CNSC-39. Use of Magnetic Resonance-Guided Focused Ultrasound in the Treatment of Diffuse Intrinsic Pontine Glioma

Diffuse intrinsic pontine glioma (DIPG) is the leading cause of brain tumour-related deaths in childhood. Current treatment is radiation with or without chemotherapy, as surgical resection is impossible due to its location within the brainstem. A major obstacle to treatment is impaired drug delivery across an intact blood-brain barrier (BBB). However, magnetic resonance-guided focused ultrasound (MRgFUS) can transiently open the BBB and enhance the delivery of BBB-impermeable drugs. Interestingly, MRgFUS has also been shown to modulate the immune response in treated regions, although this has not been characterized in DIPG models. We hypothesize that MRgFUS can be utilized to improve treatment effects of targeted drugs and immune-based therapies for patients with DIPG, specifically through enhanced delivery of therapeutics to increase drug efficacy and immunomodulation to boost anti-tumour immune responses. We used an MRgFUS system in a controller mode where acoustic pressure is adjusted based on the acoustic feedback received, and a fixed mode where pressure remains constant. Initial experiments focused on optimization using non-tumour bearing mice. Brain tissue was collected at 24-hours (n=8), 72-hours (n=10), and 1-week (n=10) post-MRgFUS. Immunohistochemistry was conducted for immune characterization of sonicated and non-sonicated regions in MRgFUS-treated and non-treated animals. Optimization results indicate that safe and effective opening is feasible when sonicating at an acoustic pressure of 300 kPa using the fixed pressure mode, and for a sonication period of 90 seconds using the controller mode. Preliminary immunohistochemistry results show increased macrophage infiltration in sonicated regions. Altogether, our results demonstrate that BBB opening can be replicated using different MRgFUS systems and parameters. Future studies include modulating these parameters to optimize immune cell infiltration within the brainstem, which may help extend treatment efficacies when combined with radiotherapy and chemotherapy. The use of MRgFUS is an exciting new tool for broadening therapeutic options for patients with DIPG.