Focused Ultrasound in Brain Tumors: Mechanisms, Imaging Guidance, and Emerging Clinical Applications

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ABSTRACT Focused ultrasound (FUS) is an emerging therapeutic and diagnostic technology in neuro-oncology, offering new strategies for molecular diagnosis, drug delivery, and tumor ablation across a range of brain tumors, including glioblastoma (GBM), brain metastases, and diffuse intrinsic pontine glioma (DIPG). The prognosis for aggressive brain tumors remains poor, despite advances in surgery, radiation, and chemotherapy. A considerable challenge is the limited ability to deliver therapeutics across the blood-brain barrier (BBB), particularly to infiltrative or non-enhancing tumor regions. FUS introduces an incisionless approach to the molecular subtyping of brain tumors, enhancing therapeutic delivery, and offers novel therapeutic approaches such as sonodynamic therapy (SDT). This review summarizes the FUS mechanisms and highlights the critical role of imaging modalities confirming target engagement, assessing bioeffects and outcomes, and ensuring safety. We also explore future directions, including the integration of liquid biopsy, artificial intelligence, and outpatient-ready FUS platforms, which will position FUS as a promising adjunct to standard neuro-oncologic care. ABBREVIATIONS: GBM = glioblastoma; FUS = focused ultrasound; HIFU = high-intensity focused ultrasound; LIFU = low-intensity focused ultrasound; MRgFUS = magnetic resonance guided focused ultrasound; BBBO = blood brain barrier opening; SDT = sonodynamic therapy; 5-ALA = 5-aminolevulinic acid

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