Differences in brain functional connectivity at resting state in neonates born to healthy obese or normal-weight mothers.

Recent studies have shown associations between maternal obesity at pre- or early pregnancy and long-term neurodevelopment in children, suggesting in utero effects of maternal obesity on offspring brain development. In this study, we examined whether brain functional connectivity to the prefrontal lobe network is different in newborns from normal-weight or obese mothers. Thirty-four full-term healthy infants from uncomplicated pregnancies were included, with 18 born to normal-weight and 16 born to obese mothers. Two weeks after delivery, the infants underwent an magnetic resonance imaging (MRI) examination during natural sleep, which included structural imaging and resting-state functional MRI (fMRI) scans. Independent component analysis was used to identify the prefrontal lobe network, and dual regression was used to compare functional connectivity between groups. Infants born to normal-weight mothers had higher recruiting (P<0.05, corrected) of dorsal anterior cingulate cortex regions to the prefrontal network after adjusting for maternal intelligence quotient, gestational weight gain and infant postmenstrual age, gender, birth weight/length, head circumference and neonatal diet. The functional connectivity strength in dorsal anterior cingulate cortex negatively correlated (P<0.05) with maternal fat mass percentage measured at early pregnancy. This preliminary study indicates that exposure to maternal obesity in utero may be associated with changes in resting-state functional connectivity in the newborn offspring's brain.

Maternal Obesity during Pregnancy is Associated with Lower Cortical Thickness in the Neonate Brain.

BACKGROUND AND PURPOSE: Recent studies have suggested that maternal obesity during pregnancy is associated with differences in neurodevelopmental outcomes in children. In this study, we aimed to investigate the relationships between maternal obesity during pregnancy and neonatal brain cortical development. MATERIALS AND METHODS: Forty-four healthy women (28 normal-weight, 16 obese) were prospectively recruited at <10 weeks' gestation, and their healthy full-term neonates (23 boys, 21 girls) underwent brain MR imaging. All pregnant women had their body composition (fat mass percentage) measured at ∼12 weeks of pregnancy. All neonates were scanned at ∼2 weeks of age during natural sleep without sedation, and their 3D T1-weighted images were postprocessed by the new iBEAT2.0 software. Brain MR imaging segmentation and cortical surface reconstruction and parcellation were completed using age-appropriate templates. Mean cortical thickness for 34 regions in each brain hemisphere defined by the UNC Neonatal Cortical Surface Atlas was measured, compared between groups, and correlated with maternal body fat mass percentage, controlled for neonate sex and race, postmenstrual age at MR imaging, maternal age at pregnancy, and the maternal intelligence quotient and education. RESULTS: Neonates born to obese mothers showed significantly lower (P ≤ .05, false discovery rate-corrected) cortical thickness in the left pars opercularis gyrus, left pars triangularis gyrus, and left rostral middle frontal gyrus. Mean cortical thickness in these frontal lobe regions negatively correlated (R = -0.34, P = .04; R = -0.50, P = .001; and R = -0.42, P = .01; respectively) with the maternal body fat mass percentage measured at early pregnancy. CONCLUSIONS: Maternal obesity during pregnancy is associated with lower neonate brain cortical thickness in several frontal lobe regions important for language and executive functions.

Maternal Anxiety and Depression during Late Pregnancy and Newborn Brain White Matter Development.

BACKGROUND AND PURPOSE: Anxiety and depression during pregnancy have been associated with an increased risk of adverse neurodevelopmental outcomes in offspring. We aimed to study the in utero effects of maternal anxiety and depression on early brain development. MATERIALS AND METHODS: Pregnant women were recruited at ∼36 weeks of gestation for this prospective study. They were assessed for anxiety symptoms by the State-Trait Anxiety Inventory and for depression symptoms by the Beck Depression Inventory, 2nd Edition. After delivery, infant underwent an MR imaging examination of the brain without sedation, including DTI, for evaluation of white matter (WM) development. Infant fractional anisotropy values, a putative marker of WM integrity, were correlated with the mothers' State-Trait Anxiety Inventory and Beck Depression Inventory scores by using both tract-based spatial statistics and ROI methods. RESULTS: Thirty-four infants were included in this study. Both maternal State-Anxiety and Trait-Anxiety scores negatively correlated (P < .05, corrected) with fractional anisotropy values in widespread brain WM regions; Beck Depression Inventory scores also negatively correlated (P < .05) with fractional anisotropy values in one cluster in the brain. Further ROI analyses confirmed significant negative correlations between average fractional anisotropy values in ROIs including left and right prefrontal WM, left and right middle frontal gyrus WM, and the fornix, and State-Anxiety (R values, -0.47 to -0.67; P values, .008 to <.001), Trait-Anxiety (R, -0.37 to -0.59; P, .04 to <.001), and Beck Depression Inventory (R values, -0.36 to -0.55; P, .05 to .002) scores. CONCLUSIONS: Higher maternal anxiety and depression symptom scores during late pregnancy were associated with lower estimated infant brain WM development, which indicated in utero influences of maternal mental health during pregnancy on the developing brain.

