In silico model of the early effects of radiation therapy on the microcirculation and the surrounding tissues. (May 2020)

• Record Type: Journal Article
• Authors: Cicchetti, Alessandro; Laurino, Federica; Possenti, Luca; Rancati, Tiziana; Zunino, Paolo
• Is Part Of: Physica medica. Volume 73(2020)
• Page Start: 125
• Page End: 134
• Publication Date: 2020-05
• Subjects: Simulations -- Microcirculation -- Computational model -- Radiation toxicity -- Microenvironment; Medical physics -- Periodicals; Biophysics -- Periodicals; Biophysics -- Periodicals; Imagerie médicale -- Périodiques; Radiothérapie -- Périodiques; Rayons X -- Sécurité -- Mesures -- Périodiques; Physique -- Périodiques; Médecine -- Périodiques; 610.153
• DOI: 10.1016/j.ejmp.2020.04.006
• Languages: English
• ISSNs: 1120-1797

Abstract

Highlights: Detrimental process of ionizing radiation on microcirculation has a strong impact on the late toxicity of organs at risk. We retrieved from literature search the acute effects of the radiotherapy on the functional units of the capillary bed. The effects are strongly related to the inflammatory response that is manifested in tissues after each treatment fraction. Alterations are included into a computational model as a perturbation of the model parameters affected by the inflammation. We presented two studies about the consequence of impairment to the endothelial membrane and to the wall elasticity. Abstract: 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 that describes the fluid dynamics of microcirculation when the parameters of the network and the surrounding tissues are affected by radio-induced changes. Materials and methods: The effects of the ionizing radiation on the capillary bed are mediated by the inflammatory response. We derived from a literature search the possible morphological and functional variations of the network due to the process of the acute inflammation. Specifically, we considered vasodilation, increased membrane permeability with consequent fluid extravasation and increased wall elasticity. These perturbations to the system were included in a computational model, already able to describe the physics of the microcirculation and its exchanges with the surrounding tissues. Results: Two computational descriptions were considered. In the first one, we changed a set of 4 parameters associated with the increased fluid exchange from the health scenario at the baseline to a seriously compromised scenario with the edema formation. The second study investigated the effect of a perturbation to the vessel wall elasticity. Conclusions: 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.