WO2011068998A2 - Systèmes et procédés de détermination de la concentration en hémoglobine utilisant la réflectance diffuse à des longueurs d'onde isobestiques - Google Patents

Systèmes et procédés de détermination de la concentration en hémoglobine utilisant la réflectance diffuse à des longueurs d'onde isobestiques Download PDF

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WO2011068998A2
WO2011068998A2 PCT/US2010/058771 US2010058771W WO2011068998A2 WO 2011068998 A2 WO2011068998 A2 WO 2011068998A2 US 2010058771 W US2010058771 W US 2010058771W WO 2011068998 A2 WO2011068998 A2 WO 2011068998A2
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diffuse reflectance
isosbestic
isosbestic wavelengths
tissue mass
ratio
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PCT/US2010/058771
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WO2011068998A3 (fr
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Nirmala Ramanujam
Janelle E. Phelps
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Duke University
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47—Scattering, i.e. diffuse reflection
    • G01N21/49—Scattering, i.e. diffuse reflection within a body or fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0077—Devices for viewing the surface of the body, e.g. camera, magnifying lens
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/314—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry with comparison of measurements at specific and non-specific wavelengths
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47—Scattering, i.e. diffuse reflection
    • G01N21/4738—Diffuse reflection, e.g. also for testing fluids, fibrous materials
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00—Features of devices classified in G01N21/00
    • G01N2201/12—Circuits of general importance; Signal processing
    • G01N2201/129—Using chemometrical methods

Definitions

  • the subject matter disclosed herein relates to optical spectroscopy and tissue physiology. More particularly, the subject matter disclosed herein relates to systems and methods for determining hemoglobin concentration utilizing diffuse reflectance at isosbestic wavelengths.
  • Hemoglobin (Hb) concentration is a metric used for many applications in the medical field, including anemia diagnosis and transfusion guidance.
  • the current strategy for determining hemoglobin concentration is an invasive procedure where blood is drawn from an artery and sent to a laboratory for further analysis, such as arterial blood gas (ABG) measurements or optical methods of measurement.
  • the current strategy can be invasive, time-consuming, subject to operator error, and/or carry the risk of infection for a tested patient.
  • present optical methods generally require a sophisticated computational technique such as diffusion approximation or Monte Carlo modeling to extract hemoglobin concentration from the measured spectra.
  • present optical methods employing computational techniques typically require robust computer systems, thereby rendering the hemoglobin concentration measurement systems impracticable for applications requiring portability/mobility or immediate results.
  • a portable device capable of determining hemoglobin concentration would have wide applicability in various areas where rapid hemoglobin measurements are required, such as in the emergency or operating room, in the back of an ambulance, in the battlefield, and in other resource-limited settings.
  • the subject matter described herein includes systems and methods for determining hemoglobin concentration utilizing diffuse reflectance at isosbestic wavelengths.
  • the method includes emitting light onto a tissue mass, measuring diffuse reflectance from the tissue mass, and calculating a ratio of diffuse reflectance intensities at two isosbestic wavelengths using the measured diffuse reflectance.
  • the method also includes determining a hemoglobin concentration associated with the tissue mass by applying the calculated ratio to a predefined analytical expression associated with the two isosbestic wavelengths.
  • the system comprises a light source for emitting light onto a tissue mass and a measurement device for measuring diffuse reflectance from the tissue mass.
  • the system further includes a processing unit for calculating a ratio of diffuse reflectance intensities at two isosbestic wavelengths using the measured reflectance, and determining a hemoglobin concentration associated with the tissue mass by applying the calculated ratio to a predefined analytical expression associated with the two isosbestic wavelengths.
  • the subject matter described herein for determining hemoglobin concentration utilizing diffuse reflectance at isosbestic wavelengths may be implemented in hardware, software, firmware, or any combination thereof.
  • the terms “function” or “module” as used herein refer to hardware, which may also include software and/or firmware components, for implementing the feature being described.
  • the subject matter described herein may be implemented using a computer readable medium having stored thereon computer executable instructions that when executed by the processor of a computer control the computer to perform steps.
  • Exemplary computer readable media suitable for implementing the subject matter described herein include non- transitory computer-readable media, such as disk memory devices, chip memory devices, programmable logic devices, and application specific integrated circuits.
  • a computer readable medium that implements the subject matter described herein may be located on a single device or computing platform or may be distributed across multiple devices or computing platforms.
