Connectivity derived thalamic segmentation in deep brain stimulation for tremor

Abstract

The ventral intermediate nucleus (VIM) of the thalamus is an established surgical target for stereotactic ablation and deep brain stimulation (DBS) in the treatment of tremor in Parkinson's disease (PD) and essential tremor (ET). It is centrally placed on a cerebello-thalamo-cortical network connecting the primary motor cortex, to the dentate nucleus of the contralateral cerebellum through the dentato-rubro-thalamic tract (DRT). The VIM is not readily visible on conventional MR imaging, so identifying the surgical target traditionally involved indirect targeting that relies on atlas-defined coordinates. Unfortunately, this approach does not fully account for individual variability and requires surgery to be performed with the patient awake to allow for intraoperative targeting confirmation. The aim of this study is to identify the VIM and the DRT using probabilistic tractography in patients that will undergo thalamic DBS for tremor. Four male patients with tremor dominant PD and five patients (three female) with ET underwent high angular resolution diffusion imaging (HARDI) (128 diffusion directions, 1.5 mm isotropic voxels and b value = 1500) preoperatively. Patients received VIM-DBS using an MR image guided and MR image verified approach with indirect targeting. Postoperatively, using parallel Graphical Processing Unit (GPU) processing, thalamic areas with the highest diffusion connectivity to the primary motor area (M1), supplementary motor area (SMA), primary sensory area (S1) and contralateral dentate nucleus were identified. Additionally, volume of tissue activation (VTA) corresponding to active DBS contacts were modelled. Response to treatment was defined as 40% reduction in the total Fahn-Tolosa-Martin Tremor Rating Score (FTMTRS) with DBS-ON, one year from surgery. Three out of nine patients had a suboptimal, long-term response to treatment. The segmented thalamic areas corresponded well to anatomically known counterparts in the ventrolateral (VL) and ventroposterior (VP) thalamus. The dentate-thalamic area, lay within the M1-thalamic area in a ventral and lateral location. Streamlines corresponding to the DRT connected M1 to the contralateral dentate nucleus via the dentate-thalamic area, clearly crossing the midline in the mesencephalon. Good response was seen when the active contact VTA was in the thalamic area with highest connectivity to the contralateral dentate nucleus. Non-responders had active contact VTAs outside the dentate-thalamic area. We conclude that probabilistic tractography techniques can be used to segment the VL and VP thalamus based on cortical and cerebellar connectivity. The thalamic area, best representing the VIM, is connected to the contralateral dentate cerebellar nucleus. Connectivity based segmentation of the VIM can be achieved in individual patients in a clinically feasible timescale, using HARDI and high performance computing with parallel GPU processing. This same technique can map out the DRT tract with clear mesencephalic crossing.

Microstructural changes of the dentato‐rubro‐thalamic tract after transcranial MR guided focused ultrasound ablation of the posteroventral VIM in essential tremor

“…Thalamotomy for tremor is aimed to impact on the anatomical connections within the cerebello‐thalamo‐cortical system, specifically the DRTT, stopping the tremor activity from propagating from the cerebellum to the motor cortex. Using tractography it is possible to define the anatomical boundaries of this tract (Akram et al, ; Meola, Yeh, Fellows‐Mayle, Weed, & Fernandez‐Miranda, ; Nowacki, Schlaier, Debove, & Pollo, ), and so the number of studies encouraging the tractography‐based segmentation of the DRTT for targeting in either thalamotomy or DBS is growing (Akram et al, ; Coenen et al, ; Sammartino et al, ; Tian et al, ; Tsolaki, Downes, Speier, Elias, & Pouratian, ). Our results are in line with these studies, and suggest that tractography based guidance during tcMRgFUS treatment strategy could be very beneficial.…”

Comparison of tractography‐assisted to atlas‐based targeting for deep brain stimulation in essential tremor

“…In a post‐hoc analysis of feasibility using probabilistic tractography to identify the Vim thalamus and DRTt, Akram and colleagues used graphical processing unit parallelization after obtaining preoperative high‐angular‐resolution diffusion imaging (HARDI) to segment the thalamus in 4 patients with tremor‐dominant PD and 5 patients with ET who underwent Vim DBS through indirect targeting. The elucidated segmented thalamic area had that the highest diffusion connectivity to the contralateral dentate nucleus and ipsilateral red nucleus and primary motor cortex was used to generate streamlines defining the DRTt.…”

“…Additionally, in comparison to probabilistic tractography, streamlines created through deterministic means have not been found to be as reproducible when tracking through gray matter structures like the thalamus, as recently reported by Peterson and colleagues. 30 Probabilistic tractography using graphic processing unit parallelization can estimate up to three crossing fibers per voxel, thus they generate streamlines that can build a spatial connectivity distribution, a surrogate measure of anatomical connectivity 29,31 ; such resolution of crossing fibers can more realistically describe the DRTt.…”

Graph theory analysis of resting‐state functional magnetic resonance imaging in essential tremor

“…Resting-state functional MRI (rs-fMRI) is a suitable neuroimaging modality for the evaluation of many neurological and psychiatric diseases (Barkhof, Haller, & Rombouts, 2014;Hacker, Perlmutter, Criswell, Ances, & Snyder, 2012). To date, only a few studies have explored connectivity alterations in ET, and those that did were mainly focused on the cerebello-thalamo-cortical network, which is mainly related to motor symptoms (Buijink et al, 2015;Caligiuri et al, 2017;Mueller et al, 2017), or on the study of surgical therapeutic applications (Akram et al, 2018;Tuleasca et al, 2018). In a recent study, ET patients showed increased connectivity in resting-state networks involved in cognitive processes and decreased connectivity in the cerebellum and visual networks (Benito-León et al, 2015).…”