Tractographic and Microstructural Analysis of the Dentato-Rubro-Thalamo-Cortical Tracts in Children Using Diffusion MRI.

The dentato-rubro-thalamo-cortical tract (DRTC) is the main outflow pathway of the cerebellum, contributing to a finely balanced corticocerebellar loop involved in cognitive and sensorimotor functions. Damage to the DRTC has been implicated in cerebellar mutism syndrome seen in up to 25% of children after cerebellar tumor resection. Multi-shell diffusion MRI (dMRI) combined with quantitative constrained spherical deconvolution tractography and multi-compartment spherical mean technique modeling was used to explore the frontocerebellar connections and microstructural signature of the DRTC in 30 healthy children. The highest density of DRTC connections were to the precentral (M1) and superior frontal gyri (F1), and from cerebellar lobules I-IV and IX. The first evidence of a topographic organization of anterograde projections to the frontal cortex at the level of the superior cerebellar peduncle (SCP) is demonstrated, with streamlines terminating in F1 lying dorsomedially in the SCP compared to those terminating in M1. The orientation dispersion entropy of DRTC regions appears to exhibit greater contrast than that shown by fractional anisotropy. Analysis of a separate reproducibility cohort demonstrates good consistency in the dMRI metrics described. These novel anatomical insights into this well-studied pathway may prove to be of clinical relevance in the surgical resection of cerebellar tumors.

Focused Ultrasound Thalamotomy with Dentato-Rubro-Thalamic Tractography in Patients with Spinal Cord Stimulators and Cardiac Pacemakers.

Magnetic resonance image-guided high-intensity focused ultrasound (MRgFUS)-based thermal ablation of the ventral intermediate nucleus of the thalamus (VIM) is a minimally invasive treatment modality for essential tremor (ET). Dentato-rubro-thalamic tractography (DRTT) is becoming increasingly popular for direct targeting of the presumed VIM ablation focus. It is currently unclear if patients with implanted pulse generators (IPGs) can safely undergo MRgFUS ablation and reliably acquire DRTT suitable for direct targeting. We present an 80-year-old male with a spinal cord stimulator (SCS) and an 88-year-old male with a cardiac pacemaker who both underwent MRgFUS for medically refractory ET. Clinical outcomes were measured using the Clinical Rating Scale for Tremor (CRST). DRTT was successfully created and imaging parameter adjustments did not result in any delay in procedural time in either case. In the first case, 7 therapeutic sonications were delivered. The patient improved immediately and durably with a 90% CRST-disability improvement at 6-week follow-up. In our second case, 6 therapeutic sonications were delivered with durable, 75% CRST-disability improvement at 6 weeks. These are the first cases of MRgFUS thalamotomy in patients with IPGs. DRTT targeting and MRgFUS-based thermal ablation can be safely performed in these patients using a 1.5-T MRI.

Advanced Imaging and Direct Targeting of the Motor Thalamus and Dentato-Rubro-Thalamic Tract for Tremor: A Systematic Review.

Direct targeting methods for stereotactic neurosurgery in the treatment of essential tremor have been the subject of active research over the past decade but have not yet been systematically reviewed. We present a clinically oriented topic review based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses Group guidelines. Our focus is studies using advanced magnetic resonance imaging (MRI) techniques (ultrahigh-field structural MRI, diffusion-weighted imaging, diffusion-tensor tractography, and functional MRI) for patient specific, in vivo identification of the ventral intermediate nucleus and the dentato-rubro-thalamic tract.

Functional disconnection of the dentate nucleus in essential tremor.

Despite previous functional MRI studies on alterations within the cerebello-thalamo-cortical circuit in patients with essential tremor (ET), the specific role of disconnection of the dentate nucleus (DN), the main output cerebellar pathway, still needs clarification. In this study, we evaluated DN functional connectivity (FC) changes and their relationship with motor and non-motor symptoms in ET. We studied 25 ET patients and 26 healthy controls. Tremor severity was assessed using the Fahn-Tolosa-Marin tremor rating scale (FTM-TRS) and tremor amplitude and frequency were evaluated using kinematic techniques. Cognitive profile was assessed by montreal cognitive assessment (MoCA) and frontal assessment battery (FAB). All participants underwent a 3 T MRI protocol including resting-state blood oxygenation level dependent and diffusion tensor sequences. We used a seed-based approach to investigate DN FC and to explore the diffusion properties of cerebellar peduncles. There was significantly decreased DN FC with cortical, subcortical, and cerebellar areas in ET patients compared with healthy controls. Correlation analysis showed that: (1) the DN FC with the supplementary motor area, pre and postcentral gyri, and prefrontal cortex negatively correlated with FTM-TRS score and disease duration; (2) DN FC changes in the thalamus and caudate negatively correlated with peak tremor frequency, changes in the cerebellum positively correlated with tremor amplitude, and changes in the bilateral thalamus negatively correlated with tremor amplitude, and (3) DN FC with the associative prefrontal and parietal cortices, basal ganglia, and thalamus positively correlated with the MoCA score. Diffusion abnormalities were found in the three cerebellar peduncles, which did not correlate with clinical scores.

