Apparatus and method for qualitative and quantitative measurements of optical properties of turbid media using frequency-domain photon migration

• US 5,424,843 A
• Filed: 12/23/1992
• Issued: 06/13/1995
• Est. Priority Date: 12/23/1992
• Status: Expired due to Term

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Tsay, Tsong T., Svaasand, Lara O., Tromberg, Bruce J., Berns, Michael W., Haskell, Richard C.
• Primary Examiner(s): McGraw, Vincent P.
• Application Number:
  US07/996,321
• Time in Patent Office: 902 Days
• Field of Search: 356/440, 356/441, 356/442, 356/342, 356/343
• US Class Current: 356/442
• CPC Class Codes: G01N 21/49 within a body or fluid

Abstract

Optical measurements of turbid media, that is media characterized by multiple light scattering, is provided through an apparatus and method for exposing a sample to a modulated laser beam. The light beam is modulated at a fundamental frequency and at a plurality of integer harmonics thereof. Modulated light is returned from the sample and preferentially detected at cross frequencies at frequencies slightly higher than the fundamental frequency and at integer harmonics of the same. The received radiance at the beat or cross frequencies is compared against a reference signal to provide a measure of the phase lag of the radiance and modulation ratio relative to a reference beam. The phase and modulation amplitude are then provided as a frequency spectrum by an array processor to which a computer applies a complete curve fit in the case of highly scattering samples or a linear curve fit below a predetermined frequency in the case of highly absorptive samples. The curve fit in any case is determined by the absorption and scattering coefficients together with a concentration of the active substance in the sample. Therefore, the curve fitting to the frequency spectrum can be used both for qualitative and quantitative analysis of substances in the sample even though the sample is highly turbid.

Claims

1. An optical method of analysis of turbid media comprising the steps of:

generating a modulated optical radiance wave at more than two frequencies at 1 MHz and higher;

exposing a sample of said turbid media to said modulated radiance wave;

measuring said modulated radiance wave returned from said sample; and

determining from said measured returned radiance wave an optical property of said sample,

whereby said sample may be analyzed whether said sample is highly scattering, highly absorptive, or a combination of both.

2. The method of claim 1 wherein said step of generating said modulated radiance wave comprises the step of modulating said radiance wave at a plurality of frequencies.

3. The method claim 2 wherein said step of generating said plurality of frequencies comprises the step of modulating said radiance wave at a fundamental frequency and a plurality of integer harmonics thereof.

4. The method of claim 1 further comprising the step of generating said modulated radiance wave at a plurality of optical frequencies for the purpose of providing an absorption spectrum of said sample.

5. The method of claim 2 wherein step of measuring said radiance wave is performed at each of said plurality of frequencies and said step of determining comprises the step of providing a complete curve fit in the frequency domain in a computer automated process for at least one optical parameter derived from said radiance wave at said plurality of frequencies, said curve fit being determined by the coefficient of absorption and the coefficient of scattering for said sample so that said sample can be quantitatively analyzed by identification of its optical absorption and scattering coefficients.

6. The method of claim 5 further comprising the step wherein said complete curve fit is also determined by concentration of an absorbing and/or scattering substance within said sample so that the quantitative concentration of said substance is determined.

7. The method of claim 2 wherein said sample is highly absorptive and where said step of determining comprises the step of providing a linear curve fit in the frequency domain to at least one optical parameter derived from said measured radiance wave at and below a predetermined frequency, said linear curve fit being determine by the absorption coefficient of said sample so that quantitative determination of said sample may be made.

8. The method of claim 7 further comprising the step of determining said linear curve fit below said predetermined frequency according to concentration of a substance included within said sample so that quantitative determination of said substance may be made.

9. The method of claim 1 wherein said step of measuring said radiance wave comprises the derivation of modulation of said light, said modulation being defined as modulation of light returned from said sample relative to modulation of said light exposed on said sample.

10. The method of claim 1 wherein said step of measuring said radiance wave comprises the derivation of the phase lag of said light, said phase lag being defined as the phase of light returned from said sample relative to the phase of said light exposed on said sample.

11. The method of claim 1 wherein said step of measuring said radiance wave comprises the steps of receiving said returned radiance wave from said sample in a sensing device having a gain, said gain of said sensing device being modulated at a fundamental frequency increased by a cross correlation frequency and integer multiharmonics thereof.

12. The method of claim 11 wherein said step of determining comprises the step of analyzing phase and modulation amplitude response at each of said harmonic cross frequencies returned from said sample.

13. The method claim 12 wherein said step of analyzing comprises transforming phase and modulation response return from said sample to a frequency spectrum.

14. An apparatus for analyzing turbid media comprising:

means for exposing a sample to a modulated radiance wave at more than two frequencies in the range of 1 MHz or higher;

means for receiving at least a portion of said modulated radiance wave returned from said sample;

means for analyzing said returned modulated radiance wave from said sample at least one cross frequency of the frequency of modulation of said radiance wave;

means for providing a frequency spectrum of said analyzed radiance wave at said at least one cross frequency; and

means for providing a curve fit to said frequency spectrum according to the optical absorption coefficient, and optical scattering coefficient as curve fitting parameters,

whereby optical properties of said sample are identified whether said sample is high absorptive, highly scattering or both.

15. The apparatus of claim 14 wherein said means for exposing said sample to said modulated beam of light modulates said radiance wave at a predetermined fundamental frequency and integer harmonics thereof.

16. The apparatus of claim 15 wherein said means for analyzing said returned radiance wave from said sample at least one cross frequency preferentially detects said return radiance wave at a plurality of integer harmonics above said fundamental frequency.

17. The apparatus of claim 16 wherein said means for providing a curve fit to said frequency spectrum provides a complete nonlinear curve fit at said plurality of cross frequency harmonics so that a highly scattering sample may be analyzed.

18. The apparatus of claim 16 wherein said means for providing a curve fit provides a linear curve fit to said frequency spectrum at and below a predetermined frequency so that a highly absorptive sample may be analyzed.

19. The apparatus of claim 14 wherein said fundamental frequency is 5 Mhz and wherein said cross frequency is 3 Hz above said fundamental frequency and at integer harmonics thereof.

20. The apparatus of claim 14 wherein said means for providing a frequency spectrum provides a frequency spectrum of phase lag and/or modulation of said radiance wave returned from said sample.