Multicompartmental poroelasticity for the integrative modelling of fluid transport in the brain

The world population is expected to increase to approximately 11 billion by 2100. The ageing population (aged 60 and over) is projected to exceed the number of children in 2047. This will be a situation without precedent. The number of citizens with disorders of old age like Dementia will rise to 115 million worldwide by 2050. The estimated cost of Dementia will also increase, from 604 billion dollars in 2010, to 1,117 billion dollars by 2030. At the same time, medical expertise, evidence-driven policymaking and commissioning of services are increasingly evolving the definitive architecture of comprehensive long-term care to account for these changes.
Technological advances, such as those provided by computational science and biomedical engineering, will allow for an expansion in our ability to model and simulate an almost limitless variety of complex problems that have long defied traditional methods of medical practice. Numerical methods and simulation offer the prospect of improved clinically relevant predictive information, and of course optimisation, enabling more efficient use of resources for designing treatment protocols, risk assessment and urgently needed management of a long term care system for a wide spectrum of brain disorders. Within this paradigm, the importance of the relationship of senescence of cerebrospinal fluid transport to dementia in the elderly make the cerebral environment notably worthy of investigation through numerical and computational modelling.
Hydrocephalus can be succinctly described as the abnormal accumulation (imbalance between production and circulation) of cerebrospinal fluid (CSF) within the brain. Using hydrocephalus as a test bed, one is able to account for the necessary mechanisms involved in the interaction between cerebral fluid production, transport and drainage. The current state of knowledge about hydrocephalus, and more broadly integrative cerebral dynamics and its associated constitutive requirements, advocates that poroelastic theory provides a suitable framework to better understand the disease. In this work, Multiple-network poroelastic Theory (MPET) is used to develop a novel spatio-temporal model of fluid regulation and tissue displacement in various scales within the cerebral environment. The model is discretised in a variety of formats, through the established finite difference method, finite difference – finite volume coupling and also the finite element method. Both chronic and acute hydrocephalus was investigated in a variety of settings, and accompanied by emerging surgical techniques where appropriate.
In the coupled finite difference – finite volume model, a key novelty was the amalgamation of anatomically accurate choroid plexuses with their feeding arteries and a simple relationship relaxing the constraint of a unique permeability for the CSF compartment. This was done in order to account for Aquaporin-4 sensitisation. This model is used to demonstrate the impact of aqueductal stenosis and fourth ventricle outlet obstruction. The implications of treating such a clinical condition with the aid of endoscopic third (ETV) and endoscopic fourth ventriculostomy (EFV) are considered. It was observed that CSF velocity in the aqueduct, along with ventricular displacement, CSF pressure, wall shear stress and pressure difference between lateral and fourth ventricles increased with applied stenosis. The application of ETV reduced the aqueductal velocity, ventricular displacement, CSF pressure, wall shear stress and pressure difference within nominal levels. The greatest reversal of the effects of atresia come by opting for ETV rather than the more complicated procedure of EFV.
For the finite difference model incorporating nonlinear permeability, qualitatively similar results were obtained in comparison to the pertinent literature, however, there was an overall amplification of ventriculomegaly and transparenchymal pressure difference using this model. A quantitative and qualitative assessment is made of hydrocephalus cases involving aqueductal stenosis, along with the effects to CSF reabsorption in the parenchyma and subarachnoid space.
The finite element discretisation template produced for the nth- dimensional transient MPET system allowed for novel insight into hydrocephalus. In the 1D formulation, imposing the breakdown of the blood-CSF barrier responsible for clearance resulted in an increase in ventricular displacement, transparenchymal venous pressure gradient and transparenchymal CSF pressure gradient, whilst altering the compliance proved to markedly alter the rate of change of displacement and CSF pressure gradient. The influence of Poisson's ratio was investigated through the use of the dual-grid solver in order to distinguish between possible over or under prediction of the ventricular displacement. In the 2D model based on linear triangles, the importance of the MPET boundary conditions is acknowledged, along with the quality of the underlying mesh. Interesting results include that the fluid content is highest in the periventricular region and the skull, whilst after longer time scales, the peak CSF content becomes limited to the periventricular region. Venous fluid content is heavily influenced by the Biot-Willis constant, whilst both the venous and CSF/ISF compartments show to be strongly influenced by breakdown in the blood-CSF barrier. Increasing the venous compliance effects the arterial, capillary and venous compartments. Decreasing the venous compliance shows an accumulation of fluid, possibly helping to explain why the ventricles can be induced to compress rather than expand under decreased compliance. Finally, a successful application of the 3D-MPET template is shown for simple geometries.
It is envisaged that future observations into the biology of cerebral fluid flow (such as perivascular CSF-ISF fluid exchange) and its interaction with the surrounding parenchyma, will demand the evolution of the MPET model to reach a level of complexity that could allow for an experimentally guided exploration of areas that would otherwise prove too intricate and intertwined under conventional settings.

Keywords: Newton-Galerkin method
poroelasticity
finite volume method
finite difference method
finite element method
computational fluid dynamics
hydrocephalus
Advisor: Ventikos, Y