Connectome-based approaches in pediatric epilepsy surgery: "State-of-the art" and future perspectives.

Modern epilepsy science has overcome the traditional interpretation of a strict region-specific origin of epilepsy, highlighting the involvement of wider patterns of altered neuronal circuits. In selected cases, surgery may constitute a valuable option to achieve both seizure freedom and neurocognitive improvement. Although epilepsy is now considered as a brain network disease, the most relevant literature concerning the "connectome-based" epilepsy surgery mainly refers to adults, with a limited number of studies dedicated to the pediatric population. In this review, the Authors summarized the main current available knowledge on the relevance of WM surgical anatomy in epilepsy surgery, the post-surgical modifications of brain structural connectivity and the related clinical impact of such modifications within the pediatric context. In the last part, possible implications and future perspectives of this approach have been discussed, especially concerning the optimization of surgical strategies and the predictive value of the epilepsy network analysis for planning tailored approaches, with the final aim of improving case selection, presurgical planning, intraoperative management, and postoperative results.

Epidural bleeding secondary to a synovial cyst rupture: a case report and review of literature.

Hemorrhage into a juxtafacet cyst is rare and cyst rupture with hemorrhagic extension into the epidural space is even less commonly seen. We describe the case of a patient with a hemorrhagic synovial cyst with rupture associated to abundant bleeding in the epidural space. A 61-year-old man had a 5-month history of worsening low back pain radiating into the right leg with associated weakness and numbness. A magnetic resonance imaging scan showed the presence of a mild anterior spondylolisthesis of L5 on S1 with increased synovial fluid into both facet joints. A suspected synovial cyst of the right facet joint at level L5-S1, with signal characteristics consistent with hemorrhage was seen. Caudally, epidural blood was evident from S1 to S2 that involved spinal canal and right S1 and S2 foramens. These findings were confirmed at surgery.

Late Deformity Following Fronto-Orbital Reconstructive Surgery for Metopic Synostosis: The Role of Temporalis Muscle.

ABSTRACT: Theories for late-developing deformity (LDD) following fronto-orbital reconstructive surgery (FOR) for metopic synostosis (MS) must explain both its delayed onset and its physical characteristics. This study examined whether FOR-related interference with the normal childhood expansion of temporalis is responsible for its soft tissue component.Three-dimensional reformats of preoperative and postoperative computed tomography scans of MS patients were reviewed. Measurements of vertical and horizontal reach of temporalis against those of the underlying skull (to allow for normal skull growth) were compared with normal subjects. The thickness of temporalis and the development of the temporal crests were also assessed.Mean age at FOR was 17.1 months; interval between surgery and first report of LDD 4.7 years; mean age at computed tomography scan for post-FOR LDD patients 8.8 years. There was a significant difference between vertical and horizontal reach of temporalis in pre-FOR MS patients compared to normal subjects ( P < 0.0017 and P < 0.05, respectively). The vertical age-related reach of temporalis in post-FOR patients after allowing for underlying skull growth was significantly reduced ( P = 0.0045) compared to normal subjects but not its horizontal reach ( P = 0.25). Temporal crests in LDD patients were absent or aberrantly formed while muscle thickness was similar to normal subjects at the 2 levels measured.This study supports the theory that failure of the normal childhood expansion of temporalis is responsible for the soft tissue element of LDD, accounting for both its delayed onset and physical characteristics. Aberrant temporal crest development suggests FOR-related damage as the probable cause.

Multiparametric Imaging for Presurgical Planning of Craniopagus Twins: The Experience of Two Tertiary Pediatric Hospitals with Six Sets of Twins.

Conjoined twins are rare and pose a challenge to radiologists and surgeons. Craniopagus twins, where conjunction involves the cranium, are especially rare. Even in large pediatric centers, radiologists are unlikely to encounter more than one such event in their medical careers. This rarity makes it daunting to select a CT and MRI protocol for these infants. Using the experience of two tertiary pediatric hospitals with six sets of craniopagus twins, this multidisciplinary and multimodal integrated imaging approach highlights the key questions that need addressing in the decision-making process for possible surgical intervention.

Observations on the growth of temporalis muscle: A 3D CT imaging study.

