Monitoring constituents of an animal organ using discrete radiation

• US 6,195,574 B1
• Filed: 08/28/1999
• Issued: 02/27/2001
• Est. Priority Date: 09/04/1998
• Status: Expired due to Term

• Current Assignee: Perkinelmer Instruments LLC (Revvity, Inc.)
• Original Assignee: Perkinelmer Instruments LLC (Revvity, Inc.)
• Inventors: DiCesare, Joseph L., Kumar, Gitesh
• Primary Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US09/385,242
• Time in Patent Office: 549 Days
• Field of Search: 600/310, 600/322, 600/323, 600/330, 600/336, 600/473, 250/339.01, 250/339.07, 250/341.1, 356/39-41, 356/317, 356/318, 356/319, 356/323
• US Class Current: 600/323
• CPC Class Codes: A61B 5/14553 specially adapted for cerebral tissue
• CPC Class Codes: A61B 5/6814 Head

Abstract

Constituents such as oxy- and deoxy-hemoglobin are monitored non-invasively in an animal organ such as a brain with a spectrometric instrument by passing radiation through the organ. An input beam has a plurality of discrete wavelengths modulated with radio frequency. Output radiation is received by a detector from which output amplitude and output phase are determined for each wavelength. Absorption coefficient is computed from the amplitude and phase, and concentrations of constituents are thereby calculated.

Claims

1. A method of monitoring one or more selected constituents in an animal organ with a spectrometric instrument that includes a source of an input beam of discrete radiation formed of a plurality of discrete wavelengths in an infrared spectral range that includes absorbance wavelengths of the selected constituents and one or more additional constituents in the organ, wherein each wavelength has a predetermined input amplitude and is modulated with a radio frequency signal having a predetermined input phase, and the instrument further includes a radiation detector receptive of such radiation to generate representative signal data, wherein the selected constituents and the additional constituents constitute a total number of constituents having significant absorbance in the spectral range, the plurality of wavelengths is at least equal in number to the total number of constituents, and the method comprises steps of:

directing the input beam into an animal organ such that the radiation is modified by the constituents, and positioning the radiation detector so as to be receptive of the modified radiation from an exit site from the organ so as to generate a corresponding output signal for each wavelength;

determining from each output signal an output amplitude and an output phase for each wavelength;

computing an absorption coefficient for each wavelength from the input amplitude, the output amplitude, the input phase and the output phase, with respective equations relating phase, amplitude, absorption coefficient and scattering coefficient; and

calculating concentration of each of the selected constituents from a plurality of simultaneous equations at least equal to the total number of constituents, each equation being for a different wavelength relating absorption coefficient to concentrations of all of the constituents proportionately with respective predetermined extinction coefficients.

2. The method of claim 1 wherein the selected constituents comprise oxygenated hemoglobin and deoxygenated hemoglobin, and the additional constituents comprise water, protein and lipid, whereby the total number of constituents is at least five.

3. The method of claim 2 wherein the selected constituents further comprise cytochrome oxidase.

4. The method of claim 1 wherein the respective equations comprise Eqs. 3 and 4 as defined in the specification.

5. The method of claim 1 wherein the simultaneous equations comprise Eq. 6 as defined in the specification.

6. The method of claim 1 wherein, to predetermine each input amplitude and input phase, the method further comprises

passing the input beam through a neutral density filter to the radiation detector so as to generate a corresponding reference signal for each wavelength, the filter having a predetermined optical density;

determining from each reference signal a reference amplitude and a reference phase for each wavelength, whereby the input phase is equal to the reference phase; and

calculating the input amplitude from the reference amplitude and the optical density.

7. The method of claim 6 wherein the input amplitude is calculated from Eq. 5 as defined in the specification.

8. The method of claim 1 wherein the organ comprises blood containing oxygenated hemoglobin and deoxygenated hemoglobin, and the method further comprises calculating a measured oxygen saturation in the blood as a ratio of concentration of oxygenated hemoglobin to a total of concentrations of oxygenated hemoglobin and deoxygenated hemoglobin.

9. The method of claim 8 wherein the organ further comprises water and tissue matrix, and the method further comprises steps of:

providing an absorption relationship relating total absorption coefficient for the organ to oxygen saturation, specific absorption coefficients and volume fractions respectively for water, tissue matrix, blood, and for constituents of the tissue matrix and the blood, wherein the specific absorption coefficients are predetermined for each wavelength, and the volume fractions can vary;

selecting at least one set of values for the oxygen saturation and the volume fractions, and, for each set, calculating therefrom and from the specific absorption coefficients a corresponding calculated organ absorption coefficient for a selected wavelength;

utilizing the calculated organ absorption coefficients for computing concentrations of oxygenated hemoglobin and deoxygenated hemoglobin from the plurality of simultaneous equations, and further calculating oxygen saturations from the concentrations; and

comparing the calculated oxygen saturations to the selected values for oxygen saturation to obtain a correction factor, and storing the correction factor for application to the measured oxygen saturation to obtain a corrected oxygen saturation.

