Monitoring constituents of an animal organ using statistical correlation

• US 6,430,513 B1
• Filed: 01/07/2000
• Issued: 08/06/2002
• 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: Ganz, Alan M., Wang, Yongdong, Tracy, David H., Saviano, Paul G., Nishikida, Koichi, Kumar, Gitesh
• Primary Examiner(s): Hilten, John S.
• Assistant Examiner(s): LE, JOHN H
• Application Number:
  US09/479,642
• Time in Patent Office: 942 Days
• Field of Search: 702/28, 702/FOR.131, 702/FOR.139, 600/323, 600/324, 600/328, 600/344, 600/310, 128/633, 128/634, 250/339.01, 250/339.07, 250/341.1, 356/39-41, 356/317-319, 356/323
• US Class Current: 702/28
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/14553 specially adapted for cerebral tissue
• CPC Class Codes: A61B 5/6814 Head
• CPC Class Codes: G01N 21/49 within a body or fluid

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. Concentrations are computed from the spectral intensities and from a statistical correlation model. To predetermine the correlation model, the procedures are effected for a plurality of organs of a same type with each organ having established concentrations of the selected constituents, and the correlation model is statistically determined from the concentrations and corresponding intensities. For more accuracy computations are normalized to path length which may be determined by utilizing several discrete wavelengths with RF modulations.

Claims

1. A method of monitoring one or more selected molecular constituents in an animal organ, with a spectrometric instrument that includes a source of an input beam of infrared radiation having a substantially full spectrum in a spectral range that includes absorbance wavelengths of the selected constituents, and a spectral detector receptive of such radiation to generate representative signal data, the method comprising steps of directing the input beam into an animal organ at an input site, wherein the radiation is attenuated by constituents of the organ including the selected constituents, positioning the spectral detector so as to be receptive of the attenuated radiation from an exit site from the organ so as to generate signal data representative of spectral distribution of the attenuated radiation, calculating spectral intensities over the spectral range from the signal data, converting spectral intensities to absorbances, and computing concentrations of the selected constituents from the absorbances and from a predetermined statistical correlation model relating such concentrations and absorbances.

2. The method of claim 1 wherein, to predetermine the correlation model, the method further comprises steps of:

effecting the steps of directing the input beam, positioning the spectral detector and calculating spectral intensities, for a plurality of organs of a same type with each organ having established concentrations of the selected constituents; and

statistically determining the correlation model from the concentrations and corresponding intensities.

3. The method of claim 2 wherein the step of statistically determining includes applying a scaling factor to the concentrations such that each of the concentrations is scaled, wherein the scaling factor is determined statistically along with the correlation model.

4. The method of claim 1 wherein the source and the detector are disposed so that the radiation passes through a cranium, and the organ is a brain, whereby the radiation is attenuated by brain constituents.

5. The method of claim 1 wherein the spectral range is from about 700 nm to about 1100 nm, and the select molecular constituents comprise oxygenated hemoglobin and de-oxygenated hemoglobin.

6. The method of claim 1 wherein the instrument is an infrared Fourier transform spectrometric instrument, the source comprises a time varying interference pattern, and the spectral detector comprises a photodetector.

7. The method of claim 1 wherein the instrument is a dispersion instrument such that the source is a steady source of infrared radiation, and the spectral detector comprises a dispersion element receptive of the attenuated radiation to effect dispersed radiation, and a photodetector receptive of the dispersed radiation to effect the spectral signal data.

8. The method of claim 1 wherein the one or more selected constituents is a plurality of selected constituents.

9. The method of claim 8 wherein the plurality of selected constituents comprise at least two bimolecular compounds.

10. The method of claim 9 wherein the biomolecular compounds comprise oxygenated hemoglobin and de-oxygenated hemoglobin.

11. The method of claim 10 wherein the organ is a cranium, and the radiation is attenuated by brain constituents including the oxygenated hemoglobin and deoxygenated hemoglobin.

12. The method of claim 10 further computing saturation level of oxygenated hemoglobin relative to a total of the oxygenated hemoglobin and de-oxygenated hemoglobin, wherein the saturation level is independent of path length of the radiation to the spectral detector.

13. The method of claim 10 wherein the instrument is an infrared Fourier transform spectrometric instrument, the source comprises a time varying interference pattern, and the spectral detector comprises a photodetector.

14. The method of claim 13 wherein the spectral range is from about 700 nm to about 1100 nm.

15. The method of claim 14 wherein, to predetermine the correlation model, the method further comprises steps of:

effecting the steps of directing the input beam, positioning the spectral detector and calculating spectral intensities, for a plurality of organs of a same type with each organ having established concentrations of the oxygenated hemoglobin and de-oxygenated hemoglobin; and

statistically determining the correlation model from the concentrations and corresponding intensities.

