Optical apparatus and method of use for non-invasive tomographic scan of biological tissues

• US 20060015021A1
• Filed: 06/29/2004
• Published: 01/19/2006
• Est. Priority Date: 06/29/2004
• Status: Active Grant

• Current Assignee: 02 Medtech, Inc., O2 Medtech, Inc.
• Original Assignee: 02 Medtech, Inc.
• Inventors: Cheng, Xuefeng
• Granted Patent: US 7,551,950 B2
• Time in Patent Office: Days
• US Class Current: 600/310
• CPC Class Codes: A61B 5/0073 by tomography, i.e. reconstruction of 3D images from 2D projections A61B5/0066 takes precedence
• CPC Class Codes: A61B 5/14552 Details of sensors specially adapted therefor

Abstract

The present invention relates to a non-invasive optical system equipped with optical tomographic scanning method and algorithm for quantifying scattering and absorption properties and chromophore concentrations of highly scattering medium such as biological tissues, for 3D mapping and imaging reconstruction of the spatial and temporal variations in such properties. The invention further relates to a method and an apparatus for simultaneous measurement of concentrations of biochemical substances and blood oxygen saturation inside a biological tissue and arterial blood.

Claims

1. A method for quantifying at least one of scattering property, absorption coefficient or chromophore concentrations of a physical medium, said method comprising the steps of:

(a) introducing into said physical medium, at a first site, an input modulated signal with a modulation frequency (F_n);

(b) detecting, at a second site, an output modulated signal migrated over a migration path in said physical medium from said input modulated signal;

(c) comparing said output modulated signal with said input modulated signal and measuring therefrom a phase shift (φ

) between said input modulated signal and said output modulated signal;

(e) repeating steps (a)-(c) at two or more modulation frequencies and calculating average scattering property and absorption coefficient of said physical medium using the following equation;

$\mathrm{\varphi <br><br>}=\left(\underset{n=0}{\overset{1}{\sum <br><br>}}<br><br>a_n<br><br>{\mathrm{\mu <br><br>}}_s^{{\mathrm{\prime <br><br>}<br><br>\text{\hspace{1em}<br><br>}}_n}\right)<br><br>{\mathrm{\mu <br><br>}}_a^{-1}+\left(\underset{n=0}{\overset{2}{\sum <br><br>}}<br><br>b_n<br><br>{\mathrm{\mu <br><br>}}_s^{{\mathrm{\prime <br><br>}<br><br>\text{\hspace{1em}<br><br>}}_n}\right)<br><br>{\mathrm{\mu <br><br>}}_a^{-0.5}+\underset{n=0}{\overset{1}{\sum <br><br>}}<br><br>c_n<br><br>{\mathrm{\mu <br><br>}}_s^{{\mathrm{\prime <br><br>}<br><br>\text{\hspace{1em}<br><br>}}_n}$

wherein μ

a is the absorption coefficient, μ

s is the effective scattering property of said physical medium, a_n, b_n, and c_n, are parameters determined by said modulation frequency (F_n) and a distance (D) between said first site and said second site using a fitting algorithm.

2. The method of claim 1, further comprising the step of positioning a wave source at said first site and a wave detector at said second site.

3. The method of claim 1, wherein said modulation frequency (Fn) of said input waveform is higher than 50 MHz.

4. The method of claim 3, wherein said modulation frequency (Fn) of said input modulated signal is about 100 MHz, 300 MHz, or 500 MHz.

