Seeg-based Drug Delivery System - Feasibility Bench and in vivo Studies
Abstract number :
1.202
Submission category :
2. Translational Research / 2B. Devices, Technologies, Stem Cells
Year :
2024
Submission ID :
753
Source :
www.aesnet.org
Presentation date :
12/7/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Florenta Kullmann, PhD – NeuroOne
Guadalupe Zepeda, BS – NeuroOne
Su-youne Chang, PhD – Mayo Clinic
Jiwon Kim, BEng – Mayo Clinic
Inyong Kim, BEng – Mayo Clinic
Filip Mivalt, MS – Mayo Clinic
Maria Vomero, Ph.D. – NeuroOne
Mary McNeil, MS – NeuroOne
Camilo Diaz-Botia, Ph.D. – NeuroOne
Dave Rosa, MS – NeuroOne
Gregory Worrell, MD, PhD – Mayo Clinic
Alfonso Chavez, BS – NeuroOne
Rationale: Stereoelectroencephalography (sEEG) electrodes are routinely used in the evaluation of patients with drug resistant epilepsy for epileptogenic zone (EZ) identification. The electrodes are FDA-cleared for temporary (< 30 days) neural activity monitoring, recording and stimulation at the subsurface level of the brain. Recently, radiofrequency ablation (RFA) functionality was added to the sEEG electrodes, creating a temperature-controlled sEEG-guided RFA system (FDA-cleared). Building on the sEEG multifunctionality, here we present early feasibility studies for adding a drug delivery capability to these electrodes.
Methods: A drug delivery sEEG (DD-sEEG) device was designed to deliver infusate at the tip. Infusion rates, reflux and infusion/diffusion volume (Vi/Vd) relationship were evaluated in 0.6% agarose gel. Concomitant CED and neural recordings were evaluated in vivo in rodent and swine. DD-sEEG electrodes were stereotactically implanted into the hippocampus and putamen, and penicillin (5000 units/µl) was used to modulate neural activity. MRI with gadolinium (Gd; swine) and histology (rodent) were used to evaluate Vd.
Results: Bench studies demonstrated CED for infusion rates of 0.5-15 µl/min and Vi 60-300 µl, with Vd/Vi ratio of 2.7-3.4. Penicillin elicited seizure-like episodes consisting of large amplitude bursts of coordinated activity interspaced by quiet periods, in both rodent and swine hippocampus. MRI visualization of Gd demonstrated localized infusions in the putamen and hippocampus in the swine. Histological examination of the rodent brain tissue showed confined Vd.
Conclusions: These data indicate that the DD-sEEG device performs the desired functions: monitors neural activity and delivers therapeutic compounds. The availability of drug delivery capability in an sEEG allows probing of various brain areas, such as temporarily but reversibly inhibiting the EZ to evaluate the effects of EZ ablation or resection. Coupled with the ablation function, the sEEG-based platform has the potential to significantly increase the accuracy of diagnosis and offer treatment in a single procedure.
Funding: NeuroOne
Translational Research