Comparison of Dentatorubrothalamic Tractography Methods Based on the Anatomy of the Rubral Wing

Operative Neurosurgery 27:56–64, 2024

Precise localization of the dentatorubrothalamic (DRT) tract can facilitate anatomic targeting in MRI-guided high-intensity focused ultrasound (HIFU) thalamotomy and thalamic deep brain stimulation for tremor. The anatomic segment of DRT fibers adjacent to the ventral intermediate nucleus of the thalamus (VIM), referred to as the rubral wing (RW), may be directly visualized on the fast gray matter acquisition T1 inversion recovery. We compared reproducibility, lesion overlap, and clinical outcomes when reconstructing the DRT tract using a novel anatomically defined RW region of interest, DRT-RW, to an existing tractography method based on the posterior subthalamic area region of interest (DRT-PSA).

METHODS: We reviewed data of 23 patients with either essential tremor (n = 18) or tremor-predominant Parkinson’s disease (n = 5) who underwent HIFU thalamotomy, targeting the VIM. DRT tractography, ipsilateral to the lesion, was created based on either DRT-PSA or DRT-RW. Volume sections of each tract were created and dice similarity coefficients were used to measure spatial overlap between the 2 tractographies. Post-HIFU lesion size and location (on postoperative T2 MRI) was correlated with tremor outcomes and side effects for both DRT tractography methods and the RW itself.

RESULTS: DRT-PSA passed through the RW and DRT-RW intersected with the ROIs of the DRT-PSA in all 23 cases. A higher percentage of the RW was ablated in patients who achieved tremor control (18.9%, 95% CI 15.1, 22.7) vs those without tremor relief (6.7%, 95% CI% 0, 22.4, P= .017). In patients with tremor control 6 months postoperatively (n= 12), those with side effects (n = 6) had larger percentages of their tracts ablated in comparison with those without side effects in both DRT-PSA (44.8, 95% CI 31.8, 57.8 vs 24.2%, 95% CI 12.4, 36.1, P = .025) and DRT-RW (35.4%, 95% CI 21.5, 49.3 vs 21.7%, 95% CI 12.7, 30.8, P = .030).

CONCLUSION: Tractography of the DRT could be reconstructed by direct anatomic visualization of the RW on fast gray matter acquisition T1 inversion recovery-MRI. Anatomic planning is expected to be quicker, more reproducible, and less operator-dependent.

The dentato-rubro-thalamic tract as the potential common deep brain stimulation target for tremor of various origin

Acta Neurochirurgica (2020) 162: 1053–1066

Deep brain stimulation alleviates tremor of various origins. The dentato-rubro-thalamic tract (DRT) has been suspected as a common tremor-reducing structure. Statistical evidence has not been obtained. We here report the results of an uncontrolled case series of patients with refractory tremor who underwent deep brain stimulation under tractographic assistance.

Methods A total of 36 patients were enrolled (essential tremor (17), Parkinson’s tremor (8), multiple sclerosis (7), dystonic head tremor (3), tardive dystonia (1)) and received 62 DBS electrodes (26 bilateral; 10 unilateral). Preoperatively, diffusion tensor magnetic resonance imaging sequences were acquired together with high-resolution anatomical T1Wand T2W sequences. The DRTwas individually tracked and used as a direct thalamic or subthalamic target. Intraoperative tremor reduction was graded on a 4-point scale (0 = no tremor reduction to 3 = full tremor control) and recorded together with the current amplitude, respectively. Stimulation point coordinates were recorded and compared to DRT. The relation of the current amplitude needed to reduce tremor was expressed as TiCR (tremor improvement per current ratio).

Results Stimulation points of 241 were available for analysis. A total of 68 trajectories were tested (62 dB leads, 1.1 trajectories tested per implanted lead). Tremor improvement was significantly decreasing (p < 0.01) if the distance to both the border and the center of the DRT was increasing. On the initial trajectory, 56 leads (90.3%) were finally placed. Long-term outcomes were not part of this analysis.