5. The method of claim 1, wherein said input modulated signal has a wavelength of between about 600 nm and about 900 nm.

6. The method of claim 1, further comprising the step of determining the concentration of said chromophore using the following equation:

7. A method for quantifying at least one of scattering property, absorption coefficient or chromophore concentrations of a physical medium, said method comprising the steps of:

(a) positioning a source-detector pair on said physical medium, wherein said source-detector pair comprises a wave source and a wave detector, wherein said wave detector is placed at a distance (D) from said wave source;

(b) introducing into said physical medium an input modulated signal with a modulation frequency (F_n) with said wave source;

(c) detecting an output modulated signal migrated over a migration path in said physical medium from said input modulated signal with said wave detector;

(d) comparing said output modulated signal with said input modulated signal and measuring therefrom a phase shift (φ

) between said input modulated signal and said output modulated signal;

(e) repeating steps (a)-(c) at two or more modulation frequencies and calculating average scattering property and absorption coefficient of said physical medium using the following equation;

$\mathrm{\varphi <br><br>}=\left(\underset{n=0}{\overset{1}{\sum <br><br>}}<br><br>a_n<br><br>{\mathrm{\mu <br><br>}}_s^{{\mathrm{\prime <br><br>}<br><br>\text{\hspace{1em}<br><br>}}_n}\right)<br><br>{\mathrm{\mu <br><br>}}_a^{-1}+\left(\underset{n=0}{\overset{2}{\sum <br><br>}}<br><br>b_n<br><br>{\mathrm{\mu <br><br>}}_s^{{\mathrm{\prime <br><br>}<br><br>\text{\hspace{1em}<br><br>}}_n}\right)<br><br>{\mathrm{\mu <br><br>}}_a^{-0.5}+\underset{n=0}{\overset{1}{\sum <br><br>}}<br><br>c_n<br><br>{\mathrm{\mu <br><br>}}_s^{{\mathrm{\prime <br><br>}<br><br>\text{\hspace{1em}<br><br>}}_n}$

wherein μ

a is the absorption coefficient, μ

s is the effective scattering property of said physical medium, a_n, b_n, and c_n, are parameters determined by said distance (D) of said wave source and said detector and said modulation frequency (F_n) using a fitting algorithm.

8. The method of claim 7, wherein said modulation frequency (Fn) of said input modulated signal is higher than 50 MHz.

9. The method of claim 8, wherein said modulation frequency (Fn) of said input modulated signal is about 100 MHz, 300 MHz, or 500 MHz.

10. The method of claim 7, wherein said input modulated signal has a wavelength of between about 600 nm and about 900 nm.

11. The method of claim 10, further comprising the step of:

repeating steps (b) to (e) at two or more wavelengths.

12. The method of claim 11, wherein steps (b) to (e) are repeated at three wavelengths of about 690 nm, 720 nm and 830 nm.

13. The method of claim 11, further comprising the step of:

determining an absorption spectrum of said physical medium.

14. The method of claim 7, further comprising the step of:

determining the concentration of said chromophore in said physical medium using the following equation;

${\mathrm{\mu <br><br>}}_a^{\mathrm{\lambda <br><br>}}=\underset{i=1}{\overset{N}{\sum <br><br>}}<br><br>C_i<br><br>{\mathrm{\varepsilon <br><br>}}_{i,\mathrm{\lambda <br><br>}}$

wherein said C_i is the concentration of said ith chromophore, ε

_i,λ

is the absorption extinction coefficient for the ith chromophore, wherein N is the number of measurement at the different wavelengths when there are total N chromophores contributed to the signal.

15. The method of claim 7, further comprising:

dividing said physical medium into m volume elements;

performing step (a) to (e) j times with j source-detector pairs, wherein j is an integer that is equal to, or greater than 2; and

determining a ratio of absorption coefficients and said effective scattering properties of said medium by the following equation;

μ

_aⁱ=w₁ⁱμ

_a,1ⁱ+w₂ⁱμ

_a,2ⁱ+w₃ⁱμ

_a,3ⁱ+ . . . w_mⁱμ

_a,mⁱ
μ

_sⁱ=w₁ⁱμ

_s,1ⁱ+w₂ⁱμ

_s,2ⁱ+w₃ⁱμ

_s,3ⁱ+ . . . w_mⁱμ

_s,mⁱ

wherein i is the measurement of ith source-detector pair, w₁ⁱ is the weight of the first volume element corresponding to the ith source-detector pair;

w₂ⁱ is the weight of the second volume element corresponding to the ith source-detector pair, and w_mⁱ is the weight of the mth volume element corresponding to the ith source-detector pair.

