研究动态
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首个应用神经导航引导的聚焦超声波技术进行高级别脑胶质瘤患者声音活检的前瞻性人体试验。

First-in-human prospective trial of sonobiopsy in high-grade glioma patients using neuronavigation-guided focused ultrasound.

发表日期:2023 Sep 16
作者: Jinyun Yuan, Lu Xu, Chih-Yen Chien, Yaoheng Yang, Yimei Yue, Siaka Fadera, Andrew H Stark, Katherine E Schwetye, Arash Nazeri, Rupen Desai, Umeshkumar Athiraman, Aadel A Chaudhuri, Hong Chen, Eric C Leuthardt
来源: Brain Structure & Function

摘要:

声学活检是一种新兴技术,它将聚焦超声(FUS)与微泡结合起来,富集循环脑疾病特异性生物标志物,实现对脑疾病的非侵入性分子诊断。在这里,我们报告了第一项面向高级别胶质瘤患者的声学活检前瞻性试验,以评估其富集血浆循环肿瘤标志物的可行性和安全性。使用与临床神经导航系统集成的灵活FUS设备进行声学活检,按照既定的神经导航临床工作流程进行操作。对FUS聚焦超声前后收集的血液样本进行分析显示,声学活检富集了血浆循环肿瘤DNA(ctDNA),包括单核体无细胞DNA(cfDNA)片段(120-280 bp)的最大增加1.6倍、患者特异性肿瘤变异ctDNA水平1.9倍和TERT突变ctDNA水平5.6倍。通过手术切除瘤组织进行的组织学分析证实了该程序的安全性。声波活化和非声波活化肿瘤组织的转录组分析发现,FUS聚焦超声激活调控了与细胞物理结构相关的基因。与免疫途径相关的17982个检测到的基因中,只有2个基因上调。这些可行性和安全性数据支持继续研究声学活检在脑疾病非侵入性分子诊断中的应用。© 2023 Nature Publishing Group UK.
Sonobiopsy is an emerging technology that combines focused ultrasound (FUS) with microbubbles to enrich circulating brain disease-specific biomarkers for noninvasive molecular diagnosis of brain diseases. Here, we report the first-in-human prospective trial of sonobiopsy in high-grade glioma patients to evaluate its feasibility and safety in enriching plasma circulating tumor biomarkers. A nimble FUS device integrated with a clinical neuronavigation system was used to perform sonobiopsy following an established clinical workflow for neuronavigation. Analysis of blood samples collected before and after FUS sonication showed that sonobiopsy enriched plasma circulating tumor DNA (ctDNA), including a maximum increase of 1.6-fold for the mononucleosome cell-free DNA (cfDNA) fragments (120-280 bp), 1.9-fold for the patient-specific tumor variant ctDNA level, and 5.6-fold for the TERT mutation ctDNA level. Histological analysis of surgically resected tumors confirmed the safety of the procedure. Transcriptome analysis of sonicated and nonsonicated tumor tissues found that FUS sonication modulated cell physical structure-related genes. Only 2 out of 17,982 total detected genes related to the immune pathways were upregulated. These feasibility and safety data support the continued investigation of sonobiopsy for noninvasive molecular diagnosis of brain diseases.© 2023. Nature Publishing Group UK.