US20010047128A1 - Method for non-invasive spectrophotometric blood oxygenation monitoring - Google Patents

Method for non-invasive spectrophotometric blood oxygenation monitoring Download PDF

Info

Publication number
US20010047128A1
US20010047128A1 US09845146 US84514601A US2001047128A1 US 20010047128 A1 US20010047128 A1 US 20010047128A1 US 09845146 US09845146 US 09845146 US 84514601 A US84514601 A US 84514601A US 2001047128 A1 US2001047128 A1 US 2001047128A1
Authority
US
Grant status
Application
Patent type
Prior art keywords
light
hbo
wavelength
attenuation
α
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.)
Granted
Application number
US09845146
Other versions
US6456862B2 (en )
Inventor
Paul Benni
Original Assignee
Benni Paul B.
Priority date (The priority date 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 date listed.)
Filing date
Publication date

Links

Images

Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using infra-red, visible or ultra-violet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/35Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infra-red light
    • G01N21/359Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infra-red light using near infra-red light
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1455Measuring 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
    • A61B5/14551Measuring 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
    • A61B5/14553Measuring 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1495Calibrating or testing of in-vivo probes
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using infra-red, visible or ultra-violet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47Scattering, i.e. diffuse reflection
    • G01N21/49Scattering, i.e. diffuse reflection within a body or fluid

Abstract

A method and apparatus for non-invasively determining the blood oxygen saturation level within a subject's tissue is provided that utilizes a near infrared spectrophotometric (NIRS) sensor capable of transmitting a light signal into the tissue of a subject and sensing the light signal once it has passed through the tissue via transmittance or reflectance. The method includes the step of determining attenuation of the light signal as the sum of: (i) attenuation attributable to deoxyhemoglobin; (ii) attenuation attributable to oxyhemoglobin; and (iii) attenuation attributable to light scattering within the subject's tissue. The present method also makes it possible to account for attenuation attributable to fixed or constant light absorbing biological tissue components, and attenuation attributable to variable characteristics of the sensor. By determining differential attenuation as a function of wavelength, the attenuation attributable to tissue light scattering characteristics, fixed light absorbing components, and measuring apparatus characteristics are mathematically cancelled out or minimized relative to the attenuation attributable to deoxyhemoglobin, and attenuation attributable to oxyhemoglobin.

