在高级别胶质瘤患者中使用神经导航引导聚焦超声进行超声活检的首次人体前瞻性试验。

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

作者信息

Yuan Jinyun, Xu Lu, Chien Chih-Yen, Yang Yaoheng, Yue Yimei, Fadera Siaka, Stark Andrew H, Schwetye Katherine E, Nazeri Arash, Desai Rupen, Athiraman Umeshkumar, Chaudhuri Aadel A, Chen Hong, Leuthardt Eric C

机构信息

Department of Biomedical Engineering, Washington University in St. Louis, Saint Louis, MO, 63130, USA.

Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, 63110, USA.

出版信息

NPJ Precis Oncol. 2023 Sep 16;7(1):92. doi: 10.1038/s41698-023-00448-y.

DOI:10.1038/s41698-023-00448-y

PMID:37717084

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10505140/

Abstract

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.

摘要

超声活检是一种新兴技术，它将聚焦超声（FUS）与微泡相结合，以富集循环中的脑疾病特异性生物标志物，用于脑部疾病的非侵入性分子诊断。在此，我们报告了首例针对高级别胶质瘤患者的超声活检人体前瞻性试验，以评估其在富集血浆循环肿瘤生物标志物方面的可行性和安全性。使用与临床神经导航系统集成的灵活FUS设备，按照既定的神经导航临床工作流程进行超声活检。对FUS超声处理前后采集的血样分析表明，超声活检可富集血浆循环肿瘤DNA（ctDNA），其中单核小体细胞游离DNA（cfDNA）片段（120 - 280 bp）最多增加1.6倍，患者特异性肿瘤变异ctDNA水平增加1.9倍，TERT突变ctDNA水平增加5.6倍。对手术切除肿瘤的组织学分析证实了该操作的安全性。对超声处理和未超声处理的肿瘤组织进行转录组分析发现，FUS超声处理可调节与细胞物理结构相关的基因。在总共检测到的17982个与免疫途径相关的基因中，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超声活检用于脑部疾病的非侵入性分子诊断。