Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance.

We report that eight heterozygous missense mutations in TUBB3, encoding the neuron-specific beta-tubulin isotype III, result in a spectrum of human nervous system disorders that we now call the TUBB3 syndromes. Each mutation causes the ocular motility disorder CFEOM3, whereas some also result in intellectual and behavioral impairments, facial paralysis, and/or later-onset axonal sensorimotor polyneuropathy. Neuroimaging reveals a spectrum of abnormalities including hypoplasia of oculomotor nerves and dysgenesis of the corpus callosum, anterior commissure, and corticospinal tracts. A knock-in disease mouse model reveals axon guidance defects without evidence of cortical cell migration abnormalities. We show that the disease-associated mutations can impair tubulin heterodimer formation in vitro, although folded mutant heterodimers can still polymerize into microtubules. Modeling each mutation in yeast tubulin demonstrates that all alter dynamic instability whereas a subset disrupts the interaction of microtubules with kinesin motors. These findings demonstrate that normal TUBB3 is required for axon guidance and maintenance in mammals.

Success of Nonsedated Neuroradiologic MRI in Children 1-7 Years Old.

BACKGROUND. MRI use and the need for monitored anesthesia care (MAC) in children have increased. However, MAC is associated with examination delays, increased cost, and safety concerns. OBJECTIVE. The purpose of this study was to evaluate the success rate of nonsedated neuroradiologic MRI studies in children 1-7 years old and to investigate factors associated with success. METHODS. We retrospectively reviewed data from our institutional nonsedated MRI program. Inclusion criteria were outpatient nonsedated MRI referral, age 1-7 years old, and neuroradiologic indication. Exclusion criteria were MRI examinations for ventricular checks and contrast material use. Success was determined by reviewing the clinical MRI report. We recorded patient age and sex, type of MRI examination (brain, spine, craniospinal, head and neck, and brain with MRA), protocol length, presence of child life specialist, video goggle use, and MRI appointment time (routine daytime appointment or evening appointment). We used descriptive statistics to summarize patient demographics and clinical data and logistic regression models to evaluate predictors of success in the entire sample. Subset analyses were performed for children from 1 to < 3 years old and 3 to 7 years old. RESULTS. We analyzed 217 patients who underwent nonsedated MRI examinations (median age, 5.1 years). Overall success rate was 82.0% (n = 178). The success rates were 81.4% (n = 127) for brain, 90.3% (n = 28) for spine, 71.4% (n = 10) for craniospinal, 66.7% (n = 6) for head and neck, and 100% (n = 7) for brain with MRA. Age was significantly associated with success (odds ratio [OR], 1.33; p = .009). In children 1 to < 3 years old, none of the factors analyzed were significant predictors of success (all, p > .48). In children 3-7 years old, protocol duration (OR, 0.96; 95% CI, 0.93-0.99; p = .02) and video goggle use (OR, 6.38; 95% CI, 2.16-18.84; p = .001) were significantly associated with success. CONCLUSION. A multidisciplinary approach with age-appropriate resources enables a high success rate for nonsedated neuroradiologic MRI in children 1-7 years old. CLINICAL IMPACT. Using age as the primary criterion to determine the need for MAC may lead to overuse of these services. Dissemination of information regarding nonsedated MRI practice could reduce the rate of sedated MRI in young children.

Diagnostic equivalency of fast T2 and FLAIR sequences for pediatric brain MRI: a pilot study.