Discussion Tremor of various origins was acutely alleviated at different points along the DRT fiber tract (above and below the MCP plane) despite different tremor diseases. DRT is potentially a common tremor-reducing structure. Individual targeting helps to reduce brain penetrating tracts. TiCR characterizes stimulation efficacy and might help to identify an optimal stimulation point.

Prospective Tractography-Based Targeting for Improved Safety of Focused Ultrasound Thalamotomy

Neurosurgery 84:160–168, 2019

Focused ultrasound thalamotomy (FUS-T) was recently approved for the treatment of refractory essential tremor (ET). Despite its noninvasive approach, FUS-T reinitiated concerns about the adverse effects and long-term efficacy after lesioning.

OBJECTIVE: To prospectively assess the outcomes of FUS-T in 10 ET patients using tractography-based targeting of the ventral intermediate nucleus (VIM).

METHODS: VIM was identified at the intercommissural plane based on its neighboring tracts: the pyramidal tract and medial lemniscus. FUS-T was performed at the center of tractography-defined VIM. Tremor outcomes, at baseline and 3 mo, were assessed independently by the Tremor Research Group.We analyzed targeting coordinates, clinical outcomes, and adverse events. The FUS-T lesion location was analyzed in relation to unbiased thalamic parcellation using probabilisitic tractography. Quantitative diffusionweighted imaging changes were also studied in fiber tracts of interest.

RESULTS: The tractography coordinates were more anterior than the standard. Intraoperatively, therapeutic sonications at the tractography target improved tremor (>50% improvement) without motor or sensory side effects. Sustained improvement in tremor was observed at 3mo(tremor score: 18.3±6.9 vs 8.1±4.4, P=.001).Nomotorweakness and sensory deficits after FUS-T were observed during 6-mo follow-up. Ataxia was observed in 3 patients. FUS-T lesions overlapped with the VIM parcellated with probablisitic tractography. Significant microstructural changes were observed in the white matter connecting VIM with cerebellum and motor cortex.

CONCLUSION: This is the first report of prospective VIM targeting with tractography for FUS-T. These results suggest that tractography-guided targeting is safe and has satisfactory short-term clinical outcomes.

Combined thalamic and subthalamic deep brain stimulation for tremor-dominant Parkinson’s disease

Acta Neurochir (2017) 159:265–269

Deep brain stimulation (DBS) in the thalamic ventral intermediate (Vim) or the subthalamic nucleus (STN) reportedly improves medication-refractory Parkinson’s disease (PD) tremor. However, little is known about the potential synergic effects of combined Vim and STN DBS.

We describe a 79-year-old man with medication-refractory tremor-dominant PD. Bilateral Vim DBS electrode implantation produced insufficient improvement. Therefore, the patient underwent additional unilateral left-sided STN DBS. Whereas Vim or STN stimulation alone led to partial improvement, persisting tremor resolution occurred after simultaneous stimulation.

The combination of both targets may have a synergic effect and is an alternative option in suitable cases.

Modulation of the Cerebello-Thalamo-Cortical Network in Thalamic Deep Brain Stimulation for Tremor

Modulation of the Cerebello-Thalamo-Cortical Network in Thalamic Deep Brain Stimulation for Tremor- A Diffusion Tensor Imaging Study

Neurosurgery 75:657–670, 2014

Deep brain stimulation alleviates tremor of various origins. Several regions like the ventralis intermediate nucleus of thalamus, the caudal zona incerta, and the posterior subthalamic region are generally targeted. Previous work with fiber tractography has shown the involvement of the cerebello-thalamo-cortical network in tremor control.

OBJECTIVE: To report the results of a prospective trial in a group of patients with tremor who underwent post hoc tractographic analysis after treatment with traditional thalamic deep brain stimulation.

METHODS: A total of 11 patients (aged 64 6 17 years, 6 male) were enrolled (essential tremor [6], Parkinson tremor [3], and myoclonic tremor in myoclonus dystonia [2]). Patients received 1 (3 patients), 2 (7 patients), or 3 (1 patient) quadripolar electrodes. A 32-direction diffusion tensor magnetic resonance imaging sequence was acquired preoperatively. Tractography was processed postoperatively for evaluation and the dentato-rubro-thalamic tract (DRT) was individually tracked. Electrode positions were determined with helical computed tomography. Electric fields (EFs) were simulated according to individual stimulation parameters in a standardized atlas brain space (ICBMMNI 152).

