Benchmarking against the MOMS Trial: Zurich Results of Open Fetal Surgery for Spina Bifida.

INTRODUCTION: The Management of Myelomeningocele Study, a.k.a. the MOMS trial, was published in 2011 in the New England Journal of Medicine. This prospective randomized controlled trial proved to be a milestone publication that provided definitive evidence that fetal surgery is a novel standard of care for select fetuses with spina bifida aperta (SB). The goal of our study is to assess whether our center can match these benchmark results. MATERIALS AND METHODS: Our study was conducted according to the MOMS protocol using the same inclusion and exclusion criteria and looked at the same outcome parameters that were used in the MOMS trial. Zurich and MOMS results were compared. RESULTS: We enrolled 20 patients between December 2010 and May 2015 all of whom underwent fetal surgery for SB. Among 51 different outcome variables, there were only 3 favorable (multiplicity-adjusted) significant differences (gestational age at birth, hindbrain herniation, and psychomotor development). There were no statistically significant differences regarding any other parameters. CONCLUSION: Our findings confirm that rigorous apprenticeship, training, and comprehensive prospective data collection enable centers like the Zurich Center for Fetal Diagnosis and Therapy to achieve benchmark results for open fetal surgery for myelomeningocele and myeloschisis. These results justify the existence and continuation of our program. Outcome documentation is an essential element of quality management. It is medically and ethically fundamental for fetal medicine and surgery centers offering high-end innovative medical care.

Total cerebrovascular blood flow and whole brain perfusion in children sedated using propofol with or without ketamine at induction: An investigation with 2D-Cine PC and ASL.

BACKGROUND: Multiple sedation regimes may be used to facilitate pediatric MRI scans. These regimes might affect cerebral blood flow and hemodynamics to varying degrees, particularly in children who may be vulnerable to anesthetic side effects. PURPOSE: To compare the effects of propofol monosedation solely (Pm group) vs. a combination of propofol and ketamine (KP group) on brain hemodynamics and perfusion. STUDY TYPE: Prospective double-blind randomized trial. FIELD STRENGTH/SEQUENCES: 1.5T and 3T. 2D-Cine phase contrast (2D-Cine PC) and pseudocontinuous arterial spin labeling (ASL). POPULATION: Children aged from 3 months to 10 years referred for MRI with deep sedation were randomized into either the KP or the Pm group. Perfusion images were acquired with ASL followed by single-slice 2D-Cine PC acquired between the cervical vertebra C2 and C3. ASSESSMENT: Average whole-brain perfusion (WBP ml.min-1 .100 ml-1 ) was extracted from the ASL perfusion maps and total cerebrovascular blood flow (CVF) was quantified by bilaterally summing the flow in the vertebral and the internal carotid arteries. The CVF values were converted to units of ml.min-1 .100 g-1 to calculate the tissue CVF100g (ml.min-1 .100 g-1 ). Images were assessed by a neuroradiologist and data from n = 81 (ASL) and n = 55 (PC) cases with no apparent pathology were entered into the analysis. STATISTICAL TESTS: Multivariate analysis of covariance was performed to compare drug sedation effects on WBP, CVF, and CVF100g . RESULTS: No significant difference in arterial flow was observed (P = 0.57), but the KP group showed significantly higher WBP than the Pm group, covarying for scanner and age (P = 0.003). A correlation analysis showed a significant positive correlation between mean WBP (ml.min-1 .100 g-1 ) and mean CVF100g . DATA CONCLUSION: The KP group showed higher perfusion but no significant difference in vascular flow compared with the Pm group. WBP and CVF100g correlated significantly, but ASL appeared to have more susceptibility to perfusion differences arising from the different sedation regimes. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2019;50:1433-1440.

Health-related quality of life in pre-school age children with single-ventricle CHD.

