The treatment of primary brain tumors, especially malignant gliomas, remains challenging. The failure of most treatments for this disease is partially explained by the blood-brain barrier (BBB), which prevents circulating molecules from entering the brain parenchyma. Ultrasound-induced BBB disruption (US-BBBD) has recently emerged as a promising strategy to improve the delivery of therapeutic agents to brain tumors. A large body of preclinical studies has demonstrated that the association of low-intensity pulsed ultrasound with intravenous microbubbles can transiently open the BBB in a localized manner. The safety of this technique has been assessed in numerous preclinical studies in both small and large animal models. A large panel of therapeutic agents have been delivered to the brain in preclinical models, demonstrating both tumor control and increased survival. This technique has recently entered clinical trials with encouraging preliminary data. In this review, we describe the mechanisms and histological effects of US-BBBD and summarize the preclinical studies published to date. We furthermore provide an overview of the current clinical development and future potential of this promising technology.

中文翻译：

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超声诱导的血脑屏障破坏，用于治疗神经胶质瘤和其他原发性中枢神经系统肿瘤。

原发性脑肿瘤，特别是恶性神经胶质瘤的治疗仍然具有挑战性。大多数治疗该疾病的方法的失败部分是由血脑屏障（BBB）引起的，该血脑屏障可防止循环分子进入脑实质。超声诱导的BBB破坏（US-BBBD）最近作为改善治疗剂向脑肿瘤的递送的一种有前途的策略而出现。大量的临床前研究表明，低强度脉冲超声与静脉内微泡的结合可以以局部方式暂时打开血脑屏障。在许多大型和小型动物模型的临床前研究中均已评估了该技术的安全性。在临床前模型中，一大批治疗剂已被递送到大脑，证明了肿瘤的控制和生存的增加。这项技术最近以令人鼓舞的初步数据进入临床试验。在这篇综述中，我们描述了US-BBBD的机制和组织学作用，并总结了迄今为止发表的临床前研究。此外，我们还概述了该有前途技术的当前临床发展和未来潜力。