Biophysical modeling of anti-cancer therapies

Participants:
Sebastien BenzekryClair Poignard, Olivier Saut
Manon Deville

Partners:

Team of Vectorology and Anticancer Therapies at the Institut Gustave Roussy (VAT lab), Villejuif

Department of Mathematics of the University of Versailles (LMV)

Bioengineering laboratory Ampère, Lyon

M-P. Rols (Institute of Pharmacology and Structural Biology)

O. Séror (CHU J. Verdier de Bondy)

NUMEP: Numerics for Clinical Electroporation

The project NUMEP, composed of computer scientists (Inria MONC), biologists (IPBS) and radiologist (CHU J. Verdier), proposes to provide new insights in understanding biologically and in modeling numerically the effect of electroporation-based therapies on tumors, in order to provide numerical tools enriched by biological knowledge that help the clinical applications of electroporation in cancer treatment. For the sake of coherence we will focus on hepatocarcinoma to the liver. Based on medical image acquisition during the procedure (from C-arm Cone beam CT) we plan to provide accurate numerical tools for real-time simulations of the electric field distribution, which accounts for the exact position of the electrodes. We also plan to predict the different zone affected by the treatment based on new biological knowledge of electroporation­based therapies thanks to designed experiments on spheroids and mice. The long-term goal is to propose a tool that will be incorporated in the medical image processing tools to superimpose the electric field distribution and the affected zones on the image during the treatment procedure. C.P. is the head of the project, M.-P. Rols (IPBS) and O. Séror (CHU J. Verdier) are local coordinators.

MEMOVE (Multiscale Electroporation MOdeling Validated by the Experiments) is a transdisciplinary project that aims at developing new mathematical models, numerical tools as well as new experimental protocols to provide a complete understanding of the electropermeabilization from the cell to the tissue scale. The electroporation modeling will be
developed thanks to two-way links between the numerical simulations and the experiments: the experimental results
providing preliminary results to the modeling, which then will highlight a priori the main phenomena of the
experiments. The fitting of the model based on PDEs is the key point of the project. This will be performed by a data
assimilation procedure well known by the INRIA team MONC.

At the cell scale, it is proposed to develop new electrical cell PDEs models that describe simultaneously the
electropermeabilization by micropulses, and the electrophysiological changes of the cell during the process (cell swelling, ions fluxes in the cell…). Moreover a theoretical asymptotic analysis will be performed to study the electropermeabilization of  losely touching cells, while homogenization of single cell models will help in the understanding of the electroporation of cell suspension solution. From the experimental point of view, new device manufacturing to simultaneously electroporate vesicles and quantify this electroporation will be performed. These experiments will highlight the specificity of cell electroporation, when compared to the simplest experimental cell model that is liposome.

At the tissue scale, MEMOVE aims at providing a non-linear tissue conductivity modeling, with parameters that will be fitted with the experiments on potatoes, and rat liver, through data assimilation techniques based on proper orthogonal decomposition developed by MC2. Here again, both numerical and experimental influences of the pulse properties on the tissue electroporation will be investigated.

The final goal of the project, once these multiscale models will be derived, is to provide numerical tools that ensure the optimal pulse delivery for a given realistic geometry of tissue, in order to propose a code that could be useful to the physician applying
electrochemotherapy as cancer treatment. The full human body meshing developed by Ampère will be useful to perform the robust optimization to ensure the best pulse delivery that will be addressed by Ampère, MC2 and LMV. The results will be proposed to the VAT lab to test the procedure on the electroporation on small animals and to evaluate the
consistence of the optimization.

O. Kavian, M. Leguèbe, C. Poignard, L. Weynans. Classical electropermeabilization modelling at the cell scale. Accepted in Journal of Mathematical Biology.


Extra- and intra-cellular electric field, with poration in blue areas and holes of the cellular membrane.

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