  • Figure 1 is a block diagram of a system for determining hemoglobin concentration utilizing diffuse reflectance at isosbestic wavelengths according to an embodiment of the subject matter described herein;
  • Figure 2 is a flow chart of an exemplary process to generate an analytical expression for determining hemoglobin concentration according to an embodiment of the subject matter described herein.
  • Figure 3 is a flow chart of an exemplary process for determining hemoglobin concentration utilizing diffuse reflectance at isosbestic wavelengths according to an embodiment of the subject matter described herein.
  • the subject matter described herein includes systems and methods for determining hemoglobin concentration utilizing diffuse reflectance at isosbestic wavelengths.
  • the present subject matter includes a noninvasive device that is configured to measure hemoglobin concentration in near real-time due to utilizing calculated ratios of diffuse reflectance intensities.
  • Hemoglobin concentration (Hb) levels typically range from 12-16 grams of hemoglobin per deciliter of blood (g/dL). Blood transfusions are indicated when Hb levels reach between 6-10 g/dl and are also dependent upon signs of organ ischemia, the patient's intravascular volume status, and the presence of other patient risk factors.
  • Hb hemoglobin concentration
  • One embodiment of the present subject matter involves the monitoring Hb concentration in surgical patients using a fiber probe-based diffuse reflectance spectroscopy system.
  • Diffuse reflectance spectra reflect tissue absorption and scattering.
  • the primary absorbers in soft tissues are oxygenated and deoxygenated Hb (oxy- and deoxy-Hb, respectively).
  • diffuse reflectance spectroscopy measures a mixture of venous and arterial components and does not require pulsatile blood flow.
  • an optical spectrometer system may be used to obtain optical measurements and process diffuse reflectance measurement data in order to yield hemoglobin concentrations.
  • Figure 1 depicts an exemplary optical spectrometer system 100 that includes a fiber optic probe 102.
  • relay optics may be used instead of a fiber optic probe to emit (i.e., deliver) light on a tissue mass 114.
  • Spectrometer system 100 may also include a light source 104, a monochromator 106 (e.g., a scanning double-excitation monochromator), an emission monochromator 108, a charged-couple device (CCD) unit 110, and a processing unit 112 (e.g., a processor within a personal computer).
  • a monochromator 106 e.g., a scanning double-excitation monochromator
  • an emission monochromator 108 e.g., a charged-couple device (CCD) unit 110
  • processing unit 112 e.g., a processor within a personal computer.
  • the light source may include a xenon arc lamp or a light emitting diode (LED) light source.
  • monochromator 106 may comprise a double-grating excitation monochromator.
  • a filter wheel may be utilized in system 100 instead of monochromator 106.
  • an extended red photomultiplier tube (PMT), a photodiode, or a single channel detector may be used in lieu of CCD unit 110 in system 100.
  • fiber optic probe 102 may be used for obtaining in vivo measurements of blood parameters.
  • fiber optic probe 102 may be used to quantitatively determine the concentration of "total hemoglobin" (e.g., the total hemoglobin content in a tissue mass), blood loss, dilutional effects from fluid intake, porphyrin levels, cellular metabolism, and the hemoglobin saturation of a tissue mass in vivo.
  • fiber optic probe 102 may be configured to measure the concentration of a hemoglobin analyte by being placed in an oral mucosa, under the tongue, or taped to any exposed surfaces (such as an arm), thereby providing real-time measurements of the analyte of interest.
  • fiber optic probe 102 comprises a flexible steel sheathed tubing that contains a plurality of optical fibers (i.e., illumination and collection fibers).
  • Fiber optic probe 102 may further include a rigid probe tip on one end that may include a plurality of fibers arranged in any number of different illumination-collection configurations.
  • the fiber optic probe may comprise a plurality of illumination fibers centrally grouped to form an illumination core.
  • fiber optic probe 102 may include a single collection ring comprising 18 collection fibers that may be interfaced with tissue mass 114 positioned around a 19-fiber illumination core.
  • fiber optic probe 102 includes at least one collection fiber and at least one illumination fiber.
  • the illumination core may include any number of fibers to obtain an illumination core diameter that maximizes the coupling efficiency for the light source.
  • the illumination fibers are used to emit light on the tissue mass to be examined.
  • the light may be generated by light source 104 and provided to fiber optic probe 102 via monochromator 106. Specifically, light is emitted into one end of one or more illumination fibers. After the light is emitted by the illumination fibers on tissue mass 114, at least one collection fiber in the fiber optic probe 102 captures the diffuse reflected light which is ultimately provided to monochromator 108.
