The Numerical Waterscape of the Brain

Rundt om i hjernen vår strekker det seg et nettverk av vannveier, i form av vannkanaler i de biologiske cellene, vannfylte hylser rundt blodårene og i tillegg væskefylte hulrom dypt inne i hjernen. Ny medisinsk forskning har vist at disse vannveiene er mer interessante enn man tidligere har trodd. Spesielt så tenker man at vannveiene er viktige for å unngå at vann og avfallsstoffer samler seg opp i hjernen. Slik oppsamling av avfallsstoffer er knyttet til nevrologiske sykdommer som Alzheimers eller opphovning i vevet (hjerneødem). I dag undersøker man disse mekanismene først og fremst med eksperimentelle metoder der man tar ut deler av hjernevev hos mus og studerer det i mikroskop. Men, slike metoder har svakheter: det er vanskelig eller umulig å se dypt nok inn i hjernen og det er ofte ikke forsvarlig å studere hjernen til mennesker med disse teknikkene. Prosjektet "Numeriske beregninger av hjernens vannveier" (Waterscape) har utviklet en ny teknologiplatform der man kan studere hjernens vannveier ved hjelp av beregninger og simuleringer. Prosjektet har utviklet nye, pålitelige numeriske metoder for å beregne væskeflyten gjennom vevet, vurdere forskjellige modeller opp mot hverandre og sammenligne resultatene fra simuleringene med resultater fra fysiske eksperimenter.

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.