP94911595A patent/EP0689398B1/en not_active Expired - Lifetime
- 1994-03-15 DE DE69433205T patent/DE69433205T2/en not_active Expired - Lifetime
- 1994-03-15 CA CA002158435A patent/CA2158435A1/en not_active Abandoned
-
1996
- 1996-10-15 US US08/731,443 patent/US6134460A/en not_active Expired - Lifetime
Also Published As
Publication number | Publication date |
---|---|
JPH08509880A (en) | 1996-10-22 |
EP0689398B1 (en) | 2003-10-01 |
US6134460A (en) | 2000-10-17 |
CN1089571C (en) | 2002-08-28 |
EP0689398A1 (en) | 1996-01-03 |
DE69433205T2 (en) | 2004-08-19 |
WO1994021173A1 (en) | 1994-09-29 |
EP0689398A4 (en) | 1998-10-14 |
CN1119410A (en) | 1996-03-27 |
DE69433205D1 (en) | 2003-11-06 |
US5564417A (en) | 1996-10-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US5564417A (en) | Pathlength corrected oximeter and the like | |
US6708048B1 (en) | Phase modulation spectrophotometric apparatus | |
US20030023140A1 (en) | Pathlength corrected oximeter and the like | |
US6263221B1 (en) | Quantitative analyses of biological tissue using phase modulation spectroscopy | |
US6246892B1 (en) | Phase modulation spectroscopy | |
Chance et al. | Phase measurement of light absorption and scatter in human tissue | |
KR100612827B1 (en) | Method and apparatus for noninvasively measuring hemoglobin concentration and oxygen saturation | |
US5187672A (en) | Phase modulation spectroscopic system | |
US5553614A (en) | Examination of biological tissue using frequency domain spectroscopy | |
JP3844815B2 (en) | Method and apparatus for measuring absorption information of scatterers | |
US6801799B2 (en) | Pulse oximeter and method of operation | |
CA2494030C (en) | Method for spectrophotometric blood oxygenation monitoring | |
US4880304A (en) | Optical sensor for pulse oximeter | |
US8606342B2 (en) | Pulse and active pulse spectraphotometry | |
CA2649187A1 (en) | Photoplethysmography | |
US20120310062A1 (en) | Photon density wave based determination of physiological blood parameters | |
US5513642A (en) | Reflectance sensor system | |
EP0568628B1 (en) | Time and frequency domain spectroscopy determining hypoxia | |
Myllylä et al. | Measurement of cerebral blood flow and metabolism using high power light-emitting diodes | |
RU2040912C1 (en) | Optical method and device for determining blood oxygenation | |
JP3359756B2 (en) | Biological light measurement device | |
US20090030296A1 (en) | Predictive oximetry model and method | |
US8712492B2 (en) | Photon density wave based determination of physiological blood parameters | |
US20070208231A1 (en) | Process and Device for Deep-Selective Detection of Spontaneous Activities and General Muscle Activites | |
Fantini et al. | Frequency-domain multisource optical spectrometer and oximeter |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
FZDE | Dead |