  • the present subject matter may collect on a diffuse reflectance spectrum, such as in the ultraviolet and visible (UV-VIS) range.
  • fiber optic probe 102 is configured to collect wavelength dependent diffuse reflectance spectra measured from 350-800 nm.
  • the diffuse reflectance signals from the various collection fibers are spatially separated by CCD unit 110, thereby enabling diffuse reflectance spectra to be measured at different illumination-collection separations simultaneously.
  • a PMT is configured to measure the diffuse reflectance. Once the diffuse reflectance spectra is measured, the data is provided to processing unit 112, which then calculates a ratio of diffuse reflectance intensities at two isosbestic wavelengths using the measured diffuse reflectance.
  • processing unit 112 may be configured to calculate a ratio of diffuse reflectance intensities at two isosbestic wavelengths includes dividing the diffuse reflectance intensity of a first isosbestic wavelength by the diffuse reflectance intensity of a second isosbestic wavelength.
  • a ratio for wavelength ratio pair of 545/390 nm may be calculated by dividing the diffuse reflectance intensity found at 545 nm by the diffuse reflectance intensity found at 390 nm.
  • Processing unit 112 may be configured to calculate a calculate a ratio of diffuse reflectance intensities at any two wavelengths, but is typically adapted to perform a calculation using a isosbestic wavelength ratio pair that has been determined to be highly correlated to hemoglobin concentration levels.
  • processing unit 112 is further configured to determine a hemoglobin concentration associated with tissue mass 114 by applying the calculated ratio to a predefined analytical expression associated with the two isosbestic wavelengths (e.g., there are other predefined analytical expressions that are respectively associated to other isosbestic wavelength pairs).
  • the predefined analytical expression may be a linear equation that defines or indicates the relationship between the calculated ratio and hemoglobin concentration.
  • the present subject matter is able to determine a hemoglobin concentration much faster than a system that relies on a Monte Carlo algorithm to process diffuse reflectance data.
  • the analytical expression needs to be derived, such as through linear regression or some other mathematical technique.
  • the present subject matter determines a total Hb concentration estimation, independent of Hb saturation and scattering, using a simple isosbestic ratiometric analysis of diffuse reflectance intensities developed using Monte Carlo simulations.
  • Analytical expressions may be derived through the use of tissue-mimicking phantoms and in vivo human tissue data. Diffuse reflectance spectra may be generated using a forward Monte Carlo model, then equations of linear regression between Hb concentration and the ratios may be established from the simulations and applied to phantom data.
  • a single reference phantom may be used to calibrate a Monte Carlo-generated reflectance to the same scale as the experimentally-measured data.
  • the simulation equations are specific to the probe and instrument used experimentally.
  • simulations may be conducted for five scattering levels for each of ten absorption levels (Hb concentrations). There may be 28 total ratios tested for isosbestic points between 350-600 nm. Using this data, a simple analytical equation can ultimately be developed to predict Hb concentration. Twenty-five of the 28 ratios had average percent errors within 20% for the simulations when the ratios were averaged over all five scattering levels, four of which were below 5%, nine of which were between 5-10%, and seven of which were between 10-15%. Linear regression equations from the simulations may then then applied to three sets of experimental phantom data.
  • the average percent error was below 15% for both phantom sets.
  • the average percent error was below 10% for 452/390 nm, between 10-15% for 529/390 and 500/390 nm, and between 15-20% for 545/390, 570/390, and 584/390 nm.
  • the average percent error was between 10-15% for 545/390, 452/390, 570/390, and 584/390 nm and between 15-20% for 529/390 and 500/390 nm.
  • the six best ratios may be tested for two sets of phantoms with variable scattering and Hb concentration measured with a CCD, PMT, or other measurement device. Three of these ratios - 545/390, 452/390, and 529/390 nm - had similarly low errors within 20%, indicating this method can be considered independent of the instrument and probe used. In one instance, data from human tissue measurements measured with both instruments was used to test the correlations with Hb concentration extracted with either the ratiometric method or a more complex inverse Monte Carlo model.
  • FIG. 2 is a flow diagram illustrating the steps of an exemplary process to generate an analytical expression that is used to determine hemoglobin concentration according to an embodiment of the subject matter described herein.
