System and method for measuring absolute oxygen saturation

• US 20020058865A1
• Filed: 06/07/2001
• Published: 05/16/2002
• Est. Priority Date: 09/18/2000
• Status: Active Grant

• Current Assignee: ViOptix, Inc.
• Original Assignee: ViOptix, Inc.
• Inventors: Wang, Lai, Zhou, Shuoming, Cheng, Xuefeng, Xu, Xiaorong
• Granted Patent: US 6,587,703 B2
• Time in Patent Office: Days
• US Class Current: 600/323
• CPC Class Codes: A61B 2562/0233 Special features of optical sensors or probes classified in A61B5/00
• CPC Class Codes: A61B 2562/0242 for varying or adjusting the optical path length in the tissue
• CPC Class Codes: A61B 2562/043 in a linear array
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/14551 for measuring blood gases
• CPC Class Codes: A61B 5/14552 Details of sensors specially adapted therefor
• CPC Class Codes: A61B 5/14553 specially adapted for cerebral tissue
• CPC Class Codes: A61B 5/413 Monitoring transplanted tissue or organ, e.g. for possible rejection reactions after a transplant
• CPC Class Codes: G01N 2021/3144 for oxymetry
• CPC Class Codes: G01N 21/359 using near infrared light
• CPC Class Codes: G01N 21/49 within a body or fluid

Abstract

The present invention generally relates to apparatus and methods for obtaining absolute values of concentrations of chromophores of a medium and/or absolute values of their ratios. In particular, the present invention relates to continuous wave spectroscopic optical systems and methods for determining the absolute values of deoxygenated and/or oxygenated hemoglobins and their ratios in a physiological medium. The optical system typically includes (1) a source module optically coupling with the medium and irradiating into the medium multiple sets of electromagnetic waves with different wave characteristics, (2) a detector module optically coupling with the medium and detecting electromagnetic waves, and (3) a processing module operatively coupling with the detector module, and determining the absolute values of the concentrations and the ratios thereof from multiple wave equations applied to the source and detector modules. The processing module is designed to obtain such absolute values by a method typically including the steps of (1) obtaining multiple sets of wave equations, (2) eliminating source-dependent and detector-dependent parameters therefrom to obtain a set of intermediate equations, (3) providing a correlation between medium-dependent and geometry-dependent parameters and the chromophore concentrations or ratios thereof, (4) incorporating the correlation into the set of intermediate equations, and (5) obtaining the absolute values of the chromophore concentrations and ratios thereof.

Claims

1. A system for determining concentrations of chromophores in a physiological medium, comprising:

a source module to irradiate into said medium at least two sets of electromagnetic radiation having different wave characteristics;

a detector module to detect electromagnetic radiation transmitted through said medium; and

a processing module operatively coupled with said detector module to determine an absolute value of at least one of said concentrations from electromagnetic radiation irradiated from and detected by said source and detector modules,

wherein said determination is based only on intensity measurements of continuous wave electromagnetic radiation from the source module.

2. A system according to claim 1, wherein said chromophores are hemoglobins including oxygenated hemoglobin and deoxygenated hemoglobin.

3. A system according to claim 1, wherein said physiological medium includes cells of at least one of organs, tissues, and body fluids.

4. A system according to claim 3, wherein at least some cells are abnormal.

5. A system according to claim 4, wherein said abnormal cells are tumor cells.

6. A system according to claim 4, wherein said cells are disposed in at least one of epidermis, and corium of an internal organ including at least one of a brain, heart, lung, liver, and kidney.

7. A system according to claim 4, wherein said cells are those of a transplanted organ.

8. A system according to claim 7, wherein said transplanted organ includes at least one of a brain, heart, lung, liver, and kidney.

9. A system according to claim 1, wherein said wave characteristics include at least one of wavelengths, phase angles, amplitudes and harmonics.

10. A system according to claim 9, wherein a first set of said electromagnetic waves has a first wavelength and a second set of said electromagnetic waves has a second wavelength, which is different from said first wavelength.

11. A system according to claim 9, wherein a first set of said electromagnetic waves includes a first carrier wave and a second set of said electromagnetic waves includes a second carrier wave which has wave characteristics different from those of said first carrier wave.

12. A system according to claim 11, wherein said wave characteristics include at least one of wavelengths, phase angles, amplitudes, harmonics, and a combination thereof.

13. A system according to claim 1, wherein said processing module determines said absolute value a parameter accounting for optical interaction properties of electromagnetic waves with said medium.

14. A system according to claim 13, wherein said processing module uses a mathematical expression including at least one parameter dependent on one of:

optical properties of said medium and configuration of said source module and detector module.

15. A system according to claim 14, wherein said mathematical expression comprises a polynomial of at least one of said concentrations and said ratios thereof.