Cesarean Delivery Impacts Infant Brain Development.

BACKGROUND AND PURPOSE: The cesarean delivery rate has increased globally in the past few decades. Neurodevelopmental outcomes associated with cesarean delivery are still unclear. This study investigated whether cesarean delivery has any effect on the brain development of offspring. MATERIALS AND METHODS: A total of 306 healthy children were studied retrospectively. We included 3 cohorts: 2-week-old neonates (cohort 1, n = 32/11 for vaginal delivery/cesarean delivery) and 8-year-old children (cohort 2, n = 37/23 for vaginal delivery/cesarean delivery) studied at Arkansas Children's Hospital, and a longitudinal cohort of 3-month to 5-year-old children (cohort 3, n = 164/39 for vaginal delivery/cesarean delivery) studied independently at Brown University. Diffusion tensor imaging, myelin water fraction imaging, voxel-based morphometry, and/or resting-state fMRI data were analyzed to evaluate white matter integrity, myelination, gray matter volume, and/or functional connectivity, respectively. RESULTS: While not all MR imaging techniques were shared across the institutions/cohorts, post hoc analyses showed similar results of potential effects of cesarean delivery. The cesarean delivery group in cohort 1 showed significantly lower white matter development in widespread brain regions and significantly lower functional connectivity in the brain default mode network, controlled for a number of potential confounders. No group differences were found in cohort 2 in white matter integrity or gray matter volume. Cohort 3 had significantly different trajectories of white matter myelination between groups, with those born by cesarean delivery having reduced myelin in infancy but normalizing with age. CONCLUSIONS: Cesarean delivery may influence infant brain development. The impact may be transient because similar effects were not observed in older children. Further prospective and longitudinal studies may be needed to confirm these novel findings.

Gestational Age at Birth and Brain White Matter Development in Term-Born Infants and Children.

BACKGROUND AND PURPOSE: Studies on infants and children born preterm have shown that adequate gestational length is critical for brain white matter development. Less is known regarding how variations in gestational age at birth in term infants and children affect white matter development, which was evaluated in this study. MATERIALS AND METHODS: Using DTI tract-based spatial statistics methods, we evaluated white matter microstructures in 2 groups of term-born (≥37 weeks of gestation) healthy subjects: 2-week-old infants (n = 44) and 8-year-old children (n = 63). DTI parameters including fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were calculated by voxelwise and ROI methods and were correlated with gestational age at birth, with potential confounding factors such as postnatal age and sex controlled. RESULTS: Fractional anisotropy values, which are markers for white matter microstructural integrity, positively correlated (P < .05, corrected) with gestational age at birth in most major white matter tracts/regions for the term infants. Mean diffusivity values, which are measures of water diffusivities in the brain, and axial and radial diffusivity values, which are markers for axonal growth and myelination, respectively, negatively correlated (P < .05, corrected) with gestational age at birth in all major white matter tracts/regions excluding the body and splenium of the corpus callosum for the term infants. No significant correlations with gestational age were observed for any tracts/regions for the term-born 8-year-old children. CONCLUSIONS: Our results indicate that longer gestation during the normal term period is associated with significantly greater infant white matter development (as reflected by higher fractional anisotropy and lower mean diffusivity, axial diffusivity, and radial diffusivity values); however, similar associations were not observable in later childhood.

Evaluation of the reconstructed carotid artery following extracorporeal membrane oxygenation.

