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.

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.

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.

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.

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.

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.

Imaging after direct and indirect extracranial-intracranial bypass surgery.

OBJECTIVE: The purpose of this article is to describe the imaging features of different types of surgical cerebral revascularization techniques. CONCLUSION: Surgical cerebral revascularization involves direct and indirect techniques. Direct revascularization entails anastomosing a branch of the external carotid artery to a cerebral artery. Indirect revascularization involves delivering an extracranial vascular supply in proximity to the surface of the brain. The results of these techniques have distinctive imaging features.

Adolescents with d-transposition of the great arteries corrected with the arterial switch procedure: neuropsychological assessment and structural brain imaging.

BACKGROUND: We report neuropsychological and structural brain imaging assessments in children 16 years of age with d-transposition of the great arteries who underwent the arterial switch operation as infants. Children were randomly assigned to a vital organ support method, deep hypothermia with either total circulatory arrest or continuous low-flow cardiopulmonary bypass. METHODS AND RESULTS: Of 159 eligible adolescents, 139 (87%) participated. Academic achievement, memory, executive functions, visual-spatial skills, attention, and social cognition were assessed. Few significant treatment group differences were found. The occurrence of seizures in the postoperative period was the medical variable most consistently related to worse outcomes. The scores of both treatment groups tended to be lower than those of the test normative populations, with substantial proportions scoring ≥1 SDs below the expected mean. Although the test scores of most adolescents in this trial cohort are in the average range, a substantial proportion have received remedial academic or behavioral services (65%). Magnetic resonance imaging abnormalities were more frequent in the d-transposition of the great arteries group (33%) than in a referent group (4%). CONCLUSIONS: Adolescents with d-transposition of the great arteries who have undergone the arterial switch operation are at increased neurodevelopmental risk. These data suggest that children with congenital heart disease may benefit from ongoing surveillance to identify emerging difficulties. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000470.

Regional cerebellar volumes predict functional outcome in children with cerebellar malformations.

The cerebellum has recently been recognized for its role in high-order functions, including cognition, language, and behavior. Recent studies have also begun to describe a functional topography of the mature cerebellum that includes organization on a mediolateral axis. However, no study to date has examined the relationship between regional cerebellar volume and developmental disabilities in children with cerebellar malformations. The objective of this study was to estimate the extent to which total and regional cerebellar volumes are associated with developmental disabilities in a cohort of children with cerebellar malformations. Children aged 1 to 6 years with a diagnosis of cerebellar malformation underwent standardized outcome measures and quantitative magnetic resonance scanning. The cerebellum was parcellated into seven mediolateral zones (three for each hemisphere plus the vermis) for regional volume analysis. In children with cerebellar malformations, decreased total cerebellar volume was associated with delays in global development, expressive language, cognition, as well as gross and fine motor function. Decreased volume in the right lateral cerebellar hemisphere was related to impaired cognition, expressive language, and gross motor function. Additionally, reduced vermis volume was associated with impaired global development, cognition, expressive language, and gross and fine motor skills, as well as behavior problems and a higher rate of positive autism spectrum screening test. These results begin to define the structural topography of functional outcome in children with cerebellar malformations and should lead to greater accuracy of prognostication as well as timely early developmental interventions.

Brain volume and metabolism in fetuses with congenital heart disease: evaluation with quantitative magnetic resonance imaging and spectroscopy.

BACKGROUND: Adverse neurodevelopmental outcome is an important source of morbidity in children with congenital heart disease (CHD). A significant proportion of newborns with complex CHD have abnormalities of brain size, structure, or function, which suggests that antenatal factors may contribute to childhood neurodevelopmental morbidity. METHODS AND RESULTS: Brain volume and metabolism were compared prospectively between 55 fetuses with CHD and 50 normal fetuses with the use of 3-dimensinal volumetric magnetic resonance imaging and proton magnetic resonance spectroscopy. Fetal intracranial cavity volume, cerebrospinal fluid volume, and total brain volume were measured by manual segmentation. Proton magnetic resonance spectroscopy was used to measure the cerebral N-acetyl aspartate: choline ratio (NAA:choline) and identify cerebral lactate. Complete fetal echocardiograms were performed. Gestational age at magnetic resonance imaging ranged from 25 1/7 to 37 1/7 weeks (median, 30 weeks). During the third trimester, there were progressive and significant declines in gestational age-adjusted total brain volume and intracranial cavity volume in CHD fetuses relative to controls. NAA:choline increased progressively over the third trimester in normal fetuses, but the rate of rise was significantly slower (P<0.001) in CHD fetuses. On multivariable analysis adjusted for gestational age and weight percentile, cardiac diagnosis and percentage of combined ventricular output through the aortic valve were independently associated with total brain volume. Independent predictors of lower NAA:choline included diagnosis, absence of antegrade aortic arch flow, and evidence of cerebral lactate (P<0.001). CONCLUSIONS: Third-trimester fetuses with some forms of CHD have smaller gestational age- and weight-adjusted total brain volumes than normal fetuses and evidence of impaired neuroaxonal development and metabolism. Hemodynamic factors may play an important role in this abnormal development.