BACKGROUND: Faster and motion robust magnetic resonance imaging (MRI) sequences are desirable in pediatric brain MRI as they can help reduce the need for monitored anesthesia care, which is a costly and limited resource that carries medical risks. OBJECTIVE: To evaluate the diagnostic equivalency of commercially available accelerated motion robust MR sequences relative to standard sequences. MATERIALS AND METHODS: This was an institutional review board-approved prospective study. Subjects underwent a clinical brain MRI using conventional multiplanar images at 3 Tesla followed by fast axial T2 and FLAIR (fluid-attenuated inversion recovery) sequences optimized for an approximately 50% reduction in acquisition time. Conventional and fast images from each subject were reviewed by two blinded pediatric neuroradiologists. The readers evaluated the presence of 12 findings. Intra-observer agreement was estimated for fast versus conventional sequences. For each set of sequences, interobserver agreement calculations and chi-square tests were used to evaluate differences between fast and conventional acquisitions. An independent third reader reviewed the intra-observer discrepancies and adjudicated them as being more conspicuous on fast sequence, conventional sequence or the equivalent. The readers also were asked to rate motion artifacts with a previously validated score. RESULTS: Images from 77 children (mean age: 11.3 years) were analyzed. Intra-observer agreement (fast versus conventional) ranged between 89.2% and 92.3%. Interobserver agreement ranged between 86.1% and 88.4%. Interobserver agreement was significantly higher for conventional FLAIR relative to fast FLAIR for small (<5 mm) foci of T2 in the white matter. Otherwise, interobserver agreement was not different between the fast and conventional sequences. For awake subjects, fast sequences had significantly fewer artifacts (P<0.05). CONCLUSION: Conventional T2 and FLAIR sequences can be optimized to shorten acquisition while maintaining diagnostic equivalency. These faster sequences were also less susceptible to motion artifacts.

Markerless high-frequency prospective motion correction for neuroanatomical MRI.

PURPOSE: To integrate markerless head motion tracking with prospectively corrected neuroanatomical MRI sequences and to investigate high-frequency motion correction during imaging echo trains. METHODS: A commercial 3D surface tracking system, which estimates head motion by registering point cloud reconstructions of the face, was used to adapt the imaging FOV based on head movement during MPRAGE and T2 SPACE (3D variable flip-angle turbo spin-echo) sequences. The FOV position and orientation were updated every 6 lines of k-space (< 50 ms) to enable "within-echo-train" prospective motion correction (PMC). Comparisons were made with scans using "before-echo-train" PMC, in which the FOV was updated only once per TR, before the start of each echo train (ET). Continuous-motion experiments with phantoms and in vivo were used to compare these high-frequency and low-frequency correction strategies. MPRAGE images were processed with FreeSurfer to compare estimates of brain structure volumes and cortical thickness in scans with different PMC. RESULTS: The median absolute pose differences between markerless tracking and MR image registration were 0.07/0.26/0.15 mm for x/y/z translation and 0.06º/0.02º/0.12° for rotation about x/y/z. The PMC with markerless tracking substantially reduced motion artifacts. The continuous-motion experiments showed that within-ET PMC, which minimizes FOV encoding errors during ETs that last over 1 second, reduces artifacts compared with before-ET PMC. T2 SPACE was found to be more sensitive to motion during ETs than MPRAGE. FreeSurfer morphometry estimates from within-ET PMC MPRAGE images were the most accurate. CONCLUSION: Markerless head tracking can be used for PMC, and high-frequency within-ET PMC can reduce sensitivity to motion during long imaging ETs.

Agricultural investments and hunger in Africa modeling potential contributions to SDG2 - Zero Hunger.

We use IFPRI's IMPACT framework of linked biophysical and structural economic models to examine developments in global agricultural production systems, climate change, and food security. Building on related work on how increased investment in agricultural research, resource management, and infrastructure can address the challenges of meeting future food demand, we explore the costs and implications of these investments for reducing hunger in Africa by 2030. This analysis is coupled with a new investment estimation model, based on the perpetual inventory methodology (PIM), which allows for a better assessment of the costs of achieving projected agricultural improvements. We find that climate change will continue to slow projected reductions in hunger in the coming decades-increasing the number of people at risk of hunger in 2030 by 16 million in Africa compared to a scenario without climate change. Investments to increase agricultural productivity can offset the adverse impacts of climate change and help reduce the share of people at risk of hunger in 2030 to five percent or less in Northern, Western, and Southern Africa, but the share is projected to remain at ten percent or more in Eastern and Central Africa. Investments in Africa to achieve these results are estimated to cost about 15 billion USD per year between 2015 and 2030, as part of a larger package of investments costing around 52 billion USD in developing countries.

Complex Trajectories of Brain Development in the Healthy Human Fetus.

