CLINICAL ARTICLE J Neurosurg 130:99–108, 2019 Validation of diffusion tensor imaging tractography to visualize the dentatorubrothalamic tract for surgical planning Andreas Nowacki, MD,1 Jürgen Schlaier, MD,2 Ines Debove, MD,3 and Claudio Pollo, MD1 Departments of 1Neurosurgery and 3Neurology, University Hospital Inselspital Bern, University of Bern, Switzerland; and 2Department of Neurosurgery, University of Regensburg Medical Center, Regensburg, Germany OBJECTIVE The dentatorubrothalamic tract (DRTT) has been suggested as the anatomical substrate for deep brain stimulation (DBS)–induced tremor alleviation. So far, little is known about how accurately and reliably tracking results correspond to the anatomical DRTT. The objective of this study was to systematically investigate and validate the results of different tractography approaches for surgical planning. METHODS The authors retrospectively analyzed 4 methodological approaches for diffusion tensor imaging (DTI)– based fiber tracking using different regions of interest in 6 patients with essential tremor. Tracking results were analyzed and validated with reference to MRI-based anatomical landmarks, were projected onto the stereotactic atlas of Morel at 3 predetermined levels (vertical levels -3.6, -1.8, and 0 mm below the anterior commissure–posterior commissure line), and were correlated to clinical outcome. RESULTS The 4 different methodologies for tracking the DRTT led to divergent results with respect to the MRI-based anatomical landmarks and when projected onto the stereotactic atlas of Morel. There was a statistically significant differ- ence in the lateral and anteroposterior coordinates at the 3 vertical levels (p < 0.001, 2-way ANOVA). Different fractional anisotropy values ranging from 0.1 to 0.46 were required for anatomically plausible tracking results and led to varying degrees of success. Tracking results were not correlated to postoperative tremor reduction. CONCLUSIONS Different tracking methods can yield results with good anatomical approximation. The authors recom- mend using 3 regions of interest including the dentate nucleus of the cerebellum, the posterior subthalamic area, and the precentral gyrus to visualize the DRTT. Tracking results must be cautiously evaluated for anatomical plausibility and accuracy in each patient. https://thejns.org/doi/abs/10.3171/2017.9.JNS171321 KEY WORDS dentatorubrothalamic tract; DTI fiber tracking; surgical planning; deep brain stimulation; functional neurosurgery EEP brain stimulation (DBS) is an effective option deterministic diffusion tensor imaging (DTI) tractography for treatment-refractory essential tremor (ET).4,21,26 results.11,12,25,31 Apart from other targets, the dentatorubrothalam- Current knowledge about the anatomical course of the Dic tract (DRTT) has been suggested as the anatomical sub- DRTT is mainly derived from data in monkeys.2,27 The strate for stimulation-induced tremor alleviation based on DRTT projects from the deep cerebellar nuclei mainly ABBREVIATIONS AC = anterior commissure; AP = anteroposterior; DBS = deep brain stimulation; DRTT = dentatorubrothalamic tract; DTI = diffusion tensor imaging; ET = essential tremor; FA = fractional anisotropy; fct = fasciculus cerebellothalamicus, per the Morel atlas; LAT = lateral; ML = medial lemniscus; ml = medial lemniscus, per the Morel atlas; PC = posterior commissure; PSA = posterior subthalamic area; PT = pyramidal tract; RN = red nucleus; ROI = region of interest; STN = subthalamic nucleus; TRS = Fahn-Tolosa-Marin tremor rating scale; VERT = vertical; Vim = ventral intermediate nucleus; VLp = ventrolateral posterior part of the thalamus. SUBMITTED May 30, 2017. ACCEPTED September 5, 2017. INCLUDE WHEN CITING Published online March 23, 2018; DOI: 10.3171/2017.9.JNS171321. ©AANS 2019, except where prohibited by US copyright law J Neurosurg Volume 130 • January 2019 99 Unauthenticated | Downloaded 10/05/21 07:17 AM UTC A. Nowacki et al. to the contralateral thalamus, courses through the supe- tracking based on DTI was performed using iPlan NET rior cerebellar peduncle, decussates, and passes through 3.0 software (Brainlab AG). The T2-weighted and diffu- and anterior to the red nucleus (RN) before reaching the sion-weighted sequences were fused by applying a rigid ventral thalamus. In humans, important knowledge about fusion algorithm. The DTI sequences were automatically the anatomical course of the DRTT in the subthalamic corrected for eddy current distortions and head motion. region comes from a microanatomical analysis of the The software allows one to define an arbitrary number of postmortem brain by Gallay and coworkers18 and Morel’s regions of interest (ROIs) and to adjust the minimum fiber atlas of the human thalamus and basal