Methods and apparatus for calibrating spectral data

• US 7,459,696 B2
• Filed: 04/18/2003
• Issued: 12/02/2008
• Est. Priority Date: 04/18/2003
• Status: Expired due to Fees

• Current Assignee: Luma Imaging Corp. (SpectraScience, Inc.)
• Original Assignee: Luma Imaging Corp. (SpectraScience, Inc.)
• Inventors: Zelenchuk, Alex, Meese, Thomas M., Saager, Rolf B., Schomacker, Kevin T., Flanagan, John A.
• Primary Examiner(s): Sung; Christine
• Application Number:
  US10/418,973
• Publication Number:
  US 20040206914A1
• Time in Patent Office: 2,055 Days
• Field of Search: 250/458.1, 250/461.1
• US Class Current: 250/458.1
• 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 5/7203 for noise prevention, reduction or removal
• CPC Class Codes: A61B 5/725 using specific filters therefor, e.g. Kalman or adaptive filters A61B5/316 take precedence
• CPC Class Codes: A61B 5/7257 using Fourier transforms
• CPC Class Codes: A61B 5/7264 Classification of physiological signals or data, e.g. using neural networks, statistical classifiers, expert systems or fuzzy systems neural networks per se G06N3/00; expert systems per se G06N5/00
• CPC Class Codes: A61B 5/7267 involving training the classification device
• 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: G16H 50/20 for computer-aided diagnosis, e.g. based on medical expert systems

Abstract

The invention provides methods for calibrating spectral data acquisition systems. These calibration methods produce spectral data sufficiently accurate for use in tissue classification algorithms. The invention improves the accuracy of spectral-based tissue classification schemes, in part, by properly accounting for spatial variations, instrument-to-instrument variations, and patient-to-patient variations in the acquisition of spectral data from tissue samples. Effects that are accounted for include, for example, stray light effects, electronic background effects, variation in light energy delivered to a tissue sample, spatial heterogeneities of the illumination source, chromatic aberrations of the scanning optics, variation in wavelength response of the collection optics, and efficiency of the collection optics.

Claims

1. A method of calibrating spectral data obtained from a tissue sample, the method comprising the steps of:

(a) illuminating a first calibration target and obtaining a first set of calibration data from a plurality of spaced-apart locations on said first calibration target;

(b) illuminating a second calibration target and obtaining a second set of calibration data from a plurality of spaced-apart locations on said second calibration target;

(c) illuminating a tissue sample and obtaining a set of spectral data from spaced-apart locations of said tissue sample, wherein at least some of said spaced-apart locations of said tissue sample correspond to said spaced-apart locations on said first calibration target and said spaced-apart locations on said second calibration target, and wherein said tissue sample comprises in vivo cervical, vaginal, or colorectal tissue; and

(d) calibrating said spectral data obtained from said tissue sample using said first set of calibration data and said second set of calibration data, thereby to produce calibrated data,

wherein said first calibration target has a reflectance of about 60% and said second calibration target has a reflectance of about 10%.

2. The method of claim 1, wherein said second calibration target is a single-use disposable target.

3. The method of claim 1, wherein said second set of calibration data is obtained within about 24 hours of obtaining said set of spectral data from said tissue sample.

4. The method of claim 1, wherein said second set of calibration data is obtained within about 1 hour of obtaining said set of spectral data from said tissue sample.

5. The method of claim 1, wherein said calibrating step comprises processing said spectral data according to the equation:

R(i,λ

,t′

)=[I_m(i,λ

,t′

)/(I_cp(i,λ

,t′

))_i]·

[<

I_fc(i,λ

,t_o)>

_i/I_fc(i,λ

,t_o)]·

R_cp,

wherein R(i,λ

,t′

) is an array comprising calibrated reflectance spectral data from said tissue sample at regions i, wavelengths λ

, and at time t′

, I_m(i,λ

,t′

) is an array comprising reflectance spectral data from said tissue sample, I_fc(i,λ

,t_o) is an array comprising said first set of calibration data obtained at time t_o different from t′

, <

I_fc(i,λ

,t_o)>

_i is an array comprising said first set of calibration data averaged over said i regions, (I_cp(i,λ

,t′

))_i is an array comprising said second set of calibration data averaged over said i regions, and R_cp is the reflectance of said second calibration target.

6. The method of claim 5, wherein data in array I_m(i,λ

,t′

) are background subtracted.

7. The method of claim 5, wherein data in at least one of arrays I_cp(i,λ

,t′

) and I_fc(i,λ

,t_o) are background subtracted.

8. The method of claim 1, further comprising the step of:

obtaining a third set of calibration data using said second calibration target, wherein said calibration step comprises calibrating said spectral data obtained from said tissue sample using said first set of calibration data, said second set of calibration data, and said third set of calibration data.

