A new framework for assessing subject-specific whole brain circulation and perfusion using MRI-based measurements and a multi-scale continuous flow model.

A large variety of severe medical conditions involve alterations in microvascular circulation. Hence, measurements or simulation of circulation and perfusion has considerable clinical value and can be used for diagnostics, evaluation of treatment efficacy, and for surgical planning. However, the accuracy of traditional tracer kinetic one-compartment models is limited due to scale dependency. As a remedy, we propose a scale invariant mathematical framework for simulating whole brain perfusion. The suggested framework is based on a segmentation of anatomical geometry down to imaging voxel resolution. Large vessels in the arterial and venous network are identified from time-of-flight (ToF) and quantitative susceptibility mapping (QSM). Macro-scale flow in the large-vessel-network is accurately modelled using the Hagen-Poiseuille equation, whereas capillary flow is treated as two-compartment porous media flow. Macro-scale flow is coupled with micro-scale flow by a spatially distributing support function in the terminal endings. Perfusion is defined as the transition of fluid from the arterial to the venous compartment. We demonstrate a whole brain simulation of tracer propagation on a realistic geometric model of the human brain, where the model comprises distinct areas of grey and white matter, as well as large vessels in the arterial and venous vascular network. Our proposed framework is an accurate and viable alternative to traditional compartment models, with high relevance for simulation of brain perfusion and also for restoration of field parameters in clinical brain perfusion applications. Author summary An accurate simulation of blood-flow in the human brain can be used for improved diagnostics and assignment of personalized treatment regimes. However, current algorithms are limited to simulation of blood flow within tumours only, and in terms of parameter estimation, traditional compartment models have limited accuracy due to lack of spatial connectivity within the models. As a remedy, we propose a data-driven computational fluid dynamics model where the geometric domains for simulation are defined from state-of-the art MR acquisitions enabling a segmentation of large arteries and veins. In the capillary tissue we apply a two-compartment porous media model, where the perfusion is pressure-driven and is defined as the transition of blood from arterial to venous side. In addition, we propose a model for dealing with the intermediate scale problem where the vessels are undetectable and the flow does not adhere to requirements of porous media flow. For this scale, we propose a support function distributing the fluid in a nearby region around the vessel terminals. Combining these elements, we have developed a novel full human brain blood-flow simulator.