This study investigates the hypothesis that there is, during childhood, a disproportionate age-related expansion of the origin of temporalis muscle compared to the growth of the underlying skull. Lateral projections of 50 randomly selected 3D reformatted computerized tomographic (CT) scans (yielding 100 temporalis muscles) of children aged >0.6 to 15 years scanned for conditions that did not affect the shape of their head or face were windowed to provide the optimum delineation of temporalis muscle against the underlying bone. Vertical and anterior-posterior measurements of the muscle made independently by two observers were compared with those of the skull along the same planes. The development of the anterior temporal crest was also assessed. The intraclass correlation coefficient for differences in the measurements made by each observer ranged from good to excellent. The muscle and skull measurements were used to produce a ratio of muscle-to-skull lengths in both vertical and horizontal planes. Analysis of these ratios showed a statistically significant increase in the vertical reach of temporalis with age (Pearson correlation coefficient (R) =0.7826; p < 0.05) compared to the growth of the skull along the planes chosen for the study-but less so for its horizontal reach (R = 0.5073. p < .001). There were no significant differences between right/left or male/female measurements. There was also a substantial level of agreement between both observers in their assessment of the development of the temporal crest. The mean age of children in whom a fully formed temporal crest could be identified (10.6 years) was significantly greater (p < 0.001) than that of the 38 remaining subjects (6.0 years). These results confirm that there is, in response to increased masticatory/dietary demands during childhood, a disproportionate increase in the vertical and (to a lesser extent) horizontal reach of temporalis muscle over its origin from the temporal, frontal, sphenoid, and parietal bones compared the growth of the skull. It is proposed that surgical interference with this normal process is responsible for the soft tissue component of late-developing deformity that can occur following early (at 6-18 months of age) operations for the correction of trigonocephalic head shape associated with metopic synostosis.

Quantitative MRI-Based Analysis Identifies Developmental Limbic Abnormalities in PCDH19 Encephalopathy.

Protocadherin-19 (PCDH19) is a calcium dependent cell-adhesion molecule involved in neuronal circuit formation with prevalent expression in the limbic structures. PCDH19-gene mutations cause a developmental encephalopathy with prominent infantile onset focal seizures, variably associated with intellectual disability and autistic features. Diagnostic neuroimaging is usually unrevealing. We used quantitative MRI to investigate the cortex and white matter in a group of 20 PCDH19-mutated patients. By a statistical comparison between quantitative features in PCDH19 brains and in a group of age and sex matched controls, we found that patients exhibited bilateral reductions of local gyrification index (lGI) in limbic cortical areas, including the parahippocampal and entorhinal cortex and the fusiform and lingual gyri, and altered diffusivity features in the underlying white matter. In patients with an earlier onset of seizures, worse psychiatric manifestations and cognitive impairment, reductions of lGI and diffusivity abnormalities in the limbic areas were more pronounced. Developmental abnormalities involving the limbic structures likely represent a measurable anatomic counterpart of the reduced contribution of the PCDH19 protein to local cortical folding and white matter organization and are functionally reflected in the phenotypic features involving cognitive and communicative skills as well as local epileptogenesis.

Early alterations of cortical thickness and gyrification in migraine without aura: a retrospective MRI study in pediatric patients.

BACKGROUND: Migraine is the most common neurological disease, with high social-economical burden. Although there is growing evidence of brain structural and functional abnormalities in patients with migraine, few studies have been conducted on children and no studies investigating cortical gyrification have been conducted on pediatric patients affected by migraine without aura. METHODS: Seventy-two pediatric patients affected by migraine without aura and eighty-two controls aged between 6 and 18 were retrospectively recruited with the following inclusion criteria: MRI exam showing no morphological or signal abnormalities, no systemic comorbidities, no abnormal neurological examination. Cortical thickness (CT) and local gyrification index (LGI) were obtained through a dedicated algorithm, consisting of a combination of voxel-based and surface-based morphometric techniques. The statistical analysis was performed separately on CT and LGI between: patients and controls; subgroups of controls and subgroups of patients. RESULTS: Patients showed a decreased LGI in the left superior parietal lobule and in the supramarginal gyrus, compared to controls. Female patients presented a decreased LGI in the right superior, middle and transverse temporal gyri, right postcentral gyrus and supramarginal gyrus compared to male patients. Compared to migraine patients younger than 12 years, the ≥ 12-year-old subjects showed a decreased CT in the superior and middle frontal gyri, pre- and post-central cortex, paracentral lobule, superior and transverse temporal gyri, supramarginal gyrus and posterior insula. Migraine patients experiencing nausea and/or vomiting during headache attacks presented an increased CT in the pars opercularis of the left inferior frontal gyrus. CONCLUSIONS: Differences in CT and LGI in patients affected by migraine without aura may suggest the presence of congenital and acquired abnormalities in migraine and that migraine might represent a vast spectrum of different entities. In particular, ≥ 12-year-old pediatric patients showed a decreased CT in areas related to the executive function and nociceptive networks compared to younger patients, while female patients compared to males showed a decreased CT of the auditory cortex compared to males. Therefore, early and tailored therapies are paramount to obtain migraine control, prevent cerebral reduction of cortical thickness and preserve executive function and nociception networks to ensure a high quality of life.

