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Background: Temporary disruption of the blood-brain barrier (BBB) using pulsed ultrasound leads to the clearance of both amyloid and tau from the brain, increased neurogenesis, and mitigation of cognitive decline in pre-clinical models of Alzheimer's disease (AD) while also increasing BBB penetration of therapeutic antibodies. The goal of this pilot clinical trial was to investigate the safety and efficacy of this approach in patients with mild AD using an implantable ultrasound device. Methods: An implantable, 1-MHz ultrasound device (SonoCloud-1) was implanted under local anesthesia in the skull (extradural) of 10 mild AD patients to target the left supra-marginal gyrus. Over 3.5 months, seven ultrasound sessions in combination with intravenous infusion of microbubbles were performed twice per month to temporarily disrupt the BBB. 18F-florbetapir and 18F-fluorodeoxyglucose positron emission tomography (PET) imaging were performed on a combined PET/MRI scanner at inclusion and at 4 and 8 months after the initiation of sonications to monitor the brain metabolism and amyloid levels along with cognitive evaluations. The evolution of cognitive and neuroimaging features was compared to that of a matched sample of control participants taken from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Results: A total of 63 BBB opening procedures were performed in nine subjects. The procedure was well-tolerated. A non-significant decrease in amyloid accumulation at 4 months of − 6.6% (SD = 7.2%) on 18F-florbetapir PET imaging in the sonicated gray matter targeted by the ultrasound transducer was observed compared to baseline in six subjects that completed treatments and who had evaluable imaging scans. No differences in the longitudinal change in the glucose metabolism were observed compared to the neighboring or contralateral regions or to the change observed in the same region in ADNI participants. No significant effect on cognition evolution was observed in comparison with the ADNI participants as expected due to the small sample size and duration of the trial. Conclusions: These results demonstrate the safety of ultrasound-based BBB disruption and the potential of this technology to be used as a therapy for AD patients. Research of this technique in a larger clinical trial with a device designed to sonicate larger volumes of tissue and in combination with disease-modifying drugs may further enhance the effects observed. Trial registration: ClinicalTrials.gov, NCT03119961 [ABSTRACT FROM AUTHOR]

Previous studies reported interest in intraoperative shear-wave elastography (SWE) guidance for brain-tumor and epilepsy surgeries. Focal cortical dysplasia (FCD) surgery is one of the most appropriate indications for using SWE guidance. The aim of this study was to evaluate the efficacy of ultrasound SWE techniques for the intraoperative detection of FCDs. We retrospectively analyzed data from 18 adult patients with drug-resistant epilepsy associated with FCD who had undergone SWE-guided surgery. Conventional B-mode images detected FCD in 2 patients (11.1%), while SWE detected FCD in 14 patients (77.8%). The stiffness ratios between MRI-positive and -negative cases were significantly different (3.6 ± 0.4 vs. 2.2 ± 0.6, respectively; p < 0.001). FCDs were significantly more frequently detected by interoperative SWE in women (OR 4.7, 95% CI (1.7–12.7); p = 0.004) and in patients in whom FCD was visible on magnetic resonance imaging (MRI; OR 2.3, 95% CI (1.3–4.3); p = 0.04). At 1 year after surgery and at last follow-up (mean = 21 months), seizure outcome was good (International League Against Epilepsy (ILAE) Class 1 or 2) in 72.2% and 55.6% of patients, respectively. Despite some limitations, our study highlighted the potential of SWE as an intraoperative tool to detect FCD. Future technical developments should allow for optimizing intraoperative surgical-cavity evaluation from the perspective of complete FCD resection. Interobserver reliability of SWE measurements should also be assessed by further studies. [ABSTRACT FROM AUTHOR]