Numerical investigations of some mathematical models of the diffusion MRI signal

My thesis focused on the relationship between the tissue microstructure and the macroscopic dMRI signal. Inferring tissue parameters from experimentally measured signals is very important in diffusion MRI. In spite of a long standing history of intensive research in this field, many aspects of this inverse problem remain poorly understood. We proposed and tested an approximate solution to this problem, in which the dMRI signal is first approximated by an appropriate macrosopic model and then the effective parameters of this model are estimated.We investigated two macroscopic models of the dMRI signal. The first is the Karger model that assumes a certain form of (macroscopic) multiple compartmental diffusion and intercompartment exchange, but is subject to the narrow pulse restriction on the diffusion-encoding magnetic field gradient pulses. The second is an ODE model of the multiple compartment magnetizations obtained from mathematical homogenization of the Bloch-Torrey equation, that is not subject to the narrow pulse restriction.First, we investigated the validity of these macroscopic models by comparing the dMRI signal given by the Karger and the ODE models with the dMRI signal simulated on some relatively complex tissue geometries by solving the Bloch-Torrey equation in case of semi-permeable biological cell membranes. We concluded that the validity of both macroscopic models is limited to the case where diffusion in each compartment is effectively Gaussian and where the inter-compartmental exchange can be accounted for by standard first-order kinetic terms.Second, assuming that the above conditions on the compartmental diffusion and intercompartment exchange are satisfied, we solved the least squares problem associated with fitting the Karger and the ODE model parameters to the simulated dMRI signal obtained by solving the microscopic Bloch-Torrey equation. Among various effective parameters, we considered the volume fractions of the intra-cellular and extra-cellular compartments, membrane permeability, average size of cells, inter-cellular distance, as well as apparent diffusion coefficients. We started by studying the feasibility of the least squares solution for two groups of relatively simple tissue geometries. For the first group, in which domains consist of identical or variably-sized spherical cells embedded in the extra-cellular space, we concluded that parameters estimation problem can be robustly solved, even in the presence of noise. In the second group, we considered parallel cylindrical cells, which may be covered by a thick membrane layer, and embedded in the extra-cellular space. In this case, the quality of parameter estimation strongly depends on how much the cellular structure is elongated in the gradient direction. In practice, the orientation of elongated cells is not known a priori; moreover, biological tissues may contain elongated structures randomly oriented and also mixed with other compact elements (e.g., axons and glial cells). This situation has been numerically investigated on our most complicated domain in which layers of cylindrical cells in various directions are mixed with layers of spherical cells. We checked that certain parameters can still be estimated rather accurately while the other remains inaccessible. In all considered cases, the ODE model provided more accurate estimates than the Karger model.