This study characterizes global and hemispheric brain growth in healthy human fetuses during the second half of pregnancy using three-dimensional MRI techniques. We studied 166 healthy fetuses that underwent MRI between 18 and 39 completed weeks gestation. We created three-dimensional high-resolution reconstructions of the brain and calculated volumes for left and right cortical gray matter (CGM), fetal white matter (FWM), deep subcortical structures (DSS), and the cerebellum. We calculated the rate of growth for each tissue class according to gestational age and described patterns of hemispheric growth. Each brain region demonstrated major increases in volume during the second half of gestation, the most pronounced being the cerebellum (34-fold), followed by FWM (22-fold), CGM (21-fold), and DSS (10-fold). The left cerebellar hemisphere, CGM, and DSS had larger volumes early in gestation, but these equalized by term. It has been increasingly recognized that brain asymmetry evolves throughout the human life span. Advanced quantitative MRI provides noninvasive measurements of early structural asymmetry between the left and right fetal brain that may inform functional and behavioral laterality differences seen in children and young adulthood.

Ionizing radiation from computed tomography versus anesthesia for magnetic resonance imaging in infants and children: patient safety considerations.

In the context of health care, risk assessment is the identification, evaluation and estimation of risk related to a particular clinical situation or intervention compared to accepted medical practice standards. The goal of risk assessment is to determine an acceptable level of risk for a given clinical treatment or intervention in association with the provided clinical circumstances for a patient or group of patients. In spite of the inherent challenges related to risk assessment in pediatric cross-sectional imaging, the potential risks of ionizing radiation and sedation/anesthesia in the pediatric population are thought to be quite small. Nevertheless both issues continue to be topics of discussion concerning risk and generate significant anxiety and concern for patients, parents and practicing pediatricians. Recent advances in CT technology allow for more rapid imaging with substantially lower radiation exposures, obviating the need for anesthesia for many indications and potentially mitigating concerns related to radiation exposure. In this review, we compare and contrast the potential risks of CT without anesthesia against the potential risks of MRI with anesthesia, and discuss the implications of this analysis on exam selection, providing specific examples related to neuroblastoma surveillance imaging.

Correction to: Ionizing radiation from computed tomography versus anesthesia for magnetic resonance imaging in infants and children: patient safety considerations.

The published version of this article incorrectly lists Dr. Joseph P. Cravero in the Department of Radiology at Boston Children's Hospital. Dr. Cravero's correct affiliation is given below.

Neuroimaging of Children With Surgically Treated Hydrocephalus: A Practical Approach.

OBJECTIVE: Children with surgically treated hydrocephalus commonly undergo multiple neuroimaging studies. The purpose of this article is to share an experience with use of the as low as reasonably achievable (ALARA) principle to guide the imaging approach to these patients. CONCLUSION: A reasonably achievable strategy for minimizing ionizing radiation in patients with surgically treated hydrocephalus includes rapid-sequence MRI and judicious use of dose-optimized head CT. Rapid-sequence MRI is particularly useful in the care of patients who have undergone endoscopic third ventriculostomy.

Quality measures and pediatric radiology: suggestions for the transition to value-based payment.

Recent political and economic factors have contributed to a meaningful change in the way that quality in health care, and by extension value, are viewed. While quality is often evaluated on the basis of subjective criteria, pay-for-performance programs that link reimbursement to various measures of quality require use of objective and quantifiable measures. This evolution to value-based payment was accelerated by the 2015 passage of the Medicare Access and CHIP (Children's Health Insurance Program) Reauthorization Act (MACRA). While many of the drivers of these changes are rooted in federal policy and programs such as Medicare and aimed at adult patients, the practice of pediatrics and pediatric radiology will be increasingly impacted. This article addresses issues related to the use of quantitative measures to evaluate the quality of services provided by the pediatric radiology department or sub-specialty section, particularly as seen from the viewpoint of a payer that may be considering ways to link payment to performance. The paper concludes by suggesting a metric categorization strategy to frame future work on the subject.

Quality of pediatric abdominal CT scans performed at a dedicated children's hospital and its referring institutions: a multifactorial evaluation.

