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

Abstract

BackgroundRadiation 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.MethodsImmunocompetent 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.ResultsCD31 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.ConclusionRadiation 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.

Early biomarker for radiation-induced wounds: day one post-irradiation assessment using hemoglobin concentration measured from diffuse optical reflectance spectroscopy

“…RT) and normal tissue applications. With regards to external beam radiation, Chin et al (2012) previously reported spikes on day 1 and 10 in both Hb concentration and StO 2 (as measured by hyperspectral imaging) from beta particle irradiation of mouse skin [17], and Jang et al (2016) confirmed that early cellular changes begin to occur in the first six days post irradiation [26]. These findings agree overall with the trends in our current and previous studies [16].…”

“…These findings agree overall with the trends in our current and previous studies [16]. While Chin et al (2015) correlated early trends in optical biomarker parameters with subsequent overall late microvascular damage, differential damage and patterns were due to different administered radiation doses [17]. To our knowledge, we are the first to provide evidence that Hb changes measured on day 1 associate with the severity of radiation induced wounds in connection with treatment intervention.…”

“…In this work, we used a large single radiation dose typical of preclinical mouse models of radiation skin damage [2-4, [15][16][17]26]; it is equivalent to eliciting the pathophysiology of severe, accelerated skin reactions in humans [28]. However, conventional external beam RT employs smaller fractionated dose regimens that may result in smaller day-to-day biomarker responses.…”

“…However, this stratification was measured over a time when the radiation skin damage was already perceptible. Further, in studies where optical biomarkers have been shown to demonstrate early (< day five) temporal and dose-based patterns following irradiation before overt toxicity [15,17], their relationship with the subsequent outcome (acute wound severity) and a toxicity mitigator have not been explored.…”

Review of near-infrared methods for wound assessment

“…The utility of NIR spectroscopy and in particular imaging is being explored to determine peripheral vascular perfusion, [121][122][123][124][125] burn injury assessment, [126][127][128][129] as well as the assessment of oxygenation of superficial tissues during surgery, postsurgery, and during healing. [130][131][132][133][134][135][136] Figure 11 shows a tissue oxygenation image derived from a four-wavelength multispectral reflectance image of the planter portion of the foot that has a diabetic ulceration. The ulceration has a very low value of oxygenation compared to the surrounding tissue.…”