16. A system according to claim 13, wherein said mathematical expression includes a term substantially dependent on one or more of:

optical properties of said medium and configuration of said source module and detector module, which term is approximated as a constant.

17. A system according to claim 1, wherein said processing module uses the mathematical expression:

I=α

β

γ

I₀exp{−

B Lδ

Σ

₁(ε

_iC_i)+σ

},

wherein I₀ is a variable for an intensity of electromagnetic waves irradiated by said source module, I is a variable for an intensity of electromagnetic waves detected by said detector module, a is a parameter associated with at least one of said source module and medium, β

is a parameter associated with at least one of said detector module and medium, γ

is one of a proportionality constant and a parameter associated with at least one of said source module, detector module, and medium, B is a parameter accounting for a length of an optical path of electromagnetic waves through said medium and associated with at least one of said source module, detector module, and medium, L is a parameter accounting for a distance between said source module and said detector module, 8 is one of a proportionality constant and a parameter associated with at least one of said source module, detector module, and medium, ε

₁ is a parameter accounting for an optical interaction between electromagnetic waves and an i-th chromophore in said medium, C₁ is a variable denoting concentration of said i-th chromophore, and σ

. is one of a proportionality constant and a parameter associated with at least one of said source module, detector module, and medium.

18. A system according to claim 17, wherein said parameter B is a path length factor.

19. A system according to claim 17, wherein said parameter ε

₁ is at least one of a medium extinction coefficient, medium absorption coefficient, and medium scattering coefficient.

20. A system according to claim 1, wherein said source module includes at least one wave source and said detector module includes at least two wave detectors.

21. A system according to claim 1, wherein said source module includes at least two wave sources and said detector module includes at least one wave detector.

22. A system according to claim 1, wherein said source module and said detector module include, respectively, at least two wave sources and at least two wave detectors.

23. A system according to claim 22, wherein said processing module uses the mathematical expression:

I<sub>mn=α

mβ

nγ</sub>

I_o,mexp{−

B_mnL_mnδ

Σ

₁(ε

₁C₁)+σ

},

wherein I_o,m is a variable for an intensity of electromagnetic waves irradiated by an m-th wave source, I_mn is a variable for an intensity of electromagnetic waves irradiated by said m-th wave source and detected by an n-th wave detector, α

_m is a parameter associated with at least one of said m-th wave source and medium, β

_n is a parameter associated with at least one of said n-th wave detector and medium, γ

is one of a proportionality constant and a parameter associated with at least one of said m-th wave source, n-th wave detector, and medium, B_mn is a parameter accounting for a length of an optical path of electromagnetic waves through said medium and associated with at least one of said m-th wave source, n-th wave detector, and medium, L_mn is a parameter accounting for a distance between said m-th wave source and n-th wave detector, δ

is one of a proportionality constant and a parameter associated with at least one of said m-th wave source, n-th wave detector, and medium, ε

_i is a parameter accounting for an optical interaction between electromagnetic waves and an i-th chromophore included in said medium, C₁ is a variable denoting concentration of said i-th chromophore, and σ

is one of a proportionality constant and a parameter associated with at least one of said m-th wave source, n-th wave detector, and medium, wherein both of said subscripts m and n are non-zero positive integers.

24. A system according to claim 23, wherein said parameter B_mn is a path length factor associated with at least one of said m-th wave source, n-th wave detector, and medium.

25. A system according to claim 23, wherein said parameters γ

and δ

are configured to be substantially close to a unity so that said expression is simplified to

I_mn=α

_mβ

_nI_o,mexp{−

B_mnL_mnΣ

₁(ε

₁C₁)+σ

}.

26. A system according to claim 22, wherein said source module includes a first wave source and a second wave source and wherein said detector module includes a first wave detector and a second wave detector,

said wave sources and wave detectors configured so that a distance between said first wave source and said first wave detector is substantially similar to that between said second wave source and said second wave detector, and that a distance between said first wave source and said second wave detector is substantially similar to that between said second wave source and said first wave detector.

27. A system according to claim 22, wherein said source module has at least M wave sources and said detector module has at least N wave detectors, and M and N are integers greater than 1,

said wave sources and wave detectors configured so that a distance between an M₁-th wave source and an N₁-th detector is substantially similar to that between an M₂-th wave source and an N₂-th wave detector, and that a distance between said M₁-th wave source and said N₂-th wave detector is substantially similar to that between said M₂-th wave source and said N₁-th wave detector, wherein said M₁ and M₂ are both integers between 1 and M, and wherein said N₁ and N₂ are both integers between 1 and N.

28. A system according to claim 22, wherein two or more wave detectors are disposed substantially along a straight line, and two wave sources are disposed on opposite sides of the straight line.

