Ultrasound-induced blood-brain barrier disruption for the treatment of gliomas and other primary CNS tumors

The treatment of primary brain tumors, especially malignant gliomas, remains challenging. The failure of most treatments for this disease is partially explained by the blood-brain barrier (BBB), which prevents circulating molecules from entering the brain parenchyma. Ultrasound-induced BBB disruption (US-BBBD) has recently emerged as a promising strategy to improve the delivery of therapeutic agents to brain tumors. A large body of preclinical studies has demonstrated that the association of low-intensity pulsed ultrasound with intravenous microbubbles can transiently open the BBB in a localized manner. The safety of this technique has been assessed in numerous preclinical studies in both small and large animal models. A large panel of therapeutic agents have been delivered to the brain in preclinical models, demonstrating both tumor control and increased survival. This technique has recently entered clinical trials with encouraging preliminary data. In this review, we describe the mechanisms and histological effects of US-BBBD and summarize the preclinical studies published to date. We furthermore provide an overview of the current clinical development and future potential of this promising technology. •The blood-brain barrier prevents most drug therapies from reaching brain tumors.•Low-intensity pulsed ultrasound with systemic microbubbles can open the blood-brain barrier.•Opening of the blood-brain barrier with ultrasound is safe, localized and reversible.•A large panel of therapeutic agents can be delivered to the brain with ultrasound.•Extracranial and implantable ultrasound devices are currently in clinical trials.