BACKGROUND: Little is known about health-related quality of life in young children undergoing staged palliation for single-ventricle CHD. The aim of this study was to assess the impact of CHD on daily life in pre-schoolers with single-ventricle CHD and to identify determinants of health-related quality of life. METHOD: Prospective two-centre cohort study assessing health-related quality of life using the Preschool Paediatric Cardiac Quality of Life Inventory in 46 children at a mean age of 38 months and 3 weeks. Children with genetic anomalies were excluded. Scores were compared with reference data of children with biventricular CHD. Multiple linear regression analysis was used to identify determinants of health-related quality of life. RESULTS: Health-related quality of life in pre-schoolers with single-ventricle CHD was comparable to children with biventricular CHD. Preterm birth and perioperative variables were significant predictors of low health-related quality of life. Notably, pre-Fontan brain MRI findings and neurodevelopmental status were not associated with health-related quality of life. Overall, perioperative variables explained 24% of the variability of the total health-related quality of life score.InterpretationDespite substantial health-related burden, pre-schoolers with single-ventricle CHD showed good health-related quality of life. Less-modifiable treatment-related risk factors and preterm birth had the highest impact on health-related quality of life. Long-term follow-up assessment of self-reported health-related quality of life is needed to identify patients with poorer health-related quality of life and to initiate supportive care.

Inclusion Cysts after Fetal Spina Bifida Repair: A Third Hit?

INTRODUCTION: Fetal spina bifida repair (fSBR) has proven effective in the reversibility of hindbrain herniation, lower rate of shunt-dependent hydrocephalus, and independent ambulation. Besides distinct advantages, there are also concerns related to fSBR. One of these is the postnatal occurrence of inclusion cysts (IC). METHODS: In a prospective study, 48 children who underwent fSBR were followed up. Postnatal assessment included clinical examination, cystometry, and spinal MRI. Indication for IC resection was the evidence of a spinal mass on MRI in the presence of deteriorating motor or bladder function, pain, or considerable growth of the IC. RESULTS: Fourteen children (30%) developed IC, all within the first 2 years of life. Six children underwent IC resection; 4 children due to deteriorating function, 2 children due to doubling of the mass on MRI within 1 year. Following IC resection, 4/6 children (67%) demonstrated altered motor function and 6 children (100%) were diagnosed with neurogenic bladder dysfunction. CONCLUSIONS: Systematic follow-up of patients with a history of fSBR revealed a high incidence of IC. Whether these are of dysembryogenic or iatrogenic origin, remains unclear. Since both IC per se and IC resection may lead to loss of neurologic function, IC can be considered a "third hit".

Comparison of DTI analysis methods for clinical research: influence of pre-processing and tract selection methods.

BACKGROUND: The primary aim was to compare fractional anisotropy (FA) values derived with different diffusion tensor imaging (DTI) analysis approaches (atlas-based, streamline tractography, and combined). A secondary aim was to compare FA values and number of tracts (NT) with the clinical motor outcome quantified by the functional independence measure for children (WeeFIM). METHODS: Thirty-nine DTI datasets of children with acquired brain injury were analysed. Regions of interest for the ipsilesional corticospinal tract were defined and mean FA and NT were calculated. We evaluated FA values with Spearman correlation, the Friedman and Wilcoxon tests, and Bland-Altman analysis. DTI values were compared to WeeFIM values by non-parametric partial correlation and accuracy was assessed by receiver operating characteristics analysis. RESULTS: The FA values from all approaches correlated significantly with each other (p < 0.001). However, the FA values from streamline tractography were significantly higher (mean ± standard deviation (SD), 0.52 ± 0.08) than those from the atlas-based (0.42 ± 0.11) or the combined approach (0.41 ± 0.11) (p < 0.001 for both). FA and NT values correlated significantly with WeeFIM values (atlas-based FA, partial correlation coefficient (ρ) = 0.545, p = 0.001; streamline FA, ρ = 0.505, p = 0.002; NT, ρ = 0.434, p = 0.008; combined FA, ρ = 0.611, p < 0.001). FA of the atlas-based approach (sensitivity 90%, specificity 67%, area under the curve 0.82) and the combined approach (87%, 67%, 0.82), provided the highest predictive accuracy for outcome compared to FA (70%, 67%, 0.67) and NT (50%, 100%, 0.79, respectively) of the streamline approach. CONCLUSION: FA values from streamline tractography were higher than those from the atlas-based and combined approach. The atlas-based and combined approach offer the best predictive accuracy for motor outcome, although both atlas-based and streamline tractography approaches provide significant predictors of clinical outcome.

