MR Tractography-Based Targeting and Physiological Identification of the Cuneiform Nucleus for Directional DBS in a Parkinson’s Disease Patient With Levodopa-Resistant Freezing of Gait

To determine placement of electrodes after deep brain stimulation (DBS) surgery, a novel toolbox that facilitates both reconstruction of the lead electrode trajectory and the contact placement is introduced. Using the toolbox, electrode placement can be reconstructed and visualized based on the electrode-induced artifacts on post-operative magnetic resonance (MR) or computed tomography (CT) images. Correct electrode placement is essential for efficacious treatment with DBS. Post-operative knowledge about the placement of DBS electrode contacts and trajectories is a promising tool for clinical evaluation of DBS effects and adverse effects. It may help clinicians in identifying the best stimulation contacts based on anatomical target areas and may even shorten test stimulation protocols in the future. Fifty patients that underwent DBS surgery were analyzed in this study. After normalizing the post-operative MR/CT volumes into standard Montreal Neurological Institute (MNI)-stereotactic space, electrode leads (n=104) were detected by a novel algorithm that iteratively thresholds each axial slice and isolates the centroids of the electrode artifacts within the MR/CT-images (MR only n=32, CT only n=10, MR and CT n=8). Two patients received four, the others received two quadripolar DBS leads bilaterally, summing up to a total of 120 lead localizations. In a second reconstruction step, electrode contacts along the lead trajectories were reconstructed by using templates of electrode tips that had been manually created beforehand. Reconstructions that were made by the algorithm were finally compared to manual surveys of contact localizations. The algorithm was able to robustly accomplish lead reconstructions in an automated manner in 98% of electrodes and contact reconstructions in 69% of electrodes. Using additional subsequent manual refinement of the reconstructed contact positions, 118 of 120 electrode lead and contact reconstructions could be localized using the toolbox. Taken together, the toolbox presented here allows for a precise and fast reconstruction of DBS contacts by proposing a semi-automated procedure. Reconstruction results can be directly exported to two- and three-dimensional views that show the relationship between DBS contacts and anatomical target regions. The toolbox is made available to the public in form of an open-source MATLAB repository.

Three-dimensional atlases of subcortical brain structures are valuable tools to reference anatomy in neuroscience and neurology. For instance, they can be used to study the position and shape of the three most common deep brain stimulation (DBS) targets, the subthalamic nucleus (STN), internal part of the pallidum (GPi) and ventral intermediate nucleus of the thalamus (VIM) in stereotactic space and in spatial relationship to DBS electrodes. Here, we present a composite atlas that is based on manual segmentations of a multimodal high resolution brain template, histology and structural connectivity. In a first step, four key structures were defined on the template itself using a combination of multispectral image analysis and manual segmentation. Second, these structures were used as anchor points to coregister a detailed histological atlas into standard space. Results show that this approach significantly improved coregistration accuracy over previously published methods. Finally, a sub-segmentation of STN and GPi into functional zones was achieved based on structural connectivity. The result is a composite atlas that defines key nuclei on the template itself, fills the gaps between them using histology and further subdivides them using structural connectivity. We show that the atlas can be used to segment DBS targets in single subjects, yielding more accurate results compared to priorly published atlases. The atlas will be made publicly available and constitutes a resource to study DBS electrode localizations in combination with modern neuroimaging methods.

A comprehensive map of the structural connectome in the human brain has been a coveted resource for understanding macroscopic brain networks. Here we report an expert-vetted, population-averaged atlas of the structural connectome derived from diffusion MRI data (N=842). This was achieved by creating a high-resolution template of diffusion patterns averaged across individual subjects and using tractography to generate 550,000 trajectories of representative white matter fascicles annotated by 80 anatomical labels. The trajectories were subsequently clustered and labeled by a team of experienced neuroanatomists in order to conform to prior neuroanatomical knowledge. A multi-level network topology was then described using whole-brain connectograms, with subdivisions of the association pathways showing small-worldness in intra-hemisphere connections, projection pathways showing hub structures at thalamus, putamen, and brainstem, and commissural pathways showing bridges connecting cerebral hemispheres to provide global efficiency. This atlas of the structural connectome provides representative organization of human brain white matter, complementary to traditional histologically-derived and voxel-based white matter atlases, allowing for better modeling and simulation of brain connectivity for future connectome studies.