Do the Dento-Thalamic Connections of Genetic Absence Epilepsy Rats from Strasbourg Differ from Those of Control Wistar Rats?

The thalamo-cortical circuit is important in the genesis of absence epilepsy. This circuit can be influenced by connecting pathways from various parts of central nervous system. The aim of the present study is to define the dento-thalamic connections in Wistar animals and compare the results with genetic absence epilepsy rats from Strasbourg (GAERS) using the biotinylated dextran amine (BDA) tracer. We injected BDA into the dentate nucleus of 13 (n = 6 Wistar and n = 7 GAERS) animals. The dento-thalamic connections in the Wistar animals were denser and were connected to a wider range of thalamic nuclei compared with GAERS. The dentate nucleus was bilaterally connected to the central (central medial [CM], paracentral [PC]), ventral (ventral medial [VM], ventral lateral [VL], and ventral posterior lateral [VPL]), and posterior (Po) thalamic nuclei in Wistar animals. The majority of these connections were dense contralaterally and scarce ipsilaterally. Contralateral connections were present with the parafascicular (PF), ventral posterior medial, ventral anterior (VA), and central lateral (CL) thalamic nuclei in Wistar animals. Whereas in GAERS, bilateral connections were observed with the VL and CM. Contralateral connections were present with the PC, VM, VA, and PF thalamic nuclei in GAERS. The CL, VPL, and Po thalamic nucleus connections were not observed in GAERS. The present study showed weak/deficit dento-thalamic connections in GAERS compared with control Wistar animals. The scarce information flow from the dentate nucleus to thalamus in GAERS may have a deficient modulatory role on the thalamus and thus may affect modulation of the thalamo-cortical circuit.

Comparison of posterior subthalamic area deep brain stimulation for tremor using conventional landmarks versus directly targeting the dentatorubrothalamic tract with tractography.

OBJECTIVE: To compare posterior subthalamic area deep brain stimulation (PSA-DBS) performed in the conventional manner against diffusion tensor imaging and tractography (DTIT)-guided lead implantation into the dentatorubrothalamic tract (DRTT). PATIENTS AND METHODS: Double-blind, randomised study involving 34 patients with either tremor-dominant Parkinson's disease or essential tremor. Patients were randomised to Group A (DBS leads inserted using conventional landmarks) or Group B (leads guided into the DRTT using DTIT). Tremor (Fahn-Tolosa-Marin) and quality-of-life (PDQ-39) scores were evaluated 0-, 6-, 12-, 36- and 60-months after surgery. RESULTS: PSA-DBS resulted in marked tremor reduction in both groups. However, Group B patients had significantly better arm tremor control (especially control of intention tremor), increased mobility and activities of daily living, reduced social stigma and need for social support as well as lower stimulation amplitudes and pulse widths compared to Group A patients. The better outcomes were sustained for up to 60-months from surgery. The active contacts of Group B patients were consistently closer to the centre of the DRTT than in Group A. Speech problems were more common in Group A patients. CONCLUSION: DTIT-guided lead placement results in better and more stable tremor control and fewer adverse effects compared to lead placement in the conventional manner. This is because DTIT-guidance allows closer and more consistent placement of leads to the centre of the DRTT than conventional methods.

Targeting of the dentato-rubro-thalamic tract for MR-guided focused ultrasound treatment of essential tremor.