  • block 202 diffuse reflectance intensities at isosbestic wavelengths from a specimen or sample with a known hemoglobin concentration is determined.
  • a plurality of scattering phantom samples is used.
  • each phantom sample includes a known hemoglobin concentration.
  • the phantom samples may also include varying known scattering and hemoglobin saturation values as well.
  • the phantoms may be specifically designed to have particular hemoglobin concentrations, as determined from the relative amounts of hemoglobin, scatterer, and solvent (water or PBS) that comprise a given phantom.
  • the known hemoglobin concentration of a typical tissue sample may be used since an ABG analyzer can measure the hemoglobin concentration directly from the tissue sample.
  • the hemoglobin concentration can be specified by a Monte Carlo model.
  • light is emitted on a phantom sample or tissue sample using a fiber optic probe.
  • the measurement device e.g., CCD or PMT
  • the intensities of 8 isosbestic wavelengths may be taken.
  • simulated samples with known hemoglobin concentration, scattering, and hemoglobin saturation levels are generated and used instead of phantom samples.
  • the diffuse reflectance data of the simulated samples are then generated using a Monte Carlo algorithm.
  • the diffuse reflectance data of the simulated samples is calibrated by a correction factor in order to place it on the same scale as experimental data (i.e., the measured reflectance from a tissue mass).
  • the diffuse reflectance intensity ratios of the isosbestic wavelength ratio pairs are calculated.
  • the intensity ratio of a wavelength ratio pair 529/500 nm may be calculated by dividing the diffuse reflectance intensity at the 529 nm wavelength by the diffuse reflectance intensity at the 500 nm wavelength.
  • an intensity ratio is calculated for each predefined wavelength ratio pair.
  • a database associated with each isosbestic wavelength ratio pair (i.e., two isosbestic wavelengths) is populated with the known hemoglobin concentration and the corresponding calculated intensity ratio.
  • each wavelength ratio pair is associated with its own database that contains hemoglobin concentration data and corresponding diffuse reflectance intensity ratio data.
  • each database associated with a particular wavelength ratio pair is provisioned with another set of hemoglobin concentration and intensity ratio data (that is collected at the respective isosbestic wavelengths).
  • the iterative process of selecting different hemoglobin concentration values may include the use of phantom samples that are characterized by a particular scattering level and/or hemoglobin saturation level so that the hemoglobin concentrations may exhibit some variance.
  • the end result of this process may include a database containing a plurality of hemoglobin concentrations for different scattering and hemoglobin saturation values which are associated with corresponding diffuse reflectance intensity ratios.
  • an analytical expression associated with each wavelength ratio pair is generated.
  • linear regression analysis (or some other mathematical model) is performed on the data contained within the database in order to derive or calculate an analytical expression. For example, once a database is provisioned with a designated number of sets of hemoglobin concentration and intensity ratio data, processing unit 112 may perform linear regression analysis on the data (i.e., calculated intensity ratios and known hemoglobin concentration values) in the database to determine an analytical expression.
  • the analytical expression defines or indicates the relationship between a given intensity ratio and hemoglobin concentration.
  • Diffuse reflectance ratios are expected to correlate well with Hb, because absorption of Hb is a primary source of contrast in the spectra. Isosbestic ratios are taken where the oxy-Hb and deoxy-Hb molar extinction coefficients are equal, and so they would not be expected to correlate with the partial pressure of oxygen in the arterial plasma (PaO 2 ).
  • Correlations of a wavelength ratio pair may be derived in several ways. In one embodiment, ratios of all numerator-denominator pairs from 350-600 nm are tested as simple correlates to Hb concentration. Correlations may be tested in Matlab using Pearson's linear correlation coefficients, under the assumption that the data is normally distributed. The spectra may be interpolated to a 1 nm increment using a cubic spline interpolation prior to calculating the ratios, to increase the number of wavelength combinations. Ratios are obtained from raw reflectance spectra.
  • correlations between all reflectance ratio pairs between 350-600 nm and ABG Hb values are tested. Over the wavelength range of 350-600 nm, there are eight isosbestic points for oxy- and deoxy- Hb: 390, 422, 452, 500, 529, 545, 570, and 584 nm. In one instance, the suitable correlations of optical ratios to ABG Hb (r> ⁇ 0.65) exist where the numerator is between 524-537 nm and the denominator between 482-507 nm. For numerators of 474-475 nm and denominators of 466-467 nm, the correlations were equally good (r> ⁇ 0.65).
