Ultrasound Enhanced Drug Delivery in Pediatric Neurosurgery: A New Therapeutic Strategy

Pediatric brain tumours are highly prevalent and remain one of the leading causes of cancer-related deaths in children. There are numerous different brain tumour types that are now well characterized by magnetic resonance imaging (MRI), patient clinical course, neuropathological and molecular genetic alterations. One of the challenges with treating pediatric brain tumours with systemic chemotherapy is the inability of several chemotherapeutic agents to cross the blood brain barrier (BBB) which serves as a protective mechanism for neuronal homeostasis. The BBB is primarily comprised of microvascular endothelial tight junctions. Controlling BBB permeability to allow for therapeutics to cross and combat brain tumors is now possible using MR-guided Focused Ultrasound (MRgFUS). In this approach, microbubbles are administered intra-venously prior to MRgFUS BBB disruption at the targeted tumour site in the brain. In the presence of MRgFUS, the microbubbles in the brain capillaries oscillate, and temporarily disrupt the BBB enabling systemically administered chemotherapy drugs to cross at the targeted site. In this review, we provide evidence supporting the use of MRgFUS BBB disruption to treat brain tumours in animal models, and in on-going human clinical drug trials. We conclude with efforts to harness the potency of the immune system using MRgFUS against pediatric brain tumours.