Specific brain MRI features of constitutional mismatch repair deficiency syndrome in children with high-grade gliomas.

BACKGROUND: Children with constitutional mismatch repair deficiency (CMMRD) syndrome have an increased risk of high-grade gliomas (HGG), and brain imaging abnormalities. This study analyzes brain imaging features in CMMRD syndrome children versus those with HGG without CMMRD. METHODS: Retrospective comparative analysis of brain imaging in 30 CMMRD children (20 boys, median age eight years, 22 with HGG), seven with Lynch syndrome (7 HGG), 39 with type 1 neurofibromatosis (NF1) (four with HGG) and 50 with HGG without MMR or NF1 pathogenic variant ("no-predisposition" patients). RESULTS: HGG in CMMRD and Lynch patients were predominantly hemispheric (versus midline) compared to NF1 and no-predisposition patients (91% and 86%, vs 25% and 54%, p = 0.004). CMMRD-associated tumors often had ill-defined boundaries (p = 0.008). All CMMRD patients exhibited at least one developmental venous anomaly (DVA), versus 14%, 10%, and 6% of Lynch, NF1, and no-predisposition patients (p < 0.0001). Multiple DVAs were observed in 83% of CMMRD patients, one NF1 patient (3%), and never in other groups (p < 0.0001). Cavernomas were discovered in 21% of CMMRD patients, never in other groups (p = 0.01). NF1-like focal areas of high T2-FLAIR signal intensity (FASI) were more prevalent in CMMRD patients than in Lynch or no-predisposition patients (50%, vs 20% and 0%, respectively, p < 0.0001). Subcortical and ill-limited FASI, possibly involving the cortex, were specific to CMMRD (p < 0.0001) and did not evolve in 93% of patients (13/14). CONCLUSION: Diffuse hemispherically located HGG associated with multiple DVAs, cavernomas, and NF1-like or subcortical FASI strongly suggests CMMRD syndrome compared to children with HGG in other contexts. CLINICAL RELEVANCE STATEMENT: The radiologic suggestion of CMMRD syndrome when confronted with HGGs in children may prompt genetic testing. This can influence therapeutic plans. Therefore, imaging features could potentially be incorporated into CMMRD testing recommendations. KEY POINTS: Using imaging to detect CMMRD syndrome early may improve patient care. CMMRD features include: hemispheric HGG with multiple developmental venous anomalies and NF1-like or subcortical areas with high T2-FLAIR intensity. We propose novel imaging features to improve the identification of potential CMMRD patients.

Dangers and therapeutic difficulties of intracranial hemangioma in infants: A CARE case report.

INTRODUCTION: Description of neurological complications induced by intracranial hemangioma in infants and by the initiation of beta-blocker treatment (propranolol). OBSERVATION: A 2-month-old infant was referred for grade 5 non-congenital unilateral peripheral facial palsy. Work-up revealed ipsilateral profound hearing loss and two intracranial hemangiomas: one in the ipsilateral internal auditory canal (IAC), the other in the cerebellum opposite the nodule of vermis. Initial treatment with a beta-blocker (propranolol 1mg/kg/day for 1month, then 3mg/kg/day) resulted in disappearance of symptoms and regression of lesions within 8weeks. At 20months after introduction of maintenance therapy (propranolol 3mg/kg/day), two asthma attacks occurred, leading to initiation of fluticasone and continuation of the beta-blocker. Thirty months after discontinuation of treatment, no further progression was noted. DISCUSSION: Unilateral facial palsy in an infant suggests a number of diagnoses. MRI revealed IAC hemangioma. The choice of dosage and duration of treatment was based on a review of the literature and a strategy defined in multidisciplinary consultation.

Performance of Non-EPI DW MRI for Pediatric Cholesteatoma Follow-Up.