Description

  • [0001]
    This application claims the benefit of the filing date of U.S. Provisional Application Ser. No. 60/201,359, filed May 2, 2000.
  • [0002] This invention was made with Government support under Contract No. 1R43NS39723-01 awarded by the Department of Health & Human Services. The Government has certain rights in the invention.
  • BACKGROUND OF THE INVENTION
  • [0003]
    1. Technical Field
  • [0004]
    This invention relates to methods for non-invasively determining biological tissue oxygenation in general, and to non-invasive methods utilizing near-infrared spectroscopy (NIRS) techniques in particular.
  • [0005]
    2. Background Information
  • [0006]
    The molecule that carries the oxygen in the blood is hemoglobin. Oxygenated hemoglobin is called oxyhemoglobin (HbO2) and deoxygenated hemoglobin is deoxyhemoglobin (Hb). Total hemoglobin is the summation of the two states of hemoglobin (Total Hb=HbO2+Hb), and is proportional to relative blood volume changes, provided that the hematocrit or hemoglobin concentration of the blood is unchanged. The mammalian cardiovascular system consists of a blood pumping mechanism (the heart), a blood transportation system (blood vessels), and a blood oxygenation system (the lungs). Blood oxygenated by the lungs passes through the heart and is pumped into the arterial vascular system. Under normal conditions, oxygenated arterial blood consists predominately of HbO2. Large arterial blood vessels branch off into smaller branches called arterioles, which profuse throughout biological tissue. The arterioles branch off into capillaries, the smallest blood vessels. In the capillaries, oxygen carried by hemoglobin is transported to the cells in the tissue, resulting in the release of oxygen molecules (HbO2→Hb). Under normal conditions, only a fraction of the HbO2 molecules give up oxygen to the tissue, depending on the cellular metabolic need. The capillaries then combine together into venuoles, the beginning of the venous circulatory system. Venuoles then combine into larger blood vessels called veins. The veins further combine and return to the heart, and then venous blood is pumped to the lungs. In the lungs, deoxygenated hemoglobin Hb collects oxygen becoming HbO2 again and the circulatory process is repeated.
  • [0007]
    Oxygen saturation is defined as: O 2 saturation % = HbO 2 ( HbO 2 + Hb ) × 100 % (Eqn. 1)
    Figure US20010047128A1-20011129-M00001
  • [0008]
    In the arterial circulatory system under normal conditions, there is a high proportion of HbO2 to Hb, resulting in an arterial oxygen saturation (defined as SaO2 %) of 95-100%. After delivery of oxygen to tissue via the capillaries, the proportion of HbO2 to Hb decreases. Therefore, the measured oxygen saturation of venous blood (defined as SvO2 %) is lower and may be about 70%.
  • [0009]
    One spectrophotometric method, called pulse oximetry, determines arterial oxygen saturation (SaO2) of peripheral tissue (i.e. finger, ear, nose) by monitoring pulsatile optical attenuation changes of detected light induced by pulsatile arterial blood volume changes in the arteriolar vascular system. The method of pulse oximetry requires pulsatile blood volume changes in order to make a measurement. Since venous blood is not pulsatile, pulse oximetry cannot provide any information about venous blood.
  • [0010]
    Near-infrared spectroscopy (NIRS) is an optical spectrophotometric method of continually monitoring tissue oxygenation that does not require pulsatile blood volume to calculate parameters of clinical value. The NIRS method is based on the principle that light in the near-infrared range (700 to 1,000 nm) can pass easily through skin, bone and other tissues where it encounters hemoglobin located mainly within micro-circulation passages; e.g., capillaries, arterioles, and venuoles. Hemoglobin exposed to light in the near infra-red range has specific absorption spectra that varies depending on its oxidation state; i.e., oxyhemoglobin (HbO2) and deoxyhemoglobin (Hb) each act as a distinct chromophore. By using light sources that transmit near-infrared light at specific different wavelengths, and measuring changes in transmitted or reflected light attenuation, concentration changes of the oxyhemoglobin (HbO2) and deoxyhemoglobin (Hb) can be monitored. The ability to continually monitor cerebral oxygenation levels is particularly valuable for those patients subject to a condition in which oxygenation levels in the brain may be compromised, leading to brain damage or death.
  • [0011]
    The apparatus used in NIRS analysis typically includes a plurality of light sources, one or more light detectors for detecting reflected or transmitted light, and a processor for processing signals that represent the light emanating from the light source and the light detected by the light detector. Light sources such as light emitting diodes (LEDs) or laser diodes that produce light emissions in the wavelength range of 700-1000 nm at an intensity below that which would damage the biological tissue being examined are typically used. A photodiode or other light source detector is used to detect light reflected from or passed through the tissue being examined. The processor takes the signals from the light sources and the light detector and analyzes those signals in terms of their intensity and wave properties.
  • [0012]
    It is known that relative changes of the concentrations of HbO2 and Hb can be evaluated using apparatus similar to that described above, including a processor programmed to utilize a variant of the Beer-Lambert Law, which accounts for optical attenuation in a highly scattering medium like biological tissue. The modified Beer-Lambert Law can be expressed as:
  • A λ=−log(I/I 0)λλ *C*d*B λ +G   (2)
  • [0013]
    wherein “Aλ” represents the optical attenuation in tissue at a particular wavelength λ (units: optical density or OD); “Io” represents the incident light intensity (units: W/cm2); “I” represents the detected light intensity; “αλ” represents the wavelength dependent absorption coefficient of the chromophore (units: OD * cm−1 * μM−1); “C” represents the concentration of chromophore (units: μM); “d” represents the light source to detector (optode) separation distance (units: cm); “Bλ” represents the wavelength dependent light scattering differential pathlength factor (unitless); and “G” represents light attenuation due to scattering within tissue (units: OD).
  • [0014]
    Absolute measurement of chromophore concentration (C) is very difficult because G is unknown or difficult to ascertain. However, over a reasonable measuring period of several hours to days, G can be considered to remain constant, thereby allowing for the measurement of relative changes of chromophore from a zero reference baseline. Thus, if time t1 marks the start of an optical measurement (i.e., a base line) and time t2 is an arbitrary point in time after t1, a change in attenuation (ΔA) between t1 and t2 can be calculated, and variables G and lo will cancel out providing that they remain constant.
  • [0015]
    The change in chromophore concentration (ΔC=C(t2)−C(t1)) can be determined from the change in attenuation ΔA, for example using the following equation derived from the Beer-Lambert Law:
  • ΔA=−log(I t2 /I t1)λλ *ΔC*d*B λ  (3)
  • [0016]
    Presently known NIRS algorithms that are designed to calculate the relative change in concentration of more than one chromophore use a multivariate form of Equation 2 or 3. To distinguish between, and to compute relative changes in, oxyhemoglobin (ΔHbO2) and deoxyhemoglobin (ΔHb), a minimum of two different wavelengths are typically used. The concentration of the HbO2 and Hb within the examined tissue is determined in λmoles per liter of tissue (μM).
  • [0017]
    The above-described NIRS approach to determining oxygen saturation levels is useful, but it is limited in that it only provides information regarding a change in the level of blood oxygen saturation within the tissue. It does not provide a means for determining the total level of blood oxygen saturation within the biological tissue.
  • [0018]
    At present, information regarding the relative contributions of venous and arterial blood within tissue examined by NIRS is either arbitrarily chosen or is determined by invasive sampling of the blood as a process independent from the NIRS examination. For example, It has been estimated that NIRS examined brain tissue consists of blood comprising from about 60 to 80% venous to about 20 to 40% arterial blood. Blood samples from catheters placed in venous drainage sites such as the internal jugular vein, jugular bulb, or sagittal sinus-have been used to evaluate NIRS measurements. It has been estimated in animal studies that NIRS interrogated tissue consists of a mixed vascular bed with a venous-to-arterial ratio of about 2:1 as determined from multiple linear regression analysis of sagittal sinus oxygen saturation (SSSO2) and carotid artery oxygen saturation (SaO2) in comparison to NIRS measured ΔHb and ΔHbO2. An expression representing the mixed venous/arterial oxygen saturation (SmvO2) in NIRS examined tissue is shown by the equation:
  • SmvO 2 =Kv*SvO 2 +Ka*SaO 2   (4)
  • [0019]
    where “SvO2” represents venous oxygen saturation; “SaO2” represents arterial oxygen saturation; and Kv and Ka are the weighted venous and arterial contributions respectively, with Kv+Ka=1. The parameters Kv and Ka may have constant values, or they may be a function of SvO2 and SaO2. Determined oxygen saturation from the internal jugular vein (SijvO2), jugular bulb (SjbO2), or sagittal sinus (SssO2) can be used to represent SvO2. Therefore, the value of each term in Equation 4 is empirically determined, typically by discretely sampling or continuously monitoring and subsequently evaluating patient arterial and venous blood from tissue that the NIRS sensor is examining, and using regression analysis to determine the relative contributions of venous and arterial blood independent of the NIRS examination.
  • [0020]
    What is needed, therefore, is a method for non-invasively determining the level of oxygen saturation within biological tissue that can determine the total oxygen saturation level rather than a change in level; a method that provides calibration means to account for light attenuation due to scattering within tissue (G); and a method that can non-invasively distinguish the contribution of oxygen saturation attributable to venous blood and that which is attributable to arterial blood.
  • DISCLOSURE OF THE INVENTION
  • [0021]
    It is, therefore, an object of the present invention to provide a method for non-invasively determining the total level of blood oxygen saturation within biological tissue.
  • [0022]
    It is a further object of the present invention to provide a method that provides calibration means to account for light attenuation due to scattering within tissue, light attenuation due to fixed tissue absorbers, and light attenuation due to variability between light measuring apparatuses.
  • [0023]
    It is a still further object of the present invention to provide a method that can non-invasively distinguish between the contribution of oxygen saturation attributable to venous blood and that attributable to arterial blood.
  • [0024]
    According to the present invention, a method and apparatus for non-invasively determining the blood oxygen saturation level within a subject's tissue is provided that utilizes a near infrared spectrophotometric (NIRS) sensor capable of transmitting a light signal into the tissue of a subject and sensing the light signal once it has passed through the tissue via transmittance or reflectance. The method includes the step of determining attenuation of the light signal as the sum of: (i) attenuation attributable to deoxyhemoglobin; (ii) attenuation attributable to oxyhemoglobin; and (iii) attenuation attributable to light scattering within the subject's tissue. The present method also makes it possible to account for attenuation attributable to fixed or constant light absorbing biological tissue components, and attenuation attributable to variable characteristics of the sensor. By determining differential attenuation as a function of wavelength, the attenuation attributable to tissue light scattering characteristics, fixed light absorbing components, and measuring apparatus characteristics are mathematically cancelled out or minimized relative to the attenuation attributable to deoxyhemoglobin, and attenuation attributable to oxyhemoglobin.
  • [0025]
    In order to account for the resulting minimized differential attenuation attributable to tissue light scattering characteristics, fixed light absorbing components, and measuring apparatus characteristics, each of the parameters must be measured or calibrated out. Since direct measurement is difficult, calibration to empirically determined data combined with data developed using the NIRS sensor is performed by using regression techniques. The empirically determined data is collected at or about the same time the data is developed with the NIRS sensor. Once the calibration parameters associated with attenuation attributable to tissue light scattering characteristics, fixed light absorbing components, and measuring apparatus characteristics have been determined, the NIRS sensor can be calibrated.
  • [0026]
    The calibrated sensor can then be used to accurately and non-invasively determine the total oxygen saturation level in the original subject tissue or other subject tissue. In addition, if the separation distance (“d”) between the light source to the light detector is known or is determinable, and if the value of “B”, which represents the wavelength dependent light scattering differential pathlength factor, is known, then the total amount of concentrations of deoxyhemoglobin (Hb) and oxyhemoglobin (HbO2) within the examined tissue can be determined using the present method and apparatus.
  • [0027]
    The calibrated sensor can be used subsequently to calibrate similar sensors without having to invasively produce a blood sample. Hence, the present method and apparatus enables a non-invasive determination of the blood oxygen saturation level within tissue. For example, an operator can create reference values by sensing a light signal or other reference medium using the calibrated sensor. The operator can then calibrate an uncalibrated sensor by sensing the same light signal or reference medium, and subsequently adjusting the uncalibrated sensor into agreement with the calibrated sensor. Hence, once a reference sensor is created, other similar sensors can be calibrated without the need for invasive procedure.
  • [0028]
    There are, therefore, several advantages provided by the present method and apparatus. Those advantages include: 1) a practical non-invasive method and apparatus for determining oxygen saturation within tissue that can be used to determine the total blood oxygen saturation within tissue as opposed to a change in blood oxygen saturation; 2) a calibration method that accounts for light attenuation due to scattering within tissue (G), fixed tissue absorbers (F), and measuring apparatus variability (N); and 3) a practical non-invasive method and apparatus for determining oxygen saturation within tissue that can distinguish between the contribution of oxygen saturation attributable to venous blood and that saturation attributable to arterial blood.
  • [0029]
    In an alternative embodiment, aspects of the above-described methodology are combined with pulse oximetry techniques to provide a non-invasive method of distinguishing between blood oxygen saturation within tissue that is attributable to venous blood and that which is attributable to arterial blood. Pulse oximetry is used to determine arterial oxygen saturation, and the arterial oxygen saturation is, in turn, used to determine the venous oxygen saturation.
  • [0030]
    These and other objects, features, and advantages of the present invention method and apparatus will become apparent in light of the detailed description of the invention provided below and the accompanying drawings. The methodology and apparatus described below constitute a preferred embodiment of the underlying invention and do not, therefore, constitute all aspects of the invention that will or may become apparent by one of skill in the art after consideration of the invention disclosed overall herein.
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • [0031]
    [0031]FIG. 1 is a diagrammatic representation of a NIRS sensor placed on a subject's head.
  • [0032]
    [0032]FIG. 2 is a diagrammatic representation of a NIRS sensor.
  • [0033]
    [0033]FIG. 3 is a diagrammatic view of a NIRS sensor.
  • [0034]
    [0034]FIG. 4 is a block diagram of the present methodology for calibrating a NIRS sensor.
  • [0035]
