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Biomedical Optics Express

Biomedical Optics Express

  • Editor: Joseph A. Izatt
  • Vol. 5, Iss. 5 — May. 1, 2014
  • pp: 1309–1320

Quantitative monitoring of radiation induced skin toxicities in nude mice using optical biomarkers measured from diffuse optical reflectance spectroscopy

Darren Yohan, Anthony Kim, Elina Korpela, Stanley Liu, Carolyn Niu, Brian C Wilson, and Lee CL Chin  »View Author Affiliations

Biomedical Optics Express, Vol. 5, Issue 5, pp. 1309-1320 (2014)

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Monitoring the onset of erythema following external beam radiation therapy has the potential to offer a means of managing skin toxicities via biological targeted agents – prior to full progression. However, current skin toxicity scoring systems are subjective and provide at best a qualitative evaluation. Here, we investigate the potential of diffuse optical spectroscopy (DOS) to provide quantitative metrics for scoring skin toxicity. A DOS fiberoptic reflectance probe was used to collect white light spectra at two probing depths using two short fixed source-collector pairs with optical probing depths sensitive to the skin surface. The acquired spectra were fit to a diffusion theory model of light transport in tissue to extract optical biomarkers (hemoglobin concentration, oxygen saturation, scattering power and slope) from superficial skin layers of nude mice, which were subjected to erythema inducing doses of ionizing radiation. A statistically significant increase in oxygenated hemoglobin (p < 0.0016) was found in the skin post-irradiation – confirming previous reports. More interesting, we observed for the first time that the spectral scattering parameters, A (p = 0.026) and k (p = 0.011), were an indicator of erythema at day 6 and could potentially serve as an early detection optical biomarker of skin toxicity. Our data suggests that reflectance DOS may be employed to provide quantitative assessment of skin toxicities following curative doses of external beam radiation.

© 2014 Optical Society of America

OCIS Codes
(170.4580) Medical optics and biotechnology : Optical diagnostics for medicine
(170.6510) Medical optics and biotechnology : Spectroscopy, tissue diagnostics

ToC Category:
Spectroscopic Diagnostics

Original Manuscript: October 29, 2013
Revised Manuscript: December 15, 2013
Manuscript Accepted: December 15, 2013
Published: April 1, 2014

Darren Yohan, Anthony Kim, Elina Korpela, Stanley Liu, Carolyn Niu, Brian C Wilson, and Lee CL Chin, "Quantitative monitoring of radiation induced skin toxicities in nude mice using optical biomarkers measured from diffuse optical reflectance spectroscopy," Biomed. Opt. Express 5, 1309-1320 (2014)

