Section: New Results

Cancer modelling

We have improved our generic mathematical models describing tumor growth. These models were then specialized for several types of cancer (thyroidal lung nodules, brain tumors). The algorithm used to recover the parameters of these models from medical images has also been greatly improved and is now adapted to run on HPC architectures.

• Secondary tumors in the lung:

  The mathematical models describing the growth of secondary in the lungs have now settled and are well understood. The main focus of the year was to keep on using these models on patient data. New clinical case were selected by clinicians from the Institut Bergonié, there are currently under study. The model is currently able to reproduce the growth observed on 5 clinical cases. In 2011, various improvements to the calibration algorithms were made. The initial seeding of the algorithms was a weak point of the procedure. This has been much improved using a genetic algorithm. A complete rewrite of the routines was done to improve their versatility and efficiency. Previously, the numerical simulations and calibration were performed in 2D (clinicians selected the most relevant slice showing the evolution of the tumor). Work is now ongoing to switch to full 3D computations and calibration.

• Metastasis to the liver of a GIST

  Gastro-Intestinal Stromal Tumors often create metastasis to the liver. We have modeled the response to the treatment of such lesion starting from CT-scans.

• Modeling glioblastomas:

  In 2011, a hierarchy of models describing the growth of brain tumors was developed (and described in a submitted paper) in collaboration with University of Alabama at Birmingham. As we wished to obtain models that could be calibrated from patient data and yet be reasonably accurate, we believe that these models are suitable trade-offs between the simplicity of the SwansonÕs model (the only one used on patient data of brain tumors so far) and the accuracy of more complex models (that cannot really produce quantitative results). In particular, two models were built. The first one allows to study the efficacy of anti-angiogenic therapies. It seems to predict that the efficacy of these treatments is limited, this could be confirmed by a world-wide ongoing clinical study. The second model has been validated and we are trying to recover its parameters for a patient in 3D (which is a rather unique initiative to our knowledge).

• Modelling of electrochemotherapy :

  Two articles related to the electrical cell modelling have been done ( [64] , [61] ) . The first one deals with the influence of the ionic fluxes on the transmembrane voltage potential and on the cell volume. The main insight of the results consists in linking the transmembrane potential with the cell volume: it has been observed experimentally that cells with a low voltage potential do divide, whereas cells with high voltage potential do not, and the obtained relationship between voltage potential and cell volume can provide an explanation. The second article deals with a new model of cell electroporation essentially based on the experimental results of the I.G.R. In this paper we describe precisely the model, which takes into account the main experimental results in the electroporation process, and we present a variationnal formulation inherent to the model that leads to new efficient schemes in order to numerically solve the involved P.D.E.

  The article describing a new electrical model of classical has been accepted in Journal of Math Biology [27] . This new phenomenological model involves much less parameters than the usual models, but it still provides the qualitatively good description of the electroporation. The main feature of this model lies in the fact that it provides an intrinsic behavior of the cell membrane, which seems in accordance with the preliminary experimental results of the IGR partner. We also adapted the finite difference method developed by L. Weynans and M. Cisternino for elliptic interface problems to the electropermeabilization model developed recently by C. Poignard with O. Kavian. The new method has been validated by convergence tests and comparison with other models. We have proven that in one dimension the numerical solution converges to the solution of the exact problem.

• Cell Migration modelling:

  The collaboration with IECB (University of Bordeaux) has continued with the postdocatoral position of Julie Joie. We have obtain a continuous model of cell density evolving on micropatterned polymers. The research report RR 7998 will be published in Math. Biosci. and Eng. A discrete model describing the single cells motility is being written.

  We also have started a collaboration with the University of Osaka (Japan), thanks to a PHC Sakura project, on the invadopodia. C. Poignard has been invited at Osaka in februray by Prof. Suzuki and T.Colin and C.Poignard have been at Osaka in september. A model describing the destruction of the extracellular matrix by the MMP enzyme, and then the cell migration has been obtained. R. Mahumet, a PhD student of Prof. Suzuki is developing a code to simulate the model.