Changes In Fetal Brain Research Articles

VP39.01: Assessment of the time course of postmortem fetal brain changes by DWI after radiofrequency ablation for fetal reduction in monochorionic pregnancies

VP39.01: Assessment of the time course of postmortem fetal brain changes by DWI after radiofrequency ablation for fetal reduction in monochorionic pregnancies

Congenital Cytomegalovirus Infection in Pregnancy: A Case Report with Sequential Fetal Brain Changes and the Latest Information on Diagnosis, Treatment and Prevention

Congenital cytomegalovirus (CMV) infection is the most common nongenetic cause of sensorineural hearing loss and a major cause of visual, intellectual, and neurodevelopmental impairment worldwide. The seroprevalence of CMV among women of childbearing age in developing countries reaches almost 100%, and the incidence of CMV infection in neonates is 1%–2%. Approximately 87% of the infected neonates are asymptomatic at birth and 13% of them have permanent sequelae. The burden of congenital malformations due to congenital CMV infection is higher than that due to Down syndrome, fetal alcohol syndrome, and spina bifida. Nevertheless, there is little knowledge regarding congenital CMV pathogenesis, diagnosis, treatment, and prevention. In this study, we report a case that showed sequential changes of fetal brain following CMV infection in pregnancy. Additionally, we reviewed the latest information on the diagnosis, treatment, and prevention of congenital CMV infection.

Quantification of Fetal Gyrogenesis in the Third Trimester. A Novel Algorithm for Evaluating Fetal Sulci Development.

The fetal brain changes significantly throughout gestation. From a smooth (lissencephalic) cortex, it transforms into its convolved (gyrencephalic) state. Despite its importance, the diagnosis of delay in brain gyrogenesis is a challenge for many sonographers. This study presents a novel semiautomatic image processing algorithm for simple quantification of sagittal sulci maturation in the third trimester. Mid-sagittal fetal brain ultrasound images were obtained during routine third trimester scans. Fetal brain sulci length measurements were performed using a novel semiautomatic image processing algorithm followed by manual measurements. Correlations between the total length of the sulci, gestational age, and fetal biometry were examined. The study included 64 patients. A significant positive linear correlation was found between total sulci length and gestational age (r = .658 for automated measurement, r = .7 for manual measurement, P < .0001). A similar relationship was found comparing total sulci length and fetal head circumference (r = .694 for automated measurement, r = .74 for manual measurement; P < .0001). A significant correlation was observed between automated and manual measurements (r = .947). We found that fetal gyrogenesis is linear throughout the third trimester of pregnancy. The use of a computer algorithm to measure fetal sulci can be used as a simple prenatal screening test for delayed gyralmaturation of the fetal brain.

Ultrasound and MR Imaging of the Normal Fetal Brain.

Prenatal imaging of the central nervous system has proven to be essential in the detection of anomalies to guide counseling and intrauterine and postnatal therapies. However, understanding the appearance of normal is important because the fetal brain changes dramatically during the pregnancy. In this review, normal imaging of the brain with ultrasound and MR imaging is discussed. The initial section stresses techniques for both modalities. The second section describes ultrasound and MR landmarks in a normal fetal brain.

Fetal and Postnatal Brain Imaging for the Detection of ZIKV Encephalopathy in the Fetus/Newborn