OBJECTIVE: To evaluate the accuracy, sensitivity, and specificity of nonecho planar (non-EPI) diffusion-weighted (DW) magnetic resonance imaging (MRI) to detect residual cholesteatoma in children. STUDY DESIGN: Retrospective study. SETTING: Tertiary comprehensive hospital. METHODS: Children operated on for a first-stage cholesteatoma procedure from 2010 to 2019 were included. MRIs were performed with non-EPI DW sequences. Initial reports were collected, indicating the presence or absence of hyperintensity suggestive of cholesteatoma. Three hundred twenty-three MRIs were correlated with the subsequent surgery (66%) or year-later MRI (21%), or were considered accurate if performed 5 years or more after the last surgery (13%). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each imaging procedure for the detection of cholesteatoma were calculated. RESULTS: Two hundred twenty-four children with mean age of 9 ± 4 years old presented with cholesteatoma. MRIs were performed 27 ± 24 months after surgery. Residual cholesteatoma was diagnosed in 35%. The sensitivity, specificity, PPV, and NPV of MRI were 62%, 86%, 74%, and 78%, respectively. Accuracy, sensitivity, and specificity increased significantly over time (multivariate analysis). The mean delay after last surgery was of 30 ± 2.0 months for accurate MRI (true positive or negative) versus 17 ± 2.0 months for nonaccurate (false positive or negative) MRIs (p < .001). CONCLUSION: However, long the delay after the last surgery, the sensitivity of non-EPI diffusion sequence MRI in children has limitations for the detection of residual cholesteatoma. Surveillance for residual cholesteatoma should incorporate findings at primary surgery, surgeon experience, a low threshold for second-look procedures, and routine imaging.

Imaging features to distinguish posterior fossa ependymoma subgroups.

OBJECTIVES: Posterior fossa ependymoma group A (EPN_PFA) and group B (EPN_PFB) can be distinguished by their DNA methylation and give rise to different prognoses. We compared the MRI characteristics of EPN_PFA and EPN_PFB at presentation. METHODS: Preoperative imaging of 68 patients with posterior fossa ependymoma from two centers was reviewed by three independent readers, blinded for histomolecular grouping. Location, tumor extension, tumor volume, hydrocephalus, calcifications, tissue component, enhancement or diffusion signal, and histopathological data (cellular density, calcifications, necrosis, mitoses, vascularization, and microvascular proliferation) were compared between the groups. Categorical data were compared between groups using Fisher's exact tests, and quantitative data using Mann-Whitney tests. We performed a Benjamini-Hochberg correction of the p values to account for multiple tests. RESULTS: Fifty-six patients were categorized as EPN_PFA and 12 as EPN_PFB, with median ages of 2 and 20 years, respectively (p = 0.0008). The median EPN_PFA tumoral volume was larger (57 vs 29 cm3, p = 0.003), with more pronounced hydrocephalus (p = 0.002). EPN_PFA showed an exclusive central position within the 4th ventricle in 61% of patients vs 92% for EPN_PFB (p = 0.01). Intratumor calcifications were found in 93% of EPN_PFA vs 40% of EPN_PFB (p = 0.001). Invasion of the posterior fossa foramina was mostly found for EPN_PFA, particularly the foramina of Luschka (p = 0.0008). EPN_PFA showed whole and homogeneous tumor enhancement in 5% vs 75% of EPN_PFB (p = 0.0008). All mainly cystic tumors were EPN_PFB (p = 0.002). The minimal and maximal relative ADC was slightly lower in EPN_PFA (p = 0.02 and p = 0.01, respectively). CONCLUSION: Morphological characteristics from imaging differ between posterior fossa ependymoma subtypes and may help to distinguish them preoperatively. CLINICAL RELEVANCE STATEMENT: This study provides a tool to differentiate between group A and group B ependymomas, which will ultimately allow the therapeutic strategy to be adapted in the early stages of patient management. KEY POINTS: • Posterior fossa ependymoma subtypes often have different imaging characteristics. • Posterior fossa ependymomas group A are commonly median or lateral tissular calcified masses, with incomplete enhancement, affecting young children and responsible for pronounced hydrocephalus and invasion of the posterior fossa foramina. • Posterior fossa ependymomas group B are commonly median non-calcified masses of adolescents and adults, predominantly cystic, and minimally invasive, with total and homogeneous enhancement.

Early Magnetic Resonance Imaging to Diagnose Residual Cholesteatoma in Children and Benefit of Radiological Rereview.