  • Phantom Set 1 contained 51 phantoms with variable Hb saturation and constant Hb concentration and scattering.
  • Phantom Set 2 had four Hb levels for two initial scattering levels which decreased slightly due to addition of Hb.
  • Phantom Set 3 consisted of 13 Hb levels for a single initial scattering level which decreased to a greater extent due to addition of Hb.
  • a subset of ratios was tested for Phantom Sets 2 and 3, based upon the best ratio(s) from Phantom Set 1.
  • a new set of ratios was then selected and tested on Phantom Sets 2 and 3 measured with a different instrument, to establish that this method was independent of instrument response.
  • forward Monte Carlo simulations were conducted to determine the isosbestic ratios of oxy-Hb and deoxy-Hb that could predict Hb concentration. For example, there are eight isosbestic points for oxy-Hb and deoxy-Hb over the 350-600 nm wavelength range: 390, 422, 452, 500, 529, 545, 570, and 584 nm. Combinations of ten absorption and five scattering levels were used to generate optical property inputs to the 400 simulated tissue models (10 Hb levels, 5 scattering levels, 8 wavelengths). The absorption levels (Table 1 ) corresponded to total Hb concentrations of 5-50 ⁇ with different fractions of oxy-HB and deoxy-Hb (thus different Hb saturations). The absorption coefficient (p a ) at each isosbestic wavelength was determined using the molar extinction coefficients for each hemoglobin species. Table 1. Total Hb concentration and Hb saturation used in the simulations
  • the simulations were scaled for the exact probe geometry used in the experimental measurements on which the ratios were tested.
  • the probe geometry may include of a central illumination core of 18 illumination fibers surrounded by 19 collection fibers in a concentric arrangement, with each individual fiber being 200 pm in diameter with numerical aperture (NA) of 0.22.
  • NA numerical aperture
  • the approximate spatial resolution of this probe is 1 mm, as determined by the full-width at half maximum of the collected fraction versus source detector separation distance.
  • the collected fraction was determined from convolution over the illumination and collection fibers.
  • the average 90% sensing depth over 350- 600 nm is approximately 2.2 ⁇ 0.7 mm.
  • the anisotropy factor, g was 0.8, and the refractive indices for the fibers and tissue were at 1.45 and 1.37, respectively.
  • the diffuse reflectance was determined using a lookup table method described previously. In one embodiment, reflectance ratios may be calculated from the modeled diffuse reflectance at each isosbestic point.
  • the simulations were used to determine which ratios best correlated to Hb concentration. Reflectance ratios at isosbestic wavelengths were only computed when the numerator wavelength was higher than the denominator wavelength yielding a total of 28 possible ratio combinations.
  • the criterion for the simulation data was to minimize the goodness of fit, or the average percent error, %error, defined in Equation 1 , where n is the number of Hb levels, Hb is the concentration of Hb, and fit is the linear regression equation for Hb versus ratio: fit -Hb
  • the efficacy of isosbestic ratiometric correlations to Hb concentration may evaluated by testing tissue-mimicking phantoms (e.g., 3 independent sets).
  • tissue-mimicking phantoms e.g., 3 independent sets.
  • the linear regression equations for the best ratios from the simulations were applied to the phantom data.
  • the simulated reflectance was first calibrated by a correction factor determined using a single phantom measurement to put the Monte Carlo data and the experimental data on the same scale. Briefly, the calibration phantom was selected from a set of master phantoms that has previously been found to most accurately estimate ⁇ 3 and ⁇ 5 ' over a large range of target phantom optical properties.
  • the calibration phantom can be measured prior to taking the laboratory or clinical measurements, and so the time taken to measure it is not relevant to the time it would take to estimate Hb concentration using this ratiometric method.
  • All diffuse reflectance data from the phantoms were divided by the spectrum of a reflectance standard measured on the same day prior to taking the ratios, so that the ratios were calculated from the true diffuse reflectance spectrum of the interrogated medium independent of lamp and/or detector response.
  • the percent error was calculated from Equation 1 , where the fit refers to the extracted Hb concentration using the linear regression equation derived from calibrated simulation data.
  • the analytical expression is derived for one or more wavelength ratio pairs
  • the present subject matter may be utilized in a practical setting (e.g., in surgery) in order to determine hemoglobin concentration in a tissue mass.
  • a number of analytical expressions are derived for a plurality of isosbestic wavelength ratio pairs, but only testing on one wavelength ratio pair is needed to measure hemoglobin concentration.