10. The method of claim 9 wherein the step of utilizing comprises computing an output amplitude and an output phase from the calculated organ absorption coefficients using the respective equations relating phase and amplitude to absorption coefficient, computing from the respective equations a recomputed absorption coefficient from the computed output amplitude and the computed output phase, and utilizing the recomputed absorption coefficient for calculating concentrations of oxygenated hemoglobin and deoxygenated hemoglobin from the plurality of simultaneous equations.

11. The method of claim 1 further comprising steps of:

providing at least one standardized medium of a non-absorbing material containing scattering matter with a predetermined scattering coefficient and nil absorption coefficient, and further providing standard samples of the selected and additional constituents, the standard samples having predetermined concentrations and predetermined extinction coefficients;

directing the input beam into the medium such that the radiation is modified by the medium, positioning the detector to be receptive of such modified radiation so as to generate an output signal for the medium, and determining from each output signal a measured phase for the medium for each wavelength;

computing from the predetermined scattering coefficient a computed phase for each wavelength from a model equation relating phase to scattering coefficient;

directing the input beam into each standard sample such that the radiation is modified by the sample, positioning the detector so as to be receptive of such modified radiation so as to generate an output signal for each sample, and determining from each output signal a measured amplitude for each sample for selected wavelengths;

deriving a set of hypothetical concentrations of the constituents for hypothetical organs, computing therefrom and from the predetermined concentrations a hypothetical absorption coefficient for each wavelength from an absorption equation relating absorption coefficient to concentrations and extinction coefficients, selecting a set of hypothetical scattering coefficients, and computing from the hypothetical absorption coefficient and the selected scattering coefficients a computed amplitude for each wavelength from a model equation relating amplitude to absorption coefficient and scattering coefficient;

comparing the measured phase to the computed phase for each wavelength to effect phase calibration factors, comparing the measured amplitude to the computed amplitude for each wavelength to effect amplitude calibration factors, and storing the calibration factors for application respectively to output phase and output amplitude computed from signal data for an animal organ.

12. The method of claim 1 further comprising steps of:

providing at least one standardized medium of a non-absorbing material containing scattering matter with a predetermined scattering coefficient and nil absorption coefficient, and further providing standard samples of the selected and additional constituents, the standard samples having predetermined concentrations and predetermined extinction coefficients;

directing the input beam into the medium such that the radiation is modified by the medium, positioning the detector to be receptive of such modified radiation so as to generate an output signal for the medium, and determining from each output signal a measured phase for the medium for each wavelength;

directing the input beam into each standard sample such that the radiation is modified by the sample, positioning the detector so as to be receptive of such modified radiation so as to generate an output signal for each sample, and determining from each output signal a measured amplitude for each sample for selected wavelengths;

deriving a set of hypothetical concentrations of the constituents for hypothetical organs, computing therefrom and from the predetermined concentrations a hypothetical absorption coefficient for each wavelength from an absorption equation relating absorption coefficient to concentrations and extinction coefficients;

computing from the measured phase and the measured amplitude a computed absorption coefficient from for each wavelength from the model equations relating phase, amplitude, absorption coefficient and scattering coefficient; and

comparing the computed absorption coefficient and the hypothetical absorption coefficient for each wavelength to effect coefficient calibration factors, and storing the calibration factors for application to measured absorption coefficients computed from signal data for an animal organ, to effect corrected absorption coefficients for subsequent calculation of concentrations.

13. A method of determining a correction factor for measured blood saturation in an animal organ, the saturation being measured with a spectrometric instrument that includes a source of an input beam of discrete radiation formed of a plurality of discrete wavelengths in an infrared spectral range that includes absorbance wavelengths of blood hemoglobin in the organ, the hemoglobin comprising oxygenated hemoglobin and deoxygenated hemoglobin, and the blood saturation being a ratio of oxygenated hemoglobin to a total of oxygenated hemoglobin and deoxygenated hemoglobin, wherein:

each wavelength has a predetermined input amplitude and is modulated with a radio frequency signal having a predetermined input phase, and the instrument further includes a radiation detector receptive of such radiation to generate representative signal data;

the input beam is directed into an animal organ such that the radiation is modified by the hemoglobin, and the radiation detector is positioned so as to be receptive of the modified radiation from an exit site from the organ so as to generate a corresponding output signal for each wavelength;

an output amplitude and an output phase for each wavelength are determined from each output signal;

an absorption coefficient is computed for each wavelength from the input amplitude, the output amplitude, the input phase and the output phase, from respective equations relating phase and amplitude to absorption coefficient and scattering coefficient;

concentrations of oxygenated hemoglobin and deoxygenated hemoglobin are calculated from a pair of simultaneous linear equations, each equation being for a different wavelength relating absorption coefficient to the concentrations proportionately with respective predetermined extinction coefficients; and

a measured oxygen saturation in the blood is calculated; and

the method comprises steps of;