29. A system according to claim 28, wherein all wave detectors are disposed substantially along said straight line.

30. A system according to claim 22, wherein said detector module includes at least three wave detectors disposed substantially along a straight line.

31. A system for determining concentrations of chromophores in a physiological medium, comprising:

one or more sources irradiating into said medium at least two sets of near-infrared electromagnetic waves having different wave characteristics;

one or more detectors detecting electromagnetic waves transmitted through said medium;

input means for entering input parameter data; and

a processing module determining absolute values of at least one of said concentrations,

wherein said determination is not based on measuring phase characteristics of the electromagnetic radiation received from said one or more detectors, or the response of the medium to an electromagnetic impulse from said one or more sources.

32. A system for determining concentrations of chromophores in a physiological medium, comprising:

at least one source for irradiating into said medium at least two sets of electromagnetic waves having different wave characteristics;

at least one detector for detecting electromagnetic waves transmitted through said medium;

a processor coupled to the at least one detector computing one of;

absolute values of said concentrations and ratios of said concentrations,

wherein said computation is based only on intensity measurements of continuous wave electromagnetic radiation from the source module

33. A method for determining concentrations of chromophores in a physiological medium using a system having at least one wave source and at least one wave detector, wherein electromagnetic waves are irradiated by said wave source, transmitted through the physiological medium, and detected by said wave detector, the method comprising the steps of:

irradiating at least two sets of electromagnetic waves having different wave characteristics to obtain a plurality of measurements;

providing a mathematical expression relating said plurality of measurements to parameters of the system, and parameters associated with said medium;

eliminating source-dependent and detector-dependent parameters from the provided mathematical expression; and

determining an absolute value of at least one of said concentrations, wherein said determination is based only on intensity measurements of continuous wave electromagnetic radiation and pre-determined chromophore-dependent parameters.

34. The method of claim 33, wherein the mathematical expression includes a wave equation is expressed as:

I=α

β

γ

_oexp{−

B L δ

Σ

₁(ε

₁C₁)+σ

},

wherein I_o is a variable for an intensity of electromagnetic waves irradiated by at least one source, I is a variable for an intensity of electromagnetic waves detected by at least one detector, α

is a parameter associated with at the least one source and the medium, β

is a parameter associated with the at least one detector and the medium, γ

is one of a proportionality constant and a parameter associated with at least one source, detector and medium, B is a parameter accounting for lengths of optical paths of electromagnetic waves through said medium and associated with at least one source, detector and medium, L is a parameter accounting for a distance between the source and the detector, δ

is one of a proportionality constant and a parameter associated with at least one of the source, detector, and medium, ε

₁ is a parameter accounting for A interaction between electromagnetic waves and an i-th chromophore in said medium, C₁ is a variable denoting concentration of said i-th chromophore, and σ

is one of a proportionality constant and a parameter associated with at least one of said source, detector, and medium.

36. The method of claim 35 further comprising the steps of:

applying said system to said physiological medium including cells of at least one of organs, tissues, and body fluids; and

measuring said absolute value of at least one of said concentrations based on said values of I_mn, I_o,m, and ε

₁.

37. The method of claim 36, wherein said measuring step comprises the step of:

monitoring at least one of oxygenated hemoglobin concentration, deoxygenated hemoglobin concentration, and a ratio thereof.

38. The method of claim 37 further comprising the step of determining a presence of tumor cells over a finite area of said medium.

39. The method of claim 37 further comprising the step of determining a presence of an ischemic condition over a finite area of said medium.

40. The method of claim 35 further comprising the steps of applying said system to said physiological medium including transplanted cells of at least one of organs and tissues;

and

measuring said absolute value of at least one of said concentrations and said ratios thereof based on said I_mn, I_o,m, and ε

_i.

41. The method of claim 40 further comprising the step of determining a presence of an ischemic condition over a finite area of said medium.

42. The method of claim 35, wherein said eliminating step comprises the step of:

approximating unknown equation parameters as constants.

43. The method of claim 35, wherein said obtaining step comprises the step of irradiating said first and second set of electromagnetic waves having at least one of different wavelengths, phase angles, amplitudes and harmonics.

44. The method according to claim 43, wherein said irradiating step comprises the steps of:

providing said first set of electromagnetic waves with a first wavelength; and

providing said second set of electromagnetic waves with a second wavelength which is different from said first wavelength.

45. The method of claim 35, wherein said eliminating step comprises the step of:

taking at least one first ratio of two wave equations both selected from one of said first and second sets of wave equations.

46. The method of claim 45, wherein said eliminating step comprises the step of:

solving said wave equations for the same wave source with different wave detectors, thereby eliminating α

_n, γ

, and σ

from said first ratio.

