The STEREO-DBS Study: 7-Tesla MRI Brain Network Analysis for Deep Brain Stimulation

INTRODUCTION AND RATIONALE

Deep brain stimulation for Parkinson's disease Deep brain stimulation (DBS) is an effective treatment in Parkinson's disease (PD), a debilitating neurological disorder. The effect of DBS relies on the modulation of malfunctioning brain networks by delivering electrical pulses within the subthalamic nucleus, deeply seated in the brainstem and the size of a few millimeters (STN; comparable to the size of a coffee bean). However, individual improvement after DBS remains variable and 50% of patients show insufficient benefit. By using structural 7-Tesla magnetic resonance imaging (7T MRI) connectivity to visualize malfunctioning networks, DBS-electrode placement and activation can be individualized.

Current DBS-electrode placement and settings in the highly connected STN are based on 1.5-Tesla or 3-Tesla MR-images. These low resolution modalities are unable to visualize the multiple brain networks to this small nucleus and prevent electrode activation directed at its cortical projections. Integrated structural (7T MRI) network maps will enable brain network-based and patient-specific DBS, improving motor symptoms and quality of life.

7T MRI brain network analysis Since the 1980s, DBS for PD was targeting the STN, a deep-seated grey matter brain nucleus. Current emphasis in the field of DBS is on neural networks rather than separate nuclei in the brain. Several studies showed PD to arise from pathological network activity in subthalamic-cortical projections. In recent years several DBS groups reported about using MRI connectivity to visualize the subthalamic-cortical projections, in DBS for PD.

The small STN is part of multiple large brain networks. DBS is effective in improving UDPRS and quality of life for PD patients only by modulating its motor network. For improving DBS placement and activation, it is essential to understand the networks and the modulatory effect of stimulation. Thus far, visualization of these networks was limited due to low resolution and the lack of structural connectivity (visualising subthalamic-cortical projections using diffusion weighted MRI and probabilistic connectivity).

The investigators therefore added 7T T2 and diffusion-weighted sequences at the Spinoza Centre and showed that probabilistic subthalamic network analyses (STN segmentation) successfully identifies the area within the STN that has the highest density of connections with the motor network in PD patients. In a recent pilot study the investigators showed the implementation of 7T MRI for STN segmentation is well suited within the existing surgical workflow. By generating a 7-Tesla MRI showing the STN (coloured) motor subdivision, this technique clearly visualized this new DBS target. The retrospective analysis showed for conventional MRI targeting strategies only a minority of DBS electrodes were placed in the motor STN. Moreover, the DBS electrodes that were placed in the motor STN resulted in a significantly higher mean improvement (80% versus 50%, measured by the UPDRS-III score).

Generating the 7T MRI network maps for DBS The STN and its cortical connections will be visualized using 7T T2-weighted and diffusion weighted imaging. Three major projections of the STN will be visualised: projections connecting to primary and supplementary motor cortex (motor), projections to the prefrontal cortex (associative) and projections to the basofrontal cortex (limbic). The location of the electrode (using computed tomography) will be visualised relative to the three segmented subdivisions of the STN.

The 7T MRI network map, generated by combining T2 and diffusion weighted MRI, shows the STN (coloured) subdivisions and their cortical projections. The result will then show in which STN subdivision(s) the DBS-electrode contact is situated and to which cortical area the STN subdivision projects. Clinical test scores of the electrode contact will then be correlated to the network maps. Stimulation parameters based on 7T MRI network maps are used to optimize and predict outcome in terms of beneficial clinical effects (suppression tremor, bradykinesia, rigidity) and side effects (speech, gait, apathy). As all network maps are visualised on MRI, this will readily enable both individual and group analyses (co-registrating maps of multiple patients).

Adverse effects In the 350 7T MR-scans the investigators have performed to date, we rarely encountered non-compatible implants or severe claustrophobia. Every patient undergoes screening with a MRI safety questionnaire and MRI metal detector (preventing taking ferromagnetic materials into the MRI). 7T MRI is a non-invasive technique which causes no pain and, importantly, the electromagnetic fields produce no known tissue damage of any kind. The MR system may make loud tapping, knocking, or other noises at times during the procedure. Earplugs are provided to prevent problems that may be associated with noise generated by the scanner. At all times, the patient will be (visually) monitored and will be able to communicate with the 7T MRI technologist using an intercom system. The patient may (request to) stop the acquisition at any time by using the push button (hold by the patient continuously).

In sum, due to implementation of 7T MRI brain network analysis, it is now possibly to directly visualize the motor part of the STN. In current observational study this technique will be evaluated in a prospective fashion, introducing patient specific brain network-guided DBS for PD with delivering a unique and hitherto unavailable dataset: 7T MRI visualizes the anatomical connections of the STN for each individual DBS electrode contact. Instead of a one-DBS-fits all model, the tailored network analyses enable personalized precision modelling in DBS.