providing an absorption relationship relating absorption coefficient for the organ to oxygen saturation, specific absorption coefficients and volume fractions respectively for water, tissue matrix, blood, and for constituents of the tissue matrix and the blood, wherein the specific absorption coefficients are predetermined for each wavelength, and the volume fractions can vary within predetermined ranges;

selecting at least one set of values for the oxygen saturation and the volume fractions, and, for each set, calculating therefrom a corresponding organ absorption coefficient for each wavelength;

utilizing the calculated organ absorption coefficients for calculating concentrations of oxygenated hemoglobin and deoxygenated hemoglobin from the plurality of simultaneous linear equations, and further calculating oxygen saturations from the concentrations; and

comparing the calculated oxygen saturations to the selected values for oxygen saturation to obtain one or more correction factors, and storing the correction factors for application to the measured oxygen saturation to obtain a corrected oxygen saturation.

14. The method of claim 13 wherein the step of utilizing comprises computing a computed output amplitude and a computed output phase from the calculated organ absorption coefficients using the respective equations relating phase and amplitude to absorption coefficient, computing from the respective equations a recomputed absorption coefficient from the computed output amplitude and the computed output phase, and utilizing the recomputed absorption coefficient for calculating concentrations of oxygenated hemoglobin and deoxygenated hemoglobin from the plurality of simultaneous equations.

15. An apparatus for monitoring one or more selected constituents in an animal organ, comprising:

a spectrometric instrument comprising a source of an input beam of discrete radiation formed of a plurality of discrete wavelengths in an infrared spectral range that includes absorbance wavelengths of the selected constituents and one or more additional constituents in the organ, wherein each wavelength has a predetermined input amplitude and is modulated with a radio frequency signal having a predetermined input phase, and the instrument further comprises a radiation detector receptive of such radiation to generate representative signal data, wherein the selected constituents and the additional constituents constitute a total number of constituents having significant absorbance in the spectral range, the plurality of wavelengths is at least equal in number to the total number of constituents;

means for directing the input beam into an animal organ such that the radiation is modified by the constituents;

means for positioning the radiation detector so as to be receptive of the modified radiation from an exit site from the organ so as to generate a corresponding output signal for each wavelength;

means for determining from each output signal an output amplitude and an output phase for each wavelength;

means for computing an absorption coefficient for each wavelength from the input amplitude, the output amplitude, the input phase and the output phase, with respective equations relating phase, amplitude, absorption coefficient and scattering coefficient; and

means for calculating concentration of each of the selected constituents from a plurality of simultaneous equations at least equal to the total number of constituents, each equation being for a different wavelength and relating absorption coefficient to concentrations of all of the constituents proportionately with respective predetermined extinction coefficients.

16. The apparatus of claim 15 wherein, to predetermine each input amplitude and input phase, the apparatus further comprises

means for passing the input beam through a neutral density filter to the radiation detector so as to generate a corresponding reference signal for each wavelength, the filter having a predetermined optical density;

means for determining from each reference signal a reference amplitude and a reference phase for each wavelength, whereby the input phase is equal to the reference phase; and

means for calculating the input amplitude from the reference amplitude and the optical density.

17. The apparatus of claim 15 wherein the organ comprises blood containing oxygenated hemoglobin and deoxygenated hemoglobin, and the apparatus further comprises means for calculating a measured oxygen saturation in the blood as a ratio of concentration of oxygenated hemoglobin to a total of concentrations of oxygenated hemoglobin and deoxygenated hemoglobin.

18. The apparatus of claim 17 wherein the organ further comprises water and tissue matrix, and the apparatus further comprises:

a computer-stored absorption relationship relating total absorption coefficient for the organ to oxygen saturation, specific absorption coefficients and volume fractions respectively for water, tissue matrix, blood, and for constituents of the tissue matrix and the blood, wherein the specific absorption coefficients are predetermined for each wavelength, and the volume fractions can vary;

means for selecting at least one set of values for the oxygen saturation and the volume fractions, and, for each set, means for calculating therefrom and from the specific absorption coefficients a corresponding calculated organ absorption coefficient for a selected wavelength;

means for utilizing the calculated organ absorption coefficients to compute concentrations of oxygenated hemoglobin and deoxygenated hemoglobin from the plurality of simultaneous equations, and means for further calculating oxygen saturations from the concentrations; and

means for comparing the calculated oxygen saturations to the selected values for oxygen saturation to obtain a correction factor, and means for storing the correction factor for application to the measured oxygen saturation to obtain a corrected oxygen saturation.

19. The apparatus of claim 18 wherein the means for utilizing comprises means for computing an output amplitude and an output phase from the calculated organ absorption coefficients using the respective equations relating phase and amplitude to absorption coefficient, means for computing from the respective equations a recomputed absorption coefficient from the computed output amplitude and the computed output phase, and means for utilizing the recomputed absorption coefficient to calculate concentrations of oxygenated hemoglobin and deoxygenated hemoglobin from the plurality of simultaneous equations.