Evaluation of signal intensity changes in dentate nucleus and globus pallidus on magnetic resonance imaging after intrathecal gadolinium-based contrast agent administration.

PURPOSE: Gadolinium deposition has been reported in several normal anatomical structures in the brain after repeated administration of intravenous gadolinium-based contrast agents (GBCAs) used in magnetic resonance imaging (MRI). This study presents preliminary results to see if there is any gadolinium deposition in the dentate nucleus and globus pallidus after using intrathecal GBCAs. METHODS: Between November 2018 and November 2020, 29 patients who underwent intrathecal contrast-enhanced MR cisternography with the suspicion of rhinorrhea were included in this prospective study. In contrast-enhanced MR cisternography, gadoterate meglumine was administered by intrathecal injection at a dose of 1 ml. One month later, patients had a control MRI with 3D T1 SPACE fat-saturated (FS) and susceptibility weighted images (SWI) sequences. The ratio of dentate nucleus signal intensity to middle cerebellar peduncle signal intensity (DN/MCP ratio) and the ratio of globus pallidus signal intensity to thalamus signal intensity (GP/T ratio) were calculated using region of interest (ROI) on pre-contrast and control MRI sequences. RESULTS: There was no significant difference for DN/MCP ratio and GP/T ratio on 3D T1 SPACE FS and SWI sequences after intrathecal GBCAs administration compared to baseline MRI. CONCLUSION: Administration of intrathecal GBCAs did not cause a measurable change in the signal intensity of the dentate nucleus and globus pallidus after a single injection.

Higher magnetic susceptibility of globus pallidus in patients after macrocyclic GBCAs: assessment using quantitative susceptibility mapping.

BACKGROUND: As previous studies reported, gadolinium deposits in globus pallidus (GP) and dentate nucleus (DN) after repeated administrations of gadolinium-based contrast agents (GBCAs) and a signal intensity (SI) increase on T1-weighted images were related to linear GBCAs, not macrocyclic GBCAs. PURPOSE: To identify whether quantitative susceptibility mapping (QSM) could measure a subtle increase in magnetic susceptibility in DN and GP in patients after repeated administrations of gadoteric acid meglumine (Gd-DOTA). MATERIAL AND METHODS: In this study, 50 patients with cerebral tumors who had received at least three injections of Gd-DOTA (GBCA group) and 50 individuals without a history of GBCA injections (non-GBCA group) were included. The image data for QSM and T1-weighted images were reviewed. Spearman rank correlation was used to estimate the associations between the values (magnetic susceptibility of QSM and SI ratios of T1-weighted images) and the number of Gd-DOTA injections. RESULTS: The mean magnetic susceptibility of GP in GBCA group was 0.136 ± 0.031 ppm, which was significantly higher than that in control group (0.114 ± 0.030 ppm) (P = 0.001). In the GBCA group (n = 50), we found a substantial positive correlation between magnetic susceptibility of GP and the number of Gd-DOTA injections according to Spearman rank correlation coefficient (ρ = 0.673, P = 0.0001). There was a modest but significant correlation between magnetic susceptibility of DN and the number of Gd-DOTA injections (ρ = 0.311, P = 0.028). CONCLUSION: In comparison to the control group, the magnetic susceptibility of GP in the GBCA group was significantly higher and had a substantial positive association with the number of Gd-DOTA injections.

Dentate Nucleus Signal Intensity Changes in Children with Adrenoleukodystrophy in Comparison to Primary Brain Tumor with and without Radiotherapy after Gadobutrol Administration.