    [0035]FIG. 5 is a graph showing an exemplary plot of absorption coefficient vs. wavelength.
  • DETAILED DESCRIPTION THE INVENTION
  • [0036]
    The present method of and apparatus for non-invasively determining the blood oxygen saturation level within a subject's tissue is provided that utilizes a near infrared spectrophotometric (NIRS) sensor that includes a transducer capable of transmitting a light signal into the tissue of a subject and sensing the light signal once it has passed through the tissue via transmittance or reflectance. The present method and apparatus can be used with a variety of NIRS sensors. The NIRS sensor described below, which is the subject of co-pending U.S. patent application Ser. No. 09/434,146 filed Nov. 4, 1999 commonly assigned with the present application, discloses a preferred NIRS sensor. The present method is not limited to use with this preferred NIRS sensor, however.
  • [0037]
    Referring to FIGS. 1-5, the preferred NIRS sensor includes a transducer portion 10 and processor portion 12. The transducer portion 10 includes an assembly housing 14 and a connector housing 16. The assembly housing 14, which is a flexible structure that can be attached directly to a subject's body, includes one or more light sources 18 and a light detector 20. A disposable adhesive envelope or pad is used for mounting the assembly housing 14 easily and securely to the subject's skin. Light signals of known but different wavelengths from the light sources 18 emit through a prism assembly 22. The light sources 18 are preferably laser diodes that emit light at a narrow spectral bandwidth at predetermined wavelengths. In one embodiment, the laser diodes are mounted within the connector housing 16. The laser diodes are optically interfaced with a fiber optic light guide to the prism assembly 22 that is disposed within the assembly housing 14. In a second embodiment, the light sources 18 are mounted within the assembly housing 14. A first connector cable 26 connects the assembly housing 14 to the connector housing 16 and a second connector cable 28 connects the connector housing 16 to the processor portion 12. The light detector 20 includes one or more photodiodes. The photodiodes are also operably connected to the processor portion 12 via the first and second connector cables 26,28. The processor portion 12 includes a processor for processing light intensity signals from the light sources 18 and the light detector 20.
  • [0038]
    The processor utilizes an algorithm that characterizes a change in attenuation as a function of the difference in attenuation between different wavelengths. The present method advantageously accounts for but minimizes the attenuation effects of the scattering variable “G”, pathlength B*d, and the absorption “F” due to other components present in biological tissue (i.e. bone, water, skin pigmentation, etc.) that have a relatively flat or very low absorption spectra over the measured wavelength range. In addition, the present method accounts for any offset attenuation “N” due to the characteristics of the sensor that may or may not be wavelength independent. The present method algorithm can be expressed as:
  • A λ1 −A λ2 =ΔA λ1−λ2 =ΔA λ12   (5)
  • [0039]
    where Aλ1 and Aλ2 are in the form of Equation 6 below which is a modified version of Equation 2 that accounts for attenuation due to “F” and “N”:
  • A λ=−log(I/I o)λλ *C*d*B λ +G+F+N   (6)
  • [0040]
    Substituting Equation 6 into Equation 5 for Aλ1 and Aλ2, the terms “F” and “N” within Equation 5 are subtracted out, provided they represent constant light absorption over the measurement wavelengths and provided the same sensor is used to sense the light signal at the various wavelengths. Therefore, in the case where the differential pathlength factor B is wavelength independent, then ΔAλ2 can be expressed as:
  • ΔA λ12=log[(I λ1 /Io λ1)*(I λ2 /Io λ2)]=Δαcλ12 cdB+ΔG λ12   (7)
  • [0041]
    and rewritten in expanded form:
  • ΔA λ12=(αHbλ1−αHbλ2)[Hb]dB+(αHbO 2 λ1−αHbO 2 λ2)[HbO 2 ]dB+ΔG λ12   (8)
  • [0042]
    Alternatively, the differential pathlength factor “B” may be wavelength dependent. In this case, it is desirable to separate Bλ into two components:
  • B λ =B*k 80   (9)
  • [0043]
    The parameter B is determined at one specific wavelength and the parameter kλ represents how B would change at other wavelengths. To continue with the mathematical derivations, it is then desirable to combine the pathlength wavelength dependent parameter kλ to αλ:
  • α′λλ *k λ  (10)
  • [0044]
    The parameter α′λ represents the absorption coefficient αλ adjusted by pathlength wavelength dependent parameter kλ. Incorporation of these modifications into Equation 7 results in the following:
  • ΔA λ12=(α′Hbλ1−a′Hbλ2)[Hb]dB+(α′HbO 2 λ1−α′HbO 2 λ2)[HbO 2]dB+ΔG λ12   (11)
  • [0045]
    where:
  • (α′Hbλ1−α′Hbλ2)[Hb]dB
  • [0046]
    represents the attenuation attributable to Hb;
  • (α′HbO 2 λ1−α′HbO 2 λ2)[HbO2]dB
  • [0047]
    represents the attenuation attributable to HbO2; and
  • ΔGλ12
  • [0048]
    represents the attenuation attributable to light scattering within tissue (G).
  • [0049]
    In another alternative case, the light absorption due to the fixed tissue absorbers (F), and sensor variability (N) may not be constant over the measuring wavelengths. In this case, differential attenuation as a function of wavelength would result in the parameters ΔFλ12 and ΔNλ12, to be included in Equation 7 or Equation 11.
  • ΔA λ12=(α′Hbλ1−α′Hbλ2)[Hb]dB+(α′HbO 2 λ1−α′HbO 2 λ2)[HbO 2]dB+ΔG λ12 +ΔF λ12 +ΔN λ12 (12)
  • [0050]
    The parameter ΔNλ12, does not change in magnitude for a particular NIRS sensor. The parameter ΔFλ12, by definition, would be the result of differential attenuation due to components that have a relatively flat or very low absorption spectra over the measured wavelength range, and therefore would be a very small and relatively constant value when compared to the differential attenuation due to hemoglobin. Thus, ΔFλ12 can be seen as a fixed absorber error correcting parameter in Equation 12. Therefore, these parameters then can be summed together by superposition to become ΔG′λ12:
  • ΔG′ λ12 =ΔG λ12 +ΔF λ12 +ΔN λ12   (13)
  • [0051]
    Incorporation of these modifications into Equation 12 results in the following:
  • ΔA λ12=(α′Hbλ1−α′Hbλ2)[Hb]dB+(α′HbO 2 λ1−α′HbO 2 λ2)[HbO 2 ]dB+ΔG′ λ12   (14)
  • [0052]
    Note that if ΔGλ12<<Gλ1 and Gλ2, the effect of G is minimized within Equation 11, in contrast with the effect of G within Equation 2, at the cost of utilizing one more wavelength to determine Hb and HbO2. Thus, a minimum of three different wavelengths is needed to determine Hb and HbO2. Also in the alternative case, ΔGλ12 minimizes the effects of light attenuation due to scattering within tissue (G), fixed tissue absorbers (F), and sensor variability (N), at the same cost of utilizing one more wavelength.
  • [0053]
    The multivariate form of Equation 11 or 14, after mathematical manipulation, is used to determine HbO2 and Hb with three different wavelengths: [ Δ A λ12 - Δ G λ12 Δ A λ13 - Δ G λ13 ] ( dB ) - 1 = [ Δ α Hb λ12 Δα HbO 2 λ12 Δ α Hb λ13 Δα HbO 2 λ13 ] [ Hb HbO 2 ] (Eqn. 15)
    Figure US20010047128A1-20011129-M00002
  • [0054]
    Rearranging and solving for HbO2 and Hb, simplifying the Δα′ matrix into [Δα′]: [ Δ A λ12 Δ A λ13 ] [ Δα ] - 1 ( dB ) - 1 - [ Δ G λ12 Δ G λ13 ] [ Δα ] - 1 ( dB λ ) - 1 = [ Hb HbO 2 ] (Eqn. 16)
    Figure US20010047128A1-20011129-M00003
  • [0055]
    and rewritten into: [ A Hb A HbO 2 ] ( dB ) - 1 - [ Ψ Hb Ψ HbO 2 ] ( dB ) - 1 = [ Hb HbO 2 ] (Eqn. 17)
    Figure US20010047128A1-20011129-M00004
  • [0056]
    The parameters AHb and AHbO2 represent the product of the matrices [ΔAλ] and [Δα′]−1 and the parameters ΨHb and ΨHbO2 represent the product of the matrices [ΔG′λ] and [Δα′]−1. To determine the level of cerebral blood oxygen saturation (CrSO2), Equation 17 is rearranged using the form of Equation 1 and is expressed as follows: CrSO 2 % = ( A HbO 2 - Ψ HbO 2 ) ( A HbO 2 - Ψ HbO 2 + A Hb - Ψ Hb ) * 100 % (Eqn. 18)
    Figure US20010047128A1-20011129-M00005
  • [0057]
    Note that the pathlength d*B cancels out in the manipulation from Equation 17 to Equation 18.
  • [0058]
    The value for CrSO2 is initially determined from SmvO2 using Equation 4 and the empirically determined values for SvO2 and SaO2. The empirically determined values for SvO2 and SaO2 are based on data developed by discrete sampling or continuous monitoring of the subject's blood performed at or about the same time as the sensing of the tissue with the sensor. The temporal proximity of the NIRS sensing and the development of the empirical data helps assure accuracy. The initial values for Kv and Ka within Equation 4 are clinically reasonable values for the circumstances at hand. The values for AHbO2 and AHb are determined mathematically using the values for Ioλ and Iλ for each wavelength sensed with the NIRS sensor (e.g., using Equation 2 or 6). The calibration parameters ΨHb and ΨHbO2, which account for the effects of light attenuation due to scattering within tissue (G), fixed tissue absorbers (F), and measuring apparatus variability (N), are then determined using Equation 18 and non-linear regression techniques by correlation to different weighted values of SvO2 and SaO2; i.e., different values of Ka and Kv. Statistically acceptable values of Kv and Ka and ΨHb and ΨHbO2 are converged upon using the non-linear regression techniques. Experimental findings show that after proper selection of Ka and Kv, the calibration parameters ΨHb and ΨHbO2 are constant within a statistically acceptable margin of error for an individual NIRS sensor used to monitor brain oxygenation on different human subjects. In other words, once the sensor is calibrated it can be used on various human subjects and produce accurate information for each human subject.
  • [0059]
    In the determination of the CrSO2 percentage, the photon pathlength “d*B” cancels out. If, however, the photon pathlength is known or estimated, then the determination of the total value of Hb and/or HbO2 is possible. For example, if a value for pathlength “d*B” is input into Equation 17 along with the calibration values Hb and ΨHbO2, then the total value of Hb and/or HbO2 can be calculated. The light source to detector separation (optode) distance parameter “d” in the pathlength calculation is a measurable value and can be made constant by setting a fixed distance between light source to detector in the NIRS sensor design. Alternatively, the parameter “d” can be measured once the optodes are placed on the subject by use of calipers, ruler, or other distance measurement means. The pathlength differential factor “B” is more difficult to measure and requires more sophisticated equipment. From a large data set of measured neonatal and adult head differential pathlength factor values, an estimation of the value of “B” can be determined within a statistically acceptable margin of error. Substitution of these predetermined values of “B” into Equation 17 results in the determination of the total values of Hb and HbO2.
  • [0060]
    An alternative method of determining total values of Hb and HbO2 combines Equation 3 and Equation 17 together. The multivariate form of Equation 3 is shown below: [ - log ( I t2 / I t1 ) λ1 / ( d * B λ1 ) - log ( I t2 / I t1 ) λ2 / ( d * B λ2 ) - log ( I t2 / I t1 ) λ3 / ( d * B λ3 ) ] = [ α Hb λ1 α HbO 2 λ1 α Hb λ 2 α HbO 2 λ2 α Hb λ3 α HbO 2 λ3 ] * [ Δ Hb Δ HbO 2 ] (Eqn. 19)
    Figure US20010047128A1-20011129-M00006
  • [0061]
    At time t=t1, the values of ΔHb and ΔHbO2 are zero. Applying Equation 17, and knowing the calibration values of ΨHb and ΨHbO2 at a predetermined differential pathlength factor “B” and optode separation “d”, the total absolute values of Hb and HbO2 are determined at time t=t1, which are represented by [Hb]t1 and [HbO2]t1 respectively. At time t=t2, the values of ΔHb and ΔHbO2 are then determined using Equation 19. The total values of Hb and HbO2 are then determined at time t=t2 using the following equations:
  • [Hb] t2 =ΔHb(t 2)+[Hb] t1   (20)
  • [HbO 2]t2 =ΔHbO 2(t 2)+[HbO 2]t1 (21)
  • [0062]
    Equations 20 and 21 are valid only if all the shared parameters in Equations 17 and 19 are exact. Reduced to practice, the advantage of combining Equations 17 and 19 result in improved signal to noise ratio (SNR) in the calculation of the total values for Hb and HbO2. Conversely, improved SNR in the calculation of CrSO2 is also obtained from the following expression: CrSO 2 ( t 2 ) = [ HbO 2 ] t 2 ( [ HbO2 ] t 2 + [ Hb ] t 2 ) * 100 % (Eqn. 22)
    Figure US20010047128A1-20011129-M00007
  • [0063]
    After the calibration parameters ΨHb and ΨHbO2 are determined using the above-described methodology for an individual NIRS sensor, this particular sensor is said to be calibrated. A calibrated NIRS sensor affords accurate measurement of total tissue oxygen saturation, CrSO2, by non-invasive means. The calibrated sensor can be used thereafter on any human patient, including adults and neonates. Although the present method is described above in terms of sensing blood oxygenation within cerebral tissue, the present method and apparatus are not limited to cerebral applications and can be used to determine blood oxygenation within tissue found elsewhere within the subject's body.
  • [0064]
    According to an additional aspect of the present invention, the above-described method can also be used to establish a calibrated “reference” sensor that can be used to calibrate similar sensors through the use of a phantom sample (also referred to as a “reference sample”). The phantom sample has optical characteristics that are similar to the tissue being examined by the NIRS sensor. The calibrated reference NIRS sensor is used to sense the phantom sample and produce reference values. Similar, but uncalibrated, NIRS sensors can thereafter be calibrated by sensing the same phantom sample and adjusting either the hardware of the uncalibrated sensor or the output of the uncalibrated sensor until the output of the uncalibrated sensor agrees with the reference values produced by the calibrated reference sensor. Therefore, the calibration parameters ΨHb and ΨHbO2 for the uncalibrated sensor would be determined from the phantom sample. This technique makes it unnecessary to calibrate each new sensor in the manner described above, and thereby provides a relatively quick and cost effective way to calibrate NIRS sensors.
  • [0065]
    Besides Hb and HbO2, other biological constituents of interest (e.g., cytochrome aa3, etc.) could be determined using the multivariate forms of equations 2, 3, 6 or 7. For each additional constituent to be determined, an additional measuring wavelength will be needed.
  • [0066]
    In an alternative embodiment, the above-described methodology can be combined with pulse oximetry techniques to provide an alternative non-invasive method of distinguishing between oxygen saturation attributable to venous blood and that attributable to arterial blood. As demonstrated by Equation 4, SmvO2 is determined by the ratio of venous oxygen saturation SvO2 and arterial oxygen saturation SaO2. A calibrated NIRS sensor affords accurate measurement of total tissue oxygen saturation, CrSO2, by using regression techniques by correlation to mixed venous oxygen saturation SmvO2. Therefore, the following expression will result:
  • CrSO 2 =SmvO 2 =Kv*SvO 2 +Ka*SaO 2   (23)
  • [0067]
    Non-invasive pulse oximetry techniques can be used to determine the arterial oxygen saturation (SaO2) of peripheral tissue (i.e. finger, ear, nose) by monitoring pulsatile optical attenuation changes of detected light induced by pulsatile arterial blood volume changes in the arteriolar vascular system. Arterial blood oxygen saturation determined by pulse oximetry is clinically denoted as SpO2. If NIRS monitoring and pulse oximetry monitoring are done simultaneously and SpO2 is set equal to SaO2 in Equation 23, then venous oxygen saturation can be determined from the following expression: SvO 2 = CrSO 2 - ( Ka * SpO 2 ) Kv (Eqn. 24)
    Figure US20010047128A1-20011129-M00008
  • [0068]
    For the brain, venous oxygen saturation SvO2 would be determined from internal jugular vein (SijvO2), jugular bulb (SjbO2), or sagittal sinus (SssO2) and the parameters Ka and Kv would be empirically determined during the calibration of the NIRS sensor. Under most physiological conditions, SpO2 is representative of brain arterial oxygen saturation SaO2. Therefore, depending on which venous saturation parameter was used to calibrate the NIRS sensor, this clinically important parameter (i.e., SijvO2, SjbO2, or SssO2) can be determined by Equation 24 by non-invasive means.
  • [0069]
    Since many changes and variations of the disclosed embodiment of the invention may be made without departing from the inventive concept, it is not intended to limit the invention otherwise than as required by the appended claims.

