Focused Ultrasound (FUS) and Pediatric Brain Tumors: Current Status and Future Directions

Diffuse intrinsic pontine glioma (DIPG), or as it is newly redefined, diffuse midline glioma (DMG), remains one of the most horrific diagnoses in pediatric oncology. Aggressive and inaccessible to standard treatments, it is generally considered incurable. Focused ultrasound technology has developed over the last several decades as a noninvasive means to target various types of tumors in both adults and children. Recent advances, particularly in low-intensity focused ultrasound (LIFU), have opened new avenues for enhancing drug delivery and modulating the tumor microenvironment in these challenging tumors. This review provides a comprehensive overview of preclinical and clinical research developments in the use of LIFU for pediatric DMGs. We highlight key findings from animal models demonstrating improved blood–brain barrier (BBB) permeability, increased chemotherapeutic and nanoparticle delivery, and potential immunomodulatory effects of LIFU. Emerging clinical studies, including early-phase safety and feasibility trials, are also discussed, with attention to technical parameters, imaging guidance strategies, and biomarkers of response. The review concludes by addressing the challenges of translating LIFU into routine clinical practice, including device optimization for pediatric anatomy, regulatory hurdles, and the need for standardized treatment protocols. Collectively, these recent advances underscore the promise of LIFU as a minimally invasive, image-guided adjunct to current and future therapies for pediatric DMGs, warranting continued research and collaborative clinical efforts.