title: Pre-implant modeling of depth lead placement in white matter for maximizing the extent of cortical activation during direct neurostimulation therapy.
abstract: BACKGROUND
  The objective of this work was to predict preoperatively the maximum extent to which direct stimulation therapy can propagate through an epileptic circuit for stabilizing refractory focal-onset epilepsy. A pre-surgical workflow is presented which comprises a computationally intensive process for calculating the volume of cortical activation (VOCA) surrounding cylindrical depth contacts virtually placed in white matter. The process employs an activation function (AF) derived from cable modeling of an axon. The AF was extrapolated to describe the three-dimensional activation of axon bundles facilitated by patient-specific diffusion tensor imaging (DTI).
  
  
  METHODS
  The modeling process consisted of the following steps: (1) acquisition of structural MRI and DTI; (2) computation of the electric potential using the finite element method; (3) analysis of the effect of the modeled electric field on depolarizing axon bundles using the AF; (4) predicting distant cortical activation by strategically placing the AF seeds for creating a modulated circuit tractography (MCT) map; and finally, (5) post-implant in vivo validation using Subtracted Activated SPECT (SAS).
  
  
  RESULTS
  The pre-implant simulation calculated non-spherical volumetric regions around the contacts representing areas of hyperpolarization and depolarization. Furthermore, the generated MCT map predicted the extent to which white matter connected epileptic sources were influenced during direct stimulation therapy. Validation of this map was demonstrated post-implantation employing RNS electrocorticography and SAS. The latter technique captured transient alterations in blood flow synched to neural metabolism potentially distant to the stimulated contacts.
  
  
  CONCLUSIONS
  This pre-implant modeling system offers the potential for predicting optimal depth lead implant sites with a limited set of contacts for modulating the maximal extent of a refractory epileptogenic network.
authors.affiliation: a Department of Neurological Sciences , Rush University Medical Center , Chicago , IL , USA.
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Cendejas Zaragoza
authors.affiliation: b Department of Neurosurgery , Rush University Medical Center , Chicago , IL , USA.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Byrne
authors.affiliation: a Department of Neurological Sciences , Rush University Medical Center , Chicago , IL , USA.
authors.forename: Marvin A
authors.initials: MA
authors.lastname: Rossi
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging*; D002540:Cerebral Cortex; D046690:Deep Brain Stimulation / Q000295:instrumentation / Q000379:methods*; D056324:Diffusion Tensor Imaging; D004828:Epilepsies, Partial / Q000628:therapy*; D005260:Female; D006801:Humans; D058542:Implantable Neurostimulators; D008279:Magnetic Resonance Imaging; D008959:Models, Neurological; D015899:Tomography, Emission-Computed, Single-Photon; D066127:White Matter; D055815:Young Adult
keywords: NeuroPace; Responsive neurostimulation; activation function; axon orientation; electric field; electric potential; subtracted activated SPECT; tractography