Claims (44)

    What is claimed is:
  1. 1. A method for non-invasively determining a blood oxygen saturation level within a subject's tissue using a near infrared spectrophotometric sensor, said method comprising the steps of:
    transmitting a light signal into the subject's tissue at a predetermined first intensity using the sensor, wherein the transmitted light signal includes a first wavelength, a second wavelength, and a third wavelength;
    sensing a second intensity of the light signal, using the sensor, along the first, second, and third wavelengths after the light signal travels through the subject;
    wherein the sensor is calibrated using empirical data that relates to the subject's tissue that is sensed by the sensor to account for light signal attenuation resulting from light signal scattering within the subject's tissue;
    determining an attenuation of the light signal for each of the first, second, and third wavelengths using the predetermined first intensity and the sensed second intensity of the first, second, and third wavelengths;
    determining a difference in attenuation of the light signal between the first wavelength and the second wavelength, and between the first wavelength and the third wavelength;
    determining the blood oxygen saturation level within the subject's tissue using the difference in attenuation between the first wavelength and the second wavelength, and the difference in attenuation between the first wavelength and the third wavelength.
  2. 2. The method of
    claim 1
    , wherein the sensor is calibrated using equation:
    SmvO2=Kv*SvO2+Ka*SaO2.
  3. 3. The method of
    claim 2
    , wherein the sensor is calibrated by using empirical data to determine a first calibration constant and a second calibration constant.
  4. 4. The method of
    claim 3
    , wherein the step of determining the blood oxygen saturation level within the subject's tissue utilizes the equation:
    CrSO 2 % = ( A HbO 2 - Ψ HbO 2 ) ( A HbO 2 - Ψ HbO 2 + A Hb - Ψ Hb ) * 100 %
    Figure US20010047128A1-20011129-M00009
    where ΨHbO2 represents the first calibration constant, ΨHb represents the second calibration constant, AHbO2 represents a difference in attenuation of light signal attributable to oxyhemoglobin, and AHb represents a difference in attenuation of light signal attributable to deoxyhemoglobin.
  5. 5. The method of
    claim 4
    , further comprising the steps of:
    determining a photon pathlength d*B; and
    determining a concentration of oxyhemoglobin and a concentration of deoxyhemoglobin within the subject's tissue using the first and second calibration constants.
  6. 6. The method of
    claim 5
    , wherein the concentration of oxyhemoglobin and the concentration of deoxyhemoglobin within the subject's tissue are determined using the equation:
    [ A Hb A HbO 2 ] ( dB ) - 1 - [ Ψ Hb Ψ HbO 2 ] ( dB ) - 1 = [ Hb HbO 2 ] .
    Figure US20010047128A1-20011129-M00010
  7. 7. The method of
    claim 6
    , wherein the step of determining a difference in attenuation of the light signal between the first wavelength and the second wavelength utilizes the equation:
    ΔA λ12=log[(I λ1 /Io λ1)*(I λ2 /Io λ2)]=Δαcλ12 cdB+ΔG λ12
    and the step of determining a difference in attenuation of the light signal between the first wavelength and the third wavelength utilizes the equation:
    ΔA λ13=log[(I λ1 /Io λ1)*(I λ3 /Io λ3)]=Δαcλ13 cdB+ΔG λ13.
  8. 8. The method of
    claim 6
    , wherein the step of determining a difference in attenuation of the light signal between the first wavelength and the second wavelength utilizes the equation:
    ΔA λ12=(α′Hbλ1−α′Hbλ2)[Hb]dB+(α′HbO 2 λ1−α′HbO 2 λ2)[HbO 2 ]dB+ΔG λ12
    and the step of determining a difference in attenuation of the light signal between the first wavelength and the third wavelength utilizes the equation:
    ΔA λ13=(α′Hbλ1−α′Hbλ3)[Hb]dB+(α′HbO 2 λ1−α′HbO 2 λ3)[HbO 2 ]dB+ΔG λ13.
  9. 9. The method of
    claim 6
    , wherein the step of determining a difference in attenuation of the light signal between the first wavelength and the second wavelength utilizes the equation:
    ΔA λ12=(α′Hbλ1−α′Hbλ2)[Hb]dB+(α′HbO 2 λ1−α′HbO 2 λ2)[HbO 2 ]dB+ΔG′ λ12
    and the step of determining a difference in attenuation of the light signal between the first wavelength and the third wavelength utilizes the equation:
    ΔA λ13=(α′Hbλ1−α′Hbλ3)[Hb]dB+(α′HbO 2λ1−α′HbO 2 λ3)[HbO 2 ]dB+ΔG′ λ13.
  10. 10. The method of
    claim 1
    , wherein the step of determining a difference in attenuation of the light signal between the first wavelength and the second wavelength utilizes the equation:
    ΔA λ12=log[(I λ1 /Io λ1)*(I λ2 /Io λ2)]=Δαcλ12 cdB+ΔG λ12
    and the step of determining a difference in attenuation of the light signal between the first wavelength and the third wavelength utilizes the equation:
    ΔA λ13=log[(I λ1 /Io λ1)*(I λ3 /Io λ3)]=Δαcλ13 cdB+ΔG λ13.
  11. 11. The method of
    claim 1
    , wherein the step of determining a difference in attenuation of the light signal between the first wavelength and the second wavelength utilizes the equation:
    ΔA λ12=(α′Hbλ1−α′Hbλ2)[Hb]dB+(α′HbO 2 λ1−α′HbO 2 λ2)[HbO 2 ]dB+ΔG λ12
    and the step of determining a difference in attenuation of the light signal between the first wavelength and the third wavelength utilizes the equation:
    ΔA λ13=(α′Hbλ1−α′Hbλ3)[Hb]dB+(α′HbO 2 λ1−α′HbO 2 λ3)[HbO 2 ]dB+ΔG λ13.
  12. 12. The method of
    claim 1
    , wherein the step of determining a difference in attenuation of the light signal between the first wavelength and the second wavelength utilizes the equation:
    ΔA λ12=(α′Hbλ1−α′Hbλ2)[Hb]dB+(α′HbO 2 λ1−α′HbO 2 λ2)[HbO 2 ]dB+ΔG′ λ12
    and the step of determining a difference in attenuation of the light signal between the first wavelength and the third wavelength utilizes the equation:
    ΔA λ13=(α′Hbλ1−α′Hbλ3)[Hb]dB+(α′HbO 2 λ1−α′HbO 2 λ3)[HbO 2 ]dB+ΔG′ λ13.
  13. 13. The method of
    claim 2
    , further comprising the steps of:
    determining a blood oxygen saturation level attributable to arterial blood within the subject's tissue using a pulse oximetry technique; and
    determining a blood oxygen saturation level attributable to venous blood within the subject's tissue using the equation:
    SvO 2 = CRSO 2 - ( Ka * SpO 2 ) Kv .
    Figure US20010047128A1-20011129-M00011
  14. 14. A method for determining a blood oxygen saturation level within a subject's tissue using a near infrared spectrophotometric sensor attached to the skin of the subject, said method comprising the steps of:
    transmitting a light signal into the subject's tissue at a predetermined first intensity, wherein the transmitted light signal includes a first wavelength, a second wavelength, and a third wavelength;
    sensing a second intensity of the light signal along the first, second, and third wavelengths after the light signal travels through the subject;
    determining an attenuation of the light signal for each of the first, second, and third wavelengths using the predetermined first intensity and the sensed second intensity of the first, second, and third wavelengths;
    determining a difference in attenuation of the light signal between the first wavelength and the second wavelength, and between the first wavelength and the third wavelength;
    determining a first calibration constant and a second calibration constant using empirical data developed from the subject at or about the same time as when the sensing occurs;
    determining the blood oxygen saturation level within the subject's tissue using the difference in attenuation between the first wavelength and the second wavelength, and the difference in attenuation between the first wavelength and the third wavelength, and the first calibration constant and the second calibration constant.
  15. 15. The method of
    claim 14
    wherein the empirical data is collected by discretely sampling a venous blood source and an arterial blood source from the subject.
  16. 16. The method of
    claim 14
    wherein the empirical data is collected by continuously monitoring a venous blood source and an arterial blood source from the subject.
  17. 17. The method of
    claim 14
    , wherein the sensor is calibrated using equation:
    SmvO2=Kv*SvO2+Ka*SaO2.
  18. 18. The method of
    claim 17
    , wherein the step of determining the blood oxygen saturation level within the subject's tissue utilizes the equation:
    CrSO 2 % = ( A HbO 2 - Ψ HbO 2 ) ( A HbO 2 - Ψ HbO 2 + A Hb - Ψ Hb ) * 100 %
    Figure US20010047128A1-20011129-M00012
    where ΨHbO2 represents the first calibration constant, ΨHb represents the second calibration constant, AHbO2 represents a difference in attenuation of light signal attributable to oxyhemoglobin, and AHb represents a difference in attenuation of light signal attributable to deoxyhemoglobin..
  19. 19. The method of
    claim 18
    , further comprising the steps of:
    determining a photon pathlength d*B; and
    determining the concentration of oxyhemoglobin and deoxyhemoglobin within the subject's tissue using the first and second calibration constants.
  20. 20. The method of
    claim 19
    , wherein the concentration of oxyhemoglobin and deoxyhemoglobin within the subject's tissue are determined using the equation
    [ A Hb A HbO 2 ] ( d B ) - 1 - [ Ψ Hb Ψ HbO 2 ] ( dB ) - 1 = [ Hb HbO 2 ] .
    Figure US20010047128A1-20011129-M00013
  21. 21. The method of
    claim 20
    , wherein the step of determining a difference in attenuation of the light signal between the first wavelength and the second wavelength utilizes the equation:
    ΔA λ12=log[(I λ1 /Io λ1)*(I λ2 /Io λ2)]=Δαcλ12 cdB+ΔG λ12
    and the step of determining a difference in attenuation of the light signal between the first wavelength and the third wavelength utilizes the equation:
    ΔA λ13=log[(I λ1 /Io λ1)*(I λ3 /Io λ3)]=Δαcλ13 cdB+ΔG λ13.
  22. 22. The method of
    claim 20
    , wherein the step of determining a difference in attenuation of the light signal between the first wavelength and the second wavelength utilizes the equation:
    ΔA λ12=(α′Hbλ1−α′Hbλ2)[Hb]dB+(α′HbO 2 λ1−α′HbO 2 λ2)[HbO 2 ]dB+ΔG λ12
    and the step of determining a difference in attenuation of the light signal between the first wavelength and the third wavelength utilizes the equation:
    ΔA λ13=(α′Hbλ1−α′Hbλ3)[Hb]dB+(α′HbO 2 λ1−α′HbO 2 λ3)[HbO 2 ]dB+ΔG λ13.
  23. 23. The method of
    claim 20
    , wherein the step of determining a difference in attenuation of the light signal between the first wavelength and the second wavelength utilizes the equation:
    ΔA λ12=(α′Hbλ1−α′Hbλ2)[Hb]dB+(α′HbO 2 λ1−α′HbO 2 λ2)[HbO 2 ]dB+ΔG′ λ12
    and the step of determining a difference in attenuation of the light signal between the first wavelength and the third wavelength utilizes the equation:
    ΔA λ13=(α′Hbλ1 −α′Hbλ3)[Hb]dB+(α′HbO 2 λ1−α′HbO 2 λ3)[HbO 2 ]dB+ΔG′ λ13.
  24. 24. The method of
    claim 14
    , wherein the step of determining the blood oxygen saturation level within the subject's tissue utilizes the equation:
    CrSO 2 % = ( A HbO 2 - Ψ HbO 2 ) ( A HbO 2 - Ψ HbO 2 + A Hb - Ψ Hb ) * 100 %
    Figure US20010047128A1-20011129-M00014
    where ΨHbO2 represents the first calibration constant, ΨHb represents the second calibration constant, AHbO2 represents a difference in attenuation of light signal attributable to oxyhemoglobin, and AHb represents a difference in attenuation of light signal attributable to deoxyhemoglobin.
  25. 25. The method of
    claim 24
    , further comprising the steps of:
    determining a photon pathlength d*B; and
    determining the concentration of oxyhemoglobin and deoxyhemoglobin within the subject's tissue using the first and second calibration constants.
  26. 26. The method of
    claim 25
    , wherein the concentration of oxyhemoglobin and deoxyhemoglobin within the subject's tissue are determined using the equation
    [ A Hb A HbO 2 ] ( d B ) - 1 - [ Ψ Hb Ψ HbO 2 ] ( dB ) - 1 = [ Hb HbO 2 ] .
    Figure US20010047128A1-20011129-M00015
  27. 27. The method of
    claim 26
    , wherein the step of determining a difference in attenuation of the light signal between the first wavelength and the second wavelength utilizes the equation:
    ΔA λ12=log[(I λ1 /Io λ1)*(I λ2 /Io λ2)]=Δαcλ12 cdB+ΔG λ12
    and the step of determining a difference in attenuation of the light signal between the first wavelength and the third wavelength utilizes the equation:
    ΔA λ13=log[(I λ1 /Io λ1)*(I λ3 /Io λ3)]=Δαcλ13 cdB+ΔG λ13.
  28. 28. The method of
    claim 26
    , wherein the step of determining a difference in attenuation of the light signal between the first wavelength and the second wavelength utilizes the equation:
    ΔA λ12=(α′Hbλ1−α′Hbλ2)[Hb]dB+(α′HbO 2 λ1−α′HbO 2 λ2)[HbO 2 ]dB+ΔG λ12
    and the step of determining a difference in attenuation of the light signal between the first wavelength and the third wavelength utilizes the equation:
    ΔA λ13=(α′Hbλ1−α′Hbλ3)[Hb]dB+(α′HbO 2 λ1−α′HbO 2 λ3)[HbO 2 ]dB+ΔG λ13.
  29. 29. The method of
    claim 26
    , wherein the step of determining a difference in attenuation of the light signal between the first wavelength and the second wavelength utilizes the equation:
    ΔA λ12=(α′Hbλ1−α′Hbλ2)[Hb]dB+(α′HbO 2 λ1−α′HbO 2 λ2)[HbO 2 ]dB+ΔG′ λ12
    and the step of determining a difference in attenuation of the light signal between the first wavelength and the third wavelength utilizes the equation:
    ΔA λ13=(α′Hbλ1 −α′Hbλ3)[Hb]dB+(α′HbO 2 λ1−α′HbO 2 λ3)[HbO 2 ]dB+ΔG′ λ13.
  30. 30. A method for calibrating a near infrared spectrophotometric sensor for use in determining the blood oxygen saturation level within a subject's tissue, said method comprising the steps of:
    transmitting a light signal into the subject's tissue at a predetermined first intensity, wherein the transmitted light signal includes a first wavelength, a second wavelength, and a third wavelength;
    sensing a second intensity of the light signal along the first, second, and third wavelengths after the light signal travels through the subject;
    determining an attenuation of the light signal for each of the first, second, and third wavelengths using the predetermined first intensity and the sensed second intensity of the first, second, and third wavelengths;
    determining a difference in attenuation of the light signal between the first wavelength and the second wavelength, and between the first wavelength and the third wavelength;
    determining a first calibration constant and a second calibration constant using empirical data developed from the subject at or about the same time as when the sensing occurs; and
