Abstracts

Rationale: Drug-resistant epilepsy (DRE) carries significant morbidity and risk of mortality with limited treatment options. Surgery is a good option for some patients, but only a portion of patients are candidates and outcomes vary, as is true for invasive devices. Neuromodulation is a burgeoning area in the treatment of neurologic disorders, including epilepsy. Non-invasive approaches at neuromodulation such as transcranial magnetic stimulation TMS are limited in efficacy in treating seizures, in part due to the inability to reach deep areas of epileptogenicity, including the hippocampus, one of the most common sites of seizure onset. High intensity focused ultrasound has been extremely successful in non-invasively treating tremor (1) and tumors, by means of thermal ablation. Also, low intensity focused ultrasound has been shown to suppress EEG activity in animal models of epilepsy (2). We hypothesized that low intensity focused ultrasound (LIFUS) could modulate neural tissue by mechanical vibration (sonication) without ablation. Methods: We developed a low intensity, focused ultrasound device capable of sonicating the hippocampus and lateral temporal cortex using a spherically-focused air-backed piezoceramic transducer. Ultrasound coupling was achieved at the temporal acoustic window with ultrasound gel, 0.01-mm thick polyethylene membrane, and degassed deionized water. The transducer was positioned using a manually operated 3-axis positioning system. In situ targeting was achieved using landmarked T2W MRI images, an infrared fiducial tracking camera, and neuronavigational software. For each target, 140-s sonications were performed with the following specifications: f0 548 kHz, PRF 500 Hz, duty 36-50%, burst time 500 ms, BRP 7 s, Ispta 0.5-3.0 W/cm2, PNP 0.14-0.42 MPa. Results: We report the first successful LIFUS sonication of the human hippocampus in a patient with temporal lobe epilepsy. At the time of this report, one patient with drug-resistant temporal lobe epilepsy successfully and safely underwent four sessions of sonication by LIFUS over 2 weeks, each time treating four targets within the hippocampus. Enrollment is currently open; we plan to sonicate the mesial and/or lateral temporal lobe of 10 subjects in this pilot trial. Conclusions: LIFUS is a new, innovative, non-invasive, potentially neuromodulatory treatment being investigated for DRE. This study was funded by the Brigham Research Institute BRIght Futures Prize (EJB).References:1. Elias WJ, Lipsman N, Ondo WG et al. “A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor.” N Engl J Med. 2016 Aug 25;375(8):730-9. 2. Min B-K, Bystritsky A, Jung K-I et al. “Focused ultrasound-mediated suppression of chemically-induced acute epileptic EEG activity.” BMC neuroscience 2011;12:23. Funding: Brigham Research Institute BRIght Futures Prize (EJB)