Correlation technique for analysis of clinical condition

• US 20090303462A1
• Filed: 03/30/2009
• Published: 12/10/2009
• Est. Priority Date: 09/29/2006
• Status: Active Grant

• Current Assignee: Ottawa Hospital Research Institute (Ottawa Hospital)
• Original Assignee: Ottawa Hospital Research Institute (Ottawa Hospital)
• Inventors: Lagali, Neil, Munger, Rejean
• Granted Patent: US 8,125,623 B2
• Time in Patent Office: Days
• US Class Current: 356/39
• CPC Class Codes: A61B 5/0059 using light, e.g. diagnosis by transillumination, diascopy, fluorescence A61B5/0093, A61B5/1455, A61B5/02416 and A61B5/0261 take precedence
• CPC Class Codes: A61B 5/0075 by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy A61B5/0071 takes precedence
• CPC Class Codes: A61B 5/14551 for measuring blood gases
• CPC Class Codes: A61B 5/72 Signal processing specially adapted for physiological signals or for diagnostic purposes character recognition, recognising digital ink, document-oriented image-based pattern recognition G06V30/00; recognition or understanding of postal images G06V30/424
• CPC Class Codes: G01N 21/31 Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry G01N21/72 takes precedence
• CPC Class Codes: G01N 21/64 Fluorescence; Phosphorescence
• CPC Class Codes: G01N 21/65 Raman scattering

Abstract

The present invention provides a correlation technique for analysis of changes in bodily fluid and/or tissue in order to identify or monitor appearance, progression or treatment of a disease or condition in a subject. The disclosed method involves measuring spectral properties or changes in bodily fluid and/or tissue of a subject using at least two optical techniques; and correlating the measured properties or changes to a corresponding clinical condition or change in clinical condition, respectively. The measure of spectral changes over time can be used as indicators of changes in the clinical condition, for example, in disease treatment and/or disease regulation. This method is particularly useful for identifying a disease state and for monitoring efficacies of therapies used to treat different diseases or disorders, for example, renal dialysis.

Claims

1. A method for investigating a clinical condition of a subject, comprising the steps of:

(a) measuring spectral properties of bodily fluid or tissue of said subject using at least two optical techniques; and

(b) correlating the spectral properties to a corresponding clinical condition,

wherein said spectral properties are measured in ultra-violet wavelengths, visible wavelengths, near-infrared wavelengths, mid-infrared wavelengths or a combination thereof.

2. The method of claim 1, wherein said correlation step includes deriving from the measured spectral properties an index or indices correlating with the clinical condition of said subject at a single point in time, over a period of time, quasi-continuously or continuously, in response to at least one effector.

3. The method of claim 2, wherein said at least one effector is a single treatment, multiple treatments, a single dose of a medicine or multiple doses of a medicine.

4. The method of claim 2, wherein said clinical condition is indicative of long-term health of the subject, subjective or objective clinical outcome in said subject, or a potential future change in clinical status or state of health of said subject.

5. The method of claim 4, wherein said potential future change in clinical status or state of health of said subject is a predisposition to disease.

6. The method of claim 1, further comprising the step of comparing the measured spectral properties to spectral properties obtained from a population of subjects using said at least two optical techniques, wherein said population of subjects has a known average clinical condition.

7. The method of claim 1, wherein the clinical condition is a disease state.

8. The method of claim 1, wherein the at least two optical techniques include a combination of any two of the following phenomena:

diffuse reflection, inelastic (Raman) scattering, absorption/transmission, or fluorescence.

9. The method of claim 1, wherein the bodily fluid is whole blood or blood serum.

10. The method of claim 1, further comprising the step of processing raw spectral data to obtain said measured spectral properties.

11. The method of claim 10, wherein said processing step comprises one or more of the following:

(a) normalizing raw spectral data relative to a spectral data obtained from a baseline sample;

(b) normalizing raw spectral data relative to total integrated power;

(c) combining chosen spectral bands and aggregating spectral data obtained using said at least two optical techniques;

(d) applying a spectral pretreatment correction; and

(e) applying a chemometric algorithm.

12. The method of claim 11, wherein said spectral pretreatment correction is baseline correction, standard normal variate transformation, multiple scatter correction, wavelength selection, smoothing, derivatisation, or any combination thereof.

13. The method of claim 11, wherein said chemometric algorithm is a principal component analysis.

14. A method of monitoring changes in a clinical condition of a subject, comprising the steps of:

(a) measuring spectral changes in bodily fluid or tissue of said subject using at least two optical techniques; and

(b) correlating the measured changes to a corresponding change in clinical condition,

wherein said spectral changes are measured in ultra-violet wavelengths, visible wavelengths, near-infrared wavelengths, mid-infrared wavelengths or a combination thereof.

15. The method of claim 14, wherein said correlation step includes deriving from the measured spectral properties an index or indices correlating with the clinical condition of said subject.

16. The method of claim 14, further comprising the step of comparing the measured spectral properties over time.

17. The method of claim 16, wherein said comparison step includes a comparison to baseline spectral properties obtained at an initial time point.

18. The method of claim 14, wherein the at least two optical techniques include a combination of any two of the following phenomena:

diffuse reflection, inelastic (Raman) scattering, absorption/transmission, or fluorescence.

19. The method of claim 14, wherein the bodily fluid is whole blood or blood serum.

20. The method of claim 14, further comprising the step of processing raw spectral data to obtain said measured spectral properties.

21. The method of claim 20, wherein said processing step comprises one or more of the following:

(a) normalizing raw spectral data relative to a spectral data obtained from a baseline sample;

(b) normalizing raw spectral data relative to total integrated power;

(c) combining chosen spectral bands and aggregating spectral data obtained using said at least two optical techniques;

(d) applying a spectral pretreatment correction; and

(e) applying a chemometric algorithm.

22. The method of claim 21, wherein said spectral pretreatment correction is baseline correction, standard normal variate transformation, multiple scatter correction, wavelength selection, smoothing, derivitisation, or any combination thereof.

23. The method of claim 21, wherein said chemometric algorithm is a principal component analysis.

24. The method of claim 14, wherein the method is used to monitor disease progression, onset, regulation or treatment in said subject or to monitor changes in athletic conditioning or performance of said subject.

25. A method for deriving an index or indices for correlation to an observed clinical condition of a subject comprising the steps of

(a) obtaining a body of raw spectral data by measuring spectral properties of bodily fluid or tissue of said subject using at least two optical techniques;

and

(b) comparing the raw spectral data with the clinical condition of said subject.

26. A method for overcoming confounding or interfering influences on measured optical spectra by obtaining a body of raw spectral data from measured spectral properties of a bodily fluid or tissue of a subject using at least two optical techniques.

27. The method of claim 26, wherein said confounding or interfering influences are oxygen saturation, hematocrit, hemoglobin, heparin, pH, environmental factors, temperature, humidity, or a combination thereof.