OBJECTIVE: Non-echo-planar diffusion-weighted (DW) magnetic resonance imaging (non-EPI MRI) is the appropriate sequence to detect residual cholesteatoma. In the child, MRI may be clinically useful to determine the timing of the second-look procedure. The aim of this paper was to retrospectively evaluate the performance of early MRI (before the 18th postoperative month) in detecting residual cholesteatoma in children after review by experienced specialized neuroradiologists. STUDY DESIGN: Retrospective study. SETTING: One university center comparative cohort. METHODS: All patients who had a 2-staged procedure for cholesteatoma with an MRI before the second stage from 2010 to 2020 were included and analyzed. Three pediatric neuroradiologists reviewed all the images blinded to the surgical result. RESULTS: N = 141 cholesteatoma events (140 children) were included with a mean age at MRI of 10 (±4) years old. Non-EPI MRIs were performed 10.7 (±3.8) months after the first-stage surgery and 2.2 (±2.6) months before the second-stage procedure. Non-EPI MRI had a 0.57 sensitivity (SE) and 0.83 specificity (SP). MRI was reviewed in 112 cases. The diagnosis was corrected in 17 cases (15.1%) (3 true positives, 7 false negatives, and 7 false positives). SE = 0.63 (p = 0.1) and SP = 0.92 (p = 0.08) after rereading. CONCLUSION: Early MRI's SE is poor but SP is excellent after rereading. Evidence does not support the use of early non-EPI MRI to modify the surgical strategy or to postpone the second look. If performed, early non-EPI MRI should be read by specialized experienced radiologists with all 3 sequences (T1, T2, and non-EPI DW) and apparent diffusion coefficient calculation, especially in cases of otitis media with effusion.

Case Report: Zolpidem's paradoxical restorative action: A case report of functional brain imaging.

Zolpidem is a sedative drug that has been shown to induce a paradoxical effect, restoring brain function in wide range of neurological disorders. The underlying functional mechanism of the effect of zolpidem in the brain in clinical improvement is still poorly understood. Thus, we aimed to investigate rest brain function to study zolpidem-induced symptom improvement in a patient who developed postoperative pediatric cerebellar mutism syndrome, a postoperative complication characterized by delayed onset transient mutism/reduced speech that can occur after medulloblastoma resection. The patient experienced clinical recovery after a single dose of zolpidem. Brain function was investigated using arterial spin labeling MRI and resting-state functional MRI. Imaging was performed at three time-points: preoperative, postoperative during symptoms, and after zolpidem intake when the symptoms regressed. Whole brain rest cerebral blood flow (CBF) and resting state functional connectivity using Pearson coefficient correlations between pairs of regions of interest were investigated two-by-two at the different time points. A comparison between postoperative and preoperative images showed a significant decrease in rest CBF in the left supplementary motor area, Broca's area, and the left striatum and a decrease in functional connectivity within the dentato-thalamo-cortical and cortico-striato-pallido-thalamo-cortical loops. Post-zolpidem images showed increased CBF in the left striatum and increased functional connectivity within the disrupted loops relative to postoperative images. Thus, we observed functional changes within the broader speech network and thalamo-subcortical interactions associated with the paradoxical effect of zolpidem in promoting clinical recovery. This should encourage further functional investigations in the brain to better understand the mechanism of zolpidem in neurological recovery.

Spectrum of neuroradiological manifestations in primary hemophagocytic lymphohistiocytosis: a comparative study of EBV-induced versus non-EBV-induced forms in 75 genetically confirmed pediatric cases.