BACKGROUND: Magnetic resonance-guided focused ultrasound ablation of the thalamic ventral intermediate nucleus is a safe and effective treatment for medically refractory essential tremor. However, indirect targeting of the ventral intermediate nucleus using stereotactic coordinates from normal neuroanatomy can be inefficient. We therefore evaluated the feasibility of supplementing this method with direct targeting of the dentato-rubro-thalamic tract. METHODS: We retrospectively identified four patients undergoing magnetic resonance-guided focused ultrasound ablation for essential tremor in which preoperative diffusion tractography imaging of the dentato-rubro-thalamic tract was fused with T2 weighted-imaging and utilized for intra-procedural targeting. The size and location of the dentato-rubro-thalamic tract and 24-hour lesion, as well as the center of the stereotactic coordinates, was evaluated. Finally, the amount of overlap between the dentato-rubro-thalamic tract and the lesion was calculated. RESULTS: The 24-hour lesion size was homogeneous in the cohort (mean 31.3 mm2, range 30-32 mm2), while there was substantial variation in the dentato-rubro-thalamic tract area (mean 14.3 mm2, range 3-24 mm2). The center of the stereotactic coordinates and dentato-rubro-thalamic tract diverged by more than 1 mm in mediolateral and anterposterior directions in all patients, while the dentato-rubro-thalamic tract and lesion centers were in close proximity (mean mediolateral separation 1 mm, range 0.1-2.2 mm; mean anteroposterior separation 0.75 mm, range 0.4-1.2 mm). There was greater than 50% coverage of the dentato-rubro-thalamic tract by the lesion in all patients (mean 82.9%, range 66.7-100%). All patients experienced durable tremor relief. CONCLUSION: Direct targeting of the dentato-rubro-thalamic tract using diffusion tractography imaging fused to T2 weighted-imaging may be a useful strategy for focused ultrasound treatment of essential tremor. Further investigation of the technique is warranted.

Metronidazole-induced encephalopathy caused by hyperbaric oxygen therapy in a patient with mandibular osteomyelitis.

Metronidazole (MNZ) is prescribed for the treatment of infection caused by anaerobic bacteria and protozoa. Metronidazole-induced encephalopathy (MIE) has been known to be a side-effect, although its onset ratio is unclear. However, to the best of our knowledge, MIE associated with hyperbaric oxygen therapy (HBO) has not been previously reported. Here, we present the case of a 68-year-old man with mandibular osteomyelitis who received metronidazole for 49 days and received five times HBO therapy. He visited our hospital for evaluation and treatment of peripheral neuropathy, speech disturbance, nausea, and disturbance of gait after 47 days of initiating metronidazole treatment. Brain magnetic resonance imaging revealed hyperintense lesions in the cerebellar dentate nuclei, which was consistent with MIE. The patient's ataxic symptoms improved in 15 days after the discontinuation of MNZ. This is the first report demonstrating case of MIE could be related with HBO, as far as we had searched.

Thalamic and dentate nucleus abnormalities in the brain of children with Gaucher disease.

Gaucher disease (GD) represents the most common lysosomal storage defect. It is classified into three phenotypes: type 1 non-neuronopathic, type 2 acute neuronopathic, and type 3 subacute/chronic neuronopathic. Although children affected by GD may present with a broad spectrum of neurological signs, brain magnetic resonance imaging (MRI) findings are usually normal or non-specific. We report three cases of GD with previously undescribed brain MRI changes mainly affecting the thalami and/or the dentate nuclei. We discuss the possible etiopathogenesis of these abnormalities. Correlation between brain MRI abnormalities, neurological symptoms, and treatment efficacy is still unclear.

Does renal function affect gadolinium deposition in the brain?

OBJECTIVE: Was to compare T1 signal intensity ratios of dentate nucleus to cerebellar white matter (DN/cerebellum), dentate nucleus to pons (DN/pons) and globus pallidus to thalamus (GP/thalamus) in patients with normal renal function and in patients on chronic hemodialysis. To find out if renal function affects the deposition of gadolinium in brain after administration of linear gadolinium based contrast agents (GBCA). METHODS: Seventy eight contrast enhanced brain MRIs (Magnetic Resonance Imaging) with linear GBCA of 13 patients on chronic hemodialysis and 13 patients with normal renal function retrospectively evaluated. The DN/pons, DN/cerebellum and GP/thalamus signal intensity ratios were measured from each brain MRI on unenhanced axial T1 weighted images. RESULTS: In hemodialysis group statistically significant increase in the signal intensity ratios of DN/pons, DN/cerebellum and GP/thalamus were found between the first and the last brain MRIs (p = .001). The increase in the signal intensity ratios of DN/pons, DN/cerebellum and GP/thalamus between the first and the last brain MRIs in control group were not significant (p > 0.05). The signal intensity increase in DN and globus pallidus were significantly higher in hemodialysis group than control group (p < 0.05). CONCLUSIONS: Patients on hemodialysis had significantly higher DN and GP signal intensity increase compared to the patients with normal renal function. Renal function affects the rate of gadolinium deposition in the brain after administration of linear GBCA.