BACKGROUND AND PURPOSE: To determine whether cerebral adrenoleukodystrophy (cALD) or brain irradiation in patients with primary brain tumor affects T1-weighted imaging (T1WI) signal intensity (SI) of the dentate nucleus (DN) in a pediatric cohort who had received consecutive macrocyclic gadolinium-based contrast agent (mcGBCA) gadobutrol. METHODS: This study included 97 pediatric patients who underwent mcGBCA-enhanced MRI from 2010 to 2020 (29 children with primary brain tumors without brain radiation therapy [mcGBCA group-1], 33 children with primary brain tumors and radiation treatment [mcGBCA group-2], 35 children with cALD [mcGBCA group-3], and 97 sex-/age-matched control subjects [subgroups matched to each of the three subject groups] without GBCA administration). The DN-to-middle cerebellar peduncle (MCP) SI ratios on T1WI were then determined. A paired t-test was performed to compare SI ratios between children exposed to mcGBCA in each group and control subjects. The relationships between SI ratios and confounding variables were analyzed utilizing the Pearson correlation analysis. RESULTS: The DN-to-MCP SI ratio was significantly higher of mcGBCA group-2 (1.046±.071) or mcGBCA group-3 (.972±.038) than in the control group-2 (.983±.041, P<.001) and control group-3 (.937±.051, P = .002), respectively, but no significant difference of the SI ratio was noted between mcGBCA group-1 (.984±.032) and control-group-1 (.982±.035, P = .860). No significant correlation was noted between SI ratio values and the cumulative dose or number of mcGBCA administrations, age, or the elapsed time between the MRI examinations (all P>.05). CONCLUSIONS: Hyperintense T1WI signal in the DN may be seen in children with brain tumors undergoing brain irradiation, as well as in children with cALD.

Tuber Locations Associated with Infantile Spasms Map to a Common Brain Network.

OBJECTIVE: Approximately 50% of patients with tuberous sclerosis complex develop infantile spasms, a sudden onset epilepsy syndrome associated with poor neurological outcomes. An increased burden of tubers confers an elevated risk of infantile spasms, but it remains unknown whether some tuber locations confer higher risk than others. Here, we test whether tuber location and connectivity are associated with infantile spasms. METHODS: We segmented tubers from 123 children with (n = 74) and without (n = 49) infantile spasms from a prospective observational cohort. We used voxelwise lesion symptom mapping to test for an association between spasms and tuber location. We then used lesion network mapping to test for an association between spasms and connectivity with tuber locations. Finally, we tested the discriminability of identified associations with logistic regression and cross-validation as well as statistical mediation. RESULTS: Tuber locations associated with infantile spasms were heterogenous, and no single location was significantly associated with spasms. However, >95% of tuber locations associated with spasms were functionally connected to the globi pallidi and cerebellar vermis. These connections were specific compared to tubers in patients without spasms. Logistic regression found that globus pallidus connectivity was a stronger predictor of spasms (odds ratio [OR] = 1.96, 95% confidence interval [CI] = 1.10-3.50, p = 0.02) than tuber burden (OR = 1.65, 95% CI = 0.90-3.04, p = 0.11), with a mean receiver operating characteristic area under the curve of 0.73 (±0.1) during repeated cross-validation. INTERPRETATION: Connectivity between tuber locations and the bilateral globi pallidi is associated with infantile spasms. Our findings lend insight into spasm pathophysiology and may identify patients at risk. ANN NEUROL 2021;89:726-739.

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.

Palatal Tremor - Pathophysiology, Clinical Features, Investigations, Management and Future Challenges.