OBJECTIVES: Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition affecting young children. It is potentially triggered by Epstein-Barr virus (EBV). This study describes the neuroradiological features observed in 75 children with genetically confirmed primary HLH, comparing EBV-induced with non-EBV-induced HLH forms. METHODS: Brain MRIs between 2007 and 2021 from 75 children with HLH according to the 2004 Histiocyte Society criteria and with a confirmed HLH-related mutation, were retrospectively reviewed by two pediatric neuroradiologists blinded to EBV status and to mutation status. At diagnosis, 17 children with EBV viremia above a threshold of 1000 copies/mL were included in the EBV-induced HLH group. The remaining 58 patients were included in the non-EBV-induced HLH group. RESULTS: Of the 75 children initially included, 21 had abnormal MRI (21/75 (28%); 9/17 in the EBV-induced HLH group and 12/58 in the non-EBV-induced HLH group). All patients with abnormal MRI had neurological symptoms. Abnormal MRIs showed white matter lesions; the posterior fossa was affected in all but one case. There was no significant difference between groups regarding the localization or morphology of white matter lesions. The striatum was more frequently affected in the EBV-induced HLH group (8/9 (89%) versus 1/12 (8%), p = 0.00037). All lesions, whether in the white matter or in the basal ganglia, presented increased ADC values on diffusion weighted imaging (DWI). CONCLUSION: In this study of 75 children with genetically confirmed HLH, only children with neurological signs had abnormal brain MRI. Bilateral striatum involvement suggested an EBV-induced form of HLH. KEY POINTS: • In children with genetically proven HLH, only those with neurological signs did have brain abnormalities at MRI. • All patients with abnormal brain MRI had multiple white matter lesions with increased ADC values, including in the posterior fossa in almost all cases. • Basal ganglia and in particular the striatum were bilaterally and symmetrically affected in almost all EBV-induced HLH patients, in contrast to the non-EBV-induced HLH patients.

How can we differentiate supratentorial tumor recurrence from postradiation imaging changes in children treated for primary malignant brain tumors?

OBJECTIVE: Distinguishing tumor recurrence from therapy-induced imaging changes (TIIC) on brain MRI in children treated for primary malignant brain tumors may be challenging. The authors aimed to assess the diagnostic ability of multimodal MRI in differentiating TIIC from tumor recurrence. METHODS: The authors retrospectively included children with abnormal supratentorial brain MRI findings after treatment for primary malignant brain tumors (regardless of their localization) with complete resection and radiotherapy. A total of 18 patients with TIIC and 25 patients with tumor recurrence were compared, according to structural, apparent diffusion coefficient (ADC), and arterial spin labeling (ASL) imaging data accrued over time. TIIC were defined by a new MRI scan that was stable for at least 1 year or had regressed, or by histopathology findings in specimens obtained when the anomaly was surgically treated. RESULTS: The time interval between completion of radiotherapy and the appearance of abnormal brain MRI findings was significantly shorter in the TIIC group compared with the tumor recurrence group (median 6 vs 35 months; p < 0.001). TIIC appeared as foci of increased T2-weighted signal intensity, without nodule, associated with variable contrast enhancement. Tumor recurrence appeared as a well-defined nodule with intermediate signal intensity on T2-weighted images with nodular contrast enhancement. Relative ADC values were significantly higher in the TIIC group (median 1.43 vs 0.88; p < 0.001). Relative ASL-cerebral blood flow (CBF) values were significantly lower in the TIIC group (median 0.27 vs 0.43; p = 0.04). On follow-up MRI, TIIC could progress, regress, or remain stable. In most instances (72%), they decreased in size or remained stable at 4 years of follow-up. CONCLUSIONS: MRI features of TIIC include foci of increased signal intensity without a demonstrable nodule on T2-weighted images, high ADC values, and lower ASL-CBF values, whereas tumor recurrence appears as a well-defined nodule with low ADC values and higher ASL-CBF values.

Reliability of fast-spin echo T2-weighted three-dimensional sequences to predict endoscopic third ventriculocisternostomy patency in children.

PURPOSE: Clinical and radiological assessment of endoscopic third ventriculocisternostomy (ETV) patency can be challenging in children. The objective of our study was thus to test the accuracy and interrater reliability of 3D fast-spin echo (FSE) T2-weighted sequences to assess the patency of ETV. METHODS: We included all the consecutive children who underwent surgery for ETV over a two-year period and selected the children who presented ETV dysfunction and matched them with children without dysfunction. We evaluated the Kappa interrater reliability of three experienced physicians for prediction of ETV patency using solely the flow void sign in 3D FSE T2-weighted sequences. RESULTS: Nineteen children underwent surgery for ETV dysfunction and 12 children without dysfunction were matched. Sensitivity was 0.79, 0.89 and 0.84 and specificity was 1 for all raters. None of the patent ETV was wrongly considered to be dysfunctional. Fleiss' kappa was 0.871 (p < 0.001). The interrater reliability was excellent with respect to the patency or not of the ETV. CONCLUSION: FSE T2-weighted sequence is a simple and reproducible tool that can be widely used in daily practice to assess the patency of ETV. Interrater reliability of this sequence is high and accessibility in outpatient setting is acceptable.

