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research article

Enhanced perfusion following exposure to radiotherapy: A theoretical investigation

Koery, Jakub
•
Narain, Vedang
•
Stolz, Bernadette J.  
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February 1, 2024
Plos Computational Biology

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.

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Type
research article
DOI
10.1371/journal.pcbi.1011252
Web of Science ID

WOS:001163897400002

Author(s)
Koery, Jakub
•
Narain, Vedang
•
Stolz, Bernadette J.  
•
Kaeppler, Jakob
•
Markelc, Bostjan
•
Muschel, Ruth J.
•
Maini, Philip K.
•
Pitt-Francis, Joe M.
•
Byrne, Helen M.
Date Issued

2024-02-01

Published in
Plos Computational Biology
Volume

20

Issue

2

Article Number

e1011252

Subjects

Life Sciences & Biomedicine

•

Blood-Flow

•

Tumor Vasculature

•

Networks

•

Angiogenesis

•

Hypoxia

•

Irradiation

•

Persistence

•

Mechanisms

•

Topology

•

Cancer

Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
UPHESS  
FunderGrant Number

Cancer Research UK

Isaac Newton Institute for Mathematical Sciences, Cambridge

Available on Infoscience
March 18, 2024
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/206426
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