We propose a new mathematical model to infer capillary leakage coefficients from dynamic susceptibility contrast MRI data. To this end, we derive an embedded mixed-dimension flow and transport model for brain tissue perfusion on a sub-voxel scale. This model is used to obtain the contrast agent concentration distribution in a single MRI voxel during a perfusion MRI sequence. We further present a magnetic resonance signal model for the considered sequence including a model for local susceptibility effects. This allows modeling MR signal-time curves that can be compared to clinical MRI data. The proposed model can be used as a forward model in the inverse modeling problem of inferring model parameters such as the diffusive capillary wall conductivity. Acute multiple sclerosis lesions are associated with a breach in the integrity of the blood brain barrier. Applying the model to perfusion MR data of a patient with acute multiple sclerosis lesions, we conclude that diffusive capillary wall Common indicators derived from such models are the cerebral blood volume (CBV ), 52 the cerebral blood flow (CBF ), the mean transit time (MTT ), and leakage 53 coefficients [10,12,19].
54A routinely used state-of-the-art post-processing procedure and model is described 55 in [12]. Such models have to reflect two processes: (1) the perfusion process governed 56 mainly by bio-fluid-mechanical principles, and (2) the physical process of nuclear 57 December 20, 2018 4/45 magnetic resonance (NMR) exploited to acquire the MR image. There have been many 58suggestions for improving the modeling of the latter process [20][21][22][23]. The authors 59 of [24,25] show that the local, sub-voxel tissue structure has a significant effect on the 60 NMR signal. However, all previous studies, including the recent study by [23], rely on 61 state-of-the-art two-compartment models for the perfusion process providing only 62 average concentrations in two tissue compartments within a voxel.
63To overcome the limitations of two-compartment models, we present a perfusion 64 model on a sub-voxel scale, including the capillary network structure. Fully, 65 three-dimensionally resolved fluid-mechanical models of brain tissue perfusion imply 66 prohibitively complex and computationally expensive simulations due to the large 67 number of vessels, their non-trivial geometrical embedding, and the complex geometry 68 of the extra-vascular, extra-cellular space [26]. To reduce complexity, we use a 69 mixed-dimension embedded model description, where blood vessels are represented by a 70 network of cylindrical segments which are embedded into the extra-vascular space, 71represented by a homogenized three-dimensional continuum. The model reduction, 72 which is described in more detail in the following, leads to a coupled system of 73 one-dimensional partial differential equations for flow and transport in the vessels, and 74 three-dimensional partial differential equations for flow and transport in the 75 extra-vascular space. Related models have been used to stud...