Visual pathways evaluation in Kearns Sayre syndrome: a diffusion tensor imaging study.

PURPOSE: Kearns Sayre syndrome (KSS) is a mitochondrial disorder characterized by development of visual impairment. Electroretinogram (ERG) and visual evoked potentials are not able to provide topographical information of optic damage. The purpose of this study was to explore retrochiasmatic optic pathway alteration in KSS with diffusion tractographic analysis and to compare it with different tracts. METHODS: DTI from 8 KSS subjects (14.7 years) and 10 healthy controls (HC) were acquired on a 3T scanner. Optic radiations (OR), optic tracts (OT), inferior frontooccipital fasciculus (IFOF) and corticospinal tract (CST) were reconstructed with probabilistic tractography. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), radial (RD), and axial diffusivity (AD) were calculated, evaluating group differences. T test on diffusion parameters identified significantly different track portions among cohorts. RESULTS: All patients had optic pathway alterations at electrophysiological examination. Significant lower FA were found in OT, IFOF, and CST of KSS group. RD was significantly higher in bilateral OR, IFOF, CST, and right OT, while ADC was higher in bilateral OR and CST. RD values were higher in the proximal and distal portion of OR bilaterally and in the distal portion of right OT, while widespread differences were found in IFOF and CST. No significant differences were found for AD. FA profiles analysis demonstrated significant differences between groups in several regions of OT, IFOF, and CST, while ADC assessment revealed spread differences in OR and CST. CONCLUSIONS: DTI evaluation of retrochiasmatic tracks may represent a useful tool to topographically investigate retrochiasmatic visual impairment in KSS.

Correction to: Spinal cord involvement in Kearns-Sayre syndrome: a neuroimaging study.

The original article was published with an incorrect presentation of all author names.

Non-congenital viral infections of the central nervous system: from the immunocompetent to the immunocompromised child.

Non-congenital viral infections of the central nervous system in children can represent a severe clinical condition that needs a prompt diagnosis and management. However, the aetiological diagnosis can be challenging because symptoms are often nonspecific and cerebrospinal fluid analysis is not always diagnostic. In this context, neuroimaging represents a helpful tool, even though radiologic patterns sometimes overlap. The purpose of this pictorial essay is to suggest a schematic representation of different radiologic patterns of non-congenital viral encephalomyelitis based on the predominant viral tropism and vulnerability of specific regions: cortical grey matter, deep grey matter, white matter, brainstem, cerebellum and spine.

Role of non-echo-planar diffusion-weighted images in the identification of recurrent cholesteatoma of the temporal bone.

BACKGROUND AND PURPOSE: The aim of the present prospective study was to verify the specificity of non-EPI DWI-MRI in patients operated for middle ear CHO who showed positivity at imaging performed 6 to 9 months after surgery and underwent second-look surgery. MATERIALS AND METHODS: All patients underwent 1.5-T non-EPI DWI-MRI 6 to 9 months after surgery: those showing a hyper-intense signal in the middle ear underwent a revision surgery, whilst the others are still under radiological follow-up and were not considered in this study. Two radiologists independently evaluated the images; both placed a standard region of interest inside the brightest part of the observed signal alteration on coronal HASTE-DWI images. The mean and maximum signal intensity values on the DWI images were recorded for each patient. A signal intensity ratio was calculated using the inferior temporal cortex and the background noise. RESULTS: One hundred and forty-three subjects were evaluated for a total of 210 ears. In 116 (170 ears), a normal non-EPI DWI-MRI was found with exclusion from this study, whilst twenty-seven subjects showed a high signal lesion inside the middle ear and underwent revision surgery. According to the ROC analysis, SI, SIRT and SIRTmax showed the best statistical values in comparison with the other parameters. CONCLUSIONS: Residual/recurrent CHO can be accurately detected using quantitative evaluation of non-EPI DWI-MRI.

