Deep Brain Nuclei Research Articles

Different iron deposition patterns in akinetic/rigid-dominant and tremor-dominant Parkinson's disease

ObjectiveThe loss of dopaminergic cells and excessive iron deposition in some deep brain nuclei are associated with the pathophysiology of PD, and different clinical subtypes may indicate different pathological processes. This study was designed to investigate the relationships between regional iron in the cardinal subcortical nuclei and different clinical subtypes. Patients and MethodsNine Arkinetic/Rigid-dominant Parkinson’s disease (PDAR) patients, eight Tremor-dominant (PDTD)patients and 10 matched healthy controls were recruited for this study. The iron content in 8 cardinal subcortical nuclei was measured through SWI sequence scanning (3.0 T), and different patterns of iron deposition were analyzed not only between the PD patients and HC groups but also between the different clinical subtypes. ResultsCompared with the healthy controls, the iron content in the substantia nigra pars compacta(SNc), substantia nigra pars reticulata(SNr) from both the severe and milder side in PD groups were significantly increased (P < 0.01 and P < 0.02 for SNc; both P < 0.01 for SNr), and the iron content in the GP of both the severe and milder side of the PDAR patients was significantly increased compared with the PDTD patients (P < 0.01 and P = 0.02, respectively) ConclusionSWI is a very good technique for the in vivo assessment of subcortical nucleus iron content, and abnormal deposition of iron in the SNc and SNr is an obvious characteristic in PD patients. Furthermore, our data indicates that PDAR patients have higher iron content in the GP than PDTD patients and HCs, indicating that abnormal iron deposition in GP is related to the phenotype of Akinetic/Rigid in PD patients.

Gray Matter Nucleus Hyperintensity After Monthly Triple-Dose Gadopentetate Dimeglumine With Long-term Magnetic Resonance Imaging.

Gadolinium deposition is widely believed to occur, but questions regarding accumulation pattern and permanence remain. We conducted a retrospective study of intracranial signal changes on monthly triple-dose contrast-enhanced magnetic resonance imaging (MRI) examinations from the previously published Betaseron vs. Copaxone in Multiple Sclerosis With Triple-Dose Gadolinium and 3-Tesla MRI Endpoints Trial (N = 67) to characterize the dynamics of gadolinium deposition in several deep brain nuclei and track persistence versus washout of gadolinium deposition on long-term follow-up (LTFU) examinations (N = 28) obtained approximately 10 years after enrollment in the Betaseron vs. Copaxone in Multiple Sclerosis With Triple-Dose Gadolinium and 3-Tesla MRI Endpoints Trial. Using T2 and proton density images and using image analysis software (ITK-SNAP), manual regions of interest were created ascribing boundaries of the caudate nucleus, dentate nucleus, globus pallidus, pulvinar, putamen, white matter, and air. Intensity analysis was conducted on T1-weighted fat-saturated (fat-sat) images using the FSL package. A linear rigid-body transform was calculated from the fat-sat image at each target time point to the region of interest segmentation reference time point fat-sat image. Serial MRI signal was analyzed using linear mixed regression modeling with random intercept. Annual MRI signal changes including LTFU scans were assessed with t test. During monthly scanning, all gray matter structures demonstrated a significant (P < 0.0001) increase in contrast-to-noise ratio. Yearly changes in deposition showed distinctive patterns for the specific nucleus: globus pallidus showed complete retention, pulvinar showed partial washout, while dentate, caudate, and putamen returned to baseline (ie, complete washout). Monthly increased contrast-to-noise ratio in gray matter nuclei is consistent with gadolinium deposition over time. The study also suggests that some deep gray matter nuclei permanently retain gadolinium, whereas others demonstrate washout of soluble gadolinium.

Improved depiction of subthalamic nucleus and globus pallidus internus with optimized high-resolution quantitative susceptibility mapping at 7 T.

