The Numerical Waterscape of the Brain

Your brain has its own waterscape: whether you are reading or sleeping, fluid flows through and around your brain tissue and clears out waste. New medical research has shown that this waterscape is more key than what was previously believed and that this flow is indeed crucial for the brain's well-being. In particular, waste accumulation is linked to neurological diseases such as dementia (Alzheimer's disease) and to brain swelling caused by stroke. Up til now, our understanding of brain clearance has dominated by experimental studies on mice during which pieces of brain tissue close to the skull are removed and studied via microscopes. However, such methods have their weaknesses: it is hard or even impossible to look deep enough into the brain and it is not feasible to study the human brain with the same techniques. Our project "The Numerical Waterscape of the Brain" have developed a new computational technology platform that allows for studying the brain's waterscape through numerical computations and simulations. We have developed new, reliable numerical methods for computing the flow of tissue fluid through the brain, evaluated and compared different models and scenarios, and validated the simulation results using data from clinical studies experiments.

We have established mathematical and computational foundations for modelling solute transport and physiological fluid flow in the brain and spinal cord. These foundations can be used for further development of computational brain physiology, but also in other application areas such as geoscience. Via the technological advances, we have opened up new possibilities for investigating brain clearance specifically. We hope and expect to follow this path to better understand brain health over the next decades. Importantly, Waterscape has been instrumental in establishing a high-momentum research team at Simula Research Laboratory and a national interdisciplinary knowledge network dedicated to this topic.

Novel insights indicate that fluid-driven transport of metabolic waste through brain tissue may be much more complex and much more important than previously believed. There is a need for computer modeling and simulation of this process, but the state of the art lacks a technological framework capable of reliable predictions. The development of such a framework for computational studies of tissue fluid flow and metabolic solute transport through the brain, is the primary objective of this project. The predictive capabilities of existing mathematical theories for modeling tissue fluid flow through the brain is a wide-open scientific question. To address this question, the project adopts a holistic mathematical methodology, combining robust numerical methods, accurate error estimation, uncertainty quantification, model calibration against experimental data, and model adaption. The problem setting calls for a multidisciplinary approach and the project brings together experts in applied mathematics, computer science, bioengineering and physiology from Simula Research Laboratory, the University of Oslo, the University of Minnesota, and University College London. The project, if successful, will establish a complete methodology, complemented by freely available efficient software, for robust computational modeling of elastic media permeated by one or more fluid-filled networks. We anticipate that this technological platform can readily be used by other computational scientists and engineers for modeling brain tissue, other types of biological tissue, and also in the geosciences. Ultimately, the project will provide a new avenue for understanding physiological processes in the brain linked to sleep and neurodegenerative diseases such as Alzheimer's and Parkinson's disease.