The effects of radiotherapy on tumour microvasculature: insights from optical coherence angiography and dynamic contrast-enhanced MR imaging towards adaptive radiation medicine

Stereotactic body radiotherapy (SBRT) fractionation schedules may still be improved as its mechanism of action remains largely unknown. It has been hypothesized that accelerated hypofractionated treatment in SBRT benefits from increased microvascular damage relative to conventional fractionation treatment outcomes. We investigate tumour vasculature radiobiology preclinically in a mouse dorsal skinfold window chamber model of fluorescently labeled human tumor xenografts. We monitored both micro- (via optical coherence tomography angiography (OCTA)) and macro- (via dynamic contrast enhanced magnetic resonance imaging (DCE-MRI)) vascular responses to irradiation over time. We first studied responses to single fraction irradiation (10, 20 and 30 Gy), before proceeding to a full typical clinical SBRT regimen (3 x 10 Gy every other day). DLF150 and lambda metrics which describe the microvascular heterogeneity and molecular transport efficiency, were longitudinally extracted from OCTA images. Both metrics exhibited a gradual increase up to 2-3 weeks post-irradiation with maxima positively correlated with the single-delivered fraction (r(DLF150)=0.80, p < 10(-4), r lambda = 0.59, p similar to 10-4), before gradually returning to pre-irradiation levels. They also appear to be promising predictive biomarkers for macroscopic tumour response (assessed by tumour volume and fluorescence intensity). High Spearman correlations up to similar to 0.8 (p < 10-4) between OCTA and DCE-MRI derived metrics were obtained, thus showing promise for bridging the clinical resolution gap in monitoring the microvasculature. Insights from these modalities should yield a better understanding of tissue functional response to high doses of radiation employed in SBRT and help develop improved SBRT fractionation schedules (dose and time combinations) towards personalized and adaptive radiation therapy.