title: Hyperspectral Imaging as an Early Biomarker for Radiation Exposure and Microcirculatory Damage.
abstract: BACKGROUND
  Radiation exposure can lead to detrimental effects in skin microcirculation. The precise relationship between radiation dose received and its effect on cutaneous perfusion still remains controversial. Previously, we have shown that hyperspectral imaging (HSI) is able to demonstrate long-term reductions in cutaneous perfusion secondary to chronic microvascular injury. This study characterizes the changes in skin microcirculation in response to varying doses of ionizing radiation and investigates these microcirculatory changes as a possible early non-invasive biomarker that may correlate with the extent of long-term microvascular damage.
  
  
  METHODS
  Immunocompetent hairless mice (n = 66) were exposed to single fractions of superficial beta-irradiation in doses of 0, 5, 10, 20, 35, or 50 Gy. A HSI device was utilized to measure deoxygenated hemoglobin levels in irradiated and control areas. HSI measurements were performed at baseline before radiation exposure and for the first 3 days post-irradiation. Maximum macroscopic skin reactions were graded, and histological assessment of cutaneous microvascular densities at 4 weeks post-irradiation was performed in harvested tissue by CD31 immunohistochemistry.
  
  
  RESULTS
  CD31 immunohistochemistry demonstrated a significant correlation (r = 0.90, p < 0.0001) between dose and vessel density reduction at 4 weeks. Using HSI analysis, early changes in deoxygenated hemoglobin levels were observed during the first 3 days post-irradiation in all groups. These deoxygenated hemoglobin changes varied proportionally with dose (r = 0.98, p < 0.0001) and skin reactions (r = 0.98, p < 0.0001). There was a highly significant correlation (r = 0.91, p < 0.0001) between these early changes in deoxygenated hemoglobin and late vascular injury severity assessed at the end of 4 weeks.
  
  
  CONCLUSIONS
  Radiation dose is directly correlated with cutaneous microvascular injury severity at 4 weeks in our model. Early post-exposure measurement of cutaneous deoxygenated hemoglobin levels may be a useful biomarker for radiation dose reconstruction and predictor for chronic microvascular injury.
authors.affiliation: Department of Radiation Oncology, University of Massachusetts Medical School , Worcester, MA , USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Chin
authors.affiliation: Division of Plastic Surgery, Brigham and Women's Hospital , Boston, MA , USA.
authors.forename: Brian B
authors.initials: BB
authors.lastname: Freniere
authors.affiliation: Division of Plastic Surgery, Brigham and Women's Hospital , Boston, MA , USA.
authors.forename: Luca
authors.initials: L
authors.lastname: Lancerotto
authors.affiliation: Division of Plastic Surgery, University of Massachusetts Medical School , Worcester, MA , USA.
authors.forename: Jorge
authors.initials: J
authors.lastname: Lujan-Hernandez
authors.affiliation: Department of Radiation Oncology, University of Massachusetts Medical School , Worcester, MA , USA.
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Saleeby
authors.affiliation: Department of Radiation Oncology, University of Massachusetts Medical School , Worcester, MA , USA.
authors.forename: Yuan-Chyuan
authors.initials: YC
authors.lastname: Lo
authors.affiliation: Division of Plastic Surgery, Brigham and Women's Hospital , Boston, MA , USA.
authors.forename: Dennis P
authors.initials: DP
authors.lastname: Orgill
authors.affiliation: Division of Plastic Surgery, University of Massachusetts Medical School , Worcester, MA , USA.
authors.forename: Janice F
authors.initials: JF
authors.lastname: Lalikos
authors.affiliation: Department of Radiation Oncology, University of Massachusetts Medical School , Worcester, MA , USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Fitzgerald
keywords: diffuse reflectance imaging; hyperspectral imaging; microcirculatory damage; perfusion imaging; radiation dosage; radiation effects; radiation exposure