9. The method of claim 8, wherein said calibrating step comprises processing said spectral data according to the equation:

R(i,λ

,t′

)=[I_m(i,λ

,t′

)/(I_cp(i,λ

,t′

))_i]·

[<

I_fc(i,λ

,t_o)>

_i/I_fc(i,λ

,t_o)]·

R_cp,fitted,

wherein R(i,λ

,t′

) is an array comprising calibrated reflectance spectral data from said tissue sample at regions i, wavelengths λ

, and at time t′

, I_m(i,λ

,t′

) is an array comprising reflectance spectral data from said tissue sample, I_fc(i,λ

,t_o) is an array comprising said first set of calibration data obtained at time to different from t′

, <

I_fc(i,λ

,t_o)>

_i is an array comprising said first set of calibration data averaged over said i regions, (I_cp(i,λ

,t′

))_i is an array comprising said second set of calibration data averaged over said i regions, R_cp,fitted is an array of values of a curve fit of R_cp(λ

), where R_cp(λ

)=[<

I_cp(i,λ

,t_o)>

_i/<

I_fc(i,λ

,t_o)>

_i]·

R_fc, and where <

I_cp(i,λ

,t_o)>

_i is an array comprising said third set of calibration data obtained at time to and averaged over said i regions, and R_fc is the reflectance of said first calibration target.

10. The method of claim 1, wherein said first calibration target and said second calibration target have different diffuse reflectance.

11. The method of claim 1, wherein said first calibration target comprises a solid having a first known diffuse reflectance and said second calibration target comprises a solid having a second known diffuse reflectance.

12. The method of claim 1, wherein at least one of said first calibration target and said second calibration target is flat.

13. The method of claim 1, wherein said calibrating step comprises calibrating said spectral data obtained from said tissue sample to correct for stray light internal to an optical instrument.

14. The method of claim 1, further comprising the step of classifying said tissue sample using said calibrated data.

15. A method of correcting spectral data from a tissue sample for stray light internal to an optical instrument, the method comprising the steps of:

(a) illuminating a target using a light source internal to an optical instrument and obtaining a first set of spectral data using said target, wherein said instrument yields a residual optical signal and wherein said target has substantially no diffuse reflectance;

(b) obtaining a second set of spectral data using a light source internal to said optical instrument, with no external light source;

(c) obtaining a third set of spectral data from a tissue sample; and

(d) adjusting said third set of data using a subset of said first set of data and a subset of said second set of data.

16. The method of claim 15, wherein said second obtaining step comprises obtaining said second set of spectral data without a target.

17. The method of claim 15, further comprising the step of:

obtaining a fourth set of spectral data from a target yielding substantially no optical signal, wherein said adjusting step comprises adjusting said third set of data using a subset of said first set of data, a subset of said second set of data, and a subset of said fourth set of data.

18. The method of claim 17, wherein the step of obtaining the fourth set of spectral data is performed within about one hour of obtaining said third set of spectral data.

19. The method of claim 15, wherein said tissue sample comprises in vivo cervical, vaginal, or colorectal tissue.

20. The method of claim 15, wherein said tissue sample comprises at least one of the following:

colorectal tissue, gastroesophageal tissue, urinary bladder tissue, lung tissue, skin tissue, and tissue comprising epithelial cells.

21. The method of claim 15, further comprising the step of classifying said tissue sample using said third set of data.

22. A method of calibrating spectral data obtained from a tissue sample, the method comprising the steps of:

(a) illuminating a first calibration target and obtaining a first set of calibration data from a plurality of spaced-apart locations on said first calibration target;

(b) illuminating a second calibration target and obtaining a second set of calibration data from a plurality of spaced-apart locations on said second calibration target;

(c) illuminating a tissue sample and obtaining a set of spectral data from spaced-apart locations of said tissue sample, wherein at least some of said spaced-apart locations of said tissue sample correspond to said spaced-apart locations on said first calibration target and said spaced-apart locations on said second calibration target, and wherein said tissue sample comprises in vivo cervical, vaginal, or colorectal tissue; and

(d) calibrating said spectral data obtained from said tissue sample using said first set of calibration data and said second set of calibration data, thereby to produce calibrated data,

wherein said calibrating step comprises processing said spectral data according to the equation;

R(i,λ

,t′

)=[I_m(i,λ

,t′

)/(I_cp(i,λ

,t′

))_i]·

[<

I_fc(i,λ

,t_o)>

_i/I_fc(i,λ

,t_o)]·

R_cp,

wherein R(i,λ

,t′

) is an array comprising calibrated reflectance spectral data from said tissue sample at regions i, wavelengths λ

, and at time t′

, I_m(i,λ

,t′

) is an array comprising reflectance spectral data from said tissue sample, I_fc(i,λ

,t_o) is an array comprising said first set of calibration data obtained at time t_o different from t′

, <

I_fc(i,λ

,t_o)>

_i is an array comprising said first set of calibration data averaged over said i regions, (I_cp(i,λ

,t′

))_i is an array comprising said second set of calibration data averaged over said i regions, and R_cp is the reflectance of said second calibration target.