Background: Palatal tremor is involuntary, rhythmic and oscillatory movement of the soft palate. Palatal tremor can be classified into three subtypes; essential, symptomatic and palatal tremor associated with progressive ataxia. Methods: A thorough Pubmed search was conducted to look for the original articles, reviews, letters to editor, case reports, and teaching neuroimages, with the keywords "essential", "symptomatic palatal tremor", "myoclonus", "ataxia", "hypertrophic", "olivary" and "degeneration". Results: Essential palatal tremor is due to contraction of the tensor veli palatini muscle, supplied by the 5th cranial nerve. Symptomatic palatal tremor occurs due to the contraction of the levator veli palatini muscle, supplied by the 9%th and 10%th cranial nerves. Essential palatal tremor is idiopathic, while symptomatic palatal tremor occurs due to infarction, bleed or tumor within the Guillain-Mollaret triangle. Progressive ataxia and palatal tremor can be familial or idiopathic. Symptomatic palatal tremor and sporadic progressive ataxia with palatal tremor show signal changes in inferior olive of medulla in magnetic resonance imaging. The treatment options available for essential palatal tremor are clonazepam, lamotrigine, sodium valproate, flunarizine and botulinum toxin. The treatment of symptomatic palatal tremor involves the treatment of the underlying cause. Discussion: Further studies are required to understand the cause and pathophysiology of Essential palatal tremor and progressive ataxia and palatal tremor. Similarly, the link between tauopathy and palatal tremor associated progressive ataxia needs to be explored further. Oscillopsia and progressive ataxia are more debilitating than palatal tremor and needs new treatment approaches.

MRI and Quantitative Magnetic Susceptibility Maps of the Brain after Serial Administration of Gadobutrol: A Longitudinal Follow-up Study.

Background The relationship between administration of macrocyclic gadolinium-based contrast agents and T1-weighted signal intensity (SI) change of the globus pallidus (GP) and dentate nucleus (DN) is, to the knowledge of the authors, not known. Purpose To determine if quantitative susceptibility mapping (QSM) can detect changes in magnetic susceptibility of the GP and DN after serial administration of macrocyclic gadobutrol in patients with primary brain tumors. Materials and Methods Patients diagnosed with primary brain tumors from August 2014 to February 2019 were eligible for this single-center retrospective study. Among 501 consecutive adult patients who were given at least one administration of gadobutrol, those who were previously administered an unknown or linear gadolinium-based contrast agent were excluded. Brain MRI scans with three-dimensional gradient-recalled-echo image phase data for QSM processing were reviewed. Regions of interest were drawn on the GP and DN on the basis of semiautomatic thresholding. Univariable generalized estimation equations were used to determine the associations between MRI measures (SI on T1-weighted images and magnetic susceptibility on QSM) and number of gadobutrol doses. Potential confounding factors were adjusted for in multivariable generalized estimating equation. Results Ninety patients (mean age, 51 years ± 17 [standard deviation]; 51 men) with 199 MRI scans were analyzed. In models adjusted for repeated observations between injections, the number of injections of gadobutrol was associated with the magnetic susceptibility of the GP (1.4 × 10-3 ppm/number of gadobutrol injections; P = .01) and DN (8.1 × 10-4 ppm/number of gadobutrol injections; P = .03). After adjustment for confounders, the number of gadobutrol injections remained an independent predictor of increased magnetic susceptibility in the GP (1.3 × 10-3 ppm/number of gadobutrol injections; 95% confidence interval: 0.39 × 10-3, -2.4 × 10-3; P = .006). There were no associations between number of gadobutrol injections and SI or magnetic susceptibility in the DN. Conclusion The magnetic susceptibility of the globus pallidus increased after serial administration of gadobutrol. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Wang and Prince in this issue.

Effect of Exposure to Gadodiamide and Brain Irradiation on T1 -Weighted Images and ADC Maps of the Dentate Nucleus.

