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First-in-human prospective trial of sonobiopsy in glioblastoma patients using neuronavigation-guided focused ultrasound.

Authors: Yuan J, Xu L, Chien CY, Yang Y, Yue Y, Fadera S, Stark AH, Schwetye KE, Nazeri A, Desai R, Athiraman U, Chaudhuri AA, Chen H, Leuthardt EC

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 glioblastoma patients to evaluate its feasibility and safety in enriching 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 enhanced plasma circulating tumor biomarker levels. Histological analysis of surgically resected tumors confirmed the safety of the procedure. Transcriptome analysis of sonicated and unsonicated tumor tissues found that FUS sonication modulated cell physical structure-related genes but evoked minimal inflammatory response. These feasibility and safety data support the continued investigation of sonobiopsy for noninvasive molecular diagnosis of brain diseases.

Introduction

Purpose Sonobiopsy
Study Objective To evaluate the feasibility and safety of sonobiopsy using focused ultrasound and microbubbles to enrich circulating tumor biomarkers in glioblastoma patients.
Disease model glioblastoma
MRI or image guidance method Integrated with a clinical neuronavigation system using an established clinical neuronavigation workflow
Targeted brain region(s) Glioblastoma Tumor
Target coordinates Not provided

Outcomes and Safety

Summary of Outcomes 0.65 MHz FUS sonobiopsy safely increased plasma tumor biomarker levels in glioblastoma patients.
Duration of biological effect not reported
Safety-related matter Safe with minimal inflammatory response confirmed by histology.

Brain Region

Ultrasound Parameters

Ultrasound instrument Nimble FUS system
FUS Frequency 0.65 MHz
FUS Intensity not reported
FUS Pressure 0.9 MPa
FUS Mode pulsed
Pulse duration 10 ms
Duration of a single FUS session 3 min
Focal Characteristics none.
Treatment frequency single session
Mechanical index 1.116312611302876

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