  • a wavelength ratio pair associated with a high correlation factor is used for the benefit of greater predictive accuracy.
  • FIG. 3 is a flow diagram illustrating the steps of an exemplary method 300 for determining hemoglobin concentration utilizing diffuse reflectance at isosbestic wavelengths according to an embodiment of the subject matter described herein.
  • a light source is emitted onto a tissue mass.
  • fiber optic probe 102 configured with at least one illumination fiber may be used to emit light on tissue mass 114.
  • the tissue mass may either be ex vivo (e.g., a lab specimen) or in vivo (e.g., sublingual lining).
  • the tissue surface chosen for placement of the probe was the floor of the mouth, a highly vascular and perfused mucosal surface that can be directly accessed by the fiber optic probe.
  • the diffuse reflectance from the tissue mass is measured, in one embodiment, one or more collection fibers of fiber optic probe 102 are used to collect the diffuse reflectance emitted from the tissue mass.
  • the wavelength intensities of collected diffuse reflectance are then measured by a measurement device, such as the CCD 112 or a PMT.
  • the diffuse reflectance across the spectra of 350 nm to 800 nm is measured.
  • only isosbestic wavelength intensities are measured instead of wavelength intensities within the 350-800 nm spectra.
  • the diffuse reflectance across the spectra of 350 nm to 600 nm is measured.
  • the bandwidth for the diffuse reflectance signal that is measured which may be as high as 25 nm for each wavelength.
  • an intensity ratio using the measured reflectance at two isosbestic wavelengths is determined.
  • a ratio of diffuse reflectance intensities at two isosbestic wavelengths using the measured diffuse reflectance is calculated.
  • the isosbestic wavelength ratio pair may include any two isosbestic wavelengths.
  • the isosbestic wavelength ratio pair is a wavelength ratio pair that has been determined to be highly correlated to hemoglobin concentration.
  • processing unit 112 calculates the ratio of diffuse reflectance intensities by dividing the diffuse reflectance intensity of a first isosbestic wavelength (e.g., 545 nm) by the diffuse reflectance intensity of a second isosbestic wavelength (e.g., 390 nm).
  • a first isosbestic wavelength e.g., 545 nm
  • a second isosbestic wavelength e.g., 390 nm
  • a hemoglobin concentration is determined by applying the calculated ratio to a predefined analytical expression.
  • an associated predefined linear equation e.g., the analytical equation determined in method 200
  • processing unit 112 uses a known slope value and intercept value to determine the hemoglobin concentration of the tissue mass.
  • this processing is conducted with greater efficiency as opposed to determining the hemoglobin concentration using a Monte Carlo algorithm.

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Abstract

La présente invention a pour objet des systèmes et des procédés de détermination de la concentration en hémoglobine utilisant la réflectance diffuse à des longueurs d'onde isobestiques. Dans un mode de réalisation, le procédé comprend les étapes consistant à émettre de la lumière sur une masse tissulaire, à mesurer la réflectance diffuse en provenance de la masse tissulaire, et à calculer un rapport des intensités de réflectance diffuse à deux longueurs d'onde isobestiques à l'aide de la réflectance diffuse mesurée. Le procédé comprend également la détermination d'une concentration en hémoglobine associée à la masse tissulaire par l'application du rapport calculé à une expression analytique prédéfinie associée aux deux longueurs d'onde isobestiques.
PCT/US2010/058771 2009-12-02 2010-12-02 Systèmes et procédés de détermination de la concentration en hémoglobine utilisant la réflectance diffuse à des longueurs d'onde isobestiques WO2011068998A2 (fr)

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Cited By (4)

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Publication number Priority date Publication date Assignee Title
RU2501522C2 (ru) * 2012-03-07 2013-12-20 Белорусский Государственный Университет (Бгу) Способ определения концентрации гемоглобина в биологических тканях
WO2017060271A1 (fr) * 2015-10-05 2017-04-13 Universiteit Gent Analyse d'échantillon de sang séché
WO2020153842A1 (fr) * 2019-01-24 2020-07-30 Nederlandse Organisatie Voor Toegepast- Natuurwetenschappelijk Onderzoek Tno Mesure d'hémoglobine par imagerie rétinienne
CN112689749A (zh) * 2018-09-11 2021-04-20 皇家飞利浦有限公司 针对牙龈炎检测的光学方法

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