Sedation for magnetic resonance imaging using propofol with or without ketamine at induction in pediatrics-A prospective randomized double-blinded study.

INTRODUCTION: Deep sedation using propofol has become a standard technique in children. This double-blinded randomized clinical trial aims to compare the clinical effects of propofol-mono-sedation vs a combination of propofol and ketamine at induction and a reduced propofol infusion rate for maintenance in children undergoing diagnostic magnetic resonance imaging. METHODS: Children aged from 3 months to 10 years scheduled as outpatients for elective magnetic resonance imaging with deep sedation were included. They were randomized into 2 groups, receiving either 1 mg/kg ketamine at induction, then a propofol infusion rate of 5 mg/kg/h or a propofol infusion rate of 10 mg/kg/h without prior ketamine. Time to full recovery (modified Aldrete score = 10) was the primary outcome. Further outcomes were quality of induction, immobilization during image acquisition, recovery, postoperative nausea and vomiting, emergence delirium using the Pediatric Anesthesia Emergence Delirium scale, vital signs and adverse cardiorespiratory events. All patients and parents as well as anesthetists, imaging technicians, and postsedation personnel were blinded. Data are given as median (range). RESULTS: In total, 347 children aged 4.0 (0.25-10.9) years, weighing 15.6 (5.3-54) kg, ASA classification I, II, or III (141/188/18) were included. The ketamine-propofol group showed significantly shorter recovery times (38 (22-65) vs 54 (37-77) minutes; median difference 14 (95% CI: 8, 20) minutes; P < .001), better quality of induction, and higher blood pressure, but higher incidence of movement requiring additional sedative drugs. There were no significant differences in respiratory side effects, cardiovascular compromise, emergence delirium, or postoperative nausea and vomiting. CONCLUSION: Both sedation concepts proved to be reliable with a low incidence of side effects. Ketamine at induction with a reduced propofol infusion rate leads to faster postanesthetic recovery.

Microvascular perfusion of the placenta, developing fetal liver, and lungs assessed with intravoxel incoherent motion imaging.

BACKGROUND: In utero intravoxel incoherent motion magnetic resonance imaging (IVIM-MRI) provides a novel method for examining microvascular perfusion fraction and diffusion in the developing human fetus. PURPOSE: To characterize gestational changes in the microvascular perfusion fraction of the placenta, fetal liver, and lungs using IVIM-MRI. STUDY TYPE: Retrospective, cross-sectional study. SUBJECTS: Fifty-five datasets from 33 singleton pregnancies were acquired (17-36 gestational weeks). FIELD STRENGTH/SEQUENCE: In utero diffusion-weighted echo-planar imaging at 1.5T and 3.0T with b-factors ranging from 0 to 900 s/mm2 in 16 steps. ASSESSMENT: Using the IVIM principle, microvascular perfusion fraction (f), pseudodiffusion (D*), and diffusion coefficients (d) were estimated for the placenta, liver, and lungs with a biexponential model. A free-form nonlinear deformation algorithm was used to correct for the frame-by-frame motion of the fetal organs and the placenta. The IVIM parameters were then compared to a Doppler ultrasound-based assessment of the umbilical artery resistance index. STATISTICAL TESTS: Pearson product-moment correlation coefficient (PMCC) to reveal outlier corrected correlations between Doppler and IVIM parameters. Gestational age-related changes were assessed using linear regression analysis (LR). RESULTS: Placental f (0.29 ± 0.08) indicates high blood volume in the microvascular compartment, moderately increased during gestation (LR, R = 0.338), and correlated negatively with the umbilical artery resistance index (PMCC, R = -0.457). The f of the liver decreased sharply during gestation (LR, R = -0.436). Lung maturation was characterized by increasing perfusion fraction (LR, R = 0.547), and we found no gestational changes in d and D* values (LR, R = -0.013 and R = 0.051, respectively). The Doppler measurements of the umbilical artery and middle cerebral artery did not correlate with the IVIM parameters of the lungs and liver. DATA CONCLUSION: Gestational age-associated changes of the placental, liver, and lung IVIM parameters likely reflect changes in placental and fetal circulation, and characterize the trajectory of microstructural and functional maturation of the fetal vasculature. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017.

