Abstract
Precise neurosurgical targeting of electrode arrays within the brain is essential to the successful treatment of a range of brain disorders with deep brain stimulation (DBS) therapy. Here, we describe a set of computational tools to generate in vivo, subject-specific atlases of individual thalamic nuclei thus improving the ability to visualize thalamic targets for preclinical DBS applications on a subject-specific basis. A sequential nonlinear atlas warping technique and a Bayesian estimation technique for probabilistic crossing fiber tractography were applied to high field (7T) susceptibility-weighted and diffusion-weighted imaging, respectively, in seven rhesus macaques. Image contrast, including contrast within thalamus from the susceptibility-weighted images, informed the atlas warping process and guided the seed point placement for fiber tractography. The susceptibility-weighted imaging resulted in relative hyperintensity of the intralaminar nuclei and relative hypointensity in the medial dorsal nucleus, pulvinar, and the medial/ventral border of the ventral posterior nuclei, providing context to demarcate borders of the ventral nuclei of thalamus, which are often targeted for DBS applications. Additionally, ascending fiber tractography of the medial lemniscus, superior cerebellar peduncle, and pallidofugal pathways into thalamus provided structural demarcation of the ventral nuclei of thalamus. The thalamic substructure boundaries were validated through in vivo electrophysiological recordings and post-mortem blockface tissue sectioning. Together, these imaging tools for visualizing and segmenting thalamus have the potential to improve the neurosurgical targeting of DBS implants and enhance the selection of stimulation settings through more accurate computational models of DBS.
Highlights
Structural brain imaging has become a valuable tool to guide the implantation and programming of deep brain stimulation (DBS) systems for the treatment of numerous brain disorders (Butson et al, 2007; Lemaire et al, 2007; Larson et al, 2012b)
Improvement in structural imaging of intra-thalamic nuclei would have important implications given that interventional stereotactic procedures within thalamus have shown marked promise for the treatment of pain (Levy et al, 1987), essential tremor (Benabid et al, 1991; Lipsman et al, 2013), epilepsy (Takase et al, 2009; Fisher et al, 2010), Tourette syndrome (Visser-Vandewalle et al, 2003), disorders of consciousness (Schiff et al, 2007), with other brain disorder indications on the horizon including schizophrenia (Ewing et al, 2013; Klein et al, 2013). This is especially important because favorable behavioral outcomes with thalamic DBS hinge upon the accuracy of stimulating the desired thalamic pathway, while avoiding modulation of neuronal pathways implicated in the emergence of adverse side effects (Akbostanci et al, 1999; Papavassiliou et al, 2004; Kuncel et al, 2008; Yu et al, 2009; Keane et al, 2012)
At the conclusion of the study and in order to validate the magnetic resonance imaging data, two animals were deeply anesthetized with sodium pentobarbital and perfused with phosphate buffered saline followed by a 4% paraformaldehyde fixative solution, consistent with the recommendations of the Panel on Euthanasia of the American Veterinary Medical Association
Summary
Structural brain imaging has become a valuable tool to guide the implantation and programming of deep brain stimulation (DBS) systems for the treatment of numerous brain disorders (Butson et al, 2007; Lemaire et al, 2007; Larson et al, 2012b). Improvement in structural imaging of intra-thalamic nuclei would have important implications given that interventional stereotactic procedures within thalamus have shown marked promise for the treatment of pain (Levy et al, 1987), essential tremor (Benabid et al, 1991; Lipsman et al, 2013), epilepsy (Takase et al, 2009; Fisher et al, 2010), Tourette syndrome (Visser-Vandewalle et al, 2003), disorders of consciousness (Schiff et al, 2007), with other brain disorder indications on the horizon including schizophrenia (Ewing et al, 2013; Klein et al, 2013) This is especially important because favorable behavioral outcomes with thalamic DBS hinge upon the accuracy of stimulating the desired thalamic pathway, while avoiding modulation of neuronal pathways implicated in the emergence of adverse side effects (Akbostanci et al, 1999; Papavassiliou et al, 2004; Kuncel et al, 2008; Yu et al, 2009; Keane et al, 2012)
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