Safety and Tolerability of SonoVue R  in Patients with Large Artery Anterior Circulation Acute Stroke Claudio Baracchini, Federica Viaro, Silvia Favaretto, Anna Palmieri, Caterina Kulyk, Francesco Causin, Filippo Farina ∗ , Enzo Ballotta ∗ From the Department of Neuroscience (CB, FV, SF, AP, CK, FF); Institute of Neuroradiology (FC); and the Vascular Study Group of the Department of Surgical, Oncological and Gastroenterological Sciences (EB), University of Padua School of Medicine, Padua-Italy. ABSTRACT BACKGROUND AND PURPOSE: Ultrasound contrast agents (UCAs) are routinely used to improve the visualization of intracra- nial arteries. Since a higher rate of intracranial hemorrhage (ICH) has been observed in patients undergoing sonothrombolysis in combination with UCAs, we conducted this study with the aim of assessing safety and tolerability of SonoVue R  in patients with acute ischemic stroke due to anterior circulation large artery occlusion (LAO) and eligible to intravenous thrombolysis and/or mechanical thrombectomy. METHODS: Among 474 patients consecutively admitted to our Stroke Unit with anterior circulation ischemic stroke, SonoVue R  was administered during transcranial ultrasound evaluation to 48 patients with suspected LAO for diagnostic confirmation (group I) and to 44 patients with inadequate temporal bone window. Forty-eight stroke patients with LAO diagnosed only by computed tomography (CT) angiography /magnetic resonance (MR) angiography and matched for age, gender, and National Institutes of Health Stroke Scale score with group I represented the control group (group II). Thrombolysis, thrombectomy, or combined treatment were offered to all eligible patients. Brain MR imaging/CT was performed in both groups in case of neurological deterioration or after 1 week to check for ICH. RESULTS: SonoVue R  did not cause any serious adverse event; only mild and transient side effects were reported in six cases (6.5%). Among patients in groups I and II, there were 31 (32.3%) secondary cerebral bleedings with no statistically significant difference between the groups, but only 2 (2.1%) were symptomatic. CONCLUSIONS: According to our study, SonoVue R  can be safely administered to acute ischemic stroke patients with suspected anterior circulation LAO and/or inadequate temporal bone window. Keywords: Ultrasound contrast agents, acute ischemic stroke, large artery occlusion, thrombolysis, thrombectomy. Acceptance: Received October 9, 2016. Accepted for publication November 10, 2016. Correspondence: Address correspondence to Claudio Baracchini, Stroke Unit and Laboratory of Neurosonology, Department of Neuroscience, Uni- versity of Padua School of Medicine, Via Giustiniani 2, 32128 Padua, Italy. E-mail: claudiobaracchini@gmail.com. ∗ These authors contributed equally to this work. Acknowledgments and Disclosure: This study did not receive any academic and/or external funding. The authors have no conflicts of interest to report for this study. J Neuroimaging 2017;27:409-413. DOI: 10.1111/jon.12416 Introduction Five recently published randomized controlled trials (RCTs) demonstrated an amazing superior benefit of combining en- dovascular mechanical thrombectomy with intravenous throm- bolysis over intravenous thrombolysis alone in acute ischemic stroke patients with large artery occlusion (LAO) in the anterior circulation. 1 All these RCTs used noninvasive arterial imaging to select patients with an occlusion of the terminal internal carotid artery (ICA), M1 or M2 segment of the middle cerebral artery (MCA). This might be a reason why such RCTs were positive, in contrast to the previous thrombectomy trials (IMS III, MR RESCUE, SYNTHESIS). 2–4 Accordingly, intracranial vessel occlusion should be diagnosed with noninvasive imaging whenever possible before considering treatment with mechan- ical thrombectomy. 5 Transcranial ultrasound is the prototype of noninvasive neu- rovascular imaging and in acute stroke patients, it can evaluate up to 16 proximal intracranial arterial segments with the goal of detecting normal, stenosed, or occluded intracranial vessels. 6 Additionally, it is the most convenient method to detect col- lateral flow and the hemodynamic significance of extracra- nial or intracranial steno-occlusive lesions, monitor recanaliza- tion during thrombolytic therapy in real-time, determine stroke pathogenic mechanism, and select the next and most appropri- ate step in patient management. 7 A fast-track insonation proto- col has also been developed for rapid transcranial ultrasound performance and interpretation, in the emergency setting of acute ischemic stroke. The sequence of fast-track insonation steps is chosen according to the clinical localization of the is- chemic arterial territory. 8 Recent findings from a multicenter study support the systematic use of transcranial ultrasound also for the identification of symptomatic intracranial atherosclero- sis in patients presenting with acute ischemic stroke. 9 However, transcranial ultrasound may be hampered by in- sufficient acoustic bone windows, by unfavorable insonation angles, by low flow volumes or low flow velocities in single arte- rial segments, or by a combination of these conditions. In acute stroke patients, the basal cerebral arteries can only be detected Copyright ◦ C 2016 by the American Society of Neuroimaging 409