RESULTS: Tremor was reduced in all patients (69.4% mean) on the global (bilateral) tremor score. Effective contacts were located inside or in proximity to the DRT. In moderate tremor reduction (2 patients), the EFs were centered on its anterior border. In good and excellent tremor reduction (9 patients), EFs focused on its center.

CONCLUSION: Deep brain stimulation of the cerebello-thalamo-cortical network reduces tremor. The DRT connects 3 traditional target regions for deep brain stimulation in tremor disease. Tractography techniques can be used to directly visualize the DRT and, therefore, optimize target definition in individual patients.

Fiber tractography of basal ganglia and cerebellum in PD

Fiber tractography of basal ganglia and cerebellum in PD

J Neurosurg 120:988–996, 2014

Stimulation of white matter pathways near targeted structures may contribute to therapeutic effects of deep brain stimulation (DBS) for patients with Parkinson disease (PD). Two tracts linking the basal ganglia and cerebellum have been described in primates: the subthalamopontocerebellar tract (SPCT) and the dentatothalamic tract (DTT). The authors used fiber tractography to evaluate white matter tracts that connect the cerebellum to the region of the basal ganglia in patients with PD who were candidates for DBS.

Methods. Fourteen patients with advanced PD underwent 3-T MRI, including 30-directional diffusion-weighted imaging sequences. Diffusion tensor tractography was performed using 2 regions of interest: ipsilateral subthalamic and red nuclei, and contralateral cerebellar hemisphere. Nine patients underwent subthalamic DBS, and the course of each tract was observed relative to the location of the most effective stimulation contact and the volume of tissue activated.

Results. In all patients 2 distinct tracts were identified that corresponded closely to the described anatomical features of the SPCT and DTT, respectively. The mean overall distance from the active contact to the DTT was 2.18 ± 0.35 mm, and the mean proportional distance relative to the volume of tissue activated was 1.35 ± 0.48. There was a nonsignificant trend toward better postoperative tremor control in patients with electrodes closer to the DTT.

Conclusions. The SPCT and the DTT may be related to the expression of symptoms in PD, and this may have implications for DBS targeting. The use of tractography to identify the DTT might assist with DBS targeting in the future.

Individual Fiber Anatomy of the Subthalamic Region Revealed With Diffusion Tensor Imaging: A Concept to Identify the Deep Brain Stimulation Target for Tremor Suppression

Neurosurgery 68:1069–1076, 2011 DOI: 10.1227/NEU.0b013e31820a1a20

Deep brain stimulation (DBS) has been proven to alleviate tremor of various origins. Distinct regions have been targeted. One explanation for good clinical tremor control might be the involvement of the dentatorubrothalamic tract (DRT) as has been suggested in superficial (thalamic) and inferior (posterior subthalamic) target regions. Beyond a correlation with atlas data and the postmortem evaluation of patients treated with lesion surgery, proof for the involvement of DRT in tremor reduction in the living, the scope of this work, is elusive.

OBJECTIVE: To report a case of unilateral refractory tremor in tremor-dominant Parkinson disease treated with thalamic DBS.

METHODS: Preoperative diffusion tensor imaging (DTI) was performed. Correlation with individual DBS electrode contact locations was obtained through postoperative fusion of helical computed tomography (CT) data with DTI fiber tracking.

RESULTS: Tremor was alleviated effectively. An evaluation of the active electrode contact position revealed clear involvement of the DRT in tremor control. A closer evaluation of clinical effects and side effects revealed a highly detailed individual fiber map of the subthalamic region with DTI fiber tracking.

CONCLUSION: This is the first time the involvement of the DRT in tremor reduction through DBS has been shown in the living. The combination of DTI with postoperative CT and the evaluation of the electrophysiological environment of distinct electrode contacts led to an individual detailed fiber map and might be extrapolated to refined DTI-based targeting strategies in the future. Data acquisition for a larger study group is the topic of our ongoing research.