Structural and functional connectivity of the nondecussating dentato-rubro-thalamic tract.

The dentato-rubro-thalamic tract (DRTT) regulates motor control, connecting the cerebellum to the thalamus. This tract is modulated by deep-brain stimulation in the surgical treatment of medically refractory tremor, especially in essential tremor, where high-frequency stimulation of the thalamus can improve symptoms. The DRTT is classically described as a decussating pathway, ascending to the contralateral thalamus. However, the existence of a nondecussating (i.e. ipsilateral) DRTT in humans was recently demonstrated, and these tracts are arranged in distinct regions of the superior cerebellar peduncle. We hypothesized that the ipsilateral DRTT is connected to specific thalamic nuclei and therefore may have unique functional relevance. The goals of this study were to confirm the presence of the decussating and nondecussating DRTT pathways, identify thalamic termination zones of each tract, and compare whether structural connectivity findings agree with functional connectivity. Diffusion-weighted imaging was used to perform probabilistic tractography of the decussating and nondecussating DRTT in young healthy subjects from the Human Connectome Project (n = 91) scanned using multi-shell diffusion-weighted imaging (270 directions; TR/TE = 5500/89 ms; spatial resolution = 1.25 mm isotropic). To define thalamic anatomical landmarks, a segmentation procedure based on the Morel Atlas was employed, and DRTT targeting was quantified based on the proportion of streamlines arriving at each nucleus. In parallel, functional connectivity analysis was performed using resting-state functional MRI (TR/TE = 720/33 ms; spatial resolution = 2 mm isotropic). It was found that the decussating and nondecussating DRTTs have significantly different thalamic endpoints, with the former preferentially targeting relatively anterior and lateral thalamic nuclei, and the latter connected to more posterior and medial nuclei (p < 0.001). Functional and structural connectivity measures were found to be significantly correlated (r = 0.45, p = 0.031). These findings provide new insight into pathways through which unilateral cerebellum can exert bilateral influence on movement and raise questions about the functional implications of ipsilateral cerebellar efferents.

Validation of diffusion tensor imaging tractography to visualize the dentatorubrothalamic tract for surgical planning.

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 difference 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 recommend 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.

Changes in Signal Intensity of the Dentate Nucleus and Globus Pallidus in Pediatric Patients: Impact of Brain Irradiation and Presence of Primary Brain Tumors Independent of Linear Gadolinium-based Contrast Agent Administration.

Purpose To determine whether whole-brain irradiation, chemotherapy, and primary brain pathologic conditions affect magnetic resonance (MR) imaging signal changes in pediatric patients independent of the administration of gadolinium-based contrast agents (GBCAs). Materials and Methods This institutional review board-approved, HIPAA-compliant study included 144 pediatric patients who underwent intravenous GBCA-enhanced MR imaging examinations (55 patients with primary brain tumors and whole-brain irradiation, 19 with primary brain tumors and chemotherapy only, 52 with primary brain tumors without any treatment, and 18 with neuroblastoma without brain metastatic disease). The signal intensities (SIs) in the globus pallidus (GP), thalamus (T), dentate nucleus (DN), and pons (P) were measured on unenhanced T1-weighted images. GP:T and DN:P SI ratios were compared between groups by using the analysis of variance and were analyzed relative to group, total cumulative number of doses of GBCA, age, and sex by using multivariable linear models. Results DN:P ratio for the radiation therapy group was greater than that for the other groups except for the group of brain tumors treated with chemotherapy (P < .05). The number of GBCA doses was correlated with the DN:P ratio for the nontreated brain tumor group (P < .0001). The radiation therapy-treated brain tumor group demonstrated higher DN:P ratios than the nontreated brain tumor group for number of doses less than or equal to 10 (P < .0001), whereas ratios in the nontreated brain tumor group were higher than those in the radiation therapy-treated brain tumor group for doses greater than 20 (P = .05). The GP:T ratios for the brain tumor groups were greater than that for the neuroblastoma group (P = .01). Conclusion Changes in SI of the DN and GP that are independent of the administration of GBCA occur in patients with brain tumors undergoing brain irradiation, as well as in patients with untreated primary brain tumors. © RSNA, 2017.

Aggravation of an injured dentato-rubro-thalamic tract in a patient with mild traumatic brain injury: A case report.

