Paek, Seungleal

Abstract Objective . Stereotactic frame systems are the gold-standard for stereotactic surgeries, such as implantation of deep brain stimulation (DBS) devices for treatment of medically resistant neurologic and psychiatric disorders. However, frame-based systems require that the patient is awake with a stereotactic frame affixed to their head for the duration of the surgical planning and implantation of the DBS electrodes. While frameless systems are increasingly available, a reusable re-attachable frame system provides unique benefits. As such, we created a novel reusable MRI-compatible stereotactic frame system that maintains clinical accuracy through the detachment and reattachment of its stereotactic devices used for MRI-guided neuronavigation. Approach . We designed a reusable arc-centered frame system that includes MRI-compatible anchoring skull screws for detachment and re-attachment of its stereotactic devices. We validated the stability and accuracy of our system through phantom, in vivo mock-human porcine DBS-model and human cadaver testing. Main results . Phantom testing achieved a root mean square error (RMSE) of 0.94 ± 0.23 mm between the ground truth and the frame-targeted coordinates; and achieved an RMSE of 1.11 ± 0.40 mm and 1.33 ± 0.38 mm between the ground truth and the CT- and MRI-targeted coordinates, respectively. In vivo and cadaver testing achieved a combined 3D Euclidean localization error of 1.85 ± 0.36 mm ( p < 0.03) between the pre-operative MRI-guided placement and the post-operative CT-guided confirmation of the DBS electrode. Significance . Our system demonstrated consistent clinical accuracy that is comparable to conventional frame and frameless stereotactic systems. Our frame system is the first to demonstrate accurate relocation of stereotactic frame devices during in vivo MRI-guided DBS surgical procedures. As such, this reusable and re-attachable MRI-compatible system is expected to enable more complex, chronic neuromodulation experiments, and lead to a clinically available re-attachable frame that is expected to decrease patient discomfort and costs of DBS surgery.

Object Conventional deep brain stimulation (DBS) devices continue to rely on an open-loop system in which stimulation is independent of functional neural feedback. The authors previously proposed that as the foundation of a DBS “smart” device, a closed-loop system based on neurochemical feedback, may have the potential to improve therapeutic outcomes. Alterations in neurochemical release are thought to be linked to the clinical benefit of DBS, and fast-scan cyclic voltammetry (FSCV) has been shown to be effective for recording these evoked neurochemical changes. However, the combination of FSCV with conventional DBS devices interferes with the recording and identification of the evoked analytes. To integrate neurochemical recording with neurostimulation, the authors developed the Mayo Investigational Neuromodulation Control System (MINCS), a novel, wirelessly controlled stimulation device designed to interface with FSCV performed by their previously described Wireless Instantaneous Neurochemical Concentration Sensing System (WINCS). Methods To test the functionality of these integrated devices, various frequencies of electrical stimulation were applied by MINCS to the medial forebrain bundle of the anesthetized rat, and striatal dopamine release was recorded by WINCS. The parameters for FSCV in the present study consisted of a pyramidal voltage waveform applied to the carbon-fiber microelectrode every 100 msec, ramping between −0.4 V and +1.5 V with respect to an Ag/AgCl reference electrode at a scan rate of either 400 V/sec or 1000 V/sec. The carbon-fiber microelectrode was held at the baseline potential of −0.4 V between scans. Results By using MINCS in conjunction with WINCS coordinated through an optic fiber, the authors interleaved intervals of electrical stimulation with FSCV scans and thus obtained artifact-free wireless FSCV recordings. Electrical stimulation of the medial forebrain bundle in the anesthetized rat by MINCS elicited striatal dopamine release that was time-locked to stimulation and increased progressively with stimulation frequency. Conclusions Here, the authors report a series of proof-of-principle tests in the rat brain demonstrating MINCS to be a reliable and flexible stimulation device that, when used in conjunction with WINCS, performs wirelessly controlled stimulation concurrent with artifact-free neurochemical recording. These findings suggest that the integration of neurochemical recording with neurostimulation may be a useful first step toward the development of a closed-loop DBS system for human application.