Over a 12-month period, 28 neonatal patients in respiratory failure were supported with extracorporeal membrane oxygenation (ECMO), and 11 of these underwent successful repair of the right carotid artery post-ECMO. Nine of 11 were studied with duplex color-flow Doppler imaging between 14 and 109 days of age and again at 1 year of age. A velocity ratio (A/B) of the peak systolic velocity above the level of the anastomosis to the peak systolic velocity below the anastomosis was measured to assess the degree of stenosis, if any, at the repair site. Antegrade flow through the carotid was detected post-ECMO in 8 of 9 infants, and antegrade and retrograde flow was documented in 1 infant. A/B ratios ranged from 1.00 to 8.60 (A/B ratio of 1 is normal; 2.0 indicates at least a 50% obstruction to flow). Four of 9 patients had ratios greater than 2.0, and 8 of 9 exhibited some evidence of obstruction. Follow-up scans were performed on 8 of 9 infants between 12 and 18 months of age. All infants examined showed marked improvement in A/B ratio and patency of the vessel, documenting that initial narrowing of the vessel is reversible. No infant had evidence of embolic phenomena to the right side of the brain by magnetic resonance imaging. Repair of the common carotid artery post-ECMO is technically feasible without increasing the risk of brain injury.

Efficacy of gadoteridol for contrast-enhanced magnetic resonance imaging in children.

RATIONALE AND OBJECTIVES: This study assesses the efficacy of gadoteridol for contrast-enhanced magnetic resonance imaging (MRI) in children. METHODS: Patients were examined by MRI before and after receiving 0.10 mmol/kg gadoteridol. Blinded and unblinded readers analyzed brain and spine MRI studies from a multicenter clinical trial involving 101 patients at 11 sites. Ninety-two cases (76 brain, 16 spine) were evaluated by unblinded investigators, and 91 cases (76 brain, 15 spine) were evaluated by three neuroradiologists unaffiliated with any investigational site and blinded to clinical information. RESULTS: Unblinded readers noted enhancement of brain pathology in 70% of cases versus 50% to 67% among blinded readers. Unblinded readers determined that additional diagnostic information was available after contrast in 82% of brain studies (average, 64% for blinded readers) and would have changed patient diagnoses in 48% of these studies (average, 46% for blinded readers). In spine cases, enhancement of pathology was noted in 38% (unblinded) and 33% to 40% (blinded). Additional diagnostic information was available after contrast in 63% of spine studies (unblinded), or an average of 58% (blinded), and patient diagnoses would have changed in 20% (unblinded), or an average of 59% (blinded). CONCLUSIONS: Gadoteridol is suitable for enhanced MRI detection, localization, and characterization of central nervous system pathology in children.

Optic nerve hypoplasia. Clinical significance of associated central nervous system abnormalities on magnetic resonance imaging.

Magnetic resonance imaging demonstrated coexistent central nervous system abnormalities in 30 of 40 patients with optic nerve hypoplasia. Based on their associated neuroradiological findings, these patients were placed into one of five categories: group 1, isolated optic nerve hypoplasia; group 2, absence of the septum pellucidum; group 3, posterior pituitary ectopia; group 4, hemispheric migration anomalies; and group 5, intrauterine/perinatal hemispheric injury. Posterior pituitary ectopia (group 3) and cerebral hemispheric abnormalities (groups 4 and 5) were found to be highly predictive of pituitary hormone deficiency and neurodevelopmental deficits, respectively. Isolated absence of the septum pellucidum (group 2) was associated with normal neurodevelopmental and endocrinologic function. Thinning or agenesis of the corpus callosum was predictive of neurodevelopmental problems only by virtue of its frequent association with cerebral hemispheric abnormalities. Magnetic resonance imaging can now be used to provide specific prognostic information regarding the likelihood of neurodevelopmental deficits and pituitary hormone deficiency in infants with optic nerve hypoplasia. The prevailing notion of septo-optic dysplasia as a distinct nosologic entity should be reconsidered.

Optic nerve hypoplasia. Identification by magnetic resonance imaging.

High-resolution magnetic resonance images of the intracranial optic nerves and chiasm were obtained in 15 patients with severe optic nerve hypoplasia. These were compared, in a double-blind manner, with similar images from 30 age-matched controls. On both coronal and sagittal images, hypoplastic optic nerves were thin and demonstrated signal attenuation when compared with normal optic nerves. All patients with severe bilateral optic nerve hypoplasia also had diffuse chiasmal hypoplasia, which was seen best on coronal images. Patients with unilateral or asymmetrical optic nerve hypoplasia had variable chiasmal abnormalities. The degree to which the magnetic resonance diagnosis of optic nerve hypoplasia matched the clinical diagnosis was highly significant (P less than .001, Fisher's Exact Test) for both coronal and sagittal views of the intracranial optic nerves. Oblique axial and coronal views of the orbital optic nerves did not reliably distinguish optic nerve hypoplasia from normal optic nerves. High-resolution magnetic resonance imaging is a useful diagnostic modality to identify small optic nerves neuroradiologically.

Blindness, deafness, quadriparesis, and a retinal malformation: the ravages of neurofibromatosis 2.

