Acoustic emissions-guided focused ultrasound for liquid biopsy in infiltrative gliomas: A multicentre, open-label, phase 1/2 trial

Résumé fourni par la source

To characterize acoustic emissions (AE)-based closed-loop control and dosing for transcranial microbubble-enhanced focused ultrasound (MB-FUS) blood-brain barrier opening (BBBO) performed in the infiltrative margins of high-grade gliomas. We analyzed MB-FUS BBBO treatments performed using a 1024-element hemispheric phased-array system (Exablate Neuro Model 4000 Type II). AE signals were captured via integrated passive cavitation detectors. Sonications used a 1%–10% duty cycle, 5 ms pulse length, and 1 Hz pulse repetition frequency per subsonication. BBBO was quantified as a percentage of new T1-weighted contrast enhancement (new T1c) within each target on post-treatment MRIs. Sono-liquid biopsy profiling was performed with paired blood draws obtained immediately before and within 1 h after MB-FUS, enabling analysis of post-to-pre changes in total plasma cfDNA and fragmentomic features. cfDNA levels were analyzed in 23 participants, and cfDNA fragmentomics in 19 patients. Post-to-pre ratios of cfDNA and fragment length ratio (FLR) were significantly associated with both progression-free and overall survival (cfDNA: HR 0.45 and 0.71; FLR: HR 1.62 and 3.40; all p < 0.01). Longitudinally, increasing post-to-pre biomarker trajectories were associated with early progression, whereas decreasing trajectories were associated with long-term survival; trajectory concordance was 76% for cfDNA (PFS/OS) and 90% for FLR with PFS.

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