Reduction of brain volumes after neonatal cardiopulmonary bypass surgery in single-ventricle congenital heart disease before Fontan completion.

BackgroundLittle is known about the relationship between brain volumes and neurodevelopmental outcome at 2 years of age in children with single-ventricle congenital heart disease (CHD). We hypothesized that reduced brain volumes may be associated with adverse neurodevelopmental outcome.MethodsVolumetric segmentation of cerebral magnetic resonance imaging (MRI) scans was carried out in 44 patients without genetic comorbidities and in 8 controls. Neurodevelopmental outcome was assessed with the Bayley-III scales.ResultsGray matter (GM), deep GM, white matter (WM), and cerebrospinal fluid (CSF) volumes were 611±59, 43±4.5, 277±30, and 16.4 ml, respectively (interquartile range (IQR) 13.1, 23.3 ml). Children undergoing neonatal cardiopulmonary bypass surgery showed smaller deep GM (P=0.005) and WM (P=0.021) volumes. Brain volumes were smaller in patients compared with controls (GM: P=0.017, deep GM: P=0.012, and WM: P=0.015), whereas CSF volumes were greater (P=0.014). Of all intracranial volumes, only CSF volume was associated with neurodevelopmental outcome, accounting for 21% (P=0.011) of variability in the cognitive composite score when combined with common risk factors in a multivariable analysis.ConclusionIncreased CSF volume represents a significant risk factor for neurodevelopmental impairment in children with single-ventricle CHD. Later assessments are warranted to determine the prognostic role of intracranial volumes for long-term outcome.

In utero diffusion tensor imaging of the fetal brain: A reproducibility study.

Our purpose was to evaluate the within-subject reproducibility of in utero diffusion tensor imaging (DTI) metrics and the visibility of major white matter structures. Images for 30 fetuses (20-33. postmenstrual weeks, normal neurodevelopment: 6 cases, cerebral pathology: 24 cases) were acquired on 1.5 T or 3.0 T MRI. DTI with 15 diffusion-weighting directions was repeated three times for each case, TR/TE: 2200/63 ms, voxel size: 1 ∗ 1 mm, slice thickness: 3-5 mm, b-factor: 700 s/mm2. Reproducibility was evaluated from structure detectability, variability of DTI measures using the coefficient of variation (CV), image correlation and structural similarity across repeated scans for six selected structures. The effect of age, scanner type, presence of pathology was determined using Wilcoxon rank sum test. White matter structures were detectable in the following percentage of fetuses in at least two of the three repeated scans: corpus callosum genu 76%, splenium 64%, internal capsule, posterior limb 60%, brainstem fibers 40% and temporooccipital association pathways 60%. The mean CV of DTI metrics ranged between 3% and 14.6% and we measured higher reproducibility in fetuses with normal brain development. Head motion was negatively correlated with reproducibility, this effect was partially ameliorated by motion-correction algorithm using image registration. Structures on 3.0 T had higher variability both with- and without motion correction. Fetal DTI is reproducible for projection and commissural bundles during mid-gestation, however, in 16-30% of the cases, data were corrupted by artifacts, resulting in impaired detection of white matter structures. To achieve robust results for the quantitative analysis of diffusivity and anisotropy values, fetal-specific image processing is recommended and repeated DTI is needed to ensure the detectability of fiber pathways.

Evolution of posterior fossa and brain morphology after in utero repair of open neural tube defects assessed by MRI.