BACKGROUND: Brain irradiation is considered a cofactor influencing the dentate nucleus (DN) signal intensity (SI) on unenhanced T1 -weighted images in patients exposed to gadolinium-based contrast agents (GBCAs). PURPOSE: To assess the effect of gadodiamide and whole-brain radiation therapy (WBRT) on T1 -weighted images and on apparent diffusion coefficient (ADC) maps of DN. STUDY TYPE: Single-center retrospective. POPULATION: In all, 125 patients who underwent brain MRIs were classified into four groups: 1) patients who did neither receive intravenous GBCAs injections nor irradiation (controls); 2) patients having ≥3 GBCAs-enhanced scans and no WBRT; 3) patients having WBRT and < 3 GBCAs-enhanced scans; and 4) patients having WBRT and ≥ 3 GBCAs-enhanced scans. FIELD STRENGTH/SEQUENCE: 1.5T magnet, echo-planar diffusion weighted imaging (DWI) and unenhanced T1 -weighted sequences. ASSESSMENT: The DN-to-pons SI ratio on unenhanced T1 -weighted images and ADC values of the DN were calculated. Values were compared between groups and relative to the cumulative gadolinium dose and to the time delay after WBRT. STATISTICAL TESTS: Statistical analysis included the Mann-Whitney U-test and Spearman's rank-order correlation. RESULTS: DN ADC values were not significantly different (P = 0.34) between patients exposed to gadodiamide (0.81 ± 0.06) and controls (0.83 ± 0.07). There were no differences in DN ADC values (P = 0.28) and DN-to-pons SI ratios (P = 0.42) between patients exposed to WBRT (ADC values: 0.85 ± 0.09; SI ratio: 1.11 ± 0.10) and controls (ADC values: 0.83 ± 0.06; SI ratio: 1.09 ± 0.06). There was a significant negative correlation between DN ADC values and the time (days) since the end of WBRT (r = - 0.33; 95% confidence interval [CI]: -0.55, -0.06; P < 0.05). DATA CONCLUSION: We did not find changes suggestive of gadolinium-related tissue microstructural damage of the DN. The ADC values of the DN are associated with the time from WBRT. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 5.

Dentate Nucleus Signal Intensity Increases Following Repeated Gadobenate Dimeglumine Administrations: A Retrospective Analysis.

Background Increased cerebral signal intensity (SI) has been reported in patients undergoing MRI with gadolinium-based contrast agents (GBCAs). Published data on gadobenate dimeglumine have been somewhat contradictory. Purpose To evaluate the relationship between dosage of gadobenate dimeglumine and SI change at MRI following multiple gadobenate dimeglumine administrations. Materials and Methods In this retrospective study, patients referred for clinically indicated brain MRI from January 2006 through May 2016 were evaluated for inclusion. Eligible patients were between 18 and 90 years old at their baseline brain MRI and had never received a GBCA, had undergone three or more MRI examinations with gadobenate dimeglumine, and had the baseline scan and another brain MRI scan available for comparison. The primary group consisted of patients with four or fewer supratentorial lesions smaller than 3 cm who underwent axial T1-weighted MRI at 1.5 T. One patient had also undergone prior radiation therapy. The secondary group consisted of patients with a history of brain radiation therapy or craniotomy who underwent 1.5-T and 3-T same-plane T1-weighted MRI (in any order). The SI for up to eight brain MRI examinations per patient was measured, and relative SI changes from baseline to interval scans were calculated. A subgroup analysis was performed to assess the gadobenate dimeglumine washout since the last gadolinium exposure. All patients had normal renal and liver functions. Linear mixed regression analyses were performed for variables with P < .05. Results In 43 patients (14 men, 29 women; median age, 49 years; age range, 25-73 years), the dentate nucleus (DN)-to-middle cerebral peduncle (MCP) SI ratio showed a mean increase of 6.7% ± 3.9 in the primary group and 4.0% ± 2.7 in the secondary group (both P < .001) following the administration of 134 mL ± 141 gadobenate dimeglumine over 55 months ± 35.2. The DN/MCP SI ratio increased linearly with the amount of gadobenate dimeglumine, with a mean increase of 0.015% ± 0.004 per 1 mL of gadobenate dimeglumine (R2 = 0.3, P < .001). Conclusion In patients receiving multiple doses of gadobenate dimeglumine, a linear relationship existed between gadobenate dimeglumine administrations and an increase in the dentate nucleus-to-middle cerebral peduncle signal intensity ratio at MRI. © RSNA, 2020 See also the editorial by McDonald and Kallmes in this issue.

