Abstracts

Focal Cortical Dysplasia (FCD) is a neurodevelopmental disorder marked by abnormal cortical structures due to disorganized brain cell development, often leading to seizures and representing a common cause of drug-resistant epilepsy that frequently necessitates surgical resection (1). However, this invasive procedure carries risks such as infection and bleeding (2), and even after surgery, incomplete seizure control and the need for continued medication are common, often associated with significant morbidity (3). Here, we employ non-invasive transcranial histotripsy to ablate the epileptogenic cortical region in an in-utero electroporation (IUE)-generated FCD mouse model to evaluate its therapeutic efficacy for epilepsy.

Pretreatment fluorescence images were aligned with MR images through stereotactic co-registration to precisely target the epileptogenic cortical tissue. A 1.5 MHz transducer was used to deliver histotripsy pulses to a grid of treatment locations at an estimated free-field peak negative focal pressure of 85 MPa. Ten histotripsy pulses were applied per location, covering a total treatment volume of 10 mm³ (with 0.5 × 1 mm axial × lateral point spacing). Post-treatment T2-weighted and T2*-weighted MR images were acquired to verify the ablation zone. Electroencephalogram (EEG) implantation was performed to assess seizure outcomes following the procedure.

We found that post-treatment T2-weighted and T2*-weighted MR images revealed a 15 mm³ hypointense region in the targeted cortex, indicating accurate and successful histotripsy ablation, with no bleeding or infection observed in the days following the procedure. EEG results show no seizures and minimal spikes in 3 mice that received ablation treatment, compared to an average of 4.39 ± 0.42 per day with frequent spikes in the 3 untreated control mice.

These results suggest that non-invasive ultrasound ablation could be an effective and safe therapeutic approach for the treatment of FCD associated epilepsy.