Enhanced perfusion following exposure to radiotherapy: A theoretical investigation

Tumour angiogenesis leads to the formation of blood vessels that are structurally and spatially heterogeneous. Poor blood perfusion, in conjunction with increased hypoxia and oxygen heterogeneity, impairs a tumour's response to radiotherapy. The optimal strategy for enhancing tumour perfusion r...

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Bibliographic Details
Published in:PLoS computational biology 2024-02, Vol.20 (2), p.e1011252-e1011252
Main Authors: Köry, Jakub, Narain, Vedang, Stolz, Bernadette J, Kaeppler, Jakob, Markelc, Bostjan, Muschel, Ruth J, Maini, Philip K, Pitt-Francis, Joe M, Byrne, Helen M
Format: Article
Language:English
Subjects:
Angiogenesis
Biology and Life Sciences
Blood flow
Blood vessels
DNA damage
Heterogeneity
Hypoxia
Irradiation
Medicine and Health Sciences
Perfusion
Physical Sciences
Post-irradiation
Radiation therapy
Research and Analysis Methods
Retina
Tumors
Vascular endothelial growth factor
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Summary:Tumour angiogenesis leads to the formation of blood vessels that are structurally and spatially heterogeneous. Poor blood perfusion, in conjunction with increased hypoxia and oxygen heterogeneity, impairs a tumour's response to radiotherapy. The optimal strategy for enhancing tumour perfusion remains unclear, preventing its regular deployment in combination therapies. In this work, we first identify vascular architectural features that correlate with enhanced perfusion following radiotherapy, using in vivo imaging data from vascular tumours. Then, we present a novel computational model to determine the relationship between these architectural features and blood perfusion in silico. If perfusion is defined to be the proportion of vessels that support blood flow, we find that vascular networks with small mean diameters and large numbers of angiogenic sprouts show the largest increases in perfusion post-irradiation for both biological and synthetic tumours. We also identify cases where perfusion increases due to the pruning of hypoperfused vessels, rather than blood being rerouted. These results indicate the importance of considering network composition when determining the optimal irradiation strategy. In the future, we aim to use our findings to identify tumours that are good candidates for perfusion enhancement and to improve the efficacy of combination therapies.
ISSN:1553-7358
1553-734X
1553-7358
DOI:10.1371/journal.pcbi.1011252