16. The method of claim 7, wherein said physical medium is a biological tissue.

17. A method for quantifying at least one of scattering property, absorption coefficient or chromophore concentrations of a biological tissue using tomographic scanning, said method comprising the steps of:

(a) positioning a one-dimensional source-detector array on said biological tissue in a first position, wherein said one-dimensional source-detector array comprising at least two source-detector pairs, each said source-detector pair comprising a wave source and a wave detector, wherein said wave detector is placed at a distance (D) from said wave source; and

wherein each source-detector pair comprises the steps of;

(i) introducing into said biological tissue an input modulated signal with a modulation frequency (F_n) with said wave source;

(ii) detecting an output modulated signal migrated over a migration path in said biological tissue from said input modulated signal with said wave detector;

(iii) comparing said output modulated signal with said input modulated signal and measuring therefrom a phase shift (φ

) between said input modulated signal and said output modulated signal;

(iv) repeating steps (i)-(iii) at two or more modulation frequencies and calculating average scattering absorption properties of said tissue using the following equation;

$\mathrm{\varphi <br><br>}=\left(\underset{n=0}{\overset{1}{\sum <br><br>}}<br><br>a_n<br><br>{\mathrm{\mu <br><br>}}_s^{{\mathrm{\prime <br><br>}<br><br>\text{\hspace{1em}<br><br>}}_n}\right)<br><br>{\mathrm{\mu <br><br>}}_a^{-1}+\left(\underset{n=0}{\overset{2}{\sum <br><br>}}<br><br>b_n<br><br>{\mathrm{\mu <br><br>}}_s^{{\mathrm{\prime <br><br>}<br><br>\text{\hspace{1em}<br><br>}}_n}\right)<br><br>{\mathrm{\mu <br><br>}}_a^{-0.5}+\underset{n=0}{\overset{1}{\sum <br><br>}}<br><br>c_n<br><br>{\mathrm{\mu <br><br>}}_s^{{\mathrm{\prime <br><br>}<br><br>\text{\hspace{1em}<br><br>}}_n}$

wherein μ

a is the absorption coefficient, μ

s is the effective scattering property of said biological tissue, a_n, b_n, and c_n, are parameters determined by said distance (D) of said wave source and said detector and said modulation frequency (F_n) using a fitting algorithm; and

(b) positioning said one-dimensional source-detector array on said biological tissue in a second position, wherein said second position is perpendicular to said first position.

18. The method of claim 17, wherein said modulation frequency (Fn) of said input modulated signal is higher than 50 MHz.

19. The method of claim 18, wherein said modulation frequency (Fn) of said input modulated signal is about 100 MHz, 300 MHz, or 500 MHz.

20. A method for simultaneously determining a concentration of a biochemical substance in a biological tissue or in blood, said method comprising:

positioning multiple source-detector pairs on multiple locations of said biological tissue comprising an artery, wherein each source-detector pair comprising a wave source that produces an input modulated signal, and a wave detector that locates at a distance from said wave source and detects an output modulated signal;

determining concentrations of said biochemical substance in said biological tissue based on measurements of phase shift between input modulated signal and corresponding modulated signal;

determining a correlation between a change in an amplitude of said modulated signal and a change in blood volume using the following equation;

$\partial <br><br>I^{\mathrm{\lambda <br><br>}}/\langle <br><br>I^{\mathrm{\lambda <br><br>}}\rangle <br><br>=\left(\underset{j=1}{\overset{M}{\sum <br><br>}}<br><br>W_j^{\mathrm{\lambda <br><br>}}\right)<br><br>\text{\hspace{1em}<br><br>}<br><br>{\mathrm{\mu <br><br>}}_a^{\mathrm{\lambda <br><br>}}$

wherein <

I^λ

>

is the averaged amplitude of measurement at wavelength λ

, ∂

I^λ

is the change in signal amplitude of ith measurement, w_j^λ

is the probability for photons to reach the ith location with artery inside the biological tissue, μ

_a^λ

is the absorption of the arterial blood to the light.