23. The method of claim 22, wherein said second calibration target is a single-use disposable target.

24. The method of claim 22, wherein said first calibration target has a reflectance of about 60% and said second calibration target has a reflectance of about 10%.

25. The method of claim 22, wherein said second set of calibration data is obtained within about 24 hours of obtaining said set of spectral data from said tissue sample.

26. The method of claim 22, wherein said second set of calibration data is obtained within about 1 hour of obtaining said set of spectral data from said tissue sample.

27. The method of claim 22, wherein data in array I_m(i,λ

,t′

) are background subtracted.

28. The method of claim 22, wherein data in at least one of arrays I_cp(i,λ

,t′

) and I_fc(i,λ

,t_o) are background subtracted.

29. The method of claim 22, further comprising the step of:

obtaining a third set of calibration data using said second calibration target, wherein said calibration step comprises calibrating said spectral data obtained from said tissue sample using said first set of calibration data, said second set of calibration data, and said third set of calibration data.

30. The method of claim 22, wherein said first calibration target and said second calibration target have different diffuse reflectance.

31. The method of claim 22, wherein said first calibration target comprises a solid having a first known diffuse reflectance and said second calibration target comprises a solid having a second known diffuse reflectance.

32. The method of claim 22, wherein at least one of said first calibration target and said second calibration target is flat.

33. The method of claim 22, wherein said calibrating step comprises calibrating said spectral data obtained from said tissue sample to correct for stray light internal to an optical instrument.

34. The method of claim 22, further comprising the step of classifying said tissue sample using said calibrated data.

35. A method of calibrating spectral data obtained from a tissue sample, the method comprising the steps of:

(a) illuminating a first calibration target and obtaining a first set of calibration data from a plurality of spaced-apart locations on said first calibration target;

(b) illuminating a second calibration target and obtaining a second set of calibration data from a plurality of spaced-apart locations on said second calibration target;

(c) illuminating a tissue sample and obtaining a set of spectral data from spaced-apart locations of said tissue sample, wherein at least some of said spaced-apart locations of said tissue sample correspond to said spaced-apart locations on said first calibration target and said spaced-apart locations on said second calibration target, and wherein said tissue sample comprises in vivo cervical, vaginal, or colorectal tissue; and

(d) obtaining a third set of calibration data using said second calibration target,

(e) calibrating said spectral data obtained from said tissue sample using said first set of calibration data, said second set of calibration data, and said third set of calibration data, and

wherein said calibrating step comprises processing said spectral data according to the equation;

R(i,λ

,t′

)=[I_m(i,λ

,t′

)/(I_cp(i,λ

,t′

))_i]·

[<

I_fc(i,λ

,t_o)>

_i/I_fc(i,λ

,t_o)]·

R_cp,fitted,

wherein R(i,λ

,t′

) is an array comprising calibrated reflectance spectral data from said tissue sample at regions i, wavelengths λ

, and at time t′

, I_m(i,λ

,t′

) is an array comprising reflectance spectral data from said tissue sample, I_fc(i,λ

,t_o) is an array comprising said first set of calibration data obtained at time to different from t′

, <

I_fc(i,λ

,t_o)>

_i is an array comprising said first set of calibration data averaged over said i regions, (I_cp(i,λ

,t′

))_i is an array comprising said second set of calibration data averaged over said i regions, R_cp,fitted is an array of values of a curve fit of R_cp(λ

), where R_cp(λ

)=[<

I_cp(i,λ

,t_o)>

_i/<

I_fc(i,λ

,t_o)>

_i]·

R_fc, and where <

I_cp(i,λ

,t_o)>

_i is an array comprising said third set of calibration data obtained at time to and averaged over said i regions, and R_fc is the reflectance of said first calibration target.

36. The method of claim 35, wherein said second calibration target is a single-use disposable target.

37. The method of claim 35, wherein said first calibration target has a reflectance of about 60% and said second calibration target has a reflectance of about 10%.

38. The method of claim 35, wherein said second set of calibration data is obtained within about 24 hours of obtaining said set of spectral data from said tissue sample.

39. The method of claim 35, wherein said second set of calibration data is obtained within about 1 hour of obtaining said set of spectral data from said tissue sample.

40. The method of claim 35, wherein said first calibration target and said second calibration target have different diffuse reflectance.

41. The method of claim 35, wherein said first calibration target comprises a solid having a first known diffuse reflectance and said second calibration target comprises a solid having a second known diffuse reflectance.

42. The method of claim 35, wherein at least one of said first calibration target and said second calibration target is flat.

43. The method of claim 35, wherein said calibrating step comprises calibrating said spectral data obtained from said tissue sample to correct for stray light internal to an optical instrument.

44. The method of claim 35, further comprising the step of classifying said tissue sample using said calibrated data.