High angular resolution diffusion-weighted imaging and higher order tractography of the white matter tracts in the anterior thalamic area: Insights into deep brain stimulation targeting.

Background: Deep brain stimulation of the anterior nucleus of the thalamus (ANT) is emerging EU/US-approved form of therapy for drug-resistant focal epilepsy. Its mechanism of action is not yet fully understood, and the patient outcomes in epilepsy appear less consistent compared to for instance movement disorders. Furthermore, very little anatomy-based information, such as tractography of relevant fiber systems, exists guiding DBS therapy at present.

Objective: To demonstrate ANT-related fiber systems based on histology in vivo employing multi-shell/multi-tissue constrained spherical deconvolution (MSMT-CSD) based deterministic and probabilistic tractography using a sophisticated scanning protocol of 3T high angular resolution diffusion-weighted imaging (HARDI) data in healthy volunteers.

Method: HARDI data was acquired from five healthy volunteers in a 3T Siemens MAGNETOM Skyra Magnetic resonance imaging (MRI) machine using multiple b-values (1000, 2000, and 3000), 64 directions, and further preprocessed for tractography. MSMT-CSD-based deterministic and probabilistic tractography was performed from selected fiber systems based on existing literature.

Results: Multiple fiber systems were identified: The anterior thalamic radiation (ANT), the thalamo-cingulate tract, the inferior thalamic peduncle (with remote termination areas in the amygdala, the ventral tegmental area, and the occipital cortex), and the mammillothalamic tract. In addition, we observed three parallel connections to the hippocampus (via the cingulum bundle, the fornix, and the temporo-pulvinar pathway). Interestingly, different seed areas in ANT complex mimicking DBS contact locations resulted in visualization of different fiber systems.

Discussion: The connections of the ANT are complex and different stimulation sites are likely to affect different networks depending on lead locations and the selection of the active contact.

Conclusions: In-depth understanding of the network of anatomical structures related to the ANT is likely to influence therapy outcomes. A hypothetical model of neuronal networks affected by different DBS lead contact locations is proposed. A more profound understanding of neuroanatomic characteristics may guide stereotactic implantation and subsequent programming to optimize outcomes.