21. The method of claim 20, further comprising the step of determining the concentration of an ith chromophore using the following equation:

22. The method of claim 20, wherein said substance is oxy-hemoglobin.

23. The method of claim 20, wherein said substance is deoxy-hemoglobin.

24. The method of claim 20, wherein said biological issue comprises at least one of organ, tissue, or body fluid.

25. The method of claim 24, wherein said biological tissue is brain, heart, kidney, liver and vascular tissue which includes artery, vein, and capillary.

26. An optical system for quantifying at least one of scattering property, absorption coefficient or chromophore concentrations of highly scattering physiological medium by using phase-only measurement comprising:

a wave source optically coupled with said physiological medium for irradiating at least two electromagnetic waves having different wavelengths, wherein the intensity of said wave source has at least two modulation frequencies;

a wave detector, placed at a distance from said wave source, for detecting said at least two electromagnetic waves from said wave source and generating at least two output signals in response thereto, wherein said wave detector is capable of determining a phase shift between said introduced and detected radiation at a first wavelength and a second wavelength, and at a first modulation frequency and a second modulation frequency;

a processor configured to operatively couple with said wave detector and to determine scattering property and absorptive coefficient of said physiological medium based on phase (φ

) only measurement using the following equation;

$\mathrm{\varphi <br><br>}=\left(\underset{n=0}{\overset{1}{\sum <br><br>}}<br><br>a_n<br><br>{\mathrm{\mu <br><br>}}_s^{\mathrm{\prime <br><br>}<br><br>\text{\hspace{1em}<br><br>}<br><br>n}\right)<br><br>\text{\hspace{1em}<br><br>}<br><br>{\mathrm{\mu <br><br>}}_a^{-1}+\left(\underset{n=0}{\overset{2}{\sum <br><br>}}<br><br>b_n<br><br>\text{\hspace{1em}<br><br>}<br><br>{\mathrm{\mu <br><br>}}_s^{\mathrm{\prime <br><br>}<br><br>\text{\hspace{1em}<br><br>}<br><br>n}\right)<br><br>\text{\hspace{1em}<br><br>}<br><br>{\mathrm{\mu <br><br>}}_a^{-0.5}+\underset{n=0}{\overset{1}{\sum <br><br>}}<br><br>c_n<br><br>\text{\hspace{1em}<br><br>}<br><br>{\mathrm{\mu <br><br>}}_s^{\mathrm{\prime <br><br>}<br><br>\text{\hspace{1em}<br><br>}<br><br>n}$

wherein μ

a is the absorption coefficient, μ

s is the effective scattering property of said physiological medium, a_n, b_n, and c_n, are parameters determined by said distance (D) of said wave source and said detector and said modulation frequency (F_n) using a fitting algorithm.

27. The optical system of claim 26, wherein said wave source has wavelengths between the range of 500-2500 nm.

28. The optical system of claim 27, wherein said wave source has wavelengths between the range of 600-900 nm.

29. The optical system of claim 26, wherein said modulation frequency of said electromagnetic wave is higher than 50 MHz.

30. The optical system of claim 29, wherein said modulation frequency (F_n) of said input signal is about 100 MHz, 300 MHz, or 500 MHz.

31. The optical system of claim 26, wherein said physiological medium is a biological tissue.

32. The optical system of claim 26, further comprising two or more wave source-detector pairs, wherein each of said wave source produces electromagnetic waves with at least two wavelengths and at least two modulation frequencies to said physiological medium.

