7T MRI and Computational Modeling Supports a Critical Role of Lead Location in Determining Outcomes for Deep Brain Stimulation: A Case Report

Abstract

Subthalamic nucleus (STN) deep brain stimulation (DBS) is an established therapy for Parkinson's disease motor symptoms. The ideal site for implantation within STN, however, remains controversial. While many argue that placement of a DBS lead within the sensorimotor territory of the STN yields better motor outcomes, others report similar effects with leads placed in the associative or motor territory of the STN, while still others assert that placing a DBS lead "anywhere within a 6-mm-diameter cylinder centered at the presumed middle of the STN (based on stereotactic atlas coordinates) produces similar clinical efficacy." These discrepancies likely result from methodological differences including targeting preferences, imaging acquisition and the use of brain atlases that do not account for patient-specific anatomic variability. We present a first-in-kind within-patient demonstration of severe mood side effects and minimal motor improvement in a Parkinson's disease patient following placement of a DBS lead in the limbic/associative territory of the STN who experienced marked improvement in motor benefit and resolution of mood side effects following repositioning the lead within the STN sensorimotor territory. 7 Tesla (7 T) magnetic resonance imaging (MRI) data were used to generate a patient-specific anatomical model of the STN with parcellation into distinct functional territories and computational modeling to assess the relative degree of activation of motor, associative and limbic territories.

Keywords: Parkinson’s disease; case report; computational modeling; deep brain stimulation; electrode location; subthalamic nucleus; ultra-high field MRI.

FIGURE 1

Ultra high field 7 Tesla MR images for patient-specific STN parcellation, lead location, and computational modeling. (A) STN parcellation results. (B) Representation of white matter tracts between the STN and the cortex. (C,D) Lead locations with respect to the STN parcellation. (E) Patient-specific computational model of bilateral STN-DBS settings before and after right lead revision. The anatomical portion of the model was constructed from segmentation of high field imaging data (7T) with post-operative CT scans for lead localization. The STN volumes were then populated with biophysical multi-compartment neuron models that were perturbed with clinical DBS waveforms whose amplitudes were calculated from simulations of the tissue voltages induced through an anisotropic and inhomogeneous finite element model (FEM, COMSOL Multiphysics 5.4) of the electrode-tissue interfaces for this patient. The FEM was parameterized using diffusion-weighted imaging data from the patient. These models provided a quantitative estimate of the percentage of each neuronal pathway directly modulated by a clinical stimulation setting, with maximum possible activation of 100% for each pathway. Across all lead implants, the patient-specific models showed that stimulation of the motor STN was important to treat parkinsonian motor signs, while stronger activation of the associative and limbic territories resulted in the acute effects on mood.