    calibrating the sensor using the first calibration constant and the second calibration constant.
  31. 31. The method of
    claim 30
    , wherein the empirical data is collected by discretely sampling a venous blood source and an arterial blood source from the subject.
  32. 32. The method of
    claim 30
    , wherein the empirical data is collected by continuously monitoring a venous blood source and an arterial blood source from the subject.
  33. 33. The method of
    claim 30
    , wherein the sensor is calibrated using equation:
    SmvO2=Kv*SvO2+Ka*SaO2.
  34. 34. The method of
    claim 33
    , wherein the step of determining a difference in attenuation of the light signal between the first wavelength and the second wavelength utilizes the equation:
    ΔA λ12=log[(I λ1 /Io λ1)*(I λ2 /Io λ2)]=Δαcλ12 cdB+ΔG λ12
    and the step of determining a difference in attenuation of the light signal between the first wavelength and the third wavelength utilizes the equation:
    ΔA λ13=log[(I λ1 /Io λ1)*(I λ3 /Io λ3)]=Δαcλ13 cdB+ΔG λ13.
  35. 35. The method of
    claim 33
    , wherein the step of determining a difference in attenuation of the light signal between the first wavelength and the second wavelength utilizes the equation:
    ΔA λ12=(α′Hbλ1−α′Hbλ2)[Hb]dB+(α′HbO 2 λ1−α′HbO 2 λ2)[HbO 2 ]dB+ΔG λ12
    and the step of determining a difference in attenuation of the light signal between the first wavelength and the third wavelength utilizes the equation:
    ΔA λ13=(α′Hbλ1−α′Hbλ3)[Hb]dB+(α′HbO 2 λ1−α′HbO 2 λ3)[HbO 2 ]dB+ΔG λ13.
  36. 36. The method of
    claim 33
    , wherein the step of determining a difference in attenuation of the light signal between the first wavelength and the second wavelength utilizes the equation:
    ΔA λ12=(α′Hbλ1−α′Hbλ2)[Hb]dB+(α′HbO 2 λ1−α′HbO 2 λ2)[HbO 2 ]dB+ΔG′ λ12
    and the step of determining a difference in attenuation of the light signal between the first wavelength and the third wavelength utilizes the equation:
    ΔA λ13=(α′Hbλ1 −α′Hbλ3)[Hb]dB+(α′HbO 2 λ1−α′HbO 2 λ3)[HbO 2 ]dB+ΔG′ λ13.
  37. 37. A method for calibrating a NIRS sensor, said method comprising the steps of:
    transmitting a light signal from a calibrated NIRS sensor into a reference sample at a predetermined first intensity, wherein the transmitted light signal includes a first wavelength, a second wavelength, and a third wavelength;
    sensing a second intensity of the light signal with the calibrated NIRS sensor along the first, second, and third wavelengths after the light signal travels through the reference sample;
    determining a first attenuation of the light signal for each of the first, second, and third wavelengths using the predetermined first intensity and the second intensity of the light signal sensed with the calibrated NIRS sensor;
    transmitting a light signal from an uncalibrated second NIRS sensor into the reference sample at the predetermined first intensity, wherein the transmitted light signal includes a first wavelength, a second wavelength, and a third wavelength;
    sensing a second intensity of the light signal with the uncalibrated second NIRS sensor along the first, second, and third wavelengths after the light signal travels through the subject;
    determining a second attenuation of the light signal for each of the first, second, and third wavelengths using the predetermined first intensity and the second intensity of the first, second, and third wavelengths sensed with the uncalibrated second NIRS sensor;
    adjusting the uncalibrated second NIRS sensor so that the second attenuation substantially agrees with the first attenuation.
  38. 38. A method for determining a blood oxygen saturation level within a subject's tissue attributable to venous blood, said method comprising the steps of:
    providing a NIRS sensor for sensing the subject's tissue;
    determining a blood oxygen saturation level with the subject's tissue using the NIRS sensor:
    determining a blood oxygen saturation level attributable to arterial blood within the subject's tissue using a pulse oximetry technique; and
    determining a blood oxygen saturation level attributable to venous blood within the subject's tissue using the equation:
    SvO 2 = CRSO 2 - ( Ka * SpO 2 ) Kv .
    Figure US20010047128A1-20011129-M00016
  39. 39. The method of
    claim 38
    , wherein the blood oxygen saturation level with the subject's tissue is determined using the following steps:
    transmitting a light signal into the subject's tissue at a predetermined first intensity, wherein the transmitted light signal includes a first wavelength, a second wavelength, and a third wavelength;
    sensing a second intensity of the light signal along the first, second, and third wavelengths after the light signal travels through the subject;
    determining an attenuation of the light signal for each of the first, second, and third wavelengths using the predetermined first intensity and the sensed second intensity of the first, second, and third wavelengths;
    determining a difference in attenuation of the light signal between the first wavelength and the second wavelength, and between the first wavelength and the third wavelength;
    determining a first calibration constant and a second calibration constant using empirical data developed from the subject at or about the same time as when the sensing occurs;
    determining the blood oxygen saturation level within the subject's tissue using the difference in attenuation between the first wavelength and the second wavelength, and the difference in attenuation between the first wavelength and the third wavelength.
  40. 40. A method for non-invasively determining a concentration of oxyhemoglobin and a concentration of deoxyhemoglobin within a subject's tissue using a near infrared spectrophotometric sensor, said method comprising the steps of:
    (a) determining a blood oxygen saturation level with the subject's tissue by
    transmitting a light signal into the subject's tissue from a NIRS sensor at a predetermined first intensity, wherein the transmitted light signal includes a first wavelength, a second wavelength, and a third wavelength;
    sensing a second intensity of the light signal along the first, second, and third wavelengths after the light signal travels through the subject using the sensor;
    wherein the sensor is calibrated using empirical data that relates to the subject's tissue that is sensed by the sensor to account for light signal attenuation resulting from light signal scattering within the subject's tissue;
    determining an attenuation of the light signal for each of the first, second, and third wavelengths using the predetermined first intensity and the sensed second intensity of the first, second, and third wavelengths;
    determining a difference in attenuation of the light signal between the first wavelength and the second wavelength, and between the first wavelength and the third wavelength;
    determining a first calibration constant and a second calibration constant using empirical data developed from the subject at or about the same time as when the sensing occurs;
    determining the blood oxygen saturation level within the subject's tissue using the difference in attenuation between the first wavelength and the second wavelength, and the difference in attenuation between the first wavelength and the third wavelength, and the first calibration constant and the second calibration constant;
    (b) determining a photon pathlength d*B; and
    (c) determining the concentration of oxyhemoglobin and the concentration of deoxyhemoglobin within the subject's tissue using the first and second calibration constants.
  41. 41. The method of
    claim 40
    , wherein the concentration of oxyhemoglobin and the concentration of deoxyhemoglobin within the subject's tissue are determined using the equation:
    [ A Hb A HbO 2 ] ( d B ) - 1 - [ Ψ Hb Ψ HbO 2 ] ( dB ) - 1 = [ Hb HbO 2 ] .
    Figure US20010047128A1-20011129-M00017
    where ΨHbO2 represents the first calibration constant, ΨHb represents the second calibration constant, AHbO2 represents a difference in attenuation of light signal attributable to oxyhemoglobin, and AHb represents a difference in attenuation of light signal attributable to deoxyhemoglobin.
  42. 42. A method for non-invasively determining a concentration of oxyhemoglobin and a concentration of deoxyhemoglobin within a subject's tissue at an initial time t1 and a subsequent time t2 using a near infrared spectrophotometric sensor, said method comprising the steps of:
    (a) determining a blood oxygen saturation level with the subject's tissue by
    transmitting a light signal into the subject's tissue from a NIRS sensor at a predetermined first intensity, wherein the transmitted light signal includes a first wavelength, a second wavelength, and a third wavelength;
    sensing a second intensity of the light signal along the first, second, and third wavelengths after the light signal travels through the subject using the sensor;
    wherein the sensor is calibrated using empirical data that relates to the subject's tissue that is sensed by the sensor to account for light signal attenuation resulting from light signal scattering within the subject's tissue;
    determining an attenuation of the light signal for each of the first, second, and third wavelengths using the predetermined first intensity and the sensed second intensity of the first, second, and third wavelengths;
    determining a difference in attenuation of the light signal between the first wavelength and the second wavelength, and between the first wavelength and the third wavelength;
    determining a first calibration constant and a second calibration constant using empirical data developed from the subject at or about the same time as when the sensing occurs;
    determining the blood oxygen saturation level within the subject's tissue using the difference in attenuation between the first wavelength and the second wavelength, and the difference in attenuation between the first wavelength and the third wavelength, and the first calibration constant and the second calibration constant;
    (b) determining a photon pathlength d*B;
    (c) determining the concentration of oxyhemoglobin and the concentration of deoxyhemoglobin within the subject's tissue at the initial time t1 using the equation:
    [ A Hb A HbO 2 ] ( d B ) - 1 - [ Ψ Hb Ψ HbO 2 ] ( dB ) - 1 = [ Hb HbO 2 ] t1
    Figure US20010047128A1-20011129-M00018
    where ΨHbO2 represents the first calibration constant, ΨHb represents the second calibration constant, AHbO2 represents a difference in attenuation of light signal attributable to oxyhemoglobin, and AHb represents a difference in attenuation of light signal attributable to deoxyhemoglobin; and
    (d) determining a change in the concentration of oxyhemoglobin and a change in the concentration of deoxyhemoglobin from the initial time t1 to a subsequent second time t2 are determined using the equation:
    [ - log ( I t2 / I t1 ) λ1 / ( d * B λ1 ) - log ( I t2 / I t1 ) λ2 / ( d * B λ2 ) - log ( I t2 / I t1 ) λ3 / ( d * B λ3 ) ] = [ α Hb λ1 α HbO 2 λ1 α Hb λ2 α HbO 2 λ2 α Hb λ3 α HbO 2 λ3 ] * [ Δ Hb Δ HbO 2 ]
    Figure US20010047128A1-20011129-M00019
    ;and
    (e) determining the concentration of oxyhemoglobin and the concentration of deoxyhemoglobin within the subject's tissue at the subsequent time t2 using the equations:
    [Hb] t2 =ΔHb(t 2)+[Hb] t1
    and
    [HbO 2]t2 =ΔHbO 2(t 2)+[HbO 2]t1.
  43. 43. A method for non-invasively determining a blood oxygen saturation level within a subject's tissue using a near infrared spectrophotometric sensor, said method comprising the steps of:
    transmitting a light signal into the subject's tissue at a predetermined first intensity using the sensor;
    sensing a second intensity of the light signal along three or more selectively chosen wavelengths after the light signal travels through the subject using the sensor;
    wherein the sensor is calibrated using empirical data that relates to the subject's tissue that is sensed by the sensor to account for light signal attenuation resulting from light signal scattering within the subject's tissue;
    determining an attenuation of the light signal for at least “n” number of the selectively chosen wavelengths using the predetermined first intensity and the sensed second intensity of the selectively chosen wavelengths, where “n” is an integer equal to or greater than three;
    determining a difference in attenuation of the light signal between a first wavelength and each of “n” number of the selectively chosen wavelengths;
    determining the blood oxygen saturation level within the subject's tissue using the difference in attenuation between the first wavelength and each of the “n” number of other selectively chosen wavelengths.
  44. 44. A method for determining a blood oxygen saturation level within a subject's tissue using a near infrared spectrophotometric sensor attached to the skin of the subject, said method comprising the steps of:
    transmitting a light signal into the subject's tissue at a predetermined first intensity;
    sensing a second intensity of the light signal along three or more selectively chosen wavelengths after the light signal travels through the subject;
    determining an attenuation of the light signal for at least “n” number of the selectively chosen wavelengths using the predetermined first intensity and the sensed second intensity of the selectively chosen wavelengths, where “n” is an integer equal to or greater than three;
    determining a difference in attenuation of the light signal between a first wavelength and each of “n” number of the selectively chosen wavelengths;
    determining a first calibration constant and a second calibration constant using empirical data developed from the subject at or about the same time as when the sensing occurs;
    determining the blood oxygen saturation level within the subject's tissue using the difference in attenuation between the first wavelength and each of “n” number of the selectively chosen wavelengths, and the first calibration constant and the second calibration constant.
US09845146 2000-05-02 2001-04-30 Method for non-invasive spectrophotometric blood oxygenation monitoring Active US6456862B2 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US20135900 true 2000-05-02 2000-05-02
US09845146 US6456862B2 (en) 2000-05-02 2001-04-30 Method for non-invasive spectrophotometric blood oxygenation monitoring

