In silico model of the early effects of radiation therapy on the microcirculation and the surrounding tissues
Saturday 7th December 2019
Cicchetti, A.; Laurino, F.; Possenti, L.; Rancati, T.; Zunino, P.
Background: Radiation-induced organ dysfunction are frequently described by Normal Tissue Complication Probability models. The approximations of this radiobiological approach do not allow to consider the important role played by the microvasculature not only in the dose-response of the blood vessels, but also of the organs where it is located. To this purpose we presented a computational model of the damage induced by RT on the microcirculation and of its effects on the normal tissues surrounding the tumour. Material and Methods: The effects of the ionizing radiation on the capillary bed are mediated by the inflamma- tory response. We derived from a literature search the possible morphological and functional variations of the network due to the process of the acute in- flammation. Specifically, we considered a vasodilation, an increased membrane permeability with a consequent fluid extravasation and an increasing in the wall elasticity. These perturbations to the system were included in a computational model, already able to describe the physics of the microcirculation and of its ex- changes with the surrounding tissues. Results:Two computational descriptions were considered. In the first one, we changed a set of 4 parameters associated to the increased fluid exchange from the health scenario at the baseline to a seriously compromised scenario with the oedema formation. The second study investigated the effect of a perturbation to the vessel wall elasticity. Conclu- sions: These simulations represent a first step towards the challenging objective of understanding, and describing in a mechanistic way the effects of radiation on the vascular microenvironment.
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