The subthalamic nucleus (STN) and globus pallidus internus (GPi) are commonly used targets in deep-brain stimulation (DBS) surgery for the treatment of movement disorders. The success of DBS critically depends on the spatial precision of stimulation. By taking advantage of good contrast between iron-rich deep-brain nuclei and surrounding tissues, quantitative susceptibility mapping (QSM) has shown promise in differentiating the STN and GPi from the adjacent substantia nigra and globus pallidus externus, respectively. Nonlinear morphology-enabled dipole inversion (NMEDI) is a widely used QSM algorithm, but the image quality of reconstructed susceptibility maps relies on the regularization parameter selection. To date, few studies have systematically optimized the regularization parameter at the ultra-high field of 7 T. In this study, we optimized the regularization parameter in NMEDI to improve the depiction of STN and GPi at different spatial resolutions at both 3 T and 7 T. The optimized QSM images were further compared with other susceptibility-based images, including T2*-weighted (T2*w), R2*, susceptibility-weighted, and phase images. QSM showed better depiction of deep-brain nuclei with clearer boundaries compared with the other methods, and 7 T QSM at 0.35 × 0.35 × 1.0 mm3 demonstrated superior performance to the others. Our findings suggest that optimized high-resolution QSM at 7 T allows for improved delineation of deep-brain nuclei with clear and sharp borders between nuclei, which may become a promising tool for DBS nucleus preoperative localization.

Detailed Anatomical Volumetric Study of Deep Nuclei of Brain and Other Structures Between Parkinson’s Disease Patients Who Had Deep Brain Stimulation and Control Group

BackgroundDeep brain stimulation (DBS) was pioneered by Neuroscience team of Hospital Universiti Sains Malaysia (HUSM) nearly a decade ago to treat advanced medically refractory idiopathic Parkinson’s disease (IPD) patients.ObjectivesBrain volume reduction occurs with age, especially in Parkinson plus syndrome or psychiatric disorders. We searched to define the degree of volume discrepancy in advanced IPD patients and correlate the anatomical volumetric changes to motor symptoms and cognitive function.MethodsWe determined the magnetic resonance imaging (MRI)-based volumetry of deep brain nuclei and brain structures of DBS-IPD group and matched controls.ResultsDBS-IPD group had significant deep nuclei atrophy and volume discrepancy, yet none had cognitive or psychobehavioural disturbances. Globus pallidus volume showed positive correlation to higher mental function.ConclusionThe morphometric changes and clinical severity discrepancy in IPD may imply a more complex degenerative mechanism involving multiple neural pathways. Such alteration could be early changes before clinical manifestation.

Advanced MRI techniques for transcranial high intensity focused ultrasound targeting.

Magnetic resonance guided high intensity focused ultrasound is a novel, non-invasive, image-guided procedure that is able to ablate intracranial tissue with submillimetre precision. It is currently FDA approved for essential tremor and tremor dominant Parkinson's disease. The aim of this update is to review the limitations of current landmark-based targeting techniques of the ventral intermediate nucleus and demonstrate the role of emerging imaging techniques that are relevant for both magnetic resonance guided high intensity focused ultrasound and deep brain stimulation. A significant limitation of standard MRI sequences is that the ventral intermediate nucleus, dentatorubrothalamic tract, and other deep brain nuclei cannot be clearly identified. This paper provides original, annotated images demarcating the ventral intermediate nucleus, dentatorubrothalamic tract, and other deep brain nuclei on advanced MRI sequences such as fast grey matter acquisition T1 inversion recovery, quantitative susceptibility mapping, susceptibility weighted imaging, and diffusion tensor imaging tractography. Additionally, the paper reviews clinical efficacy of targeting with these novel MRI techniques when compared to current established landmark-based targeting techniques. The paper has widespread applicability to both deep brain stimulation and magnetic resonance guided high intensity focused ultrasound.