BackgroundUp to 15% of pregnancies complicated by maternal ZIKV infection result in Zika-virus associated brain abnormalities in the fetus/newborn. Fetal ultrasound (feUS) is the standard imaging modality for the evaluation of fetal anatomy and for brain changes from congenital infection. Fetal MRI (feMRI) may be a useful adjunct.MethodsWe performed a prospective longitudinal neuroimaging study of fetuses/newborns of pregnant women with clinical and/or lab confirmed (RT-PCR and/or IgM/PRNT) diagnosis of Zika infection in Barranquilla, Colombia (endemic) and in Washington, DC, USA (travel-related). Gestational age (GA) at exposure and timing between ZIKV exposure/symptoms and imaging was documented. Subjects had one to two feMRIs and feUS, depending upon GA at enrollment. The feMRI and feUS protocols were standardized between sites and studies were centrally interpreted at Children’s National. Postnatally, infants received an unsedated brain MRI and head US.ResultsForty-eight, ZIKV exposed/infected in first or second trimester pregnant women were enrolled (46 Colombia, 2 USA). Subjects had symptoms of ZIKV infection at mean of 8.4±5.7 week GA. The first feMRI and feUS were performed at 25.1±6.3 week GA. Thirty-six infants had a second feMRI and feUS at 31.1±4.2 week GA. Three of 48 (6%) cases had an abnormal feMRI: (1) heterotopias and abnormal cortical indent; (2) parietal encephalocele and Chiari II; (3) thin corpus callosum, dysplastic brainstem, temporal cysts, subependymal heterotopias, and generalized cerebral/cerebellar atrophy. FeUS in these three cases found (1) normal study; (2) parietal encephalocele and Chiari II; (3) significant ventriculomegaly with decreasing percentiles of head circumference from 32 to 36 week GA (38% to 3.6%). Postnatal head US revealed findings not seen on feUS: choroid plexus or germinal matrix cysts in nine infants and lenticulostriate vasculopathy in one infant.ConclusionFeMRI and feUS provide complimentary information in the assessment of fetal brain changes in ZIKV. In cases of abnormal brain structure, feMRI reveals more extensive areas of brain damage than is seen by US. Further studies are needed to determine whether cystic changes on postnatal head US are related to ZIKV infection, or are incidental findings.Disclosures All authors: No reported disclosures.

BOLD-MRI demonstrates acute placental and fetal organ hypoperfusion with fetal brain sparing during hypercapnia

IntroductionWe evaluated changes in placental and fetal hemodynamics in rodents during acute hypercapnia using BOLD-MRI and Doppler ultrasound. MethodsAnimals were anesthetized with pentobarbital and, in consecutive 4-min periods, breathed: air, 21%O2:5%CO2, and 95%O2:5%CO2. BOLD-MRI: Pregnant ICR mice (n = 6; E17.5) were scanned in a 4.7-T Bruker Biospec spectrometer. Placenta and fetal liver, heart and brain were identified on True-FISP images. Percent change in signal intensity (SI) were analyzed every 30 s from T2*-weighted GE images (TR/TE = 147/10 ms). Doppler: Pregnant Wistar rats (n = 6; E18-20) were anesthetized with pentobarbital and received abdominal Doppler ultrasound. Umbilical artery pulsatility index (PI) and fetal heart rate were assessed at baseline and after two minutes of both hypercapnic challenges. ResultsBOLD-MRI: Normoxic-hypercapnia caused immediate marked reduction in SI in placenta (−44% ± 5.5; p < 0.001), fetal liver (−32% ± 6.4; p < 0.001) and fetal heart (−53% ± 9.9; p < 0.001) but only minor changes in fetal brain (−13% ± 3.4; p < 0.01), suggesting fetal brain sparing. Doppler: Normoxic-hypercapnia caused a marked increase in umbilical artery PI (+27.4% ± 7.2; p < 0.001) and a reduction in fetal heart rate (−48 bpm; 95%CI -9.3 to −87.0; p = 0.02), suggesting acute fetal asphyxia. ConclusionsBrief maternal hypercapnic challenge caused BOLD-MRI changes consistent with acute placental and fetal hypoperfusion with fetal brain sparing. The same challenge caused increased umbilical artery PI and fetal bradycardia on Doppler ultrasound, suggestive for acute fetal asphyxia. BOLD-MRI may be a suitable noninvasive imaging strategy to assess placental and fetal organ hemodynamics.