Ultrasound and MRI of fetuses with ventriculomegaly: can cortical development be used to predict postnatal outcome?

OBJECTIVE: The purpose of this study was to assess the conspicuity of brain cortical maturation with sonography and MRI of fetuses referred because of ventriculomegaly and to determine whether sulcal visualization can be used to predict postnatal outcome. SUBJECTS AND METHODS: Women with 374 fetuses referred because of ventriculomegaly underwent sonography and MRI. Four to six radiologists rated visualization of 19 fissures or sulci. Majority opinion regarding sulcal visualization was compared among fetuses categorized by CNS abnormality: normal, isolated ventriculomegaly, and ventriculomegaly with additional CNS abnormalities. Live-born infants were categorized as having normal or abnormal development. Logistic regression analysis was used to correlate sulcal visualization and postnatal development. A subanalysis was performed with fetuses who had been classified prenatally as having a normal brain or isolated ventriculomegaly. RESULTS: Cortical sulci were visualized more frequently and at an earlier gestational age with MRI than with ultrasound. In the entire cohort, the odds ratio of normal development ranged from 3.1 to 10.0 whenever the calcarine, parietooccipital, cingulate, superior temporal, precentral, or postcentral sulcus was seen on MR images. In fetuses categorized as having a normal brain or having isolated ventriculomegaly, the odds ratio of normal development ranged from 3.5 to 9.0 whenever the parietooccipital, cingulate, or superior temporal sulcus was seen. CONCLUSION: Visualization of the sulci in fetal brains depends on the imaging modality used and the gestational age at imaging. Information regarding sulcal visualization may aid in counseling patients carrying fetuses with ventriculomegaly.

Outcome of fetuses with cerebral ventriculomegaly and septum pellucidum leaflet abnormalities.

OBJECTIVE: The objective of this study was to assess the outcomes of the prenatal diagnosis of septal leaflet abnormalities in fetuses referred for prenatal imaging with a finding of ventriculomegaly. MATERIALS AND METHODS: This study is a retrospective review of fetuses with a diagnostic code of septal leaflet abnormalities from a larger prospective study. Four hundred twenty-five pregnant women with 433 fetuses referred for ventriculomegaly were imaged with ultrasound and MRI between July 1, 2003, and May 15, 2009. Four to six radiologists independently reviewed sonographic and MR images and recorded lateral ventricular diameters at the atrium and frontal horns, ventricular configuration, and the presence of ventriculomegaly and of other CNS abnormalities. Final prenatal ultrasound, MRI, and overall diagnoses were decided by consensus. Fetuses with a diagnostic code of septal leaflet abnormalities were identified, and birth outcome, autopsy findings, postnatal imaging, and postnatal follow-up examinations were obtained. The analysis of covariance, controlling for gestational age, was used to compare ventricular dimensions between fetuses with septal leaflet abnormalities and fetuses with isolated ventriculomegaly. Interrater agreement for the detection of septal leaflet abnormalities was assessed with kappa statistics. Interrater agreement and intrarater agreement for frontal horn measurements were assessed by variance components analysis. RESULTS: Twenty-three fetuses had septal leaflet abnormalities and 229 had isolated ventriculomegaly. Atrial and frontal horn diameters, adjusted for gestational age, were 77% and 98% larger, respectively, in fetuses with septal leaflet abnormalities than in fetuses with isolated ventriculomegaly (p < 0.0001). Before the consensus conference, agreement among ultrasound readers was moderate (κ = 0.54) and among MR readers, good (κ = 0.69). Additional CNS findings were seen on MRI in 12 of 23 fetuses (52%). Eleven pregnancies with septal leaflet abnormalities underwent termination and 12 progressed to livebirth; of the 12 livebirths, three neonates died. Neurodevelopmental follow-up was abnormal in all surviving children. CONCLUSION: A septal leaflet abnormality in the setting of ventriculomegaly is most frequently associated with other CNS abnormalities and is associated with postnatal developmental delay.