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  1. E. J. Hall and A. J. Giaccia, Radiobiology for the Radiologist (J.B. Lippincott Company, Philadelphia, 2011)
  2. J. L. Ryan, “Ionizing Radiation: The Good, the Bad, and the Ugly,” J. Invest. Dermatol.132(3), 985–993 (2012). [CrossRef] [PubMed]
  3. J. O. Archambeau, R. Pezner, and T. Wasserman, “Pathophysiology of irradiated skin and breast,” In. J. Rad. Oncology Biol. Phys.31(5), 1171–1185 (1995). [CrossRef]
  4. D. Porock, L. Kristjanson, S. Nikoletti, F. Cameron, and P. Pedler, “Predicting the severity of radiation skin reactions in women with breast cancer,” Oncol. Nurs. Forum25(6), 1019–1029 (1998). [PubMed]
  5. R. Noble-Adams, “Radiation-induced skin reactions. 2: development of a measurement tool,” Br. J. Nurs.8(18), 1208–1211 (1999). [PubMed]
  6. C. Westbury, F. Hines, E. Hawkes, S. Ashley, and M. Brada, “Advice on hair and scalp care during cranial radiotherapy: a prospective randomized trial,” Radiother. Oncol.54(2), 109–116 (2000). [CrossRef] [PubMed]
  7. A. Yodh and B. Chance, “Spectroscopy and imaging with diffusing light,” Phys. Today48(3), 34 (1995). [CrossRef]
  8. A. Amelink, A. P. van den Heuvel, W. J. de Wolf, D. J. Robinson, and H. J. Sterenborg, “Monitoring PDT by means of superficial reflectance spectroscopy,” J. Photochem. Photobiol. B79(3), 243–251 (2005). [CrossRef] [PubMed]
  9. Dj. Evers, B. Hendriks, G. Lucassen, and T. Ruers, “Optical spectroscopy: current advances and future applications in cancer diagnostics and therapy,” Future Oncol.8(3), 307–320 (2012). [CrossRef] [PubMed]
  10. S. Balter, J. W. Hopewell, D. L. Miller, L. K. Wagner, and M. J. Zelefsky, “Fluoroscopically guided interventional procedures: a review of radiation effects on patients’ skin and hair,” Radiology254(2), 326–341 (2010). [CrossRef] [PubMed]
  11. N. Kollias, R. Gillies, J. A. Muccini, R. K. Uyeyama, S. B. Phillips, and L. A. Drake, “A single parameter, oxygenated hemoglobin, can be used to quantify experimental irritant-induced inflammation,” J. Invest. Dermatol.104(3), 421–424 (1995). [CrossRef] [PubMed]
  12. S. Smesny, S. Riemann, S. Riehemann, M. E. Bellemann, and H. Sauer, “[Quantitative measurement of induced skin reddening using optical reflection spectroscopy--methodology and clinical application],” Biomed. Tech. (Berl.)46(10), 280–286 (2001). [CrossRef] [PubMed]
  13. P. Simonen, C. Hamilton, S. Ferguson, P. Ostwald, M. O’Brien, P. O’Brien, M. Back, and J. Denham, “Do inflammatory processes contribute to radiation-induced erythema observed in the skin of humans?” Radiother. Oncol.46(1), 73–82 (1998). [CrossRef]
  14. M. S. Chin, B. B. Freniere, Y. C. Lo, J. H. Saleeby, S. P. Baker, H. M. Strom, R. A. Ignotz, J. F. Lalikos, and T. J. Fitzgerald, “Hyperspectral imaging for early detection of oxygenation and perfusion changes in irradiated skin,” J. Biomed. Opt.17(2), 026010 (2012). [CrossRef] [PubMed]
  15. M. Woo and R. Nordal, “Commissioning and evaluation of a new commercial small rodent x-ray irradiator,” Biomed. Imaging Interv. J.2(1), e10 (2006). [CrossRef] [PubMed]
  16. V. Holler, V. Buard, M. H. Gaugler, O. Guipaud, C. Baudelin, A. Sache, M. R. Perez, C. Squiban, R. Tamarat, F. Milliat, and M. Benderitter, “Pravastatin limits radiation-induced vascular dysfunction in the skin,” J. Invest. Dermatol.129(5), 1280–1291 (2009). [CrossRef] [PubMed]
  17. L. Chin, W. M. Whelan, and I. A. Vitkin, “Optical Fiber Sensors for Biomedical Applications,” in Optical-Thermal Response of Laser-Irradiated Tissue, A. J. Welch and M. J. C. van Gemert, eds. (Springer SBM, 2011), pp. 661.
  18. A. Kim, M. Roy, F. Dadani, and B. C. Wilson, “A fiberoptic reflectance probe with multiple source-collector separations to increase the dynamic range of derived tissue optical absorption and scattering coefficients,” Opt. Express18(6), 5580–5594 (2010). [CrossRef] [PubMed]
  19. A. Kim, M. Khurana, Y. Moriyama, and B. C. Wilson, “Quantification of in vivo fluorescence decoupled from the effects of tissue optical properties using fiber-optic spectroscopy measurements,” J. Biomed. Opt.15(6), 067006 (2010). [CrossRef] [PubMed]
  20. P. A. Valdés, A. Kim, M. Brantsch, C. Niu, Z. B. Moses, T. D. Tosteson, B. C. Wilson, K. D. Paulsen, D. W. Roberts, and B. T. Harris, “δ-aminolevulinic acid-induced protoporphyrin IX concentration correlates with histopathologic markers of malignancy in human gliomas: the need for quantitative fluorescence-guided resection to identify regions of increasing malignancy,” Neuro-oncol.13(8), 846–856 (2011). [CrossRef] [PubMed]
  21. K. Bekelis, P. A. Valdés, K. Erkmen, F. Leblond, A. Kim, B. C. Wilson, B. T. Harris, K. D. Paulsen, and D. W. Roberts, “Quantitative and qualitative 5-aminolevulinic acid-induced protoporphyrin IX fluorescence in skull base meningiomas,” Neurosurg. Focus30(5), E8 (2011). [PubMed]
  22. J. C. Finlay and T. H. Foster, “Hemoglobin oxygen saturations in phantoms and in vivo from measurements of steady-state diffuse reflectance at a single, short source-detector separation,” Med. Phys.31(7), 1949–1959 (2004). [CrossRef] [PubMed]
  23. S. Prahl, “Tabulated Molar Extinction Coefficient for Hemoglobin in Water,” http://omlc.ogi.edu/spectra/hemoglobin/summary.html .
  24. J. R. Mourant, T. Fuselier, J. Boyer, T. M. Johnson, and I. J. Bigio, “Predictions and measurements of scattering and absorption over broad wavelength ranges in tissue phantoms,” Appl. Opt.36(4), 949–957 (1997). [CrossRef] [PubMed]
  25. L. Chin, B. Lloyd, W. M. Whelan, and A. Vitkin, “Interstitial point radiance spectroscopy of turbid media,” J. Appl. Phys.105(10), 102025 (2009). [CrossRef]
  26. A. Corlu, T. Durduran, R. Choe, M. Schweiger, E. M. Hillman, S. R. Arridge, and A. G. Yodh, “Uniqueness and wavelength optimization in continuous-wave multispectral diffuse optical tomography,” Opt. Lett.28(23), 2339–2341 (2003). [CrossRef] [PubMed]
  27. A. Kim and B. C. Wilson, “Measurement of Ex Vivo and In Vivo Tissue Optical Properties,” in Optical-Thermal Response of Laser-Irradiated Tissue, A. J. Welch and M. J. C. van Gemert, eds. (Springer, 2010), pp. 267.
  28. J. D. Rogers, I. R. Capoğlu, and V. Backman, “Nonscalar elastic light scattering from continuous random media in the Born approximation,” Opt. Lett.34(12), 1891–1893 (2009). [CrossRef] [PubMed]
  29. V. Turzhitsky, N. N. Mutyal, A. J. Radosevich, and V. Backman, “Multiple scattering model for the penetration depth of low-coherence enhanced backscattering,” J. Biomed. Opt.16(9), 097006 (2011). [CrossRef] [PubMed]
  30. K. Vishwanath, D. Klein, K. Chang, T. Schroeder, M. W. Dewhirst, and N. Ramanujam, “Quantitative optical spectroscopy can identify long-term local tumor control in irradiated murine head and neck xenografts,” J. Biomed. Opt.14(5), 054051 (2009). [CrossRef] [PubMed]

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