OBJECTIVES: To describe characteristics of foetuses undergoing in utero repair of open neural tube defects (ONTD) and assess postoperative evolution of posterior fossa and brain morphology. METHODS: Analysis of pre- and postoperative foetal as well as neonatal MRI of 27 foetuses who underwent in utero repair of ONTD. Type and level of ONTD, hindbrain configuration, posterior fossa and liquor space dimensions, and detection of associated findings were compared between MRI studies and to age-matched controls. RESULTS: Level of bony spinal defect was defined with exactness of ± one vertebral body. Of surgically confirmed 18 myelomeningoceles (MMC) and 9 myeloschisis (MS), 3 MMC were misdiagnosed as MS due to non-visualisation of a flat membrane on MRI. Hindbrain herniation was more severe in MS than MMC (p < 0.001). After repair, hindbrain herniation resolved in 25/27 cases at 4 weeks and liquor spaces increased. While posterior fossa remained small (p < 0.001), its configuration normalised. Lateral ventricle diameter indexed to cerebral width decreased in 48% and increased in 12% of cases, implying a low rate of progressive obstructive hydrocephalus. Neonatally evident subependymal heterotopias were detected in 33% at preoperative and 50% at postoperative foetal MRI. CONCLUSION: MRI demonstrates change of Chiari malformation type II (CM-II) features. KEY POINTS: • Hindbrain herniation is significantly more pronounced in myeloschisis than in myelomeningocele • Resolution of hindbrain herniation 4 weeks after in utero closure of ONTD • MRI is valuable for preoperative assessment and postoperative evaluation following in utero repair.

SMCHD1 mutations associated with a rare muscular dystrophy can also cause isolated arhinia and Bosma arhinia microphthalmia syndrome.

Arhinia, or absence of the nose, is a rare malformation of unknown etiology that is often accompanied by ocular and reproductive defects. Sequencing of 40 people with arhinia revealed that 84% of probands harbor a missense mutation localized to a constrained region of SMCHD1 encompassing the ATPase domain. SMCHD1 mutations cause facioscapulohumeral muscular dystrophy type 2 (FSHD2) via a trans-acting loss-of-function epigenetic mechanism. We discovered shared mutations and comparable DNA hypomethylation patterning between these distinct disorders. CRISPR/Cas9-mediated alteration of smchd1 in zebrafish yielded arhinia-relevant phenotypes. Transcriptome and protein analyses in arhinia probands and controls showed no differences in SMCHD1 mRNA or protein abundance but revealed regulatory changes in genes and pathways associated with craniofacial patterning. Mutations in SMCHD1 thus contribute to distinct phenotypic spectra, from craniofacial malformation and reproductive disorders to muscular dystrophy, which we speculate to be consistent with oligogenic mechanisms resulting in pleiotropic outcomes.

Diffusion tensor imaging predicts motor outcome in children with acquired brain injury.

BACKGROUND: Rehabilitation in children with acquired brain injury is a challenging endeavour. There is a large variability in motor recovery between patients, and a need to optimize therapies by exploiting cerebral plasticity and recovery mechanisms. This retrospective study aims to identify tract-based markers that could serve as predictors of functional outcome following rehabilitation. METHODS: Twenty-nine children with traumatic brain injury (n = 14) or stroke (n = 15) underwent a 3 T Magnetic Resonance Imaging (MRI) measurement, including Diffusion Tensor Imaging (DTI) between admission to the Hospital and onset of rehabilitation therapy at the Rehabilitation Centre. The Functional Independence Measure for Children (WeeFIM) was routinely applied at admission and discharge from the Rehabilitation Centre. Distinguishing between children with good versus poor functional independence was performed using ROC-analysis. A non-parametric partial correlation analysis between the DTI and WeeFIM motor scores was performed with age, time in rehabilitation, and time of MRI scan after injury as covariates. RESULTS: Mean fractional anisotropy (FA) from the DTI in the ipsilesional corticospinal-tract provided the highest predictive accuracy (sensitivity = 95 %, specificity = 78 %, Youden Index = 0.73, Area under the curve = 0.9), in comparison to the lesion volume or other clinical variables. Mean FA of the ipsilesional corticospinal-tract correlated positively with the WeeFIM discharge motor scores (ρ = 0.547, p = 0.004). Prediction was poorer for the lesion volume or Glasgow Coma Scale. CONCLUSION: The results suggest that DTI data could improve the prediction of functional outcome after rehabilitation in children and adolescents with stroke or traumatic brain injury. Specifically, mean FA shows the highest predictive accuracy in comparison to lesion volume or clinical scales.