RATIONALE: We report on a patient with mild traumatic brain injury (TBI) by follow-up diffusion tensor tractography (DTT), and observed for approximately nine monthsby serial diffusion tensor tractography (DTT). PATIENT CONCERNS: A 66-year-old male patient was injured in a car crash. Approximately four weeks after the crash, he developed a tremor in the right hand and leg. His symptoms worsened over time. DIAGNOSES: Approximately six months after the crash, he developed a mild tremor in the left hand. Nine months after the crash, he manifested severe tremor in his right hand, mild resting and intentional tremor in his left hand and both legs, and mild trunkal ataxia. INTERVENTIONS: N/A. OUTCOMES: On 3-week DTT, well reconstructed DRTTs were observed in both hemispheres, except for the thinned lower portion of the right DRTT. On 9-month DTT, the right lower DRTT had thinned compared with the 3-week DTT and showed a disruption at the upper portion. The left DRTT showed thinning in the lower portion and tearing in the upper portion compared with 3-week DTT. LESSONS: Aggravation of an injured DRTT was demonstrated in a patient with mild TBI, using serial DTT examination.

Up to 52 administrations of macrocyclic ionic MR contrast agent are not associated with intracranial gadolinium deposition: Multifactorial analysis in 385 patients.

PURPOSE: To determine whether multiple repeated administrations of gadolinium-based macrocyclic ionic MR contrast agent (MICA) are associated with intracranial gadolinium deposition and identify the predisposing factors for deposition in various clinical situations. MATERIALS AND METHODS: In this institutional review board-approved retrospective study, 385 consecutive patients who underwent MICA-enhanced MR imaging were enrolled. The dentate nucleus-to-pons (DN/P) and globus pallidus-to-thalamus (GP/Th) signal intensity (SI) ratios on unenhanced T1-weighted images were recorded by 2 independent readers and averaged. The mean DN/P and GP/Th SI ratio difference between the last and the first examinations were tested using the one-sample t-test. Student's t-test and stepwise regression analysis were used to identify the predisposing factors for deposition based on the number of administrations, time interval, hepatic and renal function, magnetic field strength, and chemo- or radiation therapy. RESULTS: The mean DN/P SI ratio difference was not different from zero (P = .697), even in patients with ≥20 administrations (n = 33). Only patients with abnormal renal function showed an increase in the mean DN/P SI ratio difference (P = .019). The mean DN/P SI ratio difference was not associated with any predisposing factors. However, the mean GP/Th SI ratio difference showed decrease (P < .001), which was associated with age (P = .007), number of administrations (P = .01) and number of radiation therapy sessions (P = .022) on multivariate analysis. CONCLUSION: Multiple repeated administrations of MICA were not associated with increased T1 signal intensity in deep brain nuclei suggestive of Gd deposition in patients with normal renal function.

Injury of the dentato-rubro-thalamic tract in patients with cerebellar infarct: Case report.

RATIONALE: Several studies using diffusion tensor tractography (DTT) have reported on injury in the dentato-rubro-thalamic tract (DRTT) in patients with brain injury. However, there is no study of injury in the DRTT following cerebellar infarct. We report on patients with injury in the DRTT following cerebellar infarct, demonstrated on DTT. PATIENT CONCERNS: Three patients with cerebellar infarct were enrolled in this study. Diffusion tensor imaging data were acquired at 3 weeks (patient 1) and 2 weeks (patients 2 and 3) after onset and the DRTT was reconstructed. The Scale for Assessment and Rating of Ataxiaand the Functional Ambulation Category were used for evaluation of ataxia and gait function. DIAGNOSES AND OUTCOMES: With clinical evaluation, patient 1 scored 18, patient 2 scored 22, and patient 3 scored 28 points on the Scale for Assessment and Rating of Ataxia. On the Functional Ambulation Category patient 1 scored 2, patient 2 scored 2, and patient 3 scored 1 point. DRTT abnormalities were as follows: discontinuation (the upper portion of the left DRTT in the patient 1), narrowing (the lower portion of the left DRTT in patient 2, and the whole right DRTT in the patient 3), and nonreconstruction (the left DRTT in the patient 3). LESSONS: Using DTT, we demonstrated injury in the DRTT in 3 patients with severe ataxia following cerebellar infarct. We believe that evaluation of the DRTT would be helpful in patients who develop ataxia following cerebellar infarct.

Functional disconnection of thalamic and cerebellar dentate nucleus networks in progressive supranuclear palsy and corticobasal syndrome.

