How do targeted vessel occlusions impair brain microcirculation? Numerical modeling and experimental validation

par Maxime Berg

Projet de thèse en Dynamique des fluides

Sous la direction de Sylvie Lorthois.

Thèses en préparation à Toulouse, INPT , dans le cadre de École Doctorale Mécanique, Énergétique, Génie civil et Procédés (Toulouse) , en partenariat avec Institut de mécanique des fluides de Toulouse (laboratoire) depuis le 30-10-2015 .

  • Titre traduit

    Comment est altérée la microcirculation sanguine cérébrale lors de l'occlusion de certains vaisseaux? simulations numeriques et validations experimentales

  • Résumé

    The cerebral microvascular system is essential to a large variety of physiological processes in the brain, including blood delivery and blood flow regulation as a function of neuronal activity (neuro-vascular coupling). It plays a major role in the associated processes leading to disease (stroke, neurodegenerative diseases) but the comprehension of the basic mechanisms involved is still largely incomplete. In the last decade, cutting edge experimental technologies, including two-photon scanning laser microscopy (TPSLM) and optically-induced single-vessel occlusions, have produced huge amounts of anatomic and functional experimental data in normal and Alzheimer Disease (AD) mice. These require accurate, highly quantitative, physiologically informed modeling and analysis for any coherent understanding and for translating results between species. Our first goal is to extend the non-linear network model previously developed for blood flow simulation at IMFT by coupling a boundary integral method for computing molecule transport and transfers. Here, the coefficient describing the physics at the scale of capillary vessels (blood rheology, diffusion of relevant molecules) will be obtained by global optimization of the numerical results, based on experimental anatomical data, with the associated in vivo functional TPSLM measurements (red blood cell velocities, non-metabolizable fluorescent tracer distributions). Our second goal is to validate this approach by direct comparison of the functional consequences of single-vessel occlusions in normal mice with the simulation results based on the same anatomical data. These new methods, validated with an unprecedented level of accuracy, will be used to model how the vascular alterations observed in AD affect the microvascular functions. In particular, we will study how much these alterations impact the mean cerebral blood flow and its heterogeneity, the appearance of hypoxic regions and the clearance of metabolic waste.