Contrast-enhanced ultrasound (CEUS) has been increasingly used as an intraoperative adjunct in neuro-oncology. Although multiple studies have reported favorable imaging performance across different brain tumor types and surgical applications, the breadth of its clinical utility, imaging patterns, and safety profile remains incompletely characterized due to fragmented and heterogeneous evidence. This systematic review aimed to comprehensively evaluate the clinical applications, imaging findings, and safety of CEUS in patients with intracranial tumors.

A PRISMA-compliant systematic review was conducted using PubMed, Embase, and Web of Science. Clinical studies evaluating CEUS in patients with intra- or extra-axial brain tumors and reporting imaging-related outcomes were included. Data on study design, ultrasound protocols, CEUS applications, imaging characteristics, and adverse events were qualitatively synthesized.

Thirty-three studies involving 1,083 patients were included. CEUS was applied intraoperatively in all studies, most commonly for differentiation between tumoral and normal brain tissue, between tumor types, and between tumor recurrence and radionecrosis, resection control, intratumoral vasculature assessment, biopsy guidance, and follow-up modality. CEUS consistently improved visualization of lesion boundaries and residual tumor, with characteristic perfusion patterns correlating with histopathology and microvascular density. Reported contrast-related adverse events were rare and non-serious.

Findings indicate CEUS to be a safe and valuable intraoperative imaging adjunct in neuro-oncology, providing real-time functional and vascular information that may improve tumor characterization and surgical guidance. This systematic review offers the first comprehensive synthesis of the clinical evidence on CEUS in neuro-oncologic surgery, outlining its current applications, strengths, and limitations within an otherwise heterogeneous literature.