Prospective Imaging Trial Assessing Gadoteridol Retention in the Deep Brain Nuclei of Women Undergoing Breast MRI

To assess for indirect evidence of gadoteridol retention in the deep brain nuclei of women undergoing serial screening breast MRI. This HIPAA-compliant prospective observational noninferiority imaging trial was approved by the IRB. From December 2016 to March 2018, 12 consented subjects previously exposed to 0-1 doses of gadoteridol (group 1) and 7 consented subjects previously exposed to ≥4 doses of gadoteridol (group 2) prospectively underwent research-specific unenhanced brain MRI including T1w spin echo imaging and T1 mapping. Inclusion criteria were: (1) planned breast MRI with gadoteridol, (2) no gadolinium exposure other than gadoteridol, (3) able to undergo MRI, (4) no neurological illness, (5) no metastatic disease, (6) no chemotherapy. Regions of interest were manually drawn in the globus pallidus, thalamus, dentate nucleus, and pons. Globus pallidus/thalamus and dentate nucleus/pons signal intensities and T1-time ratios were calculated using established methods and correlated with cumulative gadoteridol dose (mL). All subjects were female (mean age: 50 ± 12 years) and previously had received an average of 0.5 ± 0.5 (group 1) and 5.9 ± 2.1 (group 2) doses of gadoteridol (cumulative dose: 8 ± 8 and 82 ± 31 mL, respectively), with the last dose an average of 492 ± 299 days prior to scanning. There was no significant correlation between cumulative gadoteridol dose (mL) and deep brain nuclei signal intensity at T1w spin echo imaging (p = 0.365-0.512) or T1 mapping (p = 0.197-0.965). We observed no indirect evidence of gadolinium retention in the deep brain nuclei of women undergoing screening breast MRI with gadoteridol.

White matter injury after neonatal encephalopathy is associated with thalamic metabolite perturbations.

BackgroundAlthough thalamic magnetic resonance (MR) spectroscopy (MRS) accurately predicts adverse outcomes after neonatal encephalopathy, its utility in infants without MR visible deep brain nuclei injury is not known. We examined thalamic MRS metabolite perturbations in encephalopathic infants with white matter (WM) injury with or without cortical injury and its associations with adverse outcomes.MethodsWe performed a subgroup analysis of all infants recruited to the MARBLE study with isolated WM or mixed WM/cortical injury, but no visible injury to the basal ganglia/thalamus (BGT) or posterior limb of the internal capsule (PLIC). We used binary logistic regression to examine the association of MRS biomarkers with three outcomes (i) WM injury score (1 vs. 2/3); (ii) cortical injury scores (0/1 vs. 2/3); and (iii) adverse outcomes (defined as death, moderate/severe disability) at two years (yes/no). We also assessed the accuracy of MRS for predicting adverse outcome.FindingsOf the 107 infants included in the analysis, five had adverse outcome. Reduced thalamic N-acetylaspartate concentration [NAA] (odds ratio 0.4 (95% CI 0.18–0.93)) and elevated thalamic Lactate/NAA peak area ratio (odds ratio 3.37 (95% CI 1.45–7.82)) were significantly associated with higher WM injury scores, but not with cortical injury. Thalamic [NAA] (≤5.6 mmol/kg/wet weight) had the best accuracy for predicting adverse outcomes (sensitivity 1.00 (95% CI 0.16–1.00); specificity 0.95 (95% CI 0.84–0.99)).InterpretationThalamic NAA is reduced in encephalopathic infants without MR visible deep brain nuclei injury and may be a useful predictor of adverse outcomes.FundingThe National Institute for Health Research (NIHR).

Evaluation of 3.0-T MRI Brain Signal after Exposure to Gadoterate Meglumine in Women with High Breast Cancer Risk and Screening Breast MRI.