Advances in molecular biology have established that the diseases once collectively referred to as neurofibromatosis are actually genetically distinct and clinically heterogenous conditions. This realization has led to separate definitions for neurofibromatosis (NF) type 1 and 2. Although ophthalmologic manifestations of NF1 have long been recognized, the distinguishing ocular features of NF2 have only recently received attention. We describe an inferior retinopapillary malformation with an overlying glial hamartoma in a deaf, quadriparetic patient with NF2. Magnetic resonance (MR) imaging initially showed bilateral vestibular schwannomas and a large cervical ependymoma. Over six years of follow-up, the patient developed multiple intracranial meningiomas.

Aicardi syndrome: more than meets the eye.

An eight-month-old girl with infantile spasms and apparent blindness had electroencephalographic findings compatible with Aicardi syndrome. In addition to optic nerve hypoplasia, there were multiple congenital retinal malformations in the right eye, including chorioretinal lacunae, anomalous retinal vessels, posterior scleral ectasia, and a peripheral fibrous ridge. Magnetic resonance imaging demonstrated agenesis of the corpus callosum, absence of the septum pellucidum, optic nerve and chiasmal hypoplasia, pachygyria, cortical heterotopias, colpocephaly, and hypoplasia of the cerebellar vermis. This patient illustrates the broad spectrum of cerebroretinal malformations now known to characterize Aicardi syndrome.

Orbital intramuscular schwannoma.

In an 8-year-old girl with asymptomatic proptosis, computed tomographic scans showed a large medial orbital mass that contoured the globe anteriorly, bowed the optic nerve laterally, and extended posteriorly to the orbital apex. T1-weighted coronal magnetic resonance images showed the mass to be a diffusely enlarged medial rectus muscle. Histopathologic examination of a medial rectus muscle biopsy specimen disclosed a multinodular, intramuscular schwannoma, separating and infiltrating normal skeletal muscle fibers. The intramuscular location and multinodular configuration of this tumor, together with its occurrence in a child, distinguish it from previous orbital schwannomas.

MR demonstration of ectopic fourth ventricular choroid plexus in Chiari II malformation.

An enhancing nodule was seen on T1-weighted enhanced scans at the tip of the caudally displaced cerebellar vermis in three patients with Chiari II malformation. The enhancing fibrovascular nodule found at the base of the cerebellum in patients with Chiari II malformation represents ectopic choroid plexus and should not be confused with a pathologic mass.

Altered vertebrobasilar flow in children: angiographic, MR, and MR angiographic findings.

PURPOSE: To characterize the clinical, MR, MR angiographic, and conventional angiographic findings in vertebrobasilar disease in children. METHODS: Eight children with posterior circulation ischemia and infarction had conventional spin-echo MR and MR angiography of the head and neck. Six patients had conventional angiography. RESULTS: Six patients had alteration of vertebral or basilar artery flow void on spin-echo images. MR angiography showed all six cases of angiographically proved vertebrobasilar dissection or occlusion despite overestimating the extent of arterial abnormality in two patients. In two patients the intracranial peripheral branch cutoff shown at angiography was correctly predicted on screening MR angiography. CONCLUSION: Posterior circulation infarction in children is usually secondary to traumatic injury to the vertebrobasilar circulation. MR and MR angiography noninvasively show vertebrobasilar flow disturbances and compare favorably with angiography in documenting dissection or occlusion of the vertebrobasilar circulation. MR angiography may obviate the need for invasive angiography in these children at diagnosis and during follow-up of anticoagulation therapy.

Meningiomas in children: MR and histopathologic findings.

PURPOSE: To present the MR and histopathologic findings in five children with meningiomas. METHODS: Five children aged 3 months to 16 years with pathologically proved meningiomas underwent preoperative contrast enhanced MR. Tissue in four patients was sent for chromosomal analysis in addition to routine histopathologic studies. RESULTS: All five tumors were extra-axial, two supratentorial and three in the posterior fossa. MR showed variable signal intensity on precontrast T1-weighted images. All of the tumors were hyperintense on proton density- and T2-weighted images and showed intense contrast enhancement. Histopathologic analysis showed two meningotheliomatous, one transitional, one chordoid, and one hemangiopericytic variant of meningioma. Chromosomal analysis showed deletions involving chromosome 22 in two of four tumors studied. CONCLUSION: Meningiomas in children have a higher incidence of posterior fossa location and different histologic types than seen in adults. MR showed the tumors in our patients to be extra-axial, hyperintense on proton density- and T2-weighted images with intense enhancement on postcontrast T1-weighted images. Chromosomal aberrations were noted in two patients.

