Method and apparatus for noninvasive assessment of skin condition and diagnosis of skin abnormalities

• US 20020091322A1
• Filed: 11/30/2001
• Published: 07/11/2002
• Est. Priority Date: 12/03/1998
• Status: Active Grant

• Current Assignee: Charles M. Peterson, Joseph Chaiken, Karen P. Peterson
• Original Assignee: Charles M. Peterson, Joseph Chaiken, Karen P. Peterson
• Inventors: Chaiken, Joseph, Peterson, Charles M., Peterson, Karen P.
• Granted Patent: US 6,681,133 B2
• Time in Patent Office: Days
• US Class Current: 600/476
• CPC Class Codes: A61B 2562/0242 for varying or adjusting the optical path length in the tissue
• 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 5/0062 Arrangements for scanning
• CPC Class Codes: A61B 5/0068 Confocal scanning
• CPC Class Codes: A61B 5/0071 by measuring fluorescence emission
• 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 5/0091 for mammography
• CPC Class Codes: A61B 5/442 Evaluating skin mechanical properties, e.g. elasticity, hardness, texture, wrinkle assessment
• CPC Class Codes: A61B 5/444 Evaluating skin marks, e.g. mole, nevi, tumour, scar
• CPC Class Codes: A61B 5/7239 using differentiation including higher order derivatives
• CPC Class Codes: G01N 21/65 Raman scattering

Abstract

Disclosed is a method for obtaining feedback to drive a servo system for aligning and maintaining alignment in optical systems that bring light to an in vivo skin sample, for adjusting the focus of the optical system, and for adjusting the net depth of focus of the optical system within the in vivo system under characterization. The invention additionally provides a method for obtaining feedback to drive a servo system for aligning and maintaining alignment in optical systems that collect light from an in vivo skin sample, and for adjusting the focus of the optical system. These methods comprise adjusting the angle of incidence of electromagnetic radiation and/or providing a shielding lens to block scattered incident light, or otherwise limiting the field of view of the Raman scattered radiation collection system to exclude optical surfaces of the excitation delivery portion of the optical system. Also provided is a method for identifying spectroscopic depth markers in tissues. In one embodiment, the method comprises discriminating between Raman signals originating on outer portions of skin from signals originating from substances deeper within the skin or other tissues. In another embodiment, the invention provides a method for detecting skin abnormalities and for assessing the aging of skin and related tissues. The method comprises characterizing the content of the skin using Raman spectroscopy. In one embodiment, the collagen, elastin, and or keratin content of the skin is characterized.

Claims

1. A method for obtaining spectroscopic information from living tissue of a subject comprising:

(a) irradiating a tissue of interest in a subject with light having an excitation wavelength and that passes from a light source through a first adjustable lens along a first optical axis;

(b) passing spectra that are emitted by the tissue through a second adjustable lens along a second optical axis;

(c) collecting spectra that are passed through the second adjustable lens;

(d) analyzing the collected spectra to determine a target signal associated with an analyte of interest;

(e) deriving a correction signal from the target signal; and

adjusting the position of the first adjustable lens or the second adjustable lens along the optical axis of the lens on the basis of the correction signal so as to enhance the target signal.

2. The method of claim 1, wherein the spectra are Raman spectra or visible fluorescence.

3. The method of claim 1, further comprising repeating steps (a)-(d) after the adjusting of step (f) and wherein the deriving of the correction signal comprises determining the difference between the target signal obtained before and after the adjusting of step (f).

4. The method of claim 1, wherein the analyzing comprises filtering out wavelengths other than the target wavelength.

5. The method of claim 1, wherein the analyzing comprises passing the collected spectra through a spectrograph.

6. The method of claim 1, wherein the tissue is skin.

7. The method of claim 1, wherein the excitation wavelength is selected from the group consisting of about 580-680, 785, 805, 808, 830, and 850 nm.

8. The method of claim 1, wherein the target wavelength is selected from the group consisting of Raman shifts of about 529-556, 811-830, 938, 1087-1101, 1245, 1269, 1297, 1445, 1650-1670, 2100-2200, 2852, 2883, 2933, 2935, 2944, 2987, and 2850-3000 cm⁻

1.

9. The method of claim 1, wherein the analyte is selected from the group consisting of phosphorous-containing bonds, carbon-hydrogen bonds, carbon-deuterium bonds, and amide linkages.

10. The method of claim 1, wherein the analyte is selected from the group consisting of moisture, protein, lipid, carbohydrate, collagen, elastin and keratin.

11. A non-invasive method for spectroscopically probing a target layer of skin in a subject comprising:

(a) irradiating a target layer of skin in a subject with light having an excitation wavelength that passes from a light source through a first adjustable lens;

(b) passing spectra that are emitted by the tissue through a second adjustable lens;

(c) collecting spectra that are passed through the second adjustable lens;

(d) analyzing the collected spectra to determine a target signal associated with the target layer of skin; and

(e) adjusting the position of the first adjustable lens or the second adjustable lens so as to increase the target signal.

12. The method of claim 11, further comprising deriving a correction signal from the target signal and relaying the correction signal to the first adjustable lens or to the second adjustable lens, wherein the correction signal effects an adjustment of the first adjustable lens or the second adjustable lens.

13. The method of claim 12, further comprising repeating steps (a)-(d) after the adjusting of step (e), and wherein the deriving of the correction signal comprises determining the difference between the target signal obtained before and after the adjusting of step (e).

14. The method of claim 11, wherein the excitation wavelength is selected from the group consisting of about 580, 680, 785, 805, 808, 830, and 850 nm.

15. The method of claim 11, wherein the target layer of skin comprises stratum corneum, intradermal capillary beds, or dermis.