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US09845146 US6456862B2 (en) 2000-05-02 2001-04-30 Method for non-invasive spectrophotometric blood oxygenation monitoring

Publications (2)

Publication Number Publication Date
US20010047128A1 true true US20010047128A1 (en) 2001-11-29
US6456862B2 US6456862B2 (en) 2002-09-24

Family

ID=22745515

Family Applications (1)

Application Number Title Priority Date Filing Date
US09845146 Active US6456862B2 (en) 2000-05-02 2001-04-30 Method for non-invasive spectrophotometric blood oxygenation monitoring

Country Status (4)

Country Link
US (1) US6456862B2 (en)
EP (1) EP1259791B1 (en)
JP (1) JP2003532107A (en)
WO (1) WO2001084107A3 (en)

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040015060A1 (en) * 2002-06-21 2004-01-22 James Samsoondar Measurement of body compounds
EP1545298A2 (en) * 2002-07-26 2005-06-29 Cas Medical Systems, Inc. Method for spectrophotometric blood oxygenation monitoring
US20080208020A1 (en) * 2007-02-28 2008-08-28 Can Cinbis Implantable tissue perfusion sensing system and method
US7738935B1 (en) * 2002-07-09 2010-06-15 Pacesetter, Inc. Methods and devices for reduction of motion-induced noise in pulse oximetry
US20100317947A1 (en) * 2009-06-10 2010-12-16 Can Cinbis Tissue Oxygenation Monitoring in Heart Failure
US20120271130A1 (en) * 2011-04-11 2012-10-25 Cas Medical Systems, Inc. Method and apparatus for determining an oxygen desaturation event
US20130274573A1 (en) * 2012-03-09 2013-10-17 University Of Georgia Research Foundation, Inc. Systems And Methods For Measuring Mitochondrial Capacity
WO2015044336A1 (en) * 2013-09-30 2015-04-02 Apd Advanced Perfusion Diagnostics Non-invasive measurement device and method for estimating local metabolic parameters
EP2503935A4 (en) * 2009-11-24 2015-11-04 Cas Medical Systems Inc Method for spectrophotometric blood oxygenation monitoring of organs in the body
US9597025B2 (en) 2013-06-13 2017-03-21 Nihon Kohden Corporation Biological signal measuring system and biological signal measuring apparatus