Central Nervous System involvement in tuberculosis: An MRI study considering differences between patients with and without Human Immunodeficiency Virus 1 infection.

BACKGROUND: Magnetic resonance imaging (MRI) is largely used in the diagnosis of central nervous system involvement of tuberculosis (CNSTB), yet there is no MRI comparison study between HIV+ and HIV- patients with CNSTB. The aim of the present study was to identify MRI differences in CNSTB between HIV+ and HIV- patients and possibly find early characteristics that could raise the suspect of this disease. METHODS: We included all patients admitted in our institution between 2011 and 2018 with confirmed diagnosis of CNSTB, and MRI performed in the first week. Patients with preexisting brain pathology or immunodeficiency not HIV related were excluded. We compared CNSTB MRI features between the two groups. RESULTS: Sixty-nine patients were included (19 HIV+; 50 HIV-). Findings in HIV+ group: 6 lung TB, 5 hydrocephalus, 4 meningeal enhancement, 6 stroke, 2 hemorrhages, and 10 tuberculomas. HIV- group: 22 lung tuberculosis, 15 hydrocephalus, 21 meningeal enhancement, 5 stroke, 4 hemorrhages, 20 tuberculomas. The only statistically significant difference between the two groups was in the stroke occurrence, more frequent in the HIV+ group (P=.028), all involving the basal ganglia. CONCLUSIONS: Stroke involving the basal ganglia best differentiates CNSTB patients who are HIV+ from those HIV-. This finding was not correlated with meningeal enhancement suggesting that small arteries involvement might precede it. Therefore, we think that HIV+ patients with a new onset of stroke should be evaluated for CNSTB. Follow-up MRI should also be planned since meningeal enhancement might appear in later stages of the disease.

Asymmetric cavernous sinus enlargement: a novel finding in Sturge-Weber syndrome.

PURPOSE: Enlargement of deep cerebral veins and choroid plexus engorgement are frequently reported in Sturge-Weber syndrome. We aim to describe cavernous sinus involvement in patients with this syndrome and to identify possible clinical-neuroimaging correlations. METHODS: Sixty patients with Sturge-Weber syndrome (31 females, mean age 4.5 years) and 120 age/sex-matched controls were included in this retrospective study. We performed a visual analysis to identify patients with asymmetric cavernous sinus enlargement. Then, we measured on axial T2WI the left (A), right (B), and bilateral (LL) transverse diameters of the cavernous sinus. We calculated the module of the difference |A-B| and the cavernous sinus asymmetry index as the ratio |A-B|/LL. Differences among groups were assessed by Mann-Whitney U and Kruskal-Wallis tests. Clinicoradiological associations were evaluated by Fisher exact test. RESULTS: We found seven subjects (11.6%) with asymmetric CS enlargement. The |A-B| and cavernous sinus asymmetry index were higher in patients with asymmetric CS enlargement compared with controls and patients without visible CS abnormalities (pB < 0.05). Asymmetric CS enlargement was always ipsilateral to facial port-wine stains (7/7), and, when present, to leptomeningeal vascular malformations (4/7). It was significantly associated with ipsilateral bone marrow changes (p = 0.013) and dilated veins (p = 0.002). Together with brain atrophy and deep venous dilatation, this sign was associated with neurological deficits (p < 0.05). CONCLUSIONS: We expanded the spectrum of venous abnormalities in SWS, showing the presence of asymmetric cavernous sinus enlargement in more than one tenth of patients, likely related to increased venous drainage.

Prediction of survival in patients affected by glioblastoma: histogram analysis of perfusion MRI.

