Pecco, N. | bioRxiv Science

bioRxiv2025

In vivo MRI measurement of microstructural constraints for direct delivery of therapeutics within the brain

Brain tissue microstructure influences the efficient delivery of therapeutics within the brain. Diffusion Tensor Imaging (DTI) enables the depiction of tissue properties in vivo, and thus is potentially relevant for planning convection-enhanced delivery (CED) within the brain. We report on the quantitative assessment of the distribution of a Gadolinium solution infused by CED within the brain of a live ovine model. Infusate distributions were measured at multiple timepoints and compared to microstructural properties as depicted by DTI, thus demonstrating the impact of tissue features and catheter positioning on drug distribution in vivo. This study contributed to the clinical translation of the CED for flow-based therapy to ultimately provide new therapeutic approaches for several brain diseases, by providing essential tools and results used to develop a better prediction model and a delivery platform to reach the therapeutic target more precisely and non-invasively.

neuroscience↗

bioRxiv2025

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 brains 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.

biophysics↗