Families Citing this family (116)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6018673A (en) 1996-10-10 2000-01-25 Nellcor Puritan Bennett Incorporated Motion compatible sensor for non-invasive optical blood analysis
US6675031B1 (en) 1999-04-14 2004-01-06 Mallinckrodt Inc. Method and circuit for indicating quality and accuracy of physiological measurements
US20020042558A1 (en) 2000-10-05 2002-04-11 Cybro Medical Ltd. Pulse oximeter and method of operation
US6898453B2 (en) * 2000-10-25 2005-05-24 The John P. Robarts Research Institute Method and apparatus for calculating blood flow parameters
EP1424934B1 (en) 2001-09-13 2008-08-06 ConMed Corporation A signal processing method and device for signal-to-noise improvement
US6748254B2 (en) 2001-10-12 2004-06-08 Nellcor Puritan Bennett Incorporated Stacked adhesive optical sensor
JP2003144439A (en) * 2001-11-09 2003-05-20 Japan Science & Technology Corp Method and device for measuring intrauterine oxygen moving state using optical technique
US6865407B2 (en) * 2002-07-11 2005-03-08 Optical Sensors, Inc. Calibration technique for non-invasive medical devices
DE60334007D1 (en) 2002-10-01 2010-10-14 Nellcor Puritan Bennett Inc Use of a headband to the voltage display and system of oximeter and headband
US8412297B2 (en) 2003-10-01 2013-04-02 Covidien Lp Forehead sensor placement
US7190986B1 (en) 2002-10-18 2007-03-13 Nellcor Puritan Bennett Inc. Non-adhesive oximeter sensor for sensitive skin
US7047056B2 (en) * 2003-06-25 2006-05-16 Nellcor Puritan Bennett Incorporated Hat-based oximeter sensor
JP2007504883A (en) 2003-09-12 2007-03-08 オル−ニム メディカル リミテッド Non-invasive optical monitoring of the target area
US7277741B2 (en) * 2004-03-09 2007-10-02 Nellcor Puritan Bennett Incorporated Pulse oximetry motion artifact rejection using near infrared absorption by water
US7706853B2 (en) * 2005-02-10 2010-04-27 Terumo Cardiovascular Systems Corporation Near infrared spectroscopy device with reusable portion
DK1863387T3 (en) 2005-03-16 2013-09-16 Or Nim Medical Ltd Non-invasive measurements in a human body
US7747301B2 (en) * 2005-03-30 2010-06-29 Skyline Biomedical, Inc. Apparatus and method for non-invasive and minimally-invasive sensing of parameters relating to blood
EP1885235B1 (en) * 2005-05-12 2013-12-18 Cas Medical Systems, Inc. Improved method for spectrophotometric blood oxygenation monitoring
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
US20070060808A1 (en) 2005-09-12 2007-03-15 Carine Hoarau Medical sensor for reducing motion artifacts and technique for using the same
US7899510B2 (en) 2005-09-29 2011-03-01 Nellcor Puritan Bennett Llc Medical sensor and technique for using the same
US7904130B2 (en) 2005-09-29 2011-03-08 Nellcor Puritan Bennett Llc Medical sensor and technique for using the same
US7869850B2 (en) 2005-09-29 2011-01-11 Nellcor Puritan Bennett Llc Medical sensor for reducing motion artifacts 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
US7881762B2 (en) 2005-09-30 2011-02-01 Nellcor Puritan Bennett Llc Clip-style medical 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
US8062221B2 (en) 2005-09-30 2011-11-22 Nellcor Puritan Bennett Llc Sensor for tissue gas detection 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
US7555327B2 (en) 2005-09-30 2009-06-30 Nellcor Puritan Bennett Llc Folding 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
WO2007048039A3 (en) * 2005-10-21 2009-05-14 Paul B Benni Method and apparatus for spectrophotometric based oximetry
WO2007056225A3 (en) * 2005-11-09 2007-10-25 Cas Medical Systems Inc Calibration device for a spectrophotometric system
US8761851B2 (en) * 2005-12-06 2014-06-24 Cas Medical Systems, Inc. Indicators for a spectrophotometric system
US8073518B2 (en) 2006-05-02 2011-12-06 Nellcor Puritan Bennett Llc Clip-style medical sensor and technique for using the same
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
US8396527B2 (en) 2006-09-22 2013-03-12 Covidien Lp Medical sensor for reducing signal artifacts and technique for using the same
US8175671B2 (en) 2006-09-22 2012-05-08 Nellcor Puritan Bennett Llc Medical sensor for reducing signal artifacts and technique for using the same
US8195264B2 (en) 2006-09-22 2012-06-05 Nellcor Puritan Bennett Llc 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
US7890153B2 (en) 2006-09-28 2011-02-15 Nellcor Puritan Bennett Llc System and method for mitigating interference in pulse oximetry
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
US8175667B2 (en) 2006-09-29 2012-05-08 Nellcor Puritan Bennett Llc Symmetric LED array for pulse oximetry
US7680522B2 (en) 2006-09-29 2010-03-16 Nellcor Puritan Bennett Llc Method and apparatus for detecting misapplied sensors
US8068891B2 (en) 2006-09-29 2011-11-29 Nellcor Puritan Bennett Llc Symmetric LED array for pulse oximetry
US7684842B2 (en) 2006-09-29 2010-03-23 Nellcor Puritan Bennett Llc System and method for preventing sensor misuse
US7476131B2 (en) 2006-09-29 2009-01-13 Nellcor Puritan Bennett Llc Device for reducing crosstalk
US8428674B2 (en) * 2006-11-14 2013-04-23 Cas Medical Systems, Inc. Apparatus for spectrometric based oximetry
US20080200784A1 (en) * 2007-02-16 2008-08-21 Xuefeng Cheng Method and device for measuring parameters of cardiac function
US8918153B2 (en) 2007-02-16 2014-12-23 Mespere Lifesciences Inc. Method and device for measuring parameters of cardiac function
JP4974711B2 (en) * 2007-03-05 2012-07-11 富士フイルム株式会社 Printing device
US7894869B2 (en) 2007-03-09 2011-02-22 Nellcor Puritan Bennett Llc Multiple configuration medical sensor and technique for using the same
US8265724B2 (en) 2007-03-09 2012-09-11 Nellcor Puritan Bennett Llc Cancellation of light shunting
US8280469B2 (en) 2007-03-09 2012-10-02 Nellcor Puritan Bennett Llc Method for detection of aberrant tissue spectra
US7541602B2 (en) 2007-06-04 2009-06-02 Or-Nim Medical Ltd. System and method for noninvasively monitoring conditions of a subject
US8352004B2 (en) 2007-12-21 2013-01-08 Covidien Lp Medical sensor and technique for using the same
US8346328B2 (en) 2007-12-21 2013-01-01 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
US8442608B2 (en) 2007-12-28 2013-05-14 Covidien Lp System and method for estimating physiological parameters by deconvolving artifacts
US8452364B2 (en) 2007-12-28 2013-05-28 Covidien LLP System and method for attaching a sensor to a patient's skin
US8070508B2 (en) 2007-12-31 2011-12-06 Nellcor Puritan Bennett Llc Method and apparatus for aligning and securing a cable strain relief
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
WO2009100423A1 (en) * 2008-02-08 2009-08-13 Cas Medical Systems, Inc. Improved method for spectrophotometric blood oxygenation monitoring
WO2009116029A3 (en) 2008-03-17 2010-01-07 Or-Nim Medical Ltd. Apparatus for non invasive acoustooptical monitoring
US8437822B2 (en) 2008-03-28 2013-05-07 Covidien Lp System and method for estimating blood analyte concentration
US8112375B2 (en) 2008-03-31 2012-02-07 Nellcor Puritan Bennett Llc Wavelength selection and outlier detection in reduced rank linear models
US7887345B2 (en) 2008-06-30 2011-02-15 Nellcor Puritan Bennett Llc Single use connector for pulse oximetry sensors
US8071935B2 (en) 2008-06-30 2011-12-06 Nellcor Puritan Bennett Llc Optical detector with an overmolded faraday shield
US7880884B2 (en) 2008-06-30 2011-02-01 Nellcor Puritan Bennett Llc System and method for coating and shielding electronic sensor components
US9027412B2 (en) 2008-07-06 2015-05-12 Or-Nim Medical Ltd. Method and system for non-invasively monitoring fluid flow in a subject
US8336391B2 (en) 2008-07-06 2012-12-25 Or-Nim Medical Ltd. Method and system for non-invasively monitoring fluid flow in a subject
US8364220B2 (en) 2008-09-25 2013-01-29 Covidien Lp Medical sensor and technique for using the same
US8417309B2 (en) 2008-09-30 2013-04-09 Covidien Lp Medical sensor
US8423112B2 (en) 2008-09-30 2013-04-16 Covidien Lp Medical sensor and technique for using the same
US8914088B2 (en) 2008-09-30 2014-12-16 Covidien Lp Medical sensor and technique for using the same
US8391942B2 (en) * 2008-10-06 2013-03-05 Cas Medical Systems, Inc. Method and apparatus for determining cerebral desaturation in patients undergoing deep hypothermic circulatory arrest
US20100105998A1 (en) * 2008-10-28 2010-04-29 Cas Medical Systems, Inc. Method and apparatus for spectrophotometric based oximetry of spinal tissue
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
US8509869B2 (en) 2009-05-15 2013-08-13 Covidien Lp Method and apparatus for detecting and analyzing variations in a physiologic parameter
US8634891B2 (en) 2009-05-20 2014-01-21 Covidien Lp Method and system for self regulation of sensor component contact pressure
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
US8505821B2 (en) 2009-06-30 2013-08-13 Covidien Lp System and method for providing sensor quality assurance
US8311601B2 (en) 2009-06-30 2012-11-13 Nellcor Puritan Bennett Llc Reflectance and/or transmissive pulse oximeter
EP2451344A4 (en) 2009-07-10 2014-04-09 Cas Medical Systems Inc Method for spectrophotometric blood oxygenation monitoring of the lower gastrointestinal tract
US8391941B2 (en) 2009-07-17 2013-03-05 Covidien Lp System and method for memory switching for multiple configuration medical sensor
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
US20110237910A1 (en) * 2010-03-23 2011-09-29 Cas Medical Systems, Inc. Stabilized multi-wavelength laser system for non-invasive spectrophotometric monitoring
US8391943B2 (en) 2010-03-31 2013-03-05 Covidien Lp Multi-wavelength photon density wave system using an optical switch
US7884933B1 (en) 2010-05-05 2011-02-08 Revolutionary Business Concepts, Inc. Apparatus and method for determining analyte concentrations
US8897848B2 (en) * 2010-09-08 2014-11-25 Cas Medical Systems, Inc. Apparatus and method for non-invasively determining oxygen saturation of venous blood and cardiac output using NIRS
US8649838B2 (en) 2010-09-22 2014-02-11 Covidien Lp Wavelength switching for pulse oximetry
US9775545B2 (en) 2010-09-28 2017-10-03 Masimo Corporation Magnetic electrical connector for patient monitors
WO2012050847A3 (en) 2010-09-28 2012-06-21 Masimo Corporation Depth of consciousness monitor including oximeter
WO2012061584A3 (en) 2010-11-03 2012-07-19 University Of Washington Through Its Center For Commercialization Deternimation of tissue oxygenation in vivo
WO2012109661A3 (en) 2011-02-13 2014-02-27 Cas Medical Systems, Inc. Nirs sensor assembly including electrically conductive and optically transparent emi shielding
US9049893B2 (en) 2011-02-25 2015-06-09 Covidien Lp Device for securing a medical sensor
US20130030267A1 (en) * 2011-07-29 2013-01-31 Nellcor Puritan Bennett Llc Multi-purpose sensor system
CA2852975A1 (en) * 2011-10-21 2013-04-25 Nonin Medical, Inc. Age calibration for tissue oximetry
US9913601B2 (en) 2012-02-03 2018-03-13 Cas Medical Systems, Inc. Method and apparatus for monitoring a blood oxygen saturation level relative to a saturation threshold value
US9907494B2 (en) 2012-04-18 2018-03-06 Hutchinson Technology Incorporated NIRS device with optical wavelength and path length correction
JP2016500290A (en) * 2012-12-10 2016-01-12 シーエーエス・メディカル・システムズ・インコーポレイテッド Methods for determining the blood oxygen parameters spectrophotometrically
US9907006B2 (en) 2013-06-03 2018-02-27 Avago Technologies General Ip (Singapore) Pte. Ltd. Cross radio access technology access with handoff and interference management using communication performance data
US9888422B2 (en) 2013-06-03 2018-02-06 Avago Technologies General Ip (Singapore) Pte. Ltd. System and method for adaptive access and handover configuration based on prior history in a multi-RAT environment
US9848808B2 (en) 2013-07-18 2017-12-26 Cas Medical Systems, Inc. Method for spectrophotometric blood oxygenation monitoring
CN103610468A (en) * 2013-12-05 2014-03-05 深圳市奥博莱特科技有限公司 Blood oxygen blood volume absolute amount detection device and method thereof
USD763938S1 (en) 2014-04-02 2016-08-16 Cephalogics, LLC Optical sensor array
USD763939S1 (en) 2014-04-02 2016-08-16 Cephalogics, LLC Optical sensor array liner with optical sensor array pad
CN105628481B (en) * 2015-12-03 2018-05-29 浙江大学 Tissues oxygen detector calibration standards and calibration means arranged methods