16. The method of claim 11, wherein the target signal is a signal associated with Raman shifts of about 938, 1245, 1269, 1297, 2852, 2883, 2933, 2944, 2955, or 2987 cm⁻

1.

18. The method of claim 17, wherein the excitation wavelength is selected from the group consisting of about 580-680, 785, 805, 808, 830, and 850 nm.

19. The method of claim 17, wherein the tissue feature is carbon-hydrogen stretching.

20. The method of claim 19, wherein the target signal is associated with a Raman shift of about 2850-3000 cm⁻

1.

21. The method of claim 17, wherein the tissue feature is carbon-deuterium stretching.

22. The method of claim 21, wherein the target signal is associated with a Raman shift of about 2000-2200 cm⁻

1.

23. The method of claim 17, wherein the tissue feature is tissue density.

24. The method of claim 23, wherein the target signal is total integrated area of collected spectra.

25. The method of claim 17, wherein the tissue feature is phosphorous-containing bonds.

26. The method of claim 25, wherein the target signal is associated with a Raman shift of about 529-556, 811-830 or 1087-1101 cm⁻

1.

27. The method of claim 17, wherein the tissue feature is lipid content.

28. The method of claim 27, wherein the target signal is associated with a Raman shift of about 1445 cm⁻

1.

29. The method of claim 17, wherein the tissue feature is protein content.

30. The method of claim 29, wherein the protein is collagen, elastin or keratin.

31. The method of claim 29, wherein the target signal is associated with a Raman shift of about 1650-1670 cm⁻

1.

32. The method of claim 17, wherein the spectra comprise Raman spectra.

33. The method of claim 17, wherein the tissue of interest comprises skin.

34. The method of claim 33, wherein the tissue of interest comprises stratum corneum.

35. The method of claim 33, wherein the tissue of interest comprises epidermis.

36. The method of claim 33, wherein the tissue of interest comprises an intradermal capillary bed.

37. The method of claim 33, wherein the tissue of interest comprises dermis.

39. The method of claim 38, wherein the specimen is skin.

40. The method of claim 38, wherein the positive target wavelength is a Raman shift of about 1640 cm⁻

1 and the negative target wavelength is Raman shift of about 1720 cm<sup>−

1</sup> relative to the excitation light.

41. The method of claim 38, wherein the specimen is living tissue and the method is performed noninvasively.

42. The method of claim 38, further comprising adjusting the position of a first adjustable lens located in an optical path of the excitation light so as to increase the determined difference between the spectra emitted at the positive target wavelength and the spectra emitted at the negative target wavelength.

43. The method of claim 38, further comprising adjusting the position of a second adjustable lens located in an optical path of the emitted spectra so as to increase the determined difference between the spectra emitted at the positive target wavelength and the spectra emitted at the negative target wavelength.

17. A method for detecting abnormalities in living tissue of a subject comprising:

(a) irradiating a tissue of interest in a subject with light having an excitation wavelength and that passes from a light source through a first adjustable lens along a first optical axis;

(b) passing spectra that are emitted by the tissue through a second adjustable lens;

(c) collecting spectra that are passed through the second adjustable lens along a second optical axis;

(d) analyzing the collected spectra to determine a target signal associated with a tissue feature indicative of an abnormality;

(e) deriving a correction signal from the target signal; and

(f) adjusting the position of the first adjustable lens or the second adjustable lens along the optical axis of the lens on the basis of the correction signal so as to enhance the target signal.

38. A method for stabilizing a wavelength of light emitted by a diode laser comprising:

(a) irradiating a specimen with excitation light from the diode laser;

(b) collecting Raman spectra at a positive target wavelength and at a negative target wavelength emitted by the irradiated specimen, wherein the positive target wavelength is associated with an abundant feature in the specimen and wherein the negative target wavelength is associated with a scant feature in the specimen;

(c) determining a quantitative difference between the spectra emitted at the positive target wavelength and the spectra emitted at the negative target wavelength;

(d) relaying to the diode laser a signal proportional to the determined difference; and

(e) regulating the temperature of the diode laser so as to maintain a maximal difference between the spectra emitted at the positive target wavelength and the spectra emitted at the negative target wavelength.

44. An apparatus for enhancing spectroscopic information obtained from living tissue of a subject comprising:

(a) a signal analyzer adapted to receive input from a detector; and

(b) a processor connected to the signal analyzer, wherein the processor is capable of producing an output signal that is proportional to a quantity of Raman spectra received by the signal analyzer from the detector.

45. The apparatus of claim 44, further comprising a diode laser connected to the processor, wherein the output signal regulates the temperature of the diode laser, thereby stabilizing the wavelength or amplitude of light emitted by the diode laser.

46. The apparatus of claim 44, further comprising an adjustable lens connected to the processor and optically aligned with an output path from a laser, wherein the output signal regulates movement of the adjustable lens along an optical axis aligned with the output path of the laser.

47. The apparatus of claim 46, further comprising an electronically controlled translation stage coupled to the adjustable lens for receiving an output signal from the processor.

48. The apparatus of claim 44, further comprising an adjustable lens connected to the processor and optically aligned with an input path to the detector, wherein the output signal regulates movement of the adjustable lens along an optical axis aligned with the input path of the detector.

49. The apparatus of claim 48, further comprising an electronically controlled translation stage coupled to the adjustable lens for receiving an output signal from the processor.

50. The apparatus of claim 44, further comprising an adjustable aperture coupled to an electronically controlled translation stage that is connected to the processor and optically aligned with an input path to the detector, wherein the output signal regulates movement or diameter of the adjustable aperture along or perpendicular to an optical axis aligned with the input path of the detector.