Background and Purpose While there have been recent reports of brain retention of gadolinium following gadolinium-based contrast agent (GBCA) administration in adults, a retrospective series of pediatric patients has not previously been reported. We investigated the relationship between the number of prior GBCA doses and increasing T1 signal in the dentate nucleus on unenhanced T1-weighted MR imaging. We hypothesized that, despite differences in pediatric physiology and the smaller GBCA doses pediatric patients are typically administered based on weighted-adjusted dosing, the pediatric brain would also demonstrate dose dependent increasing T1 signal in the dentate nucleus. Materials and methods We included children with multiple GBCA administrations at our institution. A blinded-reader placed regions of interest (ROIs) within the dentate nucleus and adjacent cerebellar white matter. To eliminate reader bias, automated ROI delineation of the dentate nucleus, cerebellar white matter, and pons was also performed. Dentate to cerebellar white matter (DN/C) and dentate to pons (DN/P) ratios were compared to the number of GBCA administrations. Results Over 20 years at our institution, 280 patients received at least 5 GBCA doses with one patient receiving 38 doses. Sixteen patients met inclusion/exclusion criteria for ROI analysis. Blinded-reader DN/C ratios were significantly associated with GBCA doses (rs=0.77, p=0.001). DN/P and DN/C ratios based on automated ROI placement were also significantly correlated with GBCA doses (t=4.98, p<0.0001 and t=2.73, p<0.02 respectively). Conclusion In pediatric patients, the number of prior GBCA doses is significantly correlated with progressive T1-weighted dentate hyperintensity. Definitive confirmation of gadolinium deposition requires tissue analysis. Any potential clinical sequelae of gadolinium retention in the developing brain are unknown. Given this uncertainty, we suggest taking a cautious stance including the use in pediatric patients of higher stability, macrocyclic agents, which in both human and animal studies have been shown to be associated with lower levels of gadolinium deposition, and detailed documentation of dosing. Most importantly, a patient should not be deprived of a well-indicated contrasted MR exam.

Individuals with more extensive white matter hyperintensities (WMH) show poorer functional outcomes after stroke, but the basis for this relationship is unclear. Wilmskoetter, Marebwa et al. report that WMH are preferentially associated with damage to long-range white matter fibres and this disruption leads to more severe post-stroke aphasia.

Many stroke survivors with aphasia in the acute period experience spontaneous recovery within the first six months after the stroke. However, approximately 30–40% sustain permanent aphasia and the factors determining incomplete recovery are unclear. Suboptimal recovery may be influenced by disruption of areas seemingly spared by the stroke due to loss of white matter connectivity and network integrity. We reconstructed individual anatomical whole-brain connectomes from 90 left hemisphere stroke survivors using diffusion MR images. We measured the modularity of the residual white matter network organization, the probability of brain regions clustering together, and the degree of fragmentation of left hemisphere networks. Greater post-stroke left hemisphere network fragmentation and higher modularity index were associated with more severe chronic aphasia, controlling for the size of the stroke lesion. Even when the left hemisphere was relatively spared, subjects with disorganized community structure had significantly worse aphasia, particularly when key temporal lobe regions were isolated into segregated modules. These results suggest that white matter integrity and disorganization of neuronal networks could be important determinants of chronic aphasia severity. Connectome white matter organization measured through modularity and other topological features could be used as a personalized variable for clinical staging and aphasia treatment planning.

Aphasia recovery after stroke depends on the condition of the remaining, extralesional brain network. Network control theory (NCT) provides a unique, quantitative approach to assess the interaction between brain networks. In this longitudinal, large-scale, whole-brain connectome study, we evaluated whether controllability measures of language-related regions are associated with treated aphasia recovery. Using probabilistic tractography and controlling for the effects of structural lesions, we reconstructed whole-brain diffusion tensor imaging (DTI) connectomes from 68 individuals (20 female, 48 male) with chronic poststroke aphasia who completed a three-week language therapy. Applying principles of NCT, we computed regional (1) average and (2) modal controllability, which decode the ability of a region to (1) spread control input through the brain network and (2) to facilitate brain state transitions. We tested the relationship between pretreatment controllability measures of 20 language-related left hemisphere regions and improvements in naming six months after language therapy using multiple linear regressions and a parsimonious elastic net regression model with cross-validation. Regional controllability of the inferior frontal gyrus (IFG) pars opercularis, pars orbitalis, and the anterior insula were associated with treatment outcomes independently of baseline aphasia severity, lesion volume, age, education, and network size. Modal controllability of the IFG pars opercularis was the strongest predictor of treated aphasia recovery with cross-validation and outperformed traditional graph theory, lesion load, and demographic measures. Regional NCT measures can reflect the status of the residual language network and its interaction with the remaining brain network, being able to predict language recovery after aphasia treatment.

Background: In this pilot study, we examined the effects of ipsilesional high-frequency rTMS (iHF-rTMS) and contralesional low-frequency rTMS (cLF-rTMS) applied via a double-cone coil on neurophysiological and gait variables in patients with chronic stroke. Objective/Hypothesis: To determine the group and individual level effects of two types of stimulation to better individualize neuromodulation for rehabilitation. Methods: Using a randomized, within-subject, double-blind, sham-controlled trial with 14 chronic stroke participants iHF-rTMS and cLF-rTMS were applied via a double-cone coil to the tibialis anterior cortical representation. Neurophysiological and gait variables were compared pre-post rTMS. Results: A small effect of cLF-rTMS indicated increased MEP amplitudes (Cohen's D; cLF-rTMS, d = −0.30). Group-level analysis via RMANOVA showed no significant group effects of stimulation (P > 0.099). However, secondary analyses of individual data