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Skin Perfusion and Oxygenation Changes in Radiation Fibrosis

Chin, Michael S. M.D.; Freniere, Brian B. B.A.; Bonney, Caitlin F. B.A.; Lancerotto, Luca M.D.; Saleeby, Jonathan H. M.S.; Lo, Yuan-Chyuan Ph.D.; Orgill, Dennis P. M.D., Ph.D.; Fitzgerald, Thomas J. M.D.; Lalikos, Janice F. M.D.

Plastic and Reconstructive Surgery: April 2013 - Volume 131 - Issue 4 - p 707–716
doi: 10.1097/PRS.0b013e3182818b94
Experimental: Original Articles

Background: Ionizing radiation is known to have deleterious chronic effects on skin, including fibrosis and poor wound healing, hypothesized as mediated by ischemia and hypoxia. Past studies have been unable to simultaneously investigate changes in perfusion and oxygenation as separate parameters. Hyperspectral imaging has emerged as a tool with which to concurrently measure skin perfusion and oxygenation. The authors investigated the use of hyperspectral imaging in a novel murine model of chronic radiation injury.

Methods: Areas of flank skin (n = 20) on hairless mice were exposed to a 50-Gy dose of beta-radiation. Hyperspectral imaging acquisition was performed at select points through 8 weeks. Immunohistochemical staining and gene expression analysis were performed to evaluate cutaneous vascular density, epidermal cell hypoxia, and angiogenic factors.

Results: All irradiated areas developed a chronic-phase wound by day 28. Hyperspectral imaging demonstrated a 21 percent decline in perfusion on day 56 (p < 0.001), whereas oxygenation levels were unchanged. A 1.7-fold reduction in blood vessel density was measured in irradiated skin compared with control tissue (p < 0.001), but no difference in epidermal cell hypoxia was observed. Vascular endothelial growth factor and related receptor expression were significantly lower in irradiated tissue.

Conclusions: The authors' analysis does not support the presence of hypoxia in chronic-phase irradiated skin but suggests that hypoperfusion may be a predominant characteristic. The concurrent states of hypoperfusion and normoxia may be explained by the lower metabolic demands of fibrosed tissue.

Worcester and Boston, Mass.

From the Divisions of Plastic Surgery and Radiation Oncology, University of Massachusetts Medical School, and the Division of Plastic Surgery, Brigham and Women's Hospital.

Received for publication August 22, 2012; accepted October 15, 2012.

Presented in part at the 22nd Annual Meeting of the Wound Healing Society, in Atlanta, Georgia, April 19 through 22, 2012.

Disclosure: The authors have no financial disclosures.

Michael S. Chin, M.D.; Division of Plastic Surgery, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Mass. 01655,

©2013American Society of Plastic Surgeons