16. The method of claim 15 wherein the step of statistically determining includes applying a scaling factor to the concentrations whereby each of the concentrations is scaled, wherein the scaling factor is determined statistically along with the correlation model.

17. The method of claim 15 further comprising computing saturation level of oxygenated hemoglobin relative to a total of the oxygenated hemoglobin and de-oxygenated hemoglobin, whereby the saturation level is independent of path length of the radiation to the spectral detector.

18. The method of claim 17 wherein the organ is a cranium, and the radiation is attenuated by brain constituents including the oxygenated hemoglobin and de-oxygenated hemoglobin.

19. The method of claim 1 wherein the step of converting comprises passing the input beam through a reference medium to the spectral detector to generate corresponding reference data, calculating reference intensities over the spectral range from the reference data, and computing absorbances from the spectral intensities and the reference intensities.

20. The method of claim 1 wherein, to predetermine the correlation model, the method further comprises steps of:

effecting the steps of directing the input beam, positioning the spectral detector, calculating spectral intensities, and converting intensities to absorbances, for a plurality of organs of a same type with each organ having established concentrations of the selected constituents; and

statistically determining the correlation model from the concentrations and corresponding absorbances.

21. The method of claim 20 wherein the step of statistically determining includes applying a scaling factor to the concentrations whereby each of the concentrations is scaled, wherein the scaling factor is determined statistically along with the correlation model.

22. The method of claim 1 further comprising the steps of ascertaining a path length of the radiation in the organ between the input site and the exit site, and dividing each absorbance for each spectral increment by the path length to effect normalized absorbances, the concentrations being computed from the correlation model and the normalized absorbances.

23. The method of claim 22 wherein the input beam is directed into the organ at the input site, and the step of ascertaining comprises:

effecting a further beam of input discrete radiation comprising at least one discrete wavelength component in the spectral range, each wavelength component being modulated with a radio frequency signal;

directing the further beam into the organ at the input site wherein the discrete radiation is modified by the organ;

positioning a radiation detector to be receptive of the modified radiation from the exit site to generate corresponding detector signals;

determining a phase shift between the radio frequency signal and the corresponding signals, and thereby between the input discrete radiation and the modified radiation for each discrete wavelength;

calculating, from each phase shift, correspondingly at least one effective path length of the discrete radiation in the organ between the input site and the exit site; and

computing, from the at least one effective path length, a spectral path length for each spectral increment in the spectral range, each absorbance for each spectral increment being divided by an increment path length for that spectral increment to effect normalized absorbances.

24. The method of claim 23 wherein the input discrete radiation comprises a plurality of discrete wavelength components in the spectral range, wherein a corresponding plurality of effective path lengths are calculated for the computing of the increment path length for each spectral increment.

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

a spectrometric instrument including a source of an input beam of infrared radiation having a substantially full spectrum in a spectral range that includes absorbance wavelengths of the selected constituents, and a spectral detector receptive of radiation to generate representative signal data;

directing means for directing the input beam into an animal organ at an input site wherein the radiation is attenuated by constituents of the organ including the selected constituents;

positioning means for positioning the spectral detector so as to be receptive of the attenuated radiation from an exit site from the organ to generate signal data representative of spectral distribution of the attenuated radiation; and

computing means for calculating spectral intensities over the spectral range from the signal data, for converting spectral intensities to absorbances, and for computing concentrations of the selected constituents from the absorbances and from a predetermined statistical correlation model relating concentrations and absorbances.

26. The apparatus of claim 25 wherein the source and the detector are disposed cooperatively wherein the radiation can pass through a cranium, and the organ is a brain, wherein the radiation is attenuated by brain constituents.

27. The apparatus of claim 25 wherein the instrument is an infrared Fourier transform spectrometric instrument, the source comprises a time varying interference pattern, and the spectral detector comprises a photodetector.

28. The apparatus of claim 25 wherein the input beam is directed into the organ at an input site, the apparatus further comprises:

means for effecting a further beam of input discrete radiation comprising at least one discrete wavelength component in the spectral range, each wavelength component being modulated with a radio frequency signal;

means for directing the further beam into the organ at the input site wherein the discrete radiation is modified by the organ;

means for positioning a radiation detector to be receptive of the modified radiation from the exit site to generate corresponding detector signals; and

means for determining a phase shift between the radio frequency signal and the corresponding signals, and thereby between the input discrete radiation and the modified radiation for each discrete wavelength; and

the computing means further comprises;

means for calculating, from each phase shift, a corresponding effective path length of

the discrete radiation in the organ between the input site and the exit site;

means for computing, from the at least one effective path length, a spectral path length for each spectral increment in the spectral range;

means for dividing each absorbance for each spectral increment by the path length for that spectral increment to effect normalized absorbances, the concentrations being computed from the correlation model and the normalized absorbances.