Hydrocephalus is a brain disease wherein the ventricles dilate and compress the parenchyma towards the skull. It is primarily characterized by the disruption of the cerebrospinal fluid (CSF) flow within the ventricular system. Normal pressure hydrocephalus (NPH) is a form of hydrocephalus for which the enlargement of ventricles occurs although the intracranial pressure (ICP) remains close to normal. The pressure gradient between the source of CSF production in the ventricles and the absorption sites is reported to be very low (∼1 mm Hg), i.e. within the experimental errors. The mechanism of NPH evolution is still obscure and its distinction from the other causes of dementia such as Alzheimer and neurodegenerative diseases is difficult. The present work contributes to a better understanding of the NPH mechanism in terms of CSF disturbances and/or parenchyma defects. To this end, imaging techniques such as Magnetic resonance imaging (MRI), Diffusion tensor imaging (DTI) and Magnetic resonance elastography (MRE) are used together with a finite element (FE) model. As a final step, NPH onset and evolution are clarified via a theoretical model for healthy and NPH brains assuming a spherical geometry. The proposed mechanism is further analyzed in a realistic 3D model of the brain parenchyma. Geometries of ventricular system and skull are obtained from MRI images of a human brain. DTI data are used to establish the fiber tracts direction as well as the local frame of anisotropic elasticity and permeability. The brain parenchyma is considered as a poro-elastic material where the tissue displacement and CSF flow are modeled using the Biot's theory. A link between the CSF diffusion and CSF permeability in brain parenchyma is established and the importance of space dependent CSF content and transverse isotropic (TI) permeability is highlighted in case of low pressure gradient hydrocephalus. Calculations are carried out to simulate the ventricular dilation using FE softwares such as MATLAB® and COMSOL®. The numerical results show that consideration of space dependent CSF content and TI permeability leads to a much more realistic model for NPH in terms of CSF velocity and CSF content. Anisotropic MRE experiment is conducted over selected slices of a healthy human brain. The experimental results are statistically refined and further used to assess the healthy brain stiffness as well as the degree of anisotropy in elasticity. Moreover, the constitutive behavior of the white matter is modeled as a composite material containing fiber tracts surrounded by a matrix; with the assumption of a low fiber-matrix bonding and fiber tract undulation. A non-linear elastic model is proposed in order to take into account the load transfer from white matter matrix to fiber tracts when these are fully stretched. The unknown value of the elastic coefficients in a sick brain is determined by using inverse modeling, i.e. by adjusting these coefficients so that the right ventricle d
Jean-Philippe Thiran, Gabriel Girard, Elda Fischi Gomez, Philipp Johannes Koch, Liana Okudzhava