BACKGROUND: Pediatric patients requiring transfer to a dedicated children's hospital from an outside institution may undergo CT imaging as part of their evaluation. Whether this imaging is performed prior to or after transfer has been shown to impact the radiation dose imparted to the patient. Other quality variables could also be affected by the pediatric experience and expertise of the scanning institution. OBJECTIVE: To identify differences in quality between abdominal CT scans and reports performed at a dedicated children's hospital, and those performed at referring institutions. MATERIALS AND METHODS: Fifty consecutive pediatric abdominal CT scans performed at outside institutions were matched (for age, gender and indication) with 50 CT scans performed at a dedicated freestanding children's hospital. We analyzed the scans for technical parameters, report findings, correlation with final clinical diagnosis, and clinical utility. Technical evaluation included use of intravenous and oral contrast agents, anatomical coverage, number of scan phases and size-specific dose estimate (SSDE) for each scan. Outside institution scans were re-reported when the child was admitted to the children's hospital; they were also re-interpreted for this study by children's hospital radiologists who were provided with only the referral information given in the outside institution's report. Anonymized original outside institutional reports and children's hospital admission re-reports were analyzed by two emergency medicine physicians for ease of understanding, degree to which the clinical question was answered, and level of confidence in the report. RESULTS: Mean SSDE was lower (8.68) for children's hospital scans, as compared to outside institution scans (13.29, P = 0.03). Concordance with final clinical diagnosis was significantly lower for original outside institution reports (38/48, 79%) than for both the admission and study children's hospital reports (48/50, 96%; P = 0.005). Children's hospital admission reports were rated higher than outside institution reports for completeness, ease of understanding, answering of clinical question, and level of confidence of the report (P < 0.001). CONCLUSION: Pediatric abdominal CT scans performed and interpreted at a dedicated children's hospital are associated with higher technical quality, lower radiation dose and a more clinically useful report than those performed at referring institutions.

Climate change effects on agriculture: economic responses to biophysical shocks.

Agricultural production is sensitive to weather and thus directly affected by climate change. Plausible estimates of these climate change impacts require combined use of climate, crop, and economic models. Results from previous studies vary substantially due to differences in models, scenarios, and data. This paper is part of a collective effort to systematically integrate these three types of models. We focus on the economic component of the assessment, investigating how nine global economic models of agriculture represent endogenous responses to seven standardized climate change scenarios produced by two climate and five crop models. These responses include adjustments in yields, area, consumption, and international trade. We apply biophysical shocks derived from the Intergovernmental Panel on Climate Change's representative concentration pathway with end-of-century radiative forcing of 8.5 W/m(2). The mean biophysical yield effect with no incremental CO2 fertilization is a 17% reduction globally by 2050 relative to a scenario with unchanging climate. Endogenous economic responses reduce yield loss to 11%, increase area of major crops by 11%, and reduce consumption by 3%. Agricultural production, cropland area, trade, and prices show the greatest degree of variability in response to climate change, and consumption the lowest. The sources of these differences include model structure and specification; in particular, model assumptions about ease of land use conversion, intensification, and trade. This study identifies where models disagree on the relative responses to climate shocks and highlights research activities needed to improve the representation of agricultural adaptation responses to climate change.

Cerebrospinal Fluid and Parenchymal Brain Development and Growth in the Healthy Fetus.

