Hyperspectral Imaging as an Early Biomarker for Radiation Exposure and Microcirculatory Damage

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 three days post-irradiation. Maximum macroscopic skin reactions were graded, and histological assessment of cutaneous microvascular densities at four 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 four weeks. Using HSI analysis, early changes in deoxygenated hemoglobin levels were observed during the first three 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 four weeks.CONCLUSIONS: Radiation dose is directly correlated with cutaneous microvascular injury severity at four 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

Hyperspectral imaging for early detection of oxygenation and perfusion changes in irradiated skin

Studies examining acute oxygenation and perfusion changes in irradiated skin are limited. Hyperspectral imaging (HSI), a method of wide-field, diffuse reflectance spectroscopy, provides noninvasive, quantified measurements of cutaneous oxygenation and perfusion. This study examines whether HSI can assess acute changes in oxygenation and perfusion following irradiation. Skin on both flanks of nude mice (n=20) was exposed to 50 Gy of beta radiation from a strontium-90 source. Hyperspectral images were obtained before irradiation and on selected days for three weeks. Skin reaction assessment was performed concurrently with HSI. Desquamative injury formed in all irradiated areas. Skin reactions were first seen on day 7, with peak formation on day 14, and resolution beginning by day 21. HSI demonstrated increased tissue oxygenation on day 1 before cutaneous changes were observed (

Cavitation rheology as a potential method for in vivo assessment of skin biomechanics

We propose cavitation rheology as a nondestructive method of assessing cutaneous biomechanical properties. Cavitation rheology may provide accurate in vivo evaluation of biomechanical changes during cutaneous wound healing or disease evolution

Skin perfusion and oxygenation changes in radiation fibrosis

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 \u3c 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 \u3c 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\u27 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