Structural cerebral abnormalities and neurodevelopmental status in single ventricle congenital heart disease before Fontan procedure.

Objectives: Neonates with single ventricle congenital heart disease are at risk for structural cerebral abnormalities. Little is known about the further evolution of cerebral abnormalities until Fontan procedure. Methods: Between August 2012 and July 2015, we conducted a prospective cross-sectional two centre study using cerebral magnetic resonance imaging (MRI) and neuro-developmental outcome assessed by the Bayley-III. Forty-seven children (31 male) were evaluated at a mean age of 25.9 ± 3.4 months with hypoplastic left heart syndrome (25) or other single ventricle (22). Results: Cerebral MRI was abnormal in 17 patients (36.2%) including liquor space enlargements (10), small grey (9) and minimal white (5) matter injuries. Eight of 17 individuals had combined lesions. Median (range) cognitive composite score (CCS) (100, 65-120) and motor composite score (MCS) (97, 55-124) were comparable to the reference data, while language composite score (LCS) (97, 68-124) was significantly lower ( P = 0.040). Liquor space enlargement was associated with poorer performance on all Bayley-III subscores (CCS: P = 0.02; LCS: P = 0.002; MCS: P = 0.013). The number of re-operations [odds ratio (OR) 2.2, 95% confidence interval (CI) 1.1-4.3] ( P = 0.03) and re-interventions (OR 2.1, 95% CI 1.1-3.8) ( P = 0.03) was associated with a higher rate of overall MRI abnormalities. Conclusions: Cerebral MRI abnormalities occur in more than one third of children with single ventricle, while the neuro-developmental status is less severely affected before Fontan procedure. Liquor space enlargement is the predominant MRI finding associated with poorer neuro-developmental status, warranting further studies to determine aetiology and further evolution until school-age.

Intra-voxel incoherent motion MRI of the living human foetus: technique and test-retest repeatability.

BACKGROUND: Our purpose was to test the within-subject (test-retest) reproducibility of the perfusion fraction, diffusion coefficient, and pseudo-diffusion coefficient measurements in various foetus organs and in the placenta based on the intra-voxel incoherent motion (IVIM) principle. METHODS: In utero diffusion-weighted IVIM magnetic resonance imaging (MRI) was performed in 15 pregnant women (pregnancy age 21-36 weeks) on 1.5-T and 3.0-T clinical scanners with b-factors in the range of 0-900 s/mm2 in 16 steps. A bi-exponential model was fitted on the volume-averaged diffusion values. Perfusion fraction (f), diffusion coefficient (d), and pseudo-diffusion coefficient (D*) were calculated. Within-subject reproducibility was evaluated as test-retest variability (VAR %) of the IVIM parameters in the foetal frontal cortex, frontal white matter, cerebellum, lungs, kidneys, liver, and in the placenta. RESULTS: For the foetal lungs, liver and the placenta, test-retest variability was in the range of 14-20% for f, 12-14% for d, and 17-25% for D*. The diffusion coefficients of the investigated brain regions were moderately to highly reproducible (VAR 5-15%). However, f and D* showed inferior reproducibility compared to corresponding measures for the lungs, liver, and placenta. The IVIM parameters of the foetal kidney were revealed to be highly variable across scans. CONCLUSIONS: IVIM MRI potentially provides a novel method for examining microvascular perfusion and diffusion in the developing human foetus. However, reproducibility of perfusion and diffusion parameters depends greatly upon data quality, foetal and maternal movements, and foetal-specific image post-processing.

Comparison of automated brain volumetry methods with stereology in children aged 2 to 3 years.