OBJECTIVE: The objective of this study was to apply quantitative magnetic resonance imaging to characterize absolute cerebrospinal fluid (CSF) development, as well as its relative development to fetal brain parenchyma in the healthy human fetus. DESIGN: We created three-dimensional high-resolution reconstructions of the developing brain for healthy fetuses between 18 and 40 weeks' gestation, segmented the parenchymal and CSF spaces, and calculated the volumes for the lateral, third, and fourth ventricles; extra-axial CSF space; and the cerebrum, cerebellum, and brainstem. From these data, we constructed normograms of the resulting volumes according to gestational age and described the relative development of CSF to fetal brain parenchyma. RESULTS: Each CSF space demonstrated major increases in volumetric growth during the second half of gestation: third ventricle (23-fold), extra-axial CSF (11-fold), fourth ventricle (8-fold), and lateral ventricle (2-fold). Total CSF volume was related to total brain volume (p < 0.01), as was lateral ventricle to cerebral volume (p < 0.01); however, the fourth ventricle was not related to cerebellar or brainstem volume (p = 0.18-0.19). RELEVANCE: Abnormalities of the CSF spaces are the most common anomalies of neurologic development detected on fetal screening using neurosonography. Normative values of absolute CSF volume, as well as relative growth in comparison to intracranial parenchyma, provide valuable insight into normal fetal neurodevelopment. These data may provide important biomarkers of early deviations from normal growth, better distinguish between benign variants and early disease, and serve as reference standards for postnatal growth and development in the premature infant.

Congenital Brain Abnormalities and Zika Virus: What the Radiologist Can Expect to See Prenatally and Postnatally.

Purpose To document the imaging findings associated with congenital Zika virus infection as found in the Instituto de Pesquisa in Campina Grande State Paraiba (IPESQ) in northeastern Brazil, where the congenital infection has been particularly severe. Materials and Methods From June 2015 to May 2016, 438 patients were referred to the IPESQ for rash occurring during pregnancy or for suspected fetal central nervous system abnormality. Patients who underwent imaging at IPESQ were included, as well as those with documented Zika virus infection in fluid or tissue (n = 17, confirmed infection cohort) or those with brain findings suspicious for Zika virus infection, with intracranial calcifications (n = 28, presumed infection cohort). Imaging examinations included 12 fetal magnetic resonance (MR) examinations, 42 postnatal brain computed tomographic examinations, and 11 postnatal brain MR examinations. Images were reviewed by four radiologists, with final opinion achieved by means of consensus. Results Brain abnormalities seen in confirmed (n = 17) and presumed (n = 28) congenital Zika virus infections were similar, with ventriculomegaly in 16 of 17 (94%) and 27 of 28 (96%) infections, respectively; abnormalities of the corpus callosum in 16 of 17 (94%) and 22 of 28 (78%) infections, respectively; and cortical migrational abnormalities in 16 of 17 (94%) and 28 of 28 (100%) infections, respectively. Although most fetuses underwent at least one examination that showed head circumference below the 5th percentile, head circumference could be normal in the presence of severe ventriculomegaly (seen in three fetuses). Intracranial calcifications were most commonly seen at the gray matter-white matter junction, in 15 of 17 (88%) and 28 of 28 (100%) confirmed and presumed infections, respectively. The basal ganglia and/or thalamus were also commonly involved with calcifications in 11 of 17 (65%) and 18 of 28 (64%) infections, respectively. The skull frequently had a collapsed appearance with overlapping sutures and redundant skin folds and, occasionally, intracranial herniation of orbital fat and clot in the confluence of sinuses. Conclusion The spectrum of findings associated with congenital Zika virus infection in the IPESQ in northeastern Brazil is illustrated to aid the radiologist in identifying Zika virus infection at imaging. (©) RSNA, 2016 Online supplemental material is available for this article.

Altered Gray Matter in Adolescents with d-Transposition of the Great Arteries.

OBJECTIVE: To investigate the structural brain characteristics of adolescent patients with d-transposition of the great arteries (d-TGA), repaired with the arterial switch operation in early infancy, using quantitative volumetric magnetic resonance imaging. STUDY DESIGN: Ninety-two patients with d-TGA from the Boston Circulatory Arrest Study (76% male; median age at scan 16.1 years) and 49 control subjects (41% male; median age at scan 15.7 years) were scanned using a 1.5-Tesla magnetic resonance imaging system. Subcortical and cortical gyral volumes and cortical gyral thicknesses were measured using surface-based morphometry. Group differences were assessed with linear regression. RESULTS: Compared with controls, patients with d-TGA demonstrated significantly reduced subcortical volumes bilaterally in the striatum and pallidum. Cortical regions that showed significant volume and thickness differences between groups were distributed throughout parietal, medial frontoparietal, cingulate, and temporal gyri. Among adolescents with d-TGA, volumes and thicknesses correlated with several perioperative variables, including age at surgery, cooling duration, total support time, and days in the cardiac intensive care unit. CONCLUSIONS: Adolescents with d-TGA repaired early in life exhibit widespread differences from control adolescents in gray matter volumes and thicknesses, particularly in parietal, midline, and subcortical brain regions, corresponding to white matter regions already known to demonstrate altered microstructure. These findings complement observations made in white matter in this group and suggest that the adolescent d-TGA cognitive profile derives from altered brain development involving both white and gray matter.