33. The optical system of claim 32, wherein said processor determines a ratio of said absorption coefficients and said effective scattering properties of said medium by arbitrarily dividing said medium into m volume elements, and calculating the ratio of said absorption coefficients and said effective scattering properties of said medium by the following equation:

μ

_aⁱ=w₁ⁱμ

_a,1ⁱ+w₂ⁱμ

_a,2ⁱ+w₃ⁱμ

_a,3ⁱ+ . . . w_mⁱμ

_a,mⁱ
μ

_sⁱ=w₁ⁱμ

_s,1¹+w₂ⁱμ

_s,2ⁱ+w₃ⁱμ

_s,3ⁱ+ . . . w_mⁱμ

_s,mⁱ

wherein i is the measurement of ith source-detector pair, w₁ⁱ is the weight of the first volume element corresponding to the ith source-detector pair;

w₂ⁱ is the weight of the second volume element corresponding to the ith source-detector pair, and w_mⁱ is the weight of the mth volume element corresponding to the ith source-detector pair.

34. A method for determining concentrations of oxygenated hemoglobin deoxygenated hemoglobin in a biological tissue or in blood comprising the steps of:

applying said optical system of claim 26 to said medium;

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

35. The method of claim 34, further comprising the step of:

determining a presence of an ischemic condition over a finite area of a biological tissue.

36. The method of claim 34, further comprising the step of detecting the location of an artery.

37. The method of claim 34, wherein said biological tissue comprises brain, heart, kidney, liver and vascular tissue which includes artery, vein, and capillary.

38. The method of claim 34, wherein said biological tissue further includes transplanted cells.

39. A method for diagnosing tumor in a biological tissue comprising the steps of:

applying said optical system of claim 26 to said biological tissue;

determining the presence of tumor cells over a finite area of said biological tissue.

40. A optical system for simultaneously determining a concentration of a biochemical substance in a biological tissue and in blood comprising:

at least two source-detector pairs on at least two locations of a medium of said biological tissue, wherein each said pair of source-detector comprising;

a wave source that produces an input modulated signal having different wavelengths, wherein the intensity of said each wave source has at least two modulation frequencies,

a wave detector that locates at a distance from said wave source and detects an output modulated signal;

wherein said wave detector is capable of determining concentrations of said biochemical substance in said biological tissue based on measurements of phase shift between input modulated signal and corresponding output modulated signal, wherein said wave detector is also capable of measuring an amplitude of an electromagnetic wave;

a processor configured to operatively couple with said wave detector and to determine a correlation between a change in an amplitude of said electromagnetic waveform and a change in blood volume using the following equation;

$\partial <br><br>I^{\mathrm{\lambda <br><br>}}/\langle <br><br>I^{\mathrm{\lambda <br><br>}}\rangle <br><br>=\left(\underset{j=1}{\overset{M}{\sum <br><br>}}<br><br>W_j^{\mathrm{\lambda <br><br>}}\right)<br><br>\text{\hspace{1em}<br><br>}<br><br>{\mathrm{\mu <br><br>}}_a^{\mathrm{\lambda <br><br>}}$

wherein <

I^λ

>

is the averaged amplitude of measurement at wavelength λ

, ∂

I^λ

is the change in signal amplitude of ith measurement, w_j^λ

is the probability for photons to reach the ith location with artery inside the biological tissue, μ

_a^λ

is the absorption of the arterial blood to the light.

41. The optical system of claim 40, wherein said wave source has wavelengths between the range of 600-900 nm.

42. The optical system of claim 40, wherein said modulation frequency of said electromagnetic wave is higher than 50 MHz.

43. The optical system of claim 40, wherein said processor is capable of determining the concentration of an ith chromophore using the following equation:

44. A method for determining concentrations of oxygenated hemoglobin deoxygenated hemoglobin in a biological tissue or blood comprising the steps of:

applying said optical system of claim 40 to said biological tissue;

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

45. The method of claim 44, further comprising the steps of:

determining a presence of an ischemic condition over a finite area of said biological tissue.

46. The method of claim 44, further comprising the step of detecting the location of an artery.

47. The method of claim 44, wherein said biological tissue comprises brain, heart, kidney, liver and vascular tissue which includes artery, vein, and capillary.

48. The method of claim 47, wherein said biological tissue further includes transplanted cells.