Decoding Brain Interstitial Transport In Vivo: A Fully Validated Bottom-Up Mechanistic Prediction Framework

The transport of fluids and substances within the brain parenchyma ( i . e . interstitial transport) is fundamental to maintaining brain health and delivering treatments for neurological disorders. However, accurately predicting these transport processes has remained a formidable challenge due to the intricate and dynamic nature of the brain’s microenvironment. Here, we report a novel, fully validated bottom-up mechanistic framework that bridges advanced mathematical modelling, ultra-high-resolution imaging, and biomechanical testing to achieve precise, in vivo predictions of interstitial transport. Using this approach, we accurately modelled the transport of MRI tracers in living sheep brains, offering unprecedented insights into the interplay between fluid dynamics and tissue properties. This platform is a transformative step forward, with the potential to revolutionise drug delivery strategies not only in the brain but also in cancer therapy and other soft biological systems. By addressing limitations in modelling complex transport in soft tissue, our work establishes a significant tool with profound implications for biomedical engineering and translational medicine.