Use of labeled tomato lectin for imaging vasculature structures.

Intravascular injections of fluorescent or biotinylated tomato lectin were tested to study labeling of vascular elements in laboratory mice. Injections of Lycopersicon esculentum agglutinin (tomato lectin) (50-100 µg/100 µl) were made intravascularly, through the tail vein, through a cannula implanted in the jugular vein, or directly into the left ventricle of the heart. Tissues cut for thin 10- to 12-µm cryostat sections, or thick 50- to 100-µm vibratome sections, were examined using fluorescence microscopy. Tissue labeled by biotinylated lectin was examined by bright field microscopy or electron microscopy after tissue processing for biotin. Intravascular injections of tomato lectin led to labeling of vascular structures in a variety of tissues, including brain, kidney, liver, intestine, spleen, skin, skeletal and cardiac muscle, and experimental tumors. Analyses of fluorescence in serum indicated the lectin was cleared from circulating blood within 2 min. Capillary labeling was apparent in tissues collected from animals within 1 min of intravascular injections, remained robust for about 1 h, and then declined markedly until difficult to detect 12 h after injection. Light microscopic images suggest the lectin bound to the endothelial cells that form capillaries and endothelial cells that line some larger vessels. Electron microscopic studies confirmed the labeling of luminal surfaces of endothelial cells. Vascular labeling by tomato lectin is compatible with a variety of other morphological labeling techniques, including histochemistry and immunocytochemistry, and thus appears to be a sensitive and useful method to reveal vascular patterns in relationship to other aspects of parenchymal development, structure, and function.

Injury to the premature cerebellum: outcome is related to remote cortical development.

Cerebellar injury is an important complication of preterm birth with far-reaching neuropsychiatric sequelae. We have previously shown a significant association between isolated injury to the premature cerebellum and subsequent impairment of regional volumetric growth in the contralateral cerebrum. In the current study, we examine the relationship between these remote regional impairments of cerebral volumetric growth and domain-specific functional deficits in these children. In 40 ex-preterm infants with isolated cerebellar injury, we performed neurodevelopmental evaluations and quantitative magnetic resonance imaging (MRI) studies at a mean age of 34 months. We measured cortical gray matter volumes in 8 parcellated regions of each cerebral hemisphere, as well as right and left cerebellar volumes. We show highly significant associations between early signs of autism and dorsolateral prefrontal cortex volume (P < 0.001); gross motor scores and sensorimotor cortical volumes (P < 0.001); and cognitive and expressive language scores and premotor and mid-temporal cortical volumes (P < 0.001). By multivariate analyses, each unit increase in the corresponding regional cerebral volume was associated with lower odds of abnormal outcome score, adjusted for age at MRI and contralateral cerebellar volume. This is the first report linking secondary impairment of remote cerebral cortical growth and functional disabilities in survivors of prematurity-related cerebellar brain injury.

Fetal magnetic resonance imaging: exposure times and functional outcomes at preschool age.

