The performance of minimally invasive molecular diagnostic tools in brain tumors, such as liquid biopsy, has so far been limited by the blood–brain barrier (BBB). The BBB hinders the release of brain tumor biomarkers into the bloodstream. The use of focused ultrasound in conjunction with microbubbles has been shown to temporarily open the BBB (FUS-BBBO). This may enhance blood-based tumor biomarker levels. This systematic review provides an overview of the data regarding FUS-BBBO-enhanced liquid biopsy for primary brain tumors. A systematic search was conducted in PubMed and Embase databases with key terms “brain tumors”, “liquid biopsy”, “FUS” and their synonyms, in accordance with PRISMA statement guidelines. Five preclinical and two clinical studies were included. Preclinical studies utilized mouse, rat and porcine glioma models. Biomarker levels were found to be higher in sonicated groups compared to control groups. Both stable and inertial microbubble cavitation increased biomarker levels, whereas only inertial cavitation induced microhemorrhages. In clinical studies involving 14 patients with high-grade brain tumors, biomarker levels were increased after FUS-BBBO with stable cavitation. In conclusion, FUS-BBBO-enhanced liquid biopsy using stable cavitation shows diagnostic potential for primary brain tumors. Further research is imperative before integrating FUS-BBBO for liquid biopsy enhancement into clinical practice.
微创分子诊断工具（如液体活检）在脑肿瘤中的应用效果，目前仍受血脑屏障（BBB）的限制。血脑屏障阻碍了脑肿瘤生物标志物向血液中的释放。研究表明，聚焦超声联合微泡技术可暂时性开放血脑屏障（FUS-BBBO），这可能提升血液中肿瘤生物标志物的水平。本系统性综述旨在总结关于FUS-BBBO增强液体活检在原发性脑肿瘤中应用的相关数据。依据PRISMA声明指南，我们在PubMed和Embase数据库中系统检索了关键词“脑肿瘤”、“液体活检”、“FUS”及其同义词。共纳入5项临床前研究和2项临床研究。临床前研究使用了小鼠、大鼠和猪的胶质瘤模型。结果显示，接受超声处理的实验组生物标志物水平高于对照组。稳定空化和惯性空化均能提高生物标志物水平，但仅惯性空化会诱发微出血。在涉及14例高级别脑肿瘤患者的临床研究中，采用稳定空化的FUS-BBBO后，患者生物标志物水平有所提升。综上所述，采用稳定空化的FUS-BBBO增强液体活检技术对原发性脑肿瘤具有诊断潜力。在将该技术整合入临床实践前，仍需开展进一步研究。
Focused Ultrasound-Enhanced Liquid Biopsy: A Promising Diagnostic Tool for Brain Tumor Patients
肿瘤(癌症)患者之家