Impact of nasopharyngeal irradiation and gadolinium administration on changes in T1 signal intensity of the dentate nucleus in nasopharyngeal malignancy patients without intracranial abnormalities.

BACKGROUND: Irradiation has been found to increase T1 signal intensity (SI) of the dentate nucleus (DN) by accelerating the gadolinium deposition in patients after multiple gadolinium-based contrast agent (GBCA) administrations. Several reports have focused on this phenomenon in patients with brain tumors; however, data in patients receiving irradiation with no intracranial abnormalities (NIAs) are lacking. PURPOSE: To explore how nasopharyngeal irradiation affected SI changes on unenhanced T1 -weighted imaging (T1 WI) in the DN in nasopharyngeal malignancy (NPM) patients who presented with NIAs and who had multiple injection doses (IDs) of linear GBCAs. STUDY TYPE: Single-center, retrospective, case-control study. POPULATION: In all, 132 subjects: 66 NPM patients, 66 matched controls. FIELD STRENGTH/SEQUENCE: 1.5T and 3T/T1 WI, T2 WI, and fluid-attenuated inversion recovery (FLAIR). ASSESSMENT: Radiation doses (RDs) were calculated by a radiotherapy technician. SIs were measured by a radiologist. The DN-to-cerebellar white matter (CWM) SI ratios and their relative percentage change (Rchange ) were compared. STATISTICAL TESTS: Shapiro-Wilk test, paired t-test, independent t-test, Mann-Whitney U-test, Pearson and Spearman correlation. RESULTS: DN/CWM b ratios or R change from the NPM group were significantly higher than those from the control group (P < 0.001). No significant difference of DN/CWM a ratios was found between the two groups (P > 0.05). Positive correlations between R change , DN/CWM b ratio, and the number of IDs were found in both the NPM and control groups (P < 0.01). The overall changes of DN/CWM b ratio or R change between NPM and control groups were higher for the higher-IDs subgroup (≥10) than for the lower-IDs subgroup (<10). DATA CONCLUSION: Nasopharyngeal irradiation appeared to increase SI in T1 WI in NPM patients with NIAs and repeated GBCA administrations relative to control patients who also underwent GBCA administrations, especially when IDs ≥10. However, no significant association between R change and RDs to the DNs was found. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:250-259.

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.

Signal intensity increases in dentate nucleus/globus pallidus/pulvinar on unenhanced T1WI MR images after multiple examinations with gadodiamide.

BACKGROUND AND PURPOSE: Elevated signal intensity (SI) in the dentate nucleus (DN), globus pallidus (GP) and pulvinar (PUL) was reportedly observed on unenhanced T1-weighted (T1WI) magnetic resonance (MR) images in patients receiving multiple enhanced MR examinations. We aimed to clarify whether this phenomenon influences the long-term neurological status of patients. MATERIALS AND METHODS: We studied 196 radiosurgically treated patients undergoing ≥10 MR examinations using a single dose of gadodiamide and the same 1.5 Tesla MR unit. SI ratios were calculated by referencing the brainstem (BS) for the DN and the thalamus (TH) for the GP and PUL. We compared the SI ratios at the first, fifth, and 10th, and at the most recent examinations. The neurological symptoms of all 196 patients were assessed at each MR examination by one of the authors (MY). RESULTS: The DN/BS and GP/TH SI ratios were significantly increased at the fifth examination ( p < .0001, p = 0.0094) and, thereafter, gradually increased. Although the PUL/TH SI ratio was not significantly increased at the fifth examination ( p = 0.2515), a significant increase was noted at the 10th examination ( p < .0001). There were no significant predictive factors for DN/BS SI increases. Younger age, no brain metastasis, and normal estimated glomerular filtration rate were related to GP/TH SI ratio increases ( p = 0.0308, p = 0.0001, p = 0.0306). Higher age and total bilirubin level were related to an increased PUL/TH SI ratio ( p = 0.0276, p = 0.0097). No patients experienced gadodiamide-related health problems. CONCLUSIONS: Although the SI ratios rose as numbers of gadodiamide administrations increased, no adverse health effects have developed to date.