PURPOSE: The identification of prognostic biomarkers plays a pivotal role in the management of glioblastoma. The aim of this study was to assess the role of magnetic resonance dynamic susceptibility contrast imaging (DSC-MRI) with histogram analysis in the prognostic evaluation of patients suffering from glioblastoma. MATERIALS AND METHODS: Sixty-eight patients with newly diagnosed pathologically verified GBM were retrospectively evaluated. All patients underwent MRI investigations, including DSC-MRI, surgical procedure and received postoperative focal radiotherapy plus daily temozolomide (TMZ), followed by adjuvant TMZ therapy. Relative cerebral blood volume (rCBV) histograms were generated from a volume of interest covering the solid portions of the tumor and statistically evaluated for kurtosis, skewness, mean, median and maximum value of rCBV. To verify if histogram parameters could predict survival at 1 and 2 years, receiver operating characteristic (ROC) curves were obtained. Kaplan-Meier method was used to calculate patient's overall survival. RESULTS: rCBV kurtosis and rCBV skewness showed significant differences between subjects surviving > 1 and > 2 years, According to ROC analysis, the rCBV kurtosis showed the best statistic performance compared to the other parameters; respectively, values of 1 and 2.45 represented an optimised cut-off point to distinguish subjects surviving over 1 or 2 years. Kaplan-Meier curves showed a significant difference between subjects with rCBV kurtosis values higher or lower than 1 (respectively 1021 and 576 days; Log-rank test: p = 0.007), and between subjects with rCBV kurtosis values higher or lower than 2.45 (respectively 802 and 408 days; Log-rank test: p = 0.001). CONCLUSION: The histogram analysis of perfusion MRI proved to be a valid method to predict survival in patients affected by glioblastoma.

White matter involvement in young non-demented Down's syndrome subjects: a tract-based spatial statistic analysis.

PURPOSE: Cognitive decline in Down syndrome generally shows neurodegenerative aspects similar to what is observed in Alzheimer's disease. Few studies reported information on white matter integrity. The aim of this study was to evaluate white matter alterations in a cohort of young Down subjects, without dementia, by means of DTI technique, compared to a normal control group. METHODS: The study group consisted of 17 right-handed subjects with DS and many control subjects. All individuals participating in this study were examined by MR exam including DTI acquisition (32 non-coplanar directions); image processing and analysis were performed using FMRIB Software Library (FSL version 4.1.9, http://www.fmrib.ox.ac.uk/fsl )) software package. Finally, the diffusion tensor was estimated voxel by voxel and the FA map derived from the tensor. A two-sample t test was performed to assess differences between DS and control subjects. RESULTS: The FA is decreased in DS subjects, compared to control subjects, in the region of the anterior thalamic radiation, the inferior fronto-occipital fasciculum, the inferior longitudinal fasciculum, and the cortico-spinal tract, bilaterally. CONCLUSIONS: The early white matter damage visible in our DS subjects could have great impact in the therapeutic management, in particular in better adapting the timing of therapies to counteract the toxic effect of the deposition of amyloid that leads to oxidative stress.

Langerhans' Cell Histiocytosis Mimicking a Pott Puffy Tumor.

Langherans' cell histiocytosis (LCH) is a rare disease mostly affecting children in the first decade of life. As clinical presentation is extremely heterogenous, a prompt diagnosis may be challenging, sometimes leading to a diagnostic delay, especially when the disease involves a single site. Herein, we report a case of a child with an unusual presentation of (LCH) mimicking a Pott puffy tumor with extracranial and epidural abscesses, surgically treated. Through this unique case we summarize possible manifestations of LCH with bone involvement and we underline the importance of considering possible complications due to bone erosions such as infection, to avoid a misdiagnosis.

Dentate nucleus T1 hyperintensity: is it always gadolinium all that glitters?

In the last few years, several scientific papers and reports have demonstrated magnetic resonance (MR) signal intensity (SI) changes on pre-contrast T1-weighted images following multiple gadolinium-based contrast agents (GBCA) administrations, particularly following the exposure to linear GBCAs. Pathological animal and human post-mortem studies have confirmed the relationship between this radiological finding and the presence of gadolinium accumulation in vulnerable brain regions in patients with normal renal function. In this short communication, we report the case of a 15-year-old patient affected by b-cell acute lymphoblastic leukemia (bALL) who developed a hyperintense signal in the dentate nuclei following multiple administrations of a macrocyclic GBCA. The purpose of this report is to discuss possible differential diagnoses of this radiological finding with special focus on the differentiation between iron or manganese accumulation, post-irradiation changes and GBCA-related Gd deposition, highlighting the importance of the acquisition of accurate clinical data to improve our scientific knowledge.

Is MRI imaging in pediatric age totally safe? A critical reprisal.

