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Background and Purpose: Sonothrombolysis is a potential adjunctive therapy for large vessel occlusion (LVO) stroke. Bedside ultrasound image‐guided high‐intensity focused ultrasound (HIFU) therapy could deliver higher energy therapeutic ultrasound to the thrombus with higher precision than what was previously accomplished in human trials. The aim is to test the feasibility of diagnostic transcranial contrast‐enhanced ultrasound (CEUS) to image the occlusion site and continuously maintain the guidance image on‐target for a sufficient exposure time for HIFU to be effective during LVO stroke evaluation and treatment. Methods: This prospective, single center, observational cohort study included adult patients, presenting within 6 hours of stroke symptom onset, with LVO identified on computed tomography angiography (CTA). A hand‐held CEUS imaging study was initiated following CTA and lasted up to 30 minutes. The primary outcome is the proportion of patients where a guidance CEUS image of the occlusion was achieved. Results: A CEUS image of the occluded artery was obtained in 32/35 of the included patients. The median total imaging time was 23 minutes (interquartile range 15‐30). Patients undergoing thrombectomy had a lower total imaging time (17 vs. 29.5 minutes, p =.002). When imaging was successful, on‐target image was maintained for only 58% (standard deviation 23.8%) of total imaging time. No complications related to CEUS were observed. Conclusions: This feasibility study explored the use of diagnostic transcranial CEUS for continuous imaging of occlusion sites in LVO strokes. Challenges in maintaining target image during HIFU were identified, highlighting the need for technical advances for clinical application. [ABSTRACT FROM AUTHOR]