Evaluation of Interactive Visualization on Mobile Computing Platforms for Selection of Deep Brain Stimulation Parameters

Despite the clinical success of deep brain stimulation (DBS) for the treatment of movement disorders, many questions remain about its effects on the nervous system. This study presents a methodology to predict the volume of tissue activated (VTA) by DBS on a patient-specific basis. Our goals were to identify the intersection between the VTA and surrounding anatomical structures and to compare activation of these structures with clinical outcomes. The model system consisted of three fundamental components: (1) a 3D anatomical model of the subcortical nuclei and DBS electrode position in the brain, each derived from magnetic resonance imaging (MRI); (2) a finite element model of the DBS electrode and electric field transmitted to the brain, with tissue conductivity properties derived from diffusion tensor MRI; (3) VTA prediction derived from the response of myelinated axons to the applied electric field, which is a function of the stimulation parameters (contact, impedance, voltage, pulse width, frequency). We used this model system to analyze the effects of subthalamic nucleus (STN) DBS in a patient with Parkinson's disease. Quantitative measurements of bradykinesia, rigidity, and corticospinal tract (CST) motor thresholds were evaluated over a range of stimulation parameter settings. Our model predictions showed good agreement with CST thresholds. Additionally, stimulation through electrode contacts that improved bradykinesia and rigidity generated VTAs that overlapped the zona incerta/fields of Forel (ZI/H2). Application of DBS technology to various neurological disorders has preceded scientific characterization of the volume of tissue directly affected by the stimulation. Synergistic integration of clinical analysis, neuroimaging, neuroanatomy, and neurostimulation modeling provides an opportunity to address wide ranging questions on the factors linked with the therapeutic benefits and side effects of DBS.

The goal of this project was to develop a quantitative understanding of the volume of axonal tissue directly activated by deep brain stimulation (DBS) of the subthalamic nucleus (STN). The 3-dimensionally inhomogeneous and anisotropic tissue medium surrounding DBS electrodes complicates our understanding of the electric field and tissue response generated by the stimulation. We developed finite element computer models to address the effects of DBS in a homogeneous isotropic medium, and a medium with tissue conductivity properties derived from human diffusion tensor magnetic resonance data. The second difference of the potential distribution generated in the tissue medium was used as a predictor of the volume of tissue supra-threshold for axonal activation. The model predicts that clinically effective stimulation parameters (-3 V; 0.1 ms; 150 Hz) result in activation of large diameter (5.7 microm) myelinated axons over a volume that spreads outside the borders of the STN. The shape of the activation volume was dependent on the strong dorsal-ventral anisotropy of the internal capsule, and the moderate anterior-posterior anisotropy of the region around zona incerta. Small deviations ( approximately 1 mm) in the electrode position within STN can substantially alter the shape of the activation volume as well as its spread to neighboring structures. STN DBS represents an effective treatment for medically refractory movement disorders such as Parkinson's disease. However, stimulation induced side effects such as tetanic muscle contraction, speech disturbance and ocular deviation are not uncommon. Quantitative characterization of the spread of stimulation will aid in the development of techniques to maximize the efficacy of DBS.

Clinical impedance measurements for deep brain stimulation (DBS) electrodes in human patients are normally in the range 500-1500 Omega. DBS devices utilize voltage-controlled stimulation; therefore, the current delivered to the tissue is inversely proportional to the impedance. The goals of this study were to evaluate the effects of various electrical properties of the tissue medium and electrode-tissue interface on the impedance and to determine the impact of clinically relevant impedance variability on the volume of tissue activated (VTA) during DBS. Axisymmetric finite-element models (FEM) of the DBS system were constructed with explicit representation of encapsulation layers around the electrode and implanted pulse generator. Impedance was calculated by dividing the stimulation voltage by the integrated current density along the active electrode contact. The models utilized a Fourier FEM solver that accounted for the capacitive components of the electrode-tissue interface during voltage-controlled stimulation. The resulting time- and space-dependent voltage waveforms generated in the tissue medium were superimposed onto cable model axons to calculate the VTA. The primary determinants of electrode impedance were the thickness and conductivity of the encapsulation layer around the electrode contact and the conductivity of the bulk tissue medium. The difference in the VTA between our low (790 Omega) and high (1244 Omega) impedance models with typical DBS settings (-3 V, 90 mus, 130 Hz pulse train) was 121 mm3, representing a 52% volume reduction. Electrode impedance has a substantial effect on the VTA and accurate representation of electrode impedance should be an explicit component of computational models of voltage-controlled DBS. Impedance is often used to identify broken leads (for values > 2000 Omega) or short circuits in the hardware (for values < 50 Omega); however, clinical impedance values also represent an important parameter in defining the spread of stimulation during DBS.