Virtual tracer transport simulations in mouse brain cortex CSF spaces

  • Koch, Timo (University of Oslo)
  • Vinje, Vegard (Simula Research Laboratory)
  • Mardal, Kent-Andr√© (University of Oslo)

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Tracer experiments and in-vivo two-photon microscopy of the mouse brain offer a unique inside into the transport of water and solutes in brain tissue which is still a poorly understood phenomenon concerning both the identification of dominant pathways and driving forces involved. We present a simulation framework to perform virtual tracer perfusion simulations in mouse brains in the subarachnoid space, perivascular spaces, and interstitial spaces under consideration of realistic microvascular networks [1]. The simulation considers molecular diffusion and dispersion driven by arterial pulsations. Advanced discretization techniques [2] and software [3] for flow and transport in porous media with embedded transport network systems allow for simulating domains with thousands of blood vessels. We show that due to the low volume fraction of the perivascular space, transport into the tissue only appears enhanced if there is a significant mixing effect due to arterial pulsations. Furthermore, we compare simulation results to published tracer perfusion data (e.g. [4]) from two-photon microscopy experiments in alive sleeping, and awake mice. We discuss three major difficulties arising when comparing simulation results to the image data and demonstrate how image data may be subject to misinterpretation in a lack of careful consideration of supporting information in the imaging process.