Preoperative Detection of Subtle Focal Cortical Dysplasia in Children by Combined Arterial Spin Labeling, Voxel-Based Morphometry, Electroencephalography-Synchronized Functional MRI, Resting-State Regional Homogeneity, and 18F-fluorodeoxyglucose Positron Emission Tomography.

BACKGROUND: Focal cortical dysplasia (FCD) causes drug-resistant epilepsy in children that can be cured surgically, but the lesions are often unseen by imaging. OBJECTIVE: To assess the efficiency of arterial spin labeling (ASL), voxel-based-morphometry (VBM), fMRI electroencephalography (EEG), resting-state regional homogeneity (ReHo), 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and their combination in detecting pediatric FCD. METHODS: We prospectively included 10 children for whom FCD was localized by surgical resection. They underwent 3T MR acquisition with concurrent EEG, including ASL perfusion, resting-state BOLD fMRI (allowing the processing of EEG-fMRI and ReHo), 3D T1-weighted images processed using VBM, and FDG PET-CT coregistered with MRI. Detection was assessed visually and by comparison with healthy controls (for ASL and VBM). RESULTS: Eight children had normal MRI, and 2 had asymmetric sulci. Using MR techniques, FCD was accurately detected by ASL for 6/10, VBM for 5/10, EEG-fMRI for 5/8 (excluding 2 with uninterpretable results), and ReHo for 4/10 patients. The combination of ASL, VBM, and ReHo allowed correct FCD detection for 9/10 patients. FDG PET alone showed higher accuracy than the other techniques (7/9), and its combination with VBM allowed correct FCD detection for 8/9 patients. The detection efficiency was better for patients with asymmetric sulci (2/2 for all techniques), but advanced MR techniques and PET were useful for MR-negative patients (7/8). CONCLUSION: A combination of multiple imaging techniques, including PET, ASL, and VBM analysis of T1-weighted images, is effective in detecting subtle FCD in children.

Abnormal Spontaneous Blood Oxygenation Level Dependent Fluctuations in Children with Focal Cortical Dysplasias: Initial Findings in Surgically Confirmed Cases.

BACKGROUND: Focal cortical dysplasias (FCD) are a frequent cause of drug-resistant epilepsy in children but are often undetected on structural magnetic resonance imaging (MRI). We aimed to measure and validate the variation of resting state functional MRI (rs-fMRI) blood oxygenation level dependent (BOLD) metrics in surgically proven FCDs in children, to assess the potential yield for detecting and understanding these lesions. METHODS: We prospectively included pediatric patients with surgically proven FCD with inconclusive structural MRI and healthy controls, who underwent a ten-minute rs-fMRI acquired at 3T. Rs-fMRI data was pre-processed and maps of values of regional homogeneity (ReHo), degree centrality (DC), amplitude of low frequency fluctuations (ALFF) and fractional ALFF (fALFF) were calculated. The variations of BOLD metrics within the to-be-resected areas were analyzed visually, and quantitatively using lateralization indices. BOLD metrics variations were also analyzed in fluorodeoxyglucose-positron emission tomography (FDG-PET) hypometabolic areas. RESULTS: We included 7 patients (range: 3-15 years) and 6 aged-matched controls (range: 6-17 years). ReHo lateralization indices were positive in the to-be-resected areas in 4/7 patients, and in 6/7 patients in the additional PET hypometabolic areas. These indices were significantly higher compared to controls in 3/7 and 4/7 patients, respectively. Visual analysis revealed a good spatial correlation between high ReHo areas and MRI structural abnormalities (when present) or PET hypometabolic areas. No consistent variation was seen using DC, ALFF, or fALFF. CONCLUSION: Resting-state fMRI metrics, noticeably increase in ReHo, may have potential to help detect MRI-negative FCDs in combination with other morphological and functional techniques, used in clinical practice and epilepsy-surgery screening.