Background Otherwise healthy women at high risk for breast cancer undergo annual contrast agent-enhanced breast MRI screening examinations, resulting in high cumulative doses of gadolinium-based contrast agents (GBCAs). Whereas the majority of studies showed no T1 signal ratio increase in deep brain nuclei after more than six doses of macrocyclic GBCA, this has not been explored in a healthy study population. Purpose To assess whether women who are administered large cumulative doses of macrocyclic GBCA with breast MRI at high-risk breast cancer screening exhibit T1 alterations in deep brain nuclei. Materials and Methods In this prospective study from November 2017 to March 2018, healthy women who were either exposed (because of high-risk breast cancer screening) or unexposed to only gadoterate meglumine underwent 3.0-T brain MRI with a dedicated head coil, including T1 mapping and magnetization-prepared rapid gradient-echo sequences. T1 times and T1 signal intensities were measured in the dentate nucleus (DN), globus pallidus (GP), crus anterior of capsula interna (CA), and pons. Ratios of DN to pons and GP to CA were calculated, and univariable Pearson correlation coefficients were calculated. Multivariable analysis included partial regression analysis. Results This study evaluated 25 women (mean age, 51 years ± 11 [standard deviation]) who were exposed to a mean GBCA dose of 129 mL (median 112 mL; range, 70-302 mL) and 16 women (mean age, 37 years ± 10) who were never exposed to any GBCA. Infratentorially, no correlation between cumulative GBCA dose and T1 times or signal intensity ratios was detected (P = .66 and .55, respectively). In partial correlation analysis by considering age as a confounder, there was a moderate negative correlation between GP-to-CA ratio and GBCA dose (r = -0.40; P = .01) but not for GP T1 times (r = 0.19; P = .24). Conclusion After administration of relatively large cumulative doses of gadoterate dimeglumine, healthy women at high risk for breast cancer who underwent annual contrast-enhanced breast MRI screening did not exhibit T1 signal increase in deep brain nuclei at 3.0-T MRI. © RSNA, 2019.

Influence of Artifact Corrections on MRI Signal Intensity Ratios for Assessment of Gadolinium Brain Retention

Differences in brain signal intensity ratios (SIRs) of deep brain nuclei in T1-weighted (T1w) magnetic resonance images were reported as an indicator of gadolinium brain retention. Variable methods of image reconstruction and inhomogeneity correction for T1w images exist, which might affect the accuracy of SIRs. The aim of our prospective study was to investigate the effect of flow artifact compensation (FAC) and intensity inhomogeneity correction (IIC) on the dentate nucleus-to-pons and globus pallidus-to-thalamus SIRs in study participants who had previously received multiple doses of gadobutrol. This study included 76 participants who received five or more gadobutrol-enhanced scans between 2007 and 2017. A control group of 25 participants without gadolinium-based contrast agent application in their patient history was included for comparison. Unenhanced brain magnetic resonance imaging including two T1w spin-echo sequences with and without FAC was performed in all participants. Both sequences were reconstructed with and without IIC. Images were assessed for flow artifacts and SIRs were calculated. Using FAC, a lower proportion of participants had to be excluded from the final analysis of dentate nucleus-to-pons SIR due to flow artifacts (15% versus 46%, p < 0.001). Without IIC, a difference was found between the study and the control group for the dentate nucleus-to-pons ratio (p = 0.004), but not for the same sequence reconstructed with IIC (p = 0.29). For the globus pallidus-to-thalamus ratio, no difference was found between the study and control group. The application of an IIC algorithm has significant impact on brain nuclei SIRs for the assessment of gadolinium brain retention.

In vivo Probabilistic Structural Atlas of the Inferior and Superior Colliculi, Medial and Lateral Geniculate Nuclei and Superior Olivary Complex in Humans Based on 7 Tesla MRI.

Despite extensive neuroimaging research of primary sensory cortices involved in auditory and visual functions, subcortical structures within these domains, such as the inferior and superior colliculi, the medial and lateral geniculate nuclei and the superior olivary complex, are currently understudied with magnetic resonance imaging (MRI) in living humans. This is because a precise localization of these nuclei is hampered by the limited contrast and sensitivity of conventional neuroimaging methods for deep brain nuclei. In this work, we used 7 Tesla multi-modal (T2-weighted and diffusion fractional anisotropy) 1.1 mm isotropic resolution MRI to achieve high sensitivity and contrast for single-subject brainstem and thalamic nuclei delineation. After precise coregistration to stereotactic space, we generated an in vivo human probabilistic atlas of auditory (medial geniculate nucleus, inferior colliculus, and superior olivary complex) and visual (lateral geniculate nucleus and superior colliculus) subcortical nuclei. We foresee the use of this atlas as a tool to precisely identify the location and shape of auditory/visual deep nuclei in research as well as clinical human studies.

