Seunghwan Choi Kum, Jeung eun Seon Young Hyun Park, Tae Young Kim, Hyungmin Sun Kwang Kim Jaeho Kim 2024-09-19T00:00:14Z 2024-09-19T00:00:14Z 2024-09-14 2024-09 1935-861X https://pubs.kist.re.kr/handle/201004/150603 Background Cerebrospinal fluid (CSF) flow is crucial for brain homeostasis and its dysfunction is highly associated with neurodegenerative diseases. Restoring CSF circulation is proposed as a key strategy for the treatment of the diseases. Among the methods to improve CSF circulation, focused ultrasound (FUS) stimulation has emerged as a promising non-invasive brain stimulation technique, with effectiveness evidenced by ex vivo studies. However, due to technical disturbances in in vivo imaging combined with FUS, direct evidence of real-time in vivo CSF flow enhancement by FUS remains elusive. Objective To investigate whether FUS administered through the skull base can enhance CSF influx in living animals with various real-time imaging techniques. Methods We demonstrate a novel method of applying FUS through the skull base, facilitating cortical CSF influx, evidenced by diverse in vivo imaging techniques. Acoustic simulation confirmed effective sonication of our approach through the skull base. After injecting fluorescent CSF tracers into cisterna magna, FUS was administered at the midline of the jaw through the skull base for 30 min, during which imaging was performed concurrently. Results Enhanced CSF influx was observed in macroscopic imaging, demonstrated by the influx area and intensity of the fluorescent dyes after FUS. In two-photon imaging, increased fluorescence was observed in the perivascular space (PVS) after stimulation. Moreover, particle tracking of microspheres showed more microspheres entering the imaging field, with increased mean speed after FUS. Conclusion Our findings provide direct real-time in vivo imaging evidence that FUS promotes CSF influx and flow in the PVS. English Elsevier BV Transcranial Focused Ultrasound Stimulation Enhances Cerebrospinal Fluid Movement: Real-Time In Vivo Two-Photon and Widefield Imaging Evidence Article 10.1016/j.brs.2024.09.006 1 Brain Stimulation, v.17, no.5, pp.1119 - 1130 Brain Stimulation 17 5 1119 1130 N scie scopus 001318202300001 Clinical Neurology Neurosciences Neurosciences & Neurology Article BASAL FOREBRAIN ATROPHY ALZHEIMERS-DISEASE AMYLOID-BETA IMPAIRMENT BLOOD-BRAIN-BARRIER PLATFORM Cerebrospinal fluid In vivo Two-photon imaging Real-time imaging Transcranial focused ultrasound stimulation