Quantitative Optical Microangiography Associates Microvasculature Preservation with Reduced Skin Toxicity In Flash Radiotherapy
Abstract
Purpose
Ultra-high dose-rate (UHDR) radiotherapy has been reported to reduce normal tissue toxicity compared to conventional dose-rate irradiation (CDR), yet objective, quantitative imaging markers associated with this effect remain limited. This study evaluates whether optical microangiography–derived metrics of skin microvasculature are associated with reduced skin toxicity following UHDR radiotherapy.
Methods
Athymic nude mouse thighs were irradiated with single-fraction doses of 20 or 30Gy delivered at either conventional (0.12Gy/s) or ultra-high dose rates (270Gy/s). Noninvasive optical coherence tomography–based microangiography was performed longitudinally from baseline through 25 weeks post-irradiation. Dermal microvasculature was quantified using speckle-variance–based vascular volume density metrics, while epidermal thickness was measured from depth-resolved structural images. Imaging metrics were compared between UHDR and CDR delivery and evaluated in relation to visual skin reaction scoring and histological assessment.
Results
Distinct microvascular trajectories were observed between dose-rate modalities. At 20Gy, CDR induced an early transient increase in vascular density followed by decline below baseline, whereas UHDR produced a more moderate early change with stabilization near baseline over time. At 30Gy, CDR resulted in pronounced vascular loss with incomplete recovery, while UHDR-treated skin exhibited greater preservation of vascular density and more consistent recovery. Across both doses, higher long-term vascular volume density in UHDR-treated skin was associated with reduced severity of skin reactions and more organized epidermal structure. Epidermal thickness changes followed similar trends, with UHDR-treated skin demonstrating more regulated remodeling compared to CDR.
Conclusion
Quantitative optical microangiography enables longitudinal, noninvasive assessment of skin microvasculature following radiotherapy and demonstrates a consistent association between microvasculature preservation and reduced skin toxicity in UHDR radiotherapy. These findings support optical microangiography as a promising imaging approach for quantitative evaluation of normal tissue responses to emerging dose-rate–based radiotherapy techniques.