Stereotactic system for accurately targeting deep brain structures in awake head-fixed mice.

Deep brain nuclei, such as the amygdala, nucleus basalis, and locus coeruleus, play a crucial role in cognition and behavior. Nonetheless, acutely recording electrical activity from these structures in head-fixed awake rodents has been very challenging due to the fact that head-fixed preparations are not designed for stereotactic accuracy. We overcome this issue by designing the DeepTarget, a system for stereotactic head fixation and recording, which allows for accurately directing recording electrodes or other probes into any desired location in the brain. We then validated it by performing intracellular recordings from optogenetically tagged amygdalar neurons followed by histological reconstruction, which revealed that it is accurate and precise to within ~100 μm. Moreover, in another group of mice we were able to target both the mammillothalamic tract and subthalamic nucleus. This approach can be adapted to any type of extracellular electrode, fiber optic, or other probe in cases where high accuracy is needed in awake, head-fixed rodents.NEW & NOTEWORTHY Accurate targeting of recording electrodes in awake head-restrained rodents is currently beyond our reach. We developed a device for stereotactic implantation of a custom head bar and a recording system that together allow the accurate and precise targeting of any brain structure, including deep and small nuclei. We demonstrated this by performing histology and intracellular recordings in the amygdala of awake mice. The system enables the targeting of any probe to any location in the awake brain.

Identification and Validation of Hematoma Volume Cutoffs in Spontaneous, Supratentorial Deep Intracerebral Hemorrhage.

Background and Purpose- Clinical trials in spontaneous intracerebral hemorrhage (ICH) have used volume cutoffs as inclusion criteria to select populations in which the effects of interventions are likely to be the greatest. However, optimal volume cutoffs for predicting poor outcome in deep locations (thalamus versus basal ganglia) are unknown. Methods- We conducted a 2-phase study to determine ICH volume cutoffs for poor outcome (modified Rankin Scale score of 4-6) in the thalamus and basal ganglia. Cutoffs with optimal sensitivity and specificity for poor outcome were identified in the ERICH ([Ethnic/Racial Variations of ICH] study; derivation cohort) using receiver operating characteristic curves. The cutoffs were then validated in the ATACH-2 trial (Antihypertensive Treatment of Acute Cerebral Hemorrhage-2) by comparing the c-statistic of regression models for outcome (including dichotomized volume) in the validation cohort. Results- Of the 3000 patients enrolled in ERICH, 1564 (52%) had deep ICH, of whom 1305 (84%) had complete neuroimaging and outcome data (660 thalamic and 645 basal ganglia hemorrhages). Receiver operating characteristic curve analysis identified 8 mL in thalamic (area under the curve, 0.79; sensitivity, 73%; specificity, 78%) and 18 mL in basal ganglia ICH (area under the curve, 0.79; sensitivity, 70%; specificity, 83%) as optimal cutoffs for predicting poor outcome. The validation cohort included 834 (84%) patients with deep ICH and complete neuroimaging data enrolled in ATACH-2 (353 thalamic and 431 basal ganglia hemorrhages). In thalamic ICH, the c-statistic of the multivariable outcome model including dichotomized ICH volume was 0.80 (95% CI, 0.75-0.85) in the validation cohort. For basal ganglia ICH, the c-statistic was 0.81 (95% CI, 0.76-0.85) in the validation cohort. Conclusions- Optimal hematoma volume cutoffs for predicting poor outcome in deep ICH vary by the specific deep brain nucleus involved. Utilization of location-specific volume cutoffs may improve clinical trial design by targeting deep ICH patients that will obtain maximal benefit from candidate therapies.