Absence of dentate nucleus resting-state functional connectivity changes in nonneurological patients with gadolinium-related hyperintensity on T1 -weighted images.

BACKGROUND: The dentate nuclei of the cerebellum are the areas where gadolinium predominantly accumulates. It is not yet known whether gadolinium deposition affects brain functions. PURPOSE/HYPOTHESIS: To assess whether gadolinium-dependent high signal intensity of the cerebellum on T1 -weighted images of nonneurological adult patients with Crohn's disease is associated with modifications of resting-state functional connectivity (RSFC) of the cerebellum and dentate nucleus. STUDY TYPE: Observational, cross-sectional. POPULATION: Fifteen patients affected by Crohn's disease were compared with 16 healthy age- and gender-matched control subjects. All participants underwent neurological, neurocognitive-psychological assessment, and blood sampling. FIELD STRENGTH/SEQUENCE: 1.5-T magnet blood oxygenation level-dependent (BOLD) functional MRI. ASSESSMENT: High signal intensity on T1 -weighted images, cerebellum functional connectivity, neurocognitive performance, and blood circulating gadolinium levels. STATISTICAL TESTS: An unpaired two-sample t-test (age and sex were nuisance variables) was used to investigate between-group differences in cerebellar and dentate nucleus functional connectivity. Z-statistical images were set using clusters determined by Z > 2.3 and a familywise error (FWE)-corrected cluster significance threshold of P = 0.05. RESULTS: Dentate nuclei RSFC was not different (P = n.s.) between patients with gadolinium-dependent high signal intensity on T1 -weighted images and controls. Pre- and postcentral gyrus bilaterally and the right supplementary motor cortex showed a decrease of RSFC with the cerebellum hemispheres (P < 0.05 FWE-corrected) and was related to disease duration but not to gadodiamide cumulative doses (P = n.s.). DATA CONCLUSION: Crohn's disease patients with gadolinium-dependent hyperintense dentate nuclei on unenhanced T1 -weighted images do not show dentate nucleus RSFC changes. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2019;50:445-455.

Longitudinal evaluation of iron concentration and atrophy in the dentate nuclei in friedreich ataxia.

BACKGROUND: Friedreich ataxia is a recessively inherited, progressive neurological disease characterized by impaired mitochondrial iron metabolism. The dentate nuclei of the cerebellum are characteristic sites of neurodegeneration in the disease, but little is known of the longitudinal progression of abnormalities in these structures. METHODS: Using in vivo magnetic resonance imaging, including quantitative susceptibility mapping, we investigated changes in iron concentration and volume in the dentate nuclei in individuals with Friedreich ataxia (n = 20) and healthy controls (n = 18) over a 2-year period. RESULTS: The longitudinal rate of iron concentration was significantly elevated bilaterally in participants with Friedreich ataxia relative to healthy controls. Atrophy rates did not differ significantly between groups. Change in iron concentration and atrophy both correlated with baseline disease severity or duration, indicating sensitivity of these measures to disease stage. Specifically, atrophy was maximal in individuals early in the disease course, whereas the rate of iron concentration increased with disease progression. CONCLUSIONS: Progressive dentate nucleus abnormalities are evident in vivo in Friedreich ataxia, and the rates of change of iron concentration and atrophy in these structures are sensitive to the disease stage. The findings are consistent with an increased rate of iron concentration and atrophy early in the disease, followed by iron accumulation and stable volume in later stages. This pattern suggests that iron dysregulation persists after loss of the vulnerable neurons in the dentate. The significant changes observed over a 2-year period highlight the utility of quantitative susceptibility mapping as a longitudinal biomarker and staging tool. © 2019 International Parkinson and Movement Disorder Society.