ganglia22 (accord- length as well as the minimum value of fractional aniso- ing to their nomenclature, the DRTT is named “fasciculus tropy (FA). cerebellothalamicus” [fct]). In previous studies, different Fiber tracking of the bilateral pyramidal tract (PT) was methods for DTI-based fiber tracking of the DRTT have performed. Three ROIs were anatomically defined based been described; however, the fiber tracking data obtained on T2-weighted sequences: a cuboid box was construct- using these different methods have been evaluated in only ed covering the precentral gyrus, identified according to a limited number of patients, and it is not known to what the Yousry criteria35 (Fig. 1A); a second cuboid box was extent the tracked fibers correspond to the anatomical constructed covering the genu and the posterior part of DRTT.11,12,19,31 This may have an impact on the comparabil- the ipsilateral internal capsule at the level of the striatum; ity between different study results and their corresponding and a manually segmented ROI constituting the ipsilateral conclusions. Furthermore, the DRTT is anatomically close lateral two-thirds of the cerebral peduncle was selected. to the medial lemniscus (ML) at the level of the midbrain. Minimal fiber length was set at 40 mm, and the FA value Therefore, fiber tracking results aiming to represent the was set between 0.29 and 0.37, resulting in the depiction of DRTT must reliably respect anatomical segregation from only 1 homogeneous fiber bundle. the ML. The ML was tracked by applying 3 ROIs: a cuboid box Given previous studies reporting different methodolo- was constructed along the postcentral gyrus, analogous gies for fiber tracking of the DRTT, the objective of our to the box constructed for the ROI for tracking the PT; study was to systematically investigate the results of differ- a second cubic box including the posterior crus of the ip- ent tractography approaches using commercially available silateral internal capsule and a third semilunar-like ROI software, for surgical planning. The tractography method- were constructed on axial slices at the level of the inferior ologies and their results are assessed in terms of feasibility colliculus covering the lateral aspect of the tegmentum, and accuracy in displaying the DRTT as well as its relation posterolateral to the substantia nigra and RN (Fig. 1H). to the ML in each patient. Additionally, tracking results Minimal fiber length was set at 40 mm and FA was set are correlated to both the anatomical DRTT based on the between 0.28 and 0.33, depending on the tracking results Morel atlas and the clinical outcome measure. in each individual patient, leaving exclusively 1 homoge- neous fiber bundle within all 3 ROIs and ignoring fibers Methods passing into the cerebellum. In the text sections below, the Patients abbreviation “ML” will be used to refer to fiber tracking results of the medial lemniscus, as opposed to “ml,” which We retrospectively analyzed 6 patients (2 male, 4 fe- will refer to the Morel atlas–based medial lemniscus. male; mean age 70 ± 10 years) with ET who had under- Fiber tracking of the DRTT was performed according gone bilateral implantation of DBS electrodes into the to 4 different approaches adapted in part from previous ventral intermediate nucleus (Vim) of the thalamus. All work by other groups. patients provided written informed consent before the en- tire procedure. The study protocol was approved by our Method 1 local ethics committee. Three different ROIs were defined: the manually seg- mented dentate nucleus of the ipsilateral cerebellum, the Magnetic Resonance Imaging ipsilateral superior cerebellar peduncle, and a cubic box Preoperative imaging was performed with a 3-T MRI including the ipsilateral precentral gyrus (Fig. 1A, C, and system (MAGNETOM Trio Tim, Siemens). Multiecho, D). The ROIs as well as the tracking parameters were fast spin echo T2-weighted sequences were obtained using adapted from the previous work of Coenen et al.11,12 Mini- the following parameters: 28 contiguous coronal slices, mum fiber length was set at 20 mm, and the FA value was slice thickness 2 mm, FOV 220 mm, acquisition matrix primarily set at 0.2 and, consequently, was adapted to dis- 128 × 128, TR 2000 msec, and multiple TEs ranging from play only 1 homogeneous fiber bundle included in all 3 12 to 96 msec in 12-msec steps. These sequences were ROIs while ignoring anatomically implausible fibers. coregistered with the DTI sequences acquired in each pa- tient: gradient directions 12, slice thickness 2.2 mm, 55 Method 2 slices, TR 10,100 msec, TE 88 msec, FOV 280 mm, ma- 2 Three different ROIs were defined based on T2-weight- trix 256 × 256, and b value 1305 sec/mm . ed images: first, the manually segmented contralateral dentate