Optical Tissue Clearing to Study the Intra-Pulmonary Biodistribution of Intravenously Delivered Mesenchymal Stromal Cells and Their Interactions with Host Lung Cells.

Mesenchymal stromal cells (MSCs) injected intravenously are trapped in the capillaries of the lungs and die within the first 24 h. Studying the biodistribution and fate of labelled therapeutic cells in the 3D pulmonary context is important to understand their function in this organ and gain insights into their mechanisms of action. Optical tissue clearing enables volumetric cell tracking at single-cell resolution. Thus, we compared three optical tissue-clearing protocols (Clear, Unobstructed Brain/Body Imaging Cocktails and Computational analysis (CUBIC), modified stabilised 3D imaging of solvent-cleared organs (s-DISCO) and ethyl cinnamate (ECi)) to evaluate their potential to track the biodistribution of human umbilical cord MSCs expressing the tdTomato fluorescence reporter and investigate how they interact with host cells in the mouse lung. The results showed that although CUBIC clearing is the only method that enables direct imaging of fluorescently labelled MSCs, combining s-DISCO or ECi with immunofluorescence or dye labelling allows the interaction of MSCs with endothelial and immune cells to be studied. Overall, this comparative study offers guidance on selecting an optical tissue-clearing method for cell tracking applications.

Development of amyloid beta gold nanorod aggregates as optoacoustic probes.

Propagation of small amyloid beta (Aß) aggregates (or seeds) has been suggested as a potential mechanism of Alzheimer's disease progression. Monitoring the propagation of Aß seeds in an organism would enable testing of this hypothesis and, if confirmed, provide mechanistic insights. This requires a contrast agent for long-term tracking of the seeds. Gold nanorods combine several attractive features for this challenging task, in particular, their strong absorbance in the infrared (enabling optoacoustic imaging) and the availability of several established protocols for surface functionalisation. In this work, polymer-coated gold nanorods were conjugated with anti-Aß antibodies and attached to pre-formed Aß seeds. The resulting complexes were characterised for their optical properties by UV/Vis spectroscopy and multispectral optoacoustic tomography. The complexes retained their biophysical properties, i.e. their ability to seed Aß fibril formation. They remained stable in biological media for at least 2 days and showed no toxicity to SH-SY5Y neuroblastoma cells up to 1.5 nM and 6 µM of gold nanorods and Aß seeds, respectively. Taken together, this study describes the first steps in the development of probes for monitoring the spread of Aß seeds in animal models.

Heterogeneity of PNPT1 neuroimaging: mitochondriopathy, interferonopathy or both?

BACKGROUND: Biallelic variants in PNPT1 cause a mitochondrial disease of variable severity. PNPT1 (polynucleotide phosphorylase) is a mitochondrial protein involved in RNA processing where it has a dual role in the import of small RNAs into mitochondria and in preventing the formation and release of mitochondrial double-stranded RNA into the cytoplasm. This, in turn, prevents the activation of type I interferon response. Detailed neuroimaging findings in PNPT1-related disease are lacking with only a few patients reported with basal ganglia lesions (Leigh syndrome) or non-specific signs. OBJECTIVE AND METHODS: To document neuroimaging data in six patients with PNPT1 highlighting novel findings. RESULTS: Two patients exhibited striatal lesions compatible with Leigh syndrome; one patient exhibited leukoencephalopathy and one patient had a normal brain MRI. Interestingly, two unrelated patients exhibited cystic leukoencephalopathy resembling RNASET2-deficient patients, patients with Aicardi-Goutières syndrome (AGS) or congenital CMV infection. CONCLUSION: We suggest that similar to RNASET2, PNPT1 be searched for in the setting of cystic leukoencephalopathy. These findings are in line with activation of type I interferon response observed in AGS, PNPT1 and RNASET2 deficiencies, suggesting a common pathophysiological pathway and linking mitochondrial diseases, interferonopathies and immune dysregulations.

A CBF decrease in the left supplementary motor areas: New insight into postoperative pediatric cerebellar mutism syndrome using arterial spin labeling perfusion MRI.