MRI-guided robotic arm drives optogenetic fMRI with concurrent Ca2+ recording

Optical fiber-mediated optogenetic activation and neuronal Ca2+ recording in combination with fMRI provide a multi-modal fMRI platform. Here, we developed an MRI-guided robotic arm (MgRA) as a flexible positioning system with high precision to real-time assist optical fiber brain intervention for multi-modal animal fMRI. Besides the ex vivo precision evaluation, we present the highly reliable brain activity patterns in the projected basal forebrain regions upon MgRA-driven optogenetic stimulation in the lateral hypothalamus. Also, we show the step-wise optical fiber targeting thalamic nuclei and map the region-specific functional connectivity with whole-brain fMRI accompanied by simultaneous calcium recordings to specify its circuit-specificity. The MgRA also guides the real-time microinjection to specific deep brain nuclei, which is demonstrated by an Mn-enhanced MRI method. The MgRA represents a clear advantage over the standard stereotaxic-based fiber implantation and opens a broad avenue to investigate the circuit-specific functional brain mapping with the multi-modal fMRI platform.

Brain volume is related to neurological impairment and to copper overload in Wilson\u2019s disease

IntroductionTo determine whether brain volume was associated with functional and neurological impairments and with copper overload markers in patients with Wilson’s disease.MethodsIn 48 treatment-naïve patients, we assessed functional and neurological impairments with the Unified Wilson’s Disease Rating Scale, measured normalized brain volumes based on magnetic resonance images, and assessed concentration of non-ceruloplasmin-bound copper. We correlated brain volume measures with functional and neurological impairment scores and copper overload indices.ResultsFunctional and neurological impairments correlated with all brain volume measures, including the total brain volume and the volumes of white matter and gray matter (both peripheral gray matter and deep brain nuclei). Higher non-ceruloplasmin-bound copper concentrations were associated with greater functional and neurological impairments and lower brain volumes.ConclusionsOur findings provided the first in vivo evidence that the severity of brain atrophy is a correlate of functional and neurological impairments in patients with Wilson’s disease and that brain volume could serve as a marker of neurodegeneration induced by copper.

Association of Intensive Blood Pressure Reduction With Risk of Hematoma Expansion in Patients With Deep Intracerebral Hemorrhage

Hypertension is the strongest risk factor for spontaneous intracerebral hemorrhage (ICH) involving deep brain regions, but it appears to be unknown if intensive blood pressure reduction in the acute care setting decreases hematoma expansion or improves outcomes in patients with deep ICH. To determine whether intensive blood pressure reduction is associated with decreased risk of hematoma expansion and changes in 90-day modified Rankin Scale scores and if these associations are modified by the specific deep-brain nuclei involved. This study is an exploratory analysis of the Antihypertensive Treatment of Acute Cerebral Hemorrhage-2 international, multicenter randomized clinical trial, which was conducted from May 2011 to September 2015, enrolled eligible patients with primary ICH, and followed up with them for 90 days. Patients who had ICH and complete neuroimaging data were included in the analysis. Data analysis was completed from July 2018 to December 2018. Participants were randomized to either intensive treatment (with a systolic blood pressure target of 110-139 mm Hg) or standard treatment (with a systolic blood pressure target of 140-179 mm Hg). The main outcome was hematoma expansion, defined as an increase greater than 33% in hematoma volume between baseline and 24 hours. Functional outcome was evaluated 90 days after the ICH via the modified Rankin Scale. Of 1000 trial participants, 870 (87.0%) had deep ICH, of whom 780 (89.7%) had complete neuroimaging data (of 336 thalamic and 444 basal ganglia hemorrhages). The baseline characteristics of the intensive and standard treatment groups remained balanced in this subgroup of the original study. Intensive treatment was associated with a decreased risk of hematoma expansion in univariable analysis (odds ratio [OR], 0.62 [95% CI, 0.43-0.87]; P = .006) and multivariable analysis (OR, 0.61 [95% CI, 0.42-0.88]; P = .009). This association was modified by the specific deep location of the ICH (OR, 0.44 [95% CI, 0.22-0.96]; interaction P = .02), with stratified analyses showing a reduction in risk of hematoma expansion with intensive vs standard treatment among basal ganglia ICH (OR, 0.44 [95% CI, 0.27-0.72]; P = .001) but not thalamic ICH (OR, 0.91 [95% CI, 0.51-0.64]; P = .76). Intensive treatment was not associated with an improvement in the modified Rankin Scale score distribution. Compared with standard treatment, intensive blood pressure treatment was associated with reduced hematoma expansion in deep ICH, specifically among basal ganglia hemorrhages.