AIM: To assess functional rearrangement following neurodegeneration in the thalamus and dentate nucleus in patients with progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). METHODS: We recruited 19 patients with PSP, 11 with CBS and 14 healthy subjects. All the subjects underwent resting-state (rs) fMRI using a 3T system. Whole brain functional connectivity of the thalamus and dentate nucleus were calculated by means of a seed-based approach with FEAT script in FSL toolbox. Thalamic volume was calculated by means of FIRST, and the dentate area by means of Jim software. RESULTS: Both thalamic volume and dentate area were significantly smaller in PSP and CBS patients than in healthy subjects. No significant difference emerged in thalamic volume between PSP and CBS patients, whereas dentate area was significantly smaller in PSP than in CBS. Thalamic functional connectivity was significantly reduced in both patient groups in various cortical, subcortical and cerebellar areas. By contrast, changes in dentate nucleus functional connectivity differed in PSP and CBS: it decreased in subcortical and prefrontal cortical areas in PSP, but increased asymmetrically in the frontal cortex in CBS. CONCLUSIONS: Evaluating the dentate nucleus size and its functional connectivity may help to differentiate patients with PSP from those with CBS.

Signal intensity change on unenhanced T1-weighted images in dentate nucleus and globus pallidus after multiple administrations of gadoxetate disodium: an intraindividual comparative study.

PURPOSE: To investigate whether there is an increased signal intensity (SI) of dentate nucleus (DN) and globus pallidus (GP) on unenhanced T1-weighted magnetic resonance imaging (MRI), in patients who had undergone multiple administrations of gadoxetate disodium. MATERIALS AND METHODS: We retrospectevely included stage III melanoma patients, who had been previously enrolled in a trial of adjuvant therapy and who had undergone whole-body contrast-enhanced MRIs with gadoxetate disodium every three months for their follow-up. The SI ratios of DN-to-pons and GP-to-thalamus on unenhanced T1-weighted images were calculated. The difference in SI ratios between the first and the last MRI examinations was assessed and a linear mixed model was performed to detect how SI ratios varied with the number of administrations. RESULTS: Eighteen patients were included in our study. The number of gadoxetate disodium administrations ranged from 2 to 18. Paired t-test did not show any significant difference in DN-to-pons (p=0.21) and GP-to-thalamus (p=0.09) SI ratios by the end of the study. DN-to-pons SI ratio and GP-to-thalamus SI ratio did not significantly increase with increasing the number of administrations (p=0.14 and p=0.06, respectively). CONCLUSION: Multiple administrations of gadoxetate disodium are not associated with increased SI in DN and GP in the brain. KEY POINTS: • Gadolinium may deposit in the human brain after multiple GBCA administrations. • Gadolinium deposition is associated with increased T1W signal intensity • Increase in signal intensity is most apparent within the DN and GP • Multiple administrations of gadoxetate disodium do not increase T1W signal.

Deep Brain Stimulation of the Dentato-Rubro-Thalamic Tract: Outcomes of Direct Targeting for Tremor.

OBJECTIVES: Targeting the dentato-rubro-thalamic tract (DRTt) has been suggested to be efficacious in deep brain stimulation (DBS) for tremor suppression, both in case reports and post-hoc analyses. This prospective observational study sought to analyze outcomes after directly targeting the DRTt in tremor patients. METHODS: 20 consecutively enrolled intention tremor patients obtained pre-operative MRI with diffusion tensor (dTi) sequences. Mean baseline tremor amplitude based on The Essential Tremor Rating Assessment Scale was recorded. The DRTt was drawn for each individual on StealthViz software (Medtronic) using the dentate nucleus as the seed region and the ipsilateral pre-central gyrus as the end region and then directly targeted during surgery. Intraoperative testing confirmed successful tremor control. Post-operative analysis of electrode position relative to the DRTt was performed, as was post-operative assessment of tremor improvement. RESULTS: The mean age of patients was 66.8 years; mean duration of tremor was 16 years. Mean voltage for the L electrode = 3.4 V; R = 2.6 V. Mean distance from the center of the active electrode contact to the DRTt was 0.9 mm on the L, and 0.8 mm on the R. Improvement in arm tremor amplitude from baseline after DBS was significant (P < 0.001). CONCLUSION: Direct targeting of the DRTt in DBS is an effective strategy for tremor suppression. Accounting for hardware, software, and model limitations, depiction of the DRTt allows for placement of electrode contacts directly within the fiber tract for modulation despite any anatomical variation, which reproducibly resulted in good tremor control.