Postoperative pediatric cerebellar mutism syndrome (pCMS), characterized mainly by delayed onset transient mutism is a poorly understood complication that may occur after pediatric medulloblastoma (MB) resection. Our aim was to investigate postoperative changes in whole-brain cerebral blood flow (CBF) at rest in pCMS patients using arterial spin labeling (ASL) perfusion imaging. This study compared preoperative and postoperative T2-weighted signal abnormalities and CBF using a voxel-wise, whole-brain analysis in 27 children undergoing MB resection, including 11 patients who developed mutism and 16 who did not. Comparison of postoperative T2 signal abnormalities between patients who developed pCMS (mean age 7.0 years) and those who did not showed that pCMS (mean age 8.9 years) patients were significantly more likely to present with T2-weighted hyperintensities in the right dentate nucleus (DN) (p = 0.02). Comparison of preoperative and postoperative CBF in patients with pCMS showed a significant postoperative CBF decrease in the left pre-supplementary motor area (pre-SMA) (p = 0.007) and SMA (p = 0.009). In patients who did not develop pCMS, no significant differences were observed. Findings provide evidence of an association between pCMS, injury to the right DN, and left pre-SMA/SMA hypoperfusion, areas responsible for speech. This supports the relevance of CBF investigations in pCMS.

Radiogenomics of diffuse intrinsic pontine gliomas (DIPGs): correlation of histological and biological characteristics with multimodal MRI features.

OBJECTIVES: The diffuse intrinsic pontine gliomas (DIPGs) are now defined by the type of histone H3 mutated at lysine 27. We aimed to correlate the multimodal MRI features of DIPGs, H3K27M mutant, with their histological and molecular characteristics. METHODS: Twenty-seven treatment-naïve children with histopathologically confirmed DIPG H3K27M mutant were prospectively included. MRI performed prior to biopsy included multi-b-value diffusion-weighted imaging, ASL, and dynamic susceptibility contrast (DSC) perfusion imaging. The ADC and cerebral blood flow (CBF) and blood volume (CBV) were measured at the biopsy site. We assessed quantitative histological data, including microvascular density, nuclear density, and H3K27M-positive nuclear density. Gene expression profiling was also assessed in the samples. We compared imaging and histopathological data according to histone subgroup. We correlated MRI quantitative data with histological data and gene expression. RESULTS: H3.1K27M mutated tumors showed higher ADC values (median 3151 µm2/s vs 1741 µm2/s, p = 0.003), and lower perfusion values (DSC-rCBF median 0.71 vs 1.43, p = 0.002, and DSC-rCBV median 1.00 vs 1.71, p = 0.02) than H3.3K27M ones. They had similar microvascular and nuclear density, but lower H3K27M-positive nuclear density (p = 0.007). The DSC-rCBV was positively correlated to the H3K27M-positive nuclear density (rho = 0.74, p = 0.02). ADC values were not correlated with nuclear density nor perfusion values with microvascular density. The expression of gated channel activity-related genes tended to be inversely correlated with ADC values and positively correlated with DSC perfusion. CONCLUSIONS: H3.1K27M mutated tumors have higher ADC and lower perfusion values than H3.3K27M ones, without direct correlation with microvascular or nuclear density. This may be due to tissular edema possibly related to gated channel activity-related gene expression. KEY POINTS: • H3.1K27M mutant DIPG had higher apparent diffusion coefficient (p = 0.003), lower α (p = 0.048), and lower relative cerebral blood volume (p = 0.02) than H3.3K27M mutant DIPG at their biopsy sites. • Biopsy samples obtained within the tumor's enhancing portion showed higher microvascular density (p = 0.03) than samples obtained outside the tumor's enhancing portion, but similar H3K27M-positive nuclear density (p = 0.84). • Relative cerebral blood volume measured at the biopsy site was significantly correlated with H3K27M-positive nuclear density (rho = 0.74, p = 0.02).

Early magnetic resonance imaging to detect presymptomatic leptomeningeal angioma in children with suspected Sturge-Weber syndrome.