Is diffuse axonal injury on susceptibility weighted imaging a biomarker for executive functioning in adolescents with traumatic brain injury?

Traumatic brain injury (TBI) is a heterogeneous disorder in which diffuse axonal injury (DAI) is an important component contributing to executive dysfunction. During adolescence, developing brain networks are especially vulnerable to acceleration-deceleration forces. We aimed to examine the correlation between DAI (number and localization) and executive functioning in adolescents with TBI. We recruited 18 adolescents with a mean age of 15y8m (SD=1y7m), averaging 2.5 years after sustaining a moderate-to-severe TBI with documented DAI. Susceptibility Weighted Imaging sequence was administered to localize the DAI lesions. The adolescents performed a neurocognitive test-battery, addressing different aspects of executive functioning (working memory, attention, processing speed, planning ability) and their parents completed the Behavior Rating Inventory of Executive Function (BRIEF) - questionnaire. Executive performance of the TBI-group was compared with an age and gender matched control group of typically developing peers. Based on these results we focused on the Stockings of Cambridge test and the BRIEF to correlate with the total number and location of DAI. Results revealed that the anatomical distribution of DAI, especially in the corpus callosum and the deep brain nuclei, may have more implications for executive functioning than the total amount of DAI in adolescents. Results of this study may help guide targeted rehabilitation to redirect the disturbed development of executive function in adolescents with TBI.

Age, But Not Repeated Exposure to Gadoterate Meglumine, Is Associated With T1- and T2-Weighted Signal Intensity Changes in the Deep Brain Nuclei of Pediatric Patients.

Current findings on gadolinium deposition in the pediatric brain due to repeated exposure to macrocyclic contrast agents are inconclusive and possibly confounded by brain maturation processes. We evaluated the longitudinal effects of repeated gadoterate meglumine exposure (Dotarem; Guerbet, Villepinte, France) on the T1- and T2-weighted signal intensity (SI) in pediatric patients, and assessed the magnitude of age-related increase in T1-weighted (and decrease in T2-weighted) SI in a control cohort without prior gadolinium exposure. In this retrospective, double-cohort study, magnetic resonance imaging (MRI) data of 24 patients (0.7-16.4 years, M = 5.74, SD = 4.15) who received at least 10 doses of exclusively gadoterate meglumine were included in the longitudinal study. The MRI data of 190 controls (age range, 1-20 years; 10 patients/bin; bin width, 1 year) without any prior gadolinium-based contrast exposure were included in the control, cross-sectional study to assess the age-dependent SI changes in the regions of interest (ROIs). We measured SI (native), T1-weighted gradient echo, and T2-weighted fast spin-echo of 12 deep brain nuclei. The ROIs were measured at each of the first 11 MRI examinations of the contrast-exposed patients and in the control subject's MRI. Regions of interest's SIs, normalized by the pons, were analyzed with mixed effects models, accounting for the potential confounding factors, such as radiotherapy and chemotherapy. The number of gadoterate meglumine administrations had no effect on the SI increase in any of the ROIs (all P > 0.05), but age significantly correlated with increased SI in T1-weighted globus pallidus (GP; P < 0.01) and caudate (P < 0.05), and with decreased SI in T2-weighted GP (P < 0.001) and dentate nucleus (P < 0.005) in the contrast-exposed group. The cross-sectional analyses of the control cohort showed a significant age-dependent T1-weighted SI increase in multiple ROIs, including the GP and caudate, and decrease in the T2-weighted GP and dentate nucleus (P < 0.05). Repeated exposure to gadoterate meglumine was not associated with brain hyperintensity in the pediatric patients, whereas age importantly contributed to the SI changes in several deep brain nuclei.