Current radiological literature is strongly focussed on radiation imaging risks. Indeed, given there is a small but actual augment in cancer risk from exposure to ionizing radiation in children, it is important to understand what the risk of alternative techniques could be. We retrospectively review literature data concerning possible MR imaging risks, focussing on the biological effects of MR, sedation and gadolinium compound risks when dealing with infant patients. The main concerns can be summarized in: (1) Biological effects of non-ionizing electromagnetic fields (EMF) employed-whose mechanisms of interaction with human tissues are polarization, induced current, and thermal heating, respectively. (2) Risks associated with noises produced during MRI examinations. (3) Hazards from ferromagnetic external and/or implanted devices-whose risk of being unintentionally brought inside MR room is higher in children than in adults. (4) Risks associated with sedation or general anaesthesia, essential problem in performing MR in very young patients, due to the exam long-lasting. (5) Risks related to gadolinium-based contrast agents, especially considering the newly reported brain deposition.

Predictive role of dynamic contrast enhanced T1-weighted MR sequences in pre-surgical evaluation of macroadenomas consistency.

PURPOSE: Our hypothesis was that pituitary macroadenomas show different areas of consistency detectable by enhanced magnetic resonance imaging (MRI) with Dynamic study during gadolinium administration. MATERIALS AND METHODS: We analysed 21 patients with pituitary macroadenomas between June 2013 and June 2015. All patients underwent trans-sphenoidal surgery and neurosurgeon described macroadenomas consistency. Similarly, two neuroradiologists manually drew regions of interest (ROIs) inside the solid-appearing portions of macroadenoma and in the normal white matter both on dynamic and post-contrast acquisitions. The ratio between these ROIs, defined as Signal Intensity Ratio (SIR), allowed obtaining signal intensity curves over time on dynamic acquisition and a single value on post-contrast MRI. SIR values best differentiating solid from soft macroadenoma components were calculated and correlated with pathologic patterns. A two-sample T test and empiric receiver operating characteristic (ROC) curve of SIR was performed. RESULTS: According to ROC analysis, the SIR value of 1.92, obtained by dynamic acquisition, best distinguished soft and hard components. All the specimens from soft components were characterized by high cellularity, high representation of vascularization and micro-haemorrhage and low percentage of collagen content. The reverse was evident in hard components. CONCLUSIONS: We demonstrated that dynamic MRI acquisition could distinguish with good accuracy macroadenomas consistency.

Signal intensity at unenhanced T1-weighted magnetic resonance in the globus pallidus and dentate nucleus after serial administrations of a macrocyclic gadolinium-based contrast agent in children.

BACKGROUND: Few studies have been conducted on the relations between T1-weighted signal intensity changes in the pediatric brain following gadolinium-based contrast agent (GBCA) exposure. OBJECTIVE: The purpose of this study is to investigate the effect of multiple administrations of a macrocyclic GBCA on signal intensity in the globus pallidus and dentate nucleus of the pediatric brain on unenhanced T1-weighted MR images. MATERIALS AND METHODS: This retrospective study included 50 patients, mean age: 8 years (standard deviation: 4.8 years), with normal renal function exposed to ≥6 administrations of the same macrocyclic GBCA (gadoterate meglumine) and a control group of 59 age-matched GBCA-naïve patients. The globus pallidus-to-thalamus signal intensity ratio and dentate nucleus-to-pons signal intensity ratio were calculated from unenhanced T1-weighted images for both patients and controls. A mixed linear model was used to evaluate the effects on signal intensity ratios of the number of GBCA administrations, the time interval between administrations, age, radiotherapy and chemotherapy. T-test analyses were performed to compare signal intensity ratio differences between successive administrations and baseline MR signal intensity ratios in patients compared to controls. P-values were considered significant if <0.05. RESULTS: A significant effect of the number of GBCA administrations on relative signal intensities globus pallidus-to-thalamus (F[8]=3.09; P=0.002) and dentate nucleus-to-pons (F[8]=2.36; P=0.021) was found. The relative signal intensities were higher at last MR examination than at baseline (P<0.001). CONCLUSION: Quantitative analysis evaluation of globus pallidus:thalamus and dentate nucleus:pons of the pediatric brain demonstrated an increase after serial administrations of macrocyclic GBCA. Further research is necessary to fully understand GBCA pharmacokinetic in children.