INTRODUCTION: The accurate and precise measurement of brain volumes in young children is important for early identification of children with reduced brain volumes and an increased risk for neurodevelopmental impairment. Brain volumes can be measured from cerebral MRI (cMRI), but most neuroimaging tools used for cerebral segmentation and volumetry were developed for use in adults and have not been validated in infants or young children. Here, we investigate the feasibility and accuracy of three automated software methods (i.e., SPM, FSL, and FreeSurfer) for brain volumetry in young children and compare the measures with corresponding volumes obtained using the Cavalieri method of modern design stereology. METHODS: Cerebral MRI data were collected from 21 children with a complex congenital heart disease (CHD) before Fontan procedure, at a median age of 27 months (range 20.9-42.4 months). Data were segmented with SPM, FSL, and FreeSurfer, and total intracranial volume (ICV) and total brain volume (TBV) were compared with corresponding measures obtained using the Cavalieri method. RESULTS: Agreement between the estimated brain volumes (ICV and TBV) relative to the gold standard stereological volumes was strongest for FreeSurfer (p < 0.001) and moderate for SPM segment (ICV p = 0.05; TBV p = 0.006). No significant association was evident between ICV and TBV obtained using SPM NewSegment and FSL FAST and the corresponding stereological volumes. CONCLUSIONS: FreeSurfer provides an accurate method for measuring brain volumes in young children, even in the presence of structural brain abnormalities.

Delayed cortical gray matter development in neonates with severe congenital heart disease.

BACKGROUND: This study aimed to assess cortical gray matter growth and maturation in neonates with congenital heart disease (CHD). METHODS: Thirty-one (near) term neonates with severe CHD (8 univentricular heart malformation (UVH), 21 d-transposition of great arteries (d-TGA) and 2 aortic coarctation) underwent cerebral MRI before (postnatal-day 7) and after (postnatal-day 24) surgery. Eighteen controls with similar gestational age had one MRI (postnatal-day 23). Cortical gray matter volume (CGM), inner cortical surface (iCS), and median cortical thickness were extracted as measures of volumetric growth, and gyrification index (GI) as measure of maturation. RESULTS: Over a median of 18 d, CGM increased by 21%, iCS by 17%, thickness and GI both by 9%. Decreased postoperative CGM and iCS were seen for CHD compared to controls (P values < 0.01), however with similar thickness and GI. UVH showed lower postoperative iCS, thickness (P values < 0.05) and GI (P value < 0.01) than d-TGA and controls. Infants requiring preoperative balloon-atrioseptostomy (BAS, 61%) had reduced postoperative CGM, iCS, and GI (P values < 0.05). CONCLUSION: Infants with severe CHD show reduced cortical volumes compared to controls with gyrification being delayed in UVH, but not in d-TGA. Infants requiring BAS show higher risk of impaired cortical volume and gyrification.

Cerebellar Bottom-of-Fissure Dysplasia-a Novel Cerebellar Gray Matter Neuroimaging Pattern.

We report on seven patients with a novel neuroimaging finding that involves exclusively the cerebellar gray matter at the bottom of several fissures of both hemispheres but spares the vermis. The abnormal fissures were predominantly located in the lower and lateral parts of the cerebellar hemispheres. The affected cerebellar cortex was hypointense on T1-weighted and hyperintense on T2-weighted and fluid attenuation inversion recovery sequences. In some patients, the involved cerebellar gray matter was mildly thickened and the affected fissures slightly widened. In three of seven patients, the neuroimaging findings were unchanged on follow-up studies up to 6 years. The seven patients had various indications for the brain magnetic resonance imaging studies, and none of them had cerebellar dysfunction. Based on the similarity of the neuroimaging pattern with the cerebral "bottom-of-sulcus dysplasia," we coined the term "cerebellar bottom-of-fissure dysplasia" to refer to this novel neuroimaging finding. The neuroimaging characteristic as well as the unchanged findings on follow-up favors a stable "developmental" (malformative) nature. The lack of cerebellar dysfunction in the affected patients suggests that cerebellar bottom-of-fissure dysplasia represents most likely an incidental finding that does not require specific diagnostic investigation but allows a reassuring attitude.