Dose-dependent atrophy of the amygdala after radiotherapy

Background and purposeThe amygdalae are deep brain nuclei critical to emotional processing and the creation and storage of memory. It is not known whether the amygdalae are affected by brain radiotherapy (RT). We sought to quantify dose-dependent amygdala change one year after brain RT. Materials and methods52 patients with primary brain tumors were retrospectively identified. Study patients underwent high-resolution, volumetric magnetic resonance imaging before RT and 1 year afterward. Images were processed using FDA-cleared software for automated segmentation of amygdala volume. Tumor, surgical changes, and segmentation errors were manually censored. Mean amygdala RT dose was tested for correlation with amygdala volume change 1 year after RT via the Pearson correlation coefficient. A linear mixed-effects model was constructed to evaluate potential predictors of amygdala volume change, including age, tumor hemisphere, sex, seizure history, and bevacizumab treatment during the study period. As 51 of 52 patients received chemotherapy, possible chemotherapy effects could not be studied. A two-tailed p-value <0.05 was considered statistically significant. ResultsMean amygdala RT dose (r = −0.28, p = 0.01) was significantly correlated with volume loss. On multivariable analysis, the only significant predictor of amygdala atrophy was radiation dose. The final linear mixed-effects model estimated amygdala volume loss of 0.17% for every 1 Gy increase in mean amygdala RT dose (p = 0.008). ConclusionsThe amygdala demonstrates dose-dependent atrophy one year after radiotherapy for brain tumors. Amygdala atrophy may mediate neuropsychological effects seen after brain RT.

Symptomatic HIV CNS viral escape among patients on effective cART

ObjectiveThe clinical syndrome in symptomatic HIV associated CNS viral escape is poorly defined. We attempted to describe the clinical syndrome, laboratory profile, radiological features and outcomes of HIV infected patients with symptomatic central nervous system (CNS) viral escape in our study. MethodsThis is a retrospective study were adult patients with HIV infection on cART admitted with a diagnosis of CD8 encephalitis or CNS viral escape in a large teaching hospital in South India was identified. ResultsThe mean age of the eleven patients included in the study was 37.5 years. Most patients had received almost a decade of antiretroviral treatment at diagnosis (mean: 11.18 years). All patients presented with global cerebral syndrome. Cognitive decline, tremors, and headaches were common manifestations. All patients had lymphocytic pleocytosis (mean cell count: 44.63 cells/ml; lymphocyte percentage: 94.81%) with elevated protein (mean: 125.36 mg/dl). All patients were on boosted protease inhibitors (81.8% on Atazanavir and 18.18% Lopinavir). All except one patient was on Tenofovir and lamivudine combination therapy. White matter changes and deep brain nuclei involvement were common. Most patients required a change of cART to regimens with better CNS penetration and suppression of the resistant virus in the plasma and improved. ConclusionCNS viral escape should be considered as a differential among patients on Atazanavir presenting with non-focal cerebral syndrome and CSF lymphocytic pleocytosis.

Gadolinium-based contrast agents - review of recent literature on magnetic resonance imaging signal intensity changes and tissue deposits, with emphasis on pediatric patients.

Gadolinium has been used as a base for contrast agents in MRI for the last three decades. Numerous studies over the last 4years have reported increased signal intensity in deep brain nuclei in non-contrast MRI images following gadolinium-based contrast agent (GBCA) administration. Pathology studies performed on adults and children, and rodent necropsy studies have also shown gadolinium deposition in brain and other tissues after GBCA administration. The purpose of this review was to summarize and discuss the knowledge gained from these reports and the relevance for imaging pediatric patients.