Brain tumours are life‑threatening. The core surgical goal is maximal safe resection while preserving neurological function. Intraoperative ultrasound (IOUS) assists in complete lesion removal. Contrast‑enhanced ultrasound (CEUS) enables more precise localisation via harmonic imaging. This review focuses on the synergistic value of IOUS and CEUS in brain tumour surgery. It traces technological evolution from 2D ultrasound to elastography, colour Doppler, microvascular imaging, and AI, emphasising CEUS for cranial tumours. It also examines clinical applications in precise resection, residual tumour identification, vascular protection, boundary differentiation from oedema, and prognostic assessment, concluding with diagnostic performance, limitations, and future directions.
Introduction
Brain tumours had ~308,000 new cases and 251,000 deaths globally in 2020. Their infiltrative growth poses surgical challenges. IOUS has been pivotal since the 1980s for real‑time localisation. Recent advances—CEUS, elastography, and Doppler—have expanded IOUS beyond anatomy to perfusion and stiffness assessment. Conventional IOUS has limitations in residual tumour detection, vascular discrimination, and boundary demarcation from oedema. CEUS enhances sensitivity for low‑velocity blood flow, providing comprehensive vascular and perfusion information. This review synthesises multimodal synergies of IOUS and CEUS.
Evolving Ultrasound Technology
IOUS: High‑frequency linear probes (7–15 MHz) enable detailed observation of tumour boundaries. Elastography (strain and shear wave) provides tissue stiffness; studies show significant stiffness differences between low‑ and high‑grade gliomas. Colour Doppler visualises blood flow direction; power Doppler offers greater sensitivity for small vessels. Microvascular flow imaging (SMI/MFI) suppresses motion artefacts and outperforms conventional Doppler in microvascular visualisation. Navigated IOUS integrates ultrasound with neuronavigation, addressing brain shift. AI‑assisted systems (YOLO11, U‑ConvNext, NeuroIGN) enable real‑time tumour segmentation and uncertainty quantification.
CEUS: CEUS uses intravenous microbubble contrast agents that remain intravascular and are eliminated via the pulmonary route. Microbubbles generate harmonic signals under low mechanical index, providing high‑contrast perfusion imaging. Imaging is performed at three surgical stages: after dural opening (baseline), during resection, and after resection (final check). CEUS enhancement patterns correlate with pathology: high‑grade gliomas show rapid, heterogeneous "ring‑like" enhancement; low‑grade gliomas show slow, homogeneous enhancement; meningiomas show marked homogeneous enhancement.
Clinical Synergy of IOUS and CEUS
Applications in tumour subgroups:
Paediatric low‑grade gliomas: IOUS and CEUS facilitate boundary delineation; navigated IOUS achieves 100% sensitivity and 84.6% specificity for residual detection.
Brain metastases: CEUS shows rapid, heterogeneous enhancement; IOUS‑guided cases achieve GTR rates >96% vs. 42.86% (OR = 5.33).
Skull base tumours: Navigated CEUS delineates tumour‑neurovascular relationships, reducing vascular injury risk.
Precise resection: IOUS provides anatomical localisation; CEUS provides perfusion and infiltrative margins. CEUS‑guided GTR rates reach 82% vs. 48% with conventional IOUS.
Residual tumour detection: CEUS shows the highest diagnostic concordance with MRI (Kappa = 0.892), outperforming B‑mode, MFI, and SWE.
Vascular protection: CDFI visualises larger vessels; SMI visualises microvessels (0.1–0.2 mm); CEUS dynamically displays feeding arteries, draining veins, and perforating vessels.
Boundary vs. oedema differentiation: Tumour shows early rapid enhancement and rapid washout; oedema shows no/delayed low enhancement due to intact BBB.
Long‑term outcomes: CEUS‑guided surgery significantly improves OS and PFS in malignant gliomas (multivariate analysis: independent prognostic factor, P<0.05). Meta‑analysis confirms higher GTR rates under CEUS (OR = 5.37).
Future Perspectives
Miniaturised probes for deep‑seated lesions.
Multimodal fusion of CEUS perfusion and SWE stiffness parameters.
Multicentre registries with standardised protocols and long‑term outcomes.
AI integration for real‑time tumour boundary delineation, residual detection, and perfusion quantification.
Limitations
Narrative review, not systematic; potential selection bias. Most evidence from single‑centre, small‑sample studies. Heterogeneity in devices, contrast protocols, and outcome measures. Rapid AI advances not fully covered. Evidence for IOUS‑CEUS synergy remains preliminary; large‑scale prospective RCTs are lacking.
Conclusions
Conventional IOUS provides real‑time, low‑cost imaging but has limitations in boundary delineation, perfusion assessment, and residual tumour detection. CEUS addresses these gaps by visualising tumour vascularisation and infiltrative margins. The synergistic use of IOUS and CEUS offers precise, real‑time decision support for tumour resection, residual identification, vascular preservation, and boundary differentiation from peritumoral oedema.
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The study was recently published in the Neurosurgical Subspecialties .
Neurosurgical Subspecialties (NSSS) is the official scientific journal of the Department of Neurosurgery at Union Hospital of Tongji Medical College, Huazhong University of Science and Technology. NSSS aims to provide a forum for clinicians and scientists in the field, dedicated to publishing high-quality and peer-reviewed original research, reviews, opinions, commentaries, case reports, and letters across all neurosurgical subspecialties. These include but are not limited to traumatic brain injury, spinal and spinal cord neurosurgery, cerebrovascular disease, stereotactic radiosurgery, neuro-oncology, neurocritical care, neurosurgical nursing, neuroendoscopy, pediatric neurosurgery, peripheral neuropathy, and functional neurosurgery.
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Neurosurgical Subspecialties
Synergistic Use of Intraoperative Ultrasound and Contrast-enhanced Ultrasound for Image-guided Brain Tumor Surgery: A Narrative Review
29-Jun-2026