Longitudinal In-Vivo Quantification of Tumour Microvascular Heterogeneity by Optical Coherence Angiography in Pre-Clinical Radiation Therapy

Abstract

Stereotactic body radiotherapy (SBRT) is an emerging cancer treatment due to its logistical and potential therapeutic benefits as compared to conventional radiotherapy. However, its mechanism of action is yet to be fully understood, likely involving the ablation of tumour microvasculature by higher doses per fraction used in SBRT. In this study, we hypothesized that longitudinal imaging and quantification of the vascular architecture may elucidate the relationship between the microvasculature and tumour response kinetics. Pancreatic human tumour xenografts were thus irradiated with single doses of 10, 20 and 30 Gy to simulate the first fraction of a SBRT protocol. Tumour microvascular changes were monitored with optical coherence angiography for up to 8 weeks following irradiation. The temporal kinetics of two microvascular architectural metrics were studied as a function of time and dose: the diffusion-limited fraction, representing poorly-vasculatized tissue >150 µm from the nearest detected vessel, and the vascular distribution convexity index, a measure of vessel aggregation at short distances. These biological metrics allowed for dose dependent temporal evaluation of tissue (re)vascularisation and vessel aggregation after radiotherapy, showing promise for determining the SBRT dose-response relationship.