AIM: We aimed to evaluate the contribution of early magnetic resonance imaging (MRI) for the presymptomatic diagnosis of Sturge-Weber syndrome (SWS) in infants with a facial port-wine birthmark (PWB). METHOD: Asymptomatic infants with a facial PWB who performed a first MRI scan before 3 months and a second MRI scan after 9 months were included in this study. Leptomeningeal enhancement on T1-weighted imaging and four indirect signs of leptomeningeal angioma (choroid plexus enlargement, cerebral atrophy, signal inversion of the white matter with T2 hyposignal, and T1 hypersignal) were screened on the first MRI scan and correlated with clinical and/or radiological diagnosis of SWS. RESULTS: Thirteen of 30 included patients had SWS with leptomeningeal angioma. Eleven had a leptomeningeal enhancement on the first MRI scan and 10 had associated indirect signs. The presence of a direct or at least one indirect sign of leptomeningeal angioma on the first MRI scan confirmed the diagnosis of SWS with a sensitivity of 100 per cent (95% confidence interval 75-100%) and a specificity of 94 per cent (71-100%). INTERPRETATION: Early diagnosis of SWS is possible on contrast-enhanced MRI performed in asymptomatic infants with a facial PWB before the age of 3 months. This early detection would help to select patients who may benefit from early neuroprotective intervention. WHAT THIS PAPER ADDS: Specific magnetic resonance imaging markers provide early diagnosis of leptomeningeal angioma in Sturge-Weber syndrome (SWS). Presymptomatic diagnosis of SWS should help to select patients for early therapy intervention.

Arterial Spin Labeling and Central Precocious Puberty.

PURPOSE: To evaluate a non-invasive method to assess the progressivity of idiopathic central precocious puberty (CPP) by quantifying perfusion of the pituitary stalk with arterial spin labeling (ASL) and using the gonadotropin-releasing hormone (GnRH) test as a reference test to define progressive CPP. METHODS: In a single center retrospective study, 52 consecutive patients, observed between October 2015 and April 2017 and referred with early signs of puberty, were evaluated using the GnRH test and cerebral magnetic resonance imaging (MRI). Patients with peripheral or non-idiopathic puberty were excluded. The distribution of perfusion values between patients with progressive and non-progressive CPP was compared using a nonparametric Mann-Whitney U­test. RESULTS: In this study 35 patients were included and 29 had progressive CPP. These patients displayed significantly higher cerebral blood flow (CBF) values than the 6 patients with non-progressive CPP (p = 0.006). The median CBF for patients with non-progressive and progressive CPP was 45.25 ml/min/100 g (interquartile range 36.9-54) vs. 65 ml/min/100 g (interquartile range 55.5-74.5), respectively. To determine if the CPP was progressive, the best CBF threshold was 55.5 ml/min/100 g with a sensitivity of 76%, a specificity of 83% and an accuracy of 77%. There were strong significant correlations between CBF and LH peak (r = 0.67, p < 0.001) and between CBF and LH/FSH peaks ratio [r = 0.71, p < 0.001] during the GnRH test. CONCLUSION: Arterial spin labelling (ASL) offers a novel tool to assess the progressivity of idiopathic CPP.

In vivo fate of free and encapsulated iron oxide nanoparticles after injection of labelled stem cells.

Nanoparticle contrast agents are useful tools to label stem cells and monitor the in vivo bio-distribution of labeled cells in pre-clinical models of disease. In this context, understanding the in vivo fate of the particles after injection of labelled cells is important for their eventual clinical use as well as for the interpretation of imaging results. We examined how the formulation of superparamagnetic iron oxide nanoparticles (SPIONs) impacts the labelling efficiency, magnetic characteristics and fate of the particles by comparing individual SPIONs with polyelectrolyte multilayer capsules containing SPIONs. At low labelling concentration, encapsulated SPIONs served as an efficient labelling agent for stem cells. The bio-distribution after intra-cardiac injection of labelled cells was monitored longitudinally by MRI and as an endpoint by inductively coupled plasma-optical emission spectrometry. The results suggest that, after being released from labelled cells after cell death, both formulations of particles are initially stored in liver and spleen and are not completely cleared from these organs 2 weeks post-injection.