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

Abstract 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.