Longitudinal in-vivo quantification of tumour microvascular heterogeneity by optical coherence angiography in pre-clinical radiation therapy

Author:

Allam Nader,Jeffrey Zabel W.,Demidov Valentin,Jones Blake,Flueraru Costel,Taylor Edward,Alex Vitkin I.

Abstract

AbstractStereotactic 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 $$10$$ 10 , $$20$$ 20 and $$30$$ 30  Gy to simulate the first fraction of a SBRT protocol. Tumour microvascular changes were monitored with optical coherence angiography for up to $$8$$ 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 vascularized tissue $$>150$$ > 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)vascularization and vessel aggregation after radiotherapy, showing promise for determining the SBRT dose–response relationship.

Funder

Natural Sciences and Engineering Research Council of Canada

Ontario Graduate Scholarship

Princess Margaret Cancer Foundation

Terry Fox Foundation’s Strategic Training in Transdisciplinary Radiation Sciences for the 21st Century

Canadian Institutes of Health Research

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

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