ABSTRACT NUMBER: ESOC2026A2176 BILATERAL TRANSCRANIAL HISTOTRIPSY ENABLES RAPID, NON-INVASIVE CLOT LYSIS THROUGH CRANIAL BONE UNDER CLINICALLY RELEVANT CONDITIONS

Abstract Background and aims Current reperfusion therapies for AIS rely on invasive catheter-based approaches and specialized infrastructure, limiting global access. Histotripsy is a non-thermal, cavitation-based focused ultrasound technology capable of mechanically fragmenting thrombus without intravascular instrumentation. We report key translational milestones demonstrating bilateral transcranial histotripsy through cranial bone, real-time cavitation confirmation within a human skull, and rapid clot lysis under relevant operating conditions. Methods Bilateral histotripsy system was evaluated using synthetic cranial bone plates representative of human skull thickness, human skull specimens, and vessel phantom models containing occlusive clot analogs. Acoustic cavitation was monitored in real time using ultrasound B-mode imaging. Clot lysis performed through bone using paired transducers with skull-compensation modeling and proprietary gel interface pads, eliminating need for degassed water environments. Treatment time, cavitation behavior, and system performance were assessed under simulated clinical conditions. Results Bilateral histotripsy achieved consistent acoustic cavitation through cranial bone plates and within a human skull, confirmed by real-time ultrasound B-mode imaging. Effective clot fragmentation and clearance were achieved through bone using gel interface pads, with complete clot lysis occurring in under two minutes. These results were reproducible outside controlled laboratory water tanks, demonstrating reliable system performance under clinically relevant conditions. No evidence of off-target tissue disruption was observed in treated models. Conclusions These findings demonstrate that bilateral transcranial histotripsy can reliably generate controlled cavitation through cranial bone and rapidly lyse clot under conditions compatible with clinical workflow. This catheter-free approach represents a potential paradigm shift in AIS treatment and may substantially expand access to reperfusion therapy beyond current endovascular capabilities. Conflict of interest Ameer E. Hassan - 1.Consultant/Speaker: Medtronic, Microvention, Stryker, Penumbra, Cerenovus, Genentech, GE Healthcare, Scientia, Balt, Viz.ai , Insera therapeutics, Proximie, NeuroVasc, NovaSignal, Vesalio, Rapid Medical, Imperative Care, Galaxy Therapeutics, Route 92, Perfuze, CorTech, Imago, Shockwave, Toro, NeuroVasX, Xcath, Kaneka, Plaga, Project Neu, Piraeus, BioPhiliQ, Medinol and Navigantis. 2.Principal Investigator: COMPLETE study – Penumbra, LVO SYNCHRONISE – Viz.ai, MARRS - Perfuze, RESCUE - ICAD - Medtronic. Neva VS Dilate - Vesalio. BASIC - ICAD. 3.Steering Committee/Publication committee member: SELECT, DAWN, SELECT 2, EXPEDITE II, EMBOLISE, CLEAR, ENVI, DELPHI, DISTALS, Rapid Pulse, SELECT LATE 4.DSMB - COMAND trial Figure 1 - belongs to Conclusions