Motivation: Long-term delivery of therapeutic agents via repeated MRgFUS is an innovative approach for enhancing glioblastoma treatment but underlying mechanisms are not well documented. Goal(s): Find the best strategy for long-term drug delivery after multiple MRgFUS mediated BBB opening. Approach: Repeated MRgFUS treatments were delivered up to 8 sessions over one month along with a multi-parametric MRI protocol follow-up to measure physiological, hemodynamic and oxygenation parameters in order to assess the safety and e ectiveness of the procedure. Results: Intensive, repeated treatments, may lead to tissue modi cations that require attention and limit the frequency of ultrasound mediated drug delivery to once a week. Impact: Long-term delivery of therapeutics through a FUS-induced permeabilized BBB rede nes therapeutic strategies as it improves patient outcomes. To ensure the best translation towards clinical treatment, evaluation of hemodynamics and oxygenation modi cations in the CNS is necessary to re ne treatment parameters.