Grant: Project Grant

High-grade gliomas (HGGs) are aggressive brain tumours that remain incurable and very difficult to treat. One of the main reasons treatments fail is the blood-brain barrier (BBB), a natural protective layer that prevents most medications in the bloodstream from reaching the brain. MR-guided focused ultrasound, together with circulating microbubbles, can safely and temporarily open the BBB without surgery or cutting the skin. Early clinical trials have shown that this technology is safe and can help drugs work better for brain tumours. We measure the degree of BBB opening by gadolinium contrast leakage at the treated regions on standard MRIs. Some areas show strong contrast leakage, while others do not, even when the same ultrasound settings are used or microbubble activities are detected. We hypothesize this variability can be explained by regional heterogeneity in vasculature and microstructure, such as vessel density and the presence of edema. Currently, the prediction of how well the barrier will open in a patient or tumour region before the procedure is poor. This study will test whether higher field strength MRI at 7-Tesla (7T) can provide more detailed images of tissue structure and blood vessels to predict where FUS will work best and how to adjust treatment settings accordingly. 7T MRI offers considerable advantages over 3T imaging, including higher spatial resolution and tissue contrast. We will also determine optimal outcome measures to harmonize the reporting of how much BBB is opened, and link this to how much drug reaches the brain or cerebrospinal fluid. The analysis will leverage existing data from completed FUS clinical trials, as well as prospectively acquired data as a sub study in an ongoing trial investigating a novel FUS device during maintenance temozolomide therapy in patients with HGGs. This will be the first project to address these questions using 7T MRI with imaging predictors that will directly impact treatment delivery and outcomes.