WP5 Multiscale Biophysical & Biochemical Modeling: Brain Substrate and its Evolution

Rationale:
Central to the integrative treatment of the brain as an organ of very high metabolic demand, is the development and expansion of a modelling platform that can handle, in an anatomically accurate, patient specific manner, the transport and interplay of blood and cerebrospinal fluid with the parenchyma – the neuronal and astrocyte tissue that constitutes the functioning brain. Furthermore, such an integrative treatment of this –essentially closed, apart from a small number of connections – organ allows us to examine its interaction with the external world and to investigate the impact that environmental factors can have, directly or indirectly on its function and homeostasis.
Objectives:

The focus of this WP is to lead and contribute to the development of a simulation platform capable of representing, for the first time, the transport processes in the cerebral environment in their entirety and in a coupled manner. This task involves the expansion of an existing proven conceptual framework – that of multicompartmental poroelasticity. It shall account for anatomically derived, healthy and diseased, cases that are utilised for equipping VPH-DARE@IT with realistic, experimentally-derived, micro-laws of transport, absorption and regulation in the cerebral environment. More specifically, the objectives of this WP are:

  • Development and customisation of a computational modelling framework for a multicompartmental poroelastic model with a three-dimensional, spatio-temporally variable properties distribution.
  • Casting of the model in an anatomically accurate, image-derived framework.
  • Design and implementation of an experimental platform for acquisition of cerebral fluid micro scale transport properties and characteristics.
  • Building of the first comprehensive public domain cerebral transport processes database.
  • Verification and validation of model predictions against clinical observations.
  • Coupling this model with the metabolic models – developed in WP4 in an integrated whole.
Activities:
  • Establishment of simplified, spatially detailed multiporoelastic modelling framework
  • Experimental investigation of micro scale water brain transport properties - permeability, absorption, etc.
  • Establishment of anatomically-accurate and spatially-detailed multiporoelastic modelling framework. Training and calibration against clinical data.
  • Establishment of anatomically-accurate and spatially-detailed multiporoelastic modelling framework. Training and calibration against clinical data.
  • Model coupling and cerebral transport processes database
  • Quantitative modelling of lifestyle and circadian influence in dementia from pervasive sensing