Incidental paranasal sinus abnormalities on CT of children: clinical correlation.

The paranasal sinuses were prospectively evaluated by CT, clinical history, and physical examination in infants and children having cranial CT for indications unrelated to upper respiratory inflammation (URI). One hundred and one CT scans were studied, and sinus abnormalities were detected in 18% of patients older than 1 year and without signs or symptoms of URI. When signs and/or symptoms of recent URI were present, the incidence of abnormalities was 31%. Maxillary antral were not identifiable or were opacified in 72% of all infants under 1 year old. Because of the high incidence of sinus abnormalities on CT in children with and without evidence of recent URI, abnormalities should not be ascribed to sinusitis without close clinical correlation.

Rectal thiopental sodium for sedation of pediatric patients undergoing MR and other imaging studies.

PURPOSE: To determine the efficacy and safety of rectal thiopental sodium as a sedation agent for pediatric imaging. METHODS: Four hundred sixty-two infants and children were sedated with rectal thiopental sodium for MR, CT, or nuclear imaging in 1992 and 1993. Patients received screening histories and physical examinations before sedation, and parents gave informed consent. Sedated patients were monitored by pulse oximetry and direct observation. Twenty-four-hour telephone follow-up to assess delayed side effects was performed successfully in 325 patients. RESULTS: Examinations were successfully completed in 96% of patients. The average time from drug administration to sedation was 12.2 minutes. The average time from sedation to discharge from radiology was 71.1 minutes. Eleven percent of patients had desaturation below the pulse oximetric baseline easily treated with oxygen and head positioning. Twenty-four-hour telephone follow-up in 325 patients revealed a 34% incidence of minor rectal irritation and diarrhea, sleepiness, nausea and vomiting, or ataxia. CONCLUSIONS: Rectal thiopental sodium is a safe and effective drug for pediatric sedation.

Clinical, neurodiagnostic, and MR findings in children with spinal and brain stem multiple sclerosis.

PURPOSE: To describe the clinical, neurodiagnostic, and MR findings in seven children with brain stem and spinal multiple sclerosis. METHODS: Spinal or brain stem multiple sclerosis was diagnosed in seven children between 1986 and 1992. All patients had neurologic and MR examinations as well as neurodiagnostic testing, including spinal fluid analysis and brain stem and auditory evoked potentials. RESULTS: Three children had clinical findings and masslike lesions in the brain stem (two) or spinal cord (one) suggestive of neoplasm, which prompted biopsy (two) or radiation therapy (one). Five of six patients with spinal involvement had cord swelling with increased signal on T2-weighted images over at least three cord segments, and two children had essentially holocord involvement. Three children had normal cranial MR at presentation. CONCLUSIONS: Multiple sclerosis involvement of the brain stem and spinal cord may be associated with extensive swelling and MR signal changes suggestive of neoplasm without typical cerebral white matter abnormalities. Serial clinical and neuroimaging examinations may be necessary to make a definitive diagnosis of multiple sclerosis in children.

CT and ultrasound imaging of retropharyngeal abscesses in children.

PURPOSE: To show the role of ultrasound (US) in distinguishing retropharyngeal abscess from adenitis in children. METHODS: Eleven infants and children had clinical symptoms suggestive of retropharyngeal infection. Radiographic evaluation included, lateral neck radiography (11/11), contrast-enhanced neck CT (10/11), contrast-enhanced neck MR (1/11), and real time US (11/11) patients. US was used to characterize masses as solid (adenitis) or complex (abscess) and for guiding intraoperative aspiration and drainage. RESULTS: Contrast CT and MR showed findings suspicious for abscess in all 11 cases. Only three children had surgically drainable abscesses. CT numbers within inflammatory masses did not distinguish adenitis from abscess. US was able to correctly diagnose abscess or adenitis in each case. CONCLUSION: Lateral neck radiography and contrast CT identify and localize retropharyngeal inflammatory masses in children. US, but not CT, distinguishes between adenitis and abscess and aids in intraoperative aspiration and drainage.

Congenital cerebral and cerebrovascular anomalies: magnetic resonance imaging.

Magnetic resonance is the imaging modality of choice for the evaluation of infants and children with known or suspected cerebral and cerebrovascular abnormalities. Entities described include cephaloceles, holoprosencephaly, dysgenesis of corpus callosum, and anomalies of neuronal migration. Congenital vascular lesions described include aneurysm, arteriovenous malformation, cavernous malformation, and Galenic malformations.