47. The method of claim 45, wherein said eliminating step comprises the step of:

solving said wave equations for at least two different wave sources and one wave detector, thereby eliminating β

_n, γ

, and a from said first ratio.

48. The method of claim 45, wherein said eliminating step comprises the step of:

taking at least one second ratio of two wave equations both selected from the other of said first and second sets of wave equations.

49. The method of claim 48, wherein said eliminating step comprises the step of:

obtaining at least one of a sum of and a difference between said first and second ratios so as to eliminate at least one of α

_m and β

_n therefrom.

50. The method of claim 35, wherein said providing step comprises the step of:

expressing a formula of said medium-dependent and said geometry-dependent parameters as a polynomial of at least one of said concentrations.

51. The method of claim 50, wherein said polynomial includes a zero-th order term.

52. The method of claim 35, wherein said providing step comprises the step of approximating at least one medium-dependent or geometry-dependent parameter as a constant.

35. A method for determining concentrations of chromophores in a physiological medium using a system having at least one wave source and at least one wave detector by application of a wave equation having a form:

I<sub>mn=β

nγ</sub>

I_o,mexp{−

B_mnL_mnδ

Σ

_i(ε

_iC_i)+σ

},

wherein I_o,m is a variable representing an intensity of electromagnetic waves irradiated by the m-th wave source, I_mn is a variable for an intensity of electromagnetic waves irradiated by the m-th wave source and detected by the n-th detector, α

_m is a parameter associated with the m-th wave source and the medium, β

_n is a parameter associated with the n-th wave detector and the medium, γ

is one of a proportionality parameter associated with at least one of wave source, detector, and medium, B_mn is a parameter accounting for lengths of optical paths of electromagnetic waves through said medium and associated with the m-th wave source, n-th wave detector, and the medium, L_mn is a parameter accounting for a distance between the m-th wave source and the n-th wave detector, δ

is one of a proportionality parameter associated with at least one wave source, wave detector, and medium, ε

₁ is a parameter accounting for an optical interaction between electromagnetic waves and an i-th chromophore in said medium, C₁ is a variable for concentration of said i-th chromophore, and C is one of a proportionality parameter associated with a wave source, wave detector, and medium, said method comprising the steps of;

irradiating a first and second set of electromagnetic waves having different wave characteristics and measuring signals received from the medium to obtain two sets of equations relating the measured signals with unknown parameters in the wave equation;

eliminating at least one of the parameters α

_m, β

_n, γ

, δ

, and σ

from the wave equation using the first and second set of equations to obtain a third set of equations;

obtaining an expression for an absolute value of at least one of said concentrations based on values associated with I_mn, I_o,m, and ε

₁, following the step of eliminating.

53. A method for determining concentrations of chromophores in a physiological medium using a system having at least one wave source and at least one wave detector using a mathematical expression having the form:

I<sub>mn=α

mβ

nγ</sub>

I_o,mexp{−

B_mnL_mnδ

Σ

₁(ε

₁C₁)+σ

},

wherein I_o,m is a variable representing an intensity of electromagnetic waves irradiated by an m-th wave source, I_mn is a variable for an intensity of electromagnetic waves irradiated by said m-th wave source and detected by an n-th wave detector, α

_m is a parameter associated with at least one of said m-th wave source and medium, β

_n is a parameter associated with at least one of said n-th wave detector and medium, γ

is one of a proportionality constant and a parameter associated with at least one of said m-th wave source, n-th wave detector, and medium, B_mn is a parameter accounting for lengths of optical paths of electromagnetic waves through said medium and associated with at least one of said m-th wave source, n-th wave detector, and medium, L_mn is a parameter accounting for a distance between said m-th wave source and n-th wave detector, δ

is a one of a proportionality constant and a parameter associated with at least one of said m-th wave source, n-th wave detector, and medium, ε

₁ is a parameter accounting for an optical interaction between electromagnetic waves and an i-th chromophore in said medium, Ci is a variable for concentration of said i-th chromophore, and σ

is one of a proportionality constant and a parameter associated with at least one of said m-th source, n-th detector, and medium, said method comprising the steps of;

irradiating a first and second set of electromagnetic waves having different wave characteristics and measuring signals received from the medium to obtain at least two sets of equations relating the measured signals with unknown parameters in the wave equation;

eliminating at least one of α

_m, β

_n, γ

, δ

, and σ

from the obtained wave equations;

defining parameters of the mathematical expression including B_mn and L_mn as a function of at least one of said concentrations; and

determining concentrations of chromophores in a physiological medium.

54. The method of claim 53 further comprising the step of obtaining values of said intensities of electromagnetic waves and said extinction coefficients of said chromophores.

55. The method of claim 54 further comprising the step of obtaining the absolute value of at least one of said concentrations and said ratios thereof.