Methods for Measuring Changes in Optical Properties of Wound Tissue and Correlating Near Infrared Absorption (FNIR) and Diffuse Reflectance Spectroscopy Scattering (DRS) With Tissue Neovascularization and Collagen Concentration to Determine Whether Wound is Healing

• US 20110124987A1
• Filed: 04/21/2009
• Published: 05/26/2011
• Est. Priority Date: 04/21/2008
• Status: Active Grant

• Current Assignee: Drexel University
• Original Assignee: Drexel University
• Inventors: Weingarten, Michael S., Neidrauer, Michael T., Zhu, Linda, Papazoglou, Elisabeth S., Zubkov, Leonid, Pourrezaei, Kambiz
• Granted Patent: US 8,812,083 B2
• Time in Patent Office: Days
• US Class Current: 600/310
• 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 5/0075 by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy A61B5/0071 takes precedence
• CPC Class Codes: A61B 5/02007 Evaluating blood vessel condition, e.g. elasticity, compliance
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/445 Evaluating skin irritation or skin trauma, e.g. rash, eczema, wound, bed sore
• CPC Class Codes: G01N 21/359 using near infrared light
• CPC Class Codes: G01N 21/4738 Diffuse reflection precedence is given to G01N21/55 - G01N21/57 if specular component is taken into consideration, e.g. also for testing fluids, fibrous materials

Abstract

Optical changes of tissue during wound healing measured by Near Infrared and Diffuse Reflectance Spectroscopy are shown to correlate with histologic changes. Near Infrared absorption coefficient correlated with blood vessel in-growth over time, while Diffuse Reflectance Spectroscopy (DRS) data correlated with collagen concentration. Changes of optical properties of wound tissue at greater depths are also quantified by Diffuse Photon Density Wave (DPDW) methodology at near infrared wavelengths. The diffusion equation for semi-infinite media is used to calculate the absorption and scattering coefficients based on measurements of phase and amplitude with a frequency domain or time domain device. An increase in the absorption and scattering coefficients and a decrease in blood saturation of the wounds compared to the non wounded sites was observed. The changes correlated with the healing stage of the wound. The methodologies used to collect information regarding the healing state of a wound may be used to clinically assess the efficacy of wound healing agents in a patient (e.g., a diabetic) and as a non-invasive method

Claims

1. A method of collecting information regarding the healing state of a wound, comprising the steps of:

illuminating wound tissue with light from a light source;

measuring the amplitude and/or phase shift of the light as it propagates through the wound tissue;

calculating an optical absorption coefficient and/or reduced scattering coefficient using the measured values;

correlating collagen concentration in the wound tissue with the reduced scattering coefficient calculated form measured parameters and/or correlating blood vessel in-growth and/or ischemia in the wound tissue with the optical absorption coefficient using the measured values; and

determining changes in collagen concentration over time from changes in the reduced scattering coefficient over time and/or determining changes in blood vessel in-growth and/or ischemia over time from changes in the optical absorption coefficient over time.

3. The method of claim 1, wherein the light is transmitted at a near infrared wavelength.

4. The method of claim 3, wherein the light has a wavelength of 650-870 nm.

5. The method of claim 3, wherein the near infrared wavelengths comprise one of 685 nm, 780 nm, 830 nm, and 950 nm.

6. The method of claim 3, wherein the light is output by a laser and modulated to produce a diffuse photon density wave (DPDW) in the wound tissue.

7. The method of claim 1, further comprising measuring size of the wound by calculating wound surface area.

8. The method of claim 7, further comprising measuring a healing rate of the wound by calculating the difference between the surface area of the wound at different points in time and dividing the difference by the original surface area of the wound.

9. The method of claim 1, wherein correlating the collagen concentration in the wound tissue with the reduced scattering coefficient includes correlating an increase in a diffuse reflectance spectroscopy scattering function obtained over time in the wound with an increase in collagen during healing of the wound.

10. The method of claim 1, further comprising measuring collagen concentration in the wound over time by taking diffuse reflectance spectroscopy (DRS) measurements over time.

11. The method of claim 1, further comprising differentiating an impaired wound from a non-impaired wound by measuring changes in blood vessel in-growth and/or ischemia in the wound over time and correlating optical absorption coefficients obtained from the wound over time with blood vessel in-growth and/or ischemia seen histologically for impaired and control wounds.

12. The method of claim 11, further comprising detecting pressure ulcers or venous ulcers in the wound from changes in the optical absorption coefficients over time.

13. The method of claim 1, wherein the illuminating and measuring steps are performed using a continuous wave, a frequency domain, or a time domain measurement device that does not contact the wound.

14. The method of claim 1, wherein the calculation of the optical absorption coefficients and/or reduced scattering coefficients and a quantification of blood oxygenation is performed using a diffusion equation form semi-infinite media.

15. The method of claim 1, further comprising monitoring changes in oxygenated hemoglobin over time as an indication of whether the wound is healing.

16. The method of claim 15, further comprising quantifying the changes in oxygenated hemoglobin by calculating a rate of change and variability in the optical absorption coefficient and hemoglobin concentration over time.

17. The method of claim 16, further comprising differentiating a healing chronic wound from a non-healing chronic wound using rates of change of the oxygenated hemoglobin concentration over time.

18. The method of claim 17, wherein the chronic wound is a diabetic ulcer.

19. The method of claim 16, further comprising determining that the wound is healing based on convergence of absolute oxygenated hemoglobin concentration at a site of the wound to a value of absolute oxygenated hemoglobin concentration at a site of non-wounded tissue of a same patient having the wound.

20. The method of claim 16, further comprising differentiating a healing chronic wound from a non-healing chronic wound using rates of change of total hemoglobin concentration over time.

21. The method of claim 16, further comprising determining that the wound is healing based on convergence of absolute total hemoglobin concentration at a site of the wound to a value of absolute total hemoglobin concentration at a site of non-wounded tissue of a same patient having the wound.

2. (canceled)