BACKGROUND: Fetal magnetic resonance imaging (MRI) has been routinely used as a noninvasive diagnostic tool for more than a decade; however, there is a paucity of follow-up studies examining the effects of prenatal exposure to 1.5-T MRI on developmental outcome. OBJECTIVE: The objective of this study was to assess the safety of 1.5-T fetal MRI by evaluating functional outcomes of preschool children who were exposed in utero. MATERIALS AND METHODS: In the context of a prospective observational study, healthy pregnant women underwent a 1.5-T MRI study using single-shot fast spin echo (SSFSE) sequences during the second or third trimester of pregnancy. The study was approved by the institutional review board at our institution, and written informed consent was obtained from all study participants. MRI scanning times were recorded, and prenatal/postnatal clinical data were collected prospectively. Functional outcomes were assessed using the Vineland Adaptive Behavior Scale (VABS), a widely used, norm-referenced and psychometrically sound functional assessment. RESULTS: We studied 72 healthy pregnant women, who underwent fetal MRI at a mean gestational age of 30.5 ± 3.1 weeks. The cohort of fetuses was composed of 43% females, and 18 fetuses were scanned during the second trimester. All fetuses were born at term with appropriate birth weights (3.54 ± 0.5 kg) for gestational age. Mean age at follow-up testing was 24.5 ± 6.7 months. All children had age-appropriate scores in the communication, daily living, socialization and motor skills subdomains of the VABS (z-scores, P > 0.05). Furthermore, all children passed their newborn otoacoustic emission test and had normal hearing at preschool age. MRI study duration and exposure time to radio frequency waves and SSFSE sequences were not associated with adverse functional outcomes or hearing impairment. CONCLUSION: Prenatal exposure to 1.5-T MRI during the second or third trimester of pregnancy in a cohort of healthy fetuses is not associated with disturbances in functional outcomes or hearing impairment at preschool age.

Adolescents with tetralogy of Fallot: neuropsychological assessment and structural brain imaging.

BACKGROUND: Few data are available on the neuropsychological, behavioural, or structural brain imaging outcomes in adolescents who underwent corrective surgery in infancy for tetralogy of Fallot. METHODS: In this single-centre cross-sectional study, we enrolled 91 adolescents (13-16 years old) with tetralogy of Fallot and 87 referent subjects. Assessments included tests of academic achievement, memory, executive functions, visual-spatial skills, attention, and social cognition, as well as brain magnetic resonance imaging. RESULTS: Genetic abnormalities or syndromes were present in 25% of tetralogy of Fallot patients, who had markedly greater neuropsychological morbidities than did patients without a syndrome. However, even patients without a syndrome performed significantly worse than the referent group or population norms in all of the neuropsychological domains assessed. In multivariable regression in those without a genetic/phenotypic syndrome, the strongest predictors of adverse late neurodevelopmental outcomes included a greater number of complications at the first operation, more total surgical complications across all operations, and occurrence of post-operative seizures. The presence of at least one abnormality on structural magnetic resonance imaging was more frequent in tetralogy of Fallot patients than the referent group (42% versus 8%). CONCLUSIONS: Adolescents with tetralogy of Fallot are at increased neurodevelopmental risk and would benefit from ongoing surveillance and educational supports even after childhood.

White matter microstructure and cognition in adolescents with congenital heart disease.

OBJECTIVE: To describe the relationship between altered white matter microstructure and neurodevelopment in children with dextro-transposition of the great arteries (d-TGA). STUDY DESIGN: We report correlations between regional white matter microstructure as measured by fractional anisotropy (FA) and cognitive outcome in a homogeneous group of adolescents with d-TGA. Subjects with d-TGA (n = 49) and controls (n = 29) underwent diffusion tensor imaging and neurocognitive testing. In the group with d-TGA, we correlated neurocognitive scores with FA in 14 composite regions of interest in which subjects with d-TGA had lower FA than controls. RESULTS: Among the patients with d-TGA, mathematics achievement correlated with left parietal FA (r = 0.39; P = .006), inattention/hyperactivity symptoms correlated with right precentral FA (r = -0.39; P = .006) and left parietal FA (r = -0.30; P = .04), executive function correlated with right precentral FA (r = -0.30; P = .04), and visual-spatial skills correlated with right frontal FA (r = 0.30; P = .04). We also found an unanticipated correlation between memory and right posterior limb of the internal capsule FA (r = 0.29; P = .047). CONCLUSION: Within the group with d-TGA, regions of reduced white matter microstructure are associated with cognitive performance in a pattern similar to that seen in healthy adolescents and adults. Diminished white matter microstructure may contribute to cognitive compromise in adolescents who underwent open-heart surgery in infancy.