Family Cites Families (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4105021A (en) 1976-08-13 1978-08-08 Joseph H. Allen Method and arrangement for measuring blood pressure
US4206764A (en) 1976-12-08 1980-06-10 Weisman & Allen Method and apparatus for analyzing cardiovascular systems
US4281645A (en) 1977-06-28 1981-08-04 Duke University, Inc. Method and apparatus for monitoring metabolism in body organs
US4321830A (en) 1979-12-10 1982-03-30 Optsonic Research Associates, Inc. Optical bichromatic position finder
US4770179A (en) 1982-09-02 1988-09-13 Nellcor Incorporated Calibrated optical oximeter probe
US4621643A (en) 1982-09-02 1986-11-11 Nellcor Incorporated Calibrated optical oximeter probe
US4700708A (en) 1982-09-02 1987-10-20 Nellcor Incorporated Calibrated optical oximeter probe
US4510838A (en) 1983-06-06 1985-04-16 Keith Alexis Cymbal stand with rotating head
US5902235A (en) 1989-03-29 1999-05-11 Somanetics Corporation Optical cerebral oximeter
US5217013A (en) 1983-10-14 1993-06-08 Somanetics Corporation Patient sensor for optical cerebral oximeter and the like
US4690492A (en) 1984-09-04 1987-09-01 Oximetrix, Inc. Optical coupling
US4913150A (en) 1986-08-18 1990-04-03 Physio-Control Corporation Method and apparatus for the automatic calibration of signals employed in oximetry
JPS6365845A (en) 1986-09-05 1988-03-24 Minolta Camera Kk Oximeter apparatus
US4865038A (en) 1986-10-09 1989-09-12 Novametrix Medical Systems, Inc. Sensor appliance for non-invasive monitoring
US4907876A (en) 1987-05-08 1990-03-13 Hamamatsu Photonics Kabushiki Kaisha Examination apparatus for measuring oxygenation in body organs
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
US4848901A (en) 1987-10-08 1989-07-18 Critikon, Inc. Pulse oximeter sensor control system
JPH0628655B2 (en) * 1988-09-30 1994-04-20 株式会社島津製作所 Oxygen saturation measuring apparatus
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
DE3912993C2 (en) 1989-04-20 1998-01-29 Nicolay Gmbh An optoelectronic sensor for generating electric signals due to physiological values
CA2025330C (en) * 1989-09-18 2002-01-22 David W. Osten Characterizing biological matter in a dynamic condition using near infrared spectroscopy
US5058588A (en) 1989-09-19 1991-10-22 Hewlett-Packard Company Oximeter and medical sensor therefor
US5080098A (en) 1989-12-18 1992-01-14 Sentinel Monitoring, Inc. Non-invasive sensor
JPH04106748U (en) 1991-02-28 1992-09-14
US5782755A (en) 1993-11-15 1998-07-21 Non-Invasive Technology, Inc. Monitoring one or more solutes in a biological system using optical techniques
EP0690692A4 (en) 1992-12-01 1999-02-10 Somanetics Corp Patient sensor for optical cerebral oximeters
US5520177A (en) 1993-03-26 1996-05-28 Nihon Kohden Corporation Oximeter probe
WO1994027494A1 (en) 1993-05-20 1994-12-08 Somanetics Corporation Improved electro-optical sensor for spectrophotometric medical devices
EP0700267A4 (en) 1993-05-28 1998-06-24 Somanetics Corp Method and apparatus for spectrophotometric cerebral oximetry
US5632273A (en) 1994-02-04 1997-05-27 Hamamatsu Photonics K.K. Method and means for measurement of biochemical components
US5421329A (en) 1994-04-01 1995-06-06 Nellcor, Inc. Pulse oximeter sensor optimized for low saturation
DE4417639A1 (en) 1994-05-19 1995-11-23 Boehringer Mannheim Gmbh Analysis of concns. of substances in a biological sample
US5697367A (en) 1994-10-14 1997-12-16 Somanetics Corporation Specially grounded sensor for clinical spectrophotometric procedures
US5758644A (en) 1995-06-07 1998-06-02 Masimo Corporation Manual and automatic probe calibration
GB9517366D0 (en) 1995-08-24 1995-10-25 Johnson & Johnson Medical Method of quantatively determining one or more characteristics of a substance
US5752914A (en) 1996-05-28 1998-05-19 Nellcor Puritan Bennett Incorporated Continuous mesh EMI shield for pulse oximetry sensor
US5879294A (en) 1996-06-28 1999-03-09 Hutchinson Technology Inc. Tissue chromophore measurement system

Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7343185B2 (en) * 2002-06-21 2008-03-11 Nir Diagnostics Inc. Measurement of body compounds
US20040015060A1 (en) * 2002-06-21 2004-01-22 James Samsoondar Measurement of body compounds
US7738935B1 (en) * 2002-07-09 2010-06-15 Pacesetter, Inc. Methods and devices for reduction of motion-induced noise in pulse oximetry
EP1545298A2 (en) * 2002-07-26 2005-06-29 Cas Medical Systems, Inc. Method for spectrophotometric blood oxygenation monitoring
US20060189861A1 (en) * 2002-07-26 2006-08-24 Cas Medical Systems, Inc. Method for spectrophotometric blood oxygenation monitoring
US8078250B2 (en) 2002-07-26 2011-12-13 Cas Medical Systems, Inc. Method for spectrophotometric blood oxygenation monitoring
EP1545298A4 (en) * 2002-07-26 2008-11-26 Cas Medical Systems Inc Method for spectrophotometric blood oxygenation monitoring
US8788004B2 (en) 2002-07-26 2014-07-22 Cas Medical Systems, Inc. Method for spectrophotometric blood oxygenation monitoring
US8886465B2 (en) 2007-02-28 2014-11-11 Medtronic, Inc. Implantable tissue perfusion sensing system and method
US20080208066A1 (en) * 2007-02-28 2008-08-28 Can Cinbis Implantable tissue perfusion sensing system and method
US8170650B2 (en) * 2007-02-28 2012-05-01 Medtronic, Inc. Implantable tissue perfusion sensing system and method
US20080208020A1 (en) * 2007-02-28 2008-08-28 Can Cinbis Implantable tissue perfusion sensing system and method
US9636059B2 (en) 2007-02-28 2017-05-02 Medtronic, Inc. Implantable tissue perfusion sensing system and method
US8515537B2 (en) * 2009-06-10 2013-08-20 Medtronic, Inc. Tissue oxygenation monitoring in heart failure
US20100317947A1 (en) * 2009-06-10 2010-12-16 Can Cinbis Tissue Oxygenation Monitoring in Heart Failure
EP2503935A4 (en) * 2009-11-24 2015-11-04 Cas Medical Systems Inc Method for spectrophotometric blood oxygenation monitoring of organs in the body
US9364175B2 (en) 2009-11-24 2016-06-14 Cas Medical Systems, Inc. Method for spectrophotometric blood oxygenation monitoring of organs in the body
US20120271130A1 (en) * 2011-04-11 2012-10-25 Cas Medical Systems, Inc. Method and apparatus for determining an oxygen desaturation event
US20130274573A1 (en) * 2012-03-09 2013-10-17 University Of Georgia Research Foundation, Inc. Systems And Methods For Measuring Mitochondrial Capacity
US9706959B2 (en) * 2012-03-09 2017-07-18 University Of Georgia Research Foundation, Inc. Systems and methods for measuring mitochondrial capacity
US9597025B2 (en) 2013-06-13 2017-03-21 Nihon Kohden Corporation Biological signal measuring system and biological signal measuring apparatus
FR3011170A1 (en) * 2013-09-30 2015-04-03 Apd Advanced Perfusion Diagnostics Device and non-invasive measuring method for estimation of local metabolic parameters
WO2015044336A1 (en) * 2013-09-30 2015-04-02 Apd Advanced Perfusion Diagnostics Non-invasive measurement device and method for estimating local metabolic parameters

Also Published As

Publication number Publication date Type
EP1259791A2 (en) 2002-11-27 application
EP1259791B1 (en) 2013-11-13 grant
WO2001084107A3 (en) 2002-08-15 application
US6456862B2 (en) 2002-09-24 grant
JP2003532107A (en) 2003-10-28 application
EP1259791A4 (en) 2007-05-02 application
WO2001084107A2 (en) 2001-11-08 application

Similar Documents

Publication Publication Date Title
Iijima et al. Cardiac output and circulating blood volume analysis by pulse dye-densitometry
Cheatle et al. Near‐infrared spectroscopy in peripheral vascular disease
Ohmae et al. Cerebral hemodynamics evaluation by near-infrared time-resolved spectroscopy: correlation with simultaneous positron emission tomography measurements
Schmitt Simple photon diffusion analysis of the effects of multiple scattering on pulse oximetry
US6263221B1 (en) Quantitative analyses of biological tissue using phase modulation spectroscopy
US5421329A (en) Pulse oximeter sensor optimized for low saturation
US6421549B1 (en) Adaptive calibration pulsed oximetry method and device
Pollard et al. Validation in volunteers of a near-infrared spectroscope for monitoring brain oxygenation in vivo
US6711425B1 (en) Pulse oximeter with calibration stabilization
US6411832B1 (en) Method of improving reproducibility of non-invasive measurements
US6671528B2 (en) Method and apparatus for non-invasive blood constituent monitoring
Sinex Pulse oximetry: principles and limitations
US6049727A (en) Implantable sensor and system for in vivo measurement and control of fluid constituent levels
US5902235A (en) Optical cerebral oximeter
Mannheimer The light–tissue interaction of pulse oximetry
Cysewska-Sobusiak Metrological problems with noninvasive transillumination of living tissues
US6064474A (en) Optical measurement of blood hematocrit incorporating a self-calibration algorithm
US20020042558A1 (en) Pulse oximeter and method of operation
US7254431B2 (en) Physiological parameter tracking system
US20050131286A1 (en) Non-invasive measurement of blood analytes
US20050240090A1 (en) Method of processing noninvasive spectra
Hampson et al. Near infrared monitoring of human skeletal muscle oxygenation during forearm ischemia
US5297548A (en) Arterial blood monitoring probe
US6635491B1 (en) Method for non-invasively determining the concentration of an analyte by compensating for the effect of tissue hydration
US20020133068A1 (en) Compensation of human variability in pulse oximetry

Legal Events

Date Code Title Description
CC Certificate of correction
FPAY Fee payment

Year of fee payment: 4

AS Assignment

Owner name: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF

Free format text: CONFIRMATORY LICENSE;ASSIGNOR:CAS MEDICAL SYSTEMS, INC.;REEL/FRAME:021050/0039

Effective date: 20030429

FPAY Fee payment

Year of fee payment: 8

AS Assignment

Owner name: NEWALLIANCE BANK,CONNECTICUT

Free format text: SECURITY AGREEMENT;ASSIGNOR:CAS MEDICAL SYSTEMS, INC.;REEL/FRAME:024128/0648

Effective date: 20100311

Owner name: NEWALLIANCE BANK, CONNECTICUT

Free format text: SECURITY AGREEMENT;ASSIGNOR:CAS MEDICAL SYSTEMS, INC.;REEL/FRAME:024128/0648

Effective date: 20100311

AS Assignment

Owner name: CAS MEDICAL SYSTEMS, INC., CONNECTICUT

Free format text: RELEASE BY SECURED PARTY;ASSIGNOR:FIRST NIAGARA BANK, N.A. SUCCESSOR BY MERGER TO NEWALLIANCE BANK;REEL/FRAME:026525/0955

Effective date: 20110623

FPAY Fee payment

Year of fee payment: 12

AS Assignment

Owner name: GENERAL ELECTRIC CAPITAL CORPORATION, AS AGENT, MA

Free format text: SECURITY INTEREST;ASSIGNOR:CAS MEDICAL SYSTEMS, INC.;REEL/FRAME:033247/0323

Effective date: 20140627

AS Assignment

Owner name: HEALTHCARE FINANCIAL SOLUTIONS, LLC, AS SUCCESSOR

Free format text: ASSIGNMENT OF INTELLECTUAL PROPERTY SECURITY AGREEMENT;ASSIGNOR:GENERAL ELECTRIC CAPITAL CORPORATION, AS RETIRING AGENT;REEL/FRAME:037112/0159

Effective date: 20151113

AS Assignment

Owner name: SOLAR CAPITAL LTD., AS SUCCESSOR AGENT, NEW YORK

Free format text: ASSIGNMENT OF INTELLECTUAL PROPERTY SECURITY AGREEMENT;ASSIGNOR:HEALTHCARE FINANCIAL SOLUTIONS, LLC, AS RETIRING AGENT;REEL/FRAME:038711/0067

Effective date: 20160513

AS Assignment

Owner name: SOLAR CAPITAL LTD., NEW YORK

Free format text: PATENT SECURITY AGREEMENT;ASSIGNOR:CAS MEDICAL SYSTEMS, INC.;REEL/FRAME:039221/0004

Effective date: 20160630

AS Assignment

Owner name: CAS MEDICAL SYSTEMS, INC., CONNECTICUT

Free format text: RELEASE BY SECURED PARTY;ASSIGNOR:SOLAR CAPITAL LTD.;REEL/FRAME:045823/0342

Effective date: 20180508