Abstract 19532: Maternal Hyperoxia Increases Cerebral Oxygenation in Fetuses With Complex Congenital Heart Disease: A Functional MRI Study

Introduction: Fetal brain growth is altered in congenital heart disease (CHD). The role of disturbed placental and fetal blood flow/oxygenation remains poorly understood. We compared the effect of maternal hyperoxia on cerebral and placental oxygenation in CHD vs control fetuses using blood oxygenation level dependent (BOLD) functional MRI (fMRI). Methods: We studied 85 pregnant women (51 healthy /34 CHD fetuses) at 22-39 weeks gestational age (GA), using MRI and Doppler. After 2min baseline recording at normoxia (NO), we made BOLD fMRI measurements in 4 phases, (1) early hyperoxia (HO; 100% O2) for 2min (2) late HO (2min), (3) early return NO (1.75min), (4) late return NO (1.75min). We measured % BOLD signal changes in fetal brain and placenta and correlated these with umbilical artery (UA) pulsatility index (PI) obtained at baseline. Results: Mean GA of CHD vs control fetuses was 32 4/7 and 32 2/7 (p=0.77). 41.2% had 1-ventricle (1V; all HLHS) vs 2-ventricle (2V) physiology. In controls, brain BOLD signal increased in phase 1 HO and remained elevated through phase 4. In CHD fetuses, the BOLD signal increased in phase 1 and continued to rise through phase 4. Differences in brain BOLD elevation in CHD vs controls (3.1% vs 0.9%, p=0.04) was significant in phase 4 (Fig. 1). Brain BOLD differed between 1V (3.4%, p=0.04) and 2V (0.9%, p=0.15) in phases 3 &amp; 4. Placental BOLD signal increased during HO in control (4.4%, p&lt;0.001) and CHD fetuses (6.4%, p&lt;0.001). UA PI in CHD fetuses was higher than controls (1.11 vs 1.03, p=0.03). UA PI correlated with placental BOLD during HO in healthy and CHD fetuses (p&lt;0.05). Conclusions: In this first report of placental and fetal brain responses to maternal HO, we show a significantly increased brain BOLD response in CHD fetuses, specifically 1V. These data suggest that maternal HO improves brain oxygenation in CHD fetuses in the short-term. Studies evaluating the prolonged effects of HO are needed to determine the role of HO management in select CHD fetuses.

Neurochemical and neurobehavioral effects of repeated gestational exposure to chlorpyrifos in maternal and developing rats

Acute exposure to the organophosphate pesticide chlorpyrifos (CPF) on gestation day 12 (GD12, 200 mg/kg/ml, SC) causes extensive neurochemical changes in maternal brain but lesser changes in fetal brain. In the present study, we examined the relative neurotoxicity of repeated, lower-level CPF exposures during gestation in rats. Pregnant Sprague-Dawley rats were exposed to CPF (6.25, 12.5, or 25 mg/kg per day, SC) from GD12–19 and sampled at either GD16, GD20, or postnatal day 3 (PND3) for measurement of various maternal and developmental neurochemical markers. In contrast to the high acute dose exposure, no maternal toxicity was noted with repeated lower-level dosing. Extensive acetylcholinesterase (AChE) inhibition (83–90%) was noted in maternal brain at all three time points following repeated exposures (25 mg/kg). Higher AChE inhibition (58%) was noted in fetal brain at GD20 compared to 19–25% on PND3 in treated pups cross-fostered to control dams and in control pups cross-fostered to treated dams following repeated exposures (25 mg/kg per day). Whereas similar reductions in brain muscarinic receptor binding were noted at GD20 and PND3 in dams and developing brain between acute and repeated dosing regimens, greater changes in [ 3H]CD and [ 3H]cytisine binding were evident following repeated exposures. Righting reflex and cliff avoidance tests were markedly altered following repeated exposures. The results suggest that lower-level repeated exposures to CPF cause extensive neurochemical and neurobehavioral changes in developing rats in the absence of maternal toxicity.

Teratogenic effects of triethylene tetramine dihydrochloride on the mouse brain.

The teratogenic effects of triethylene tetramine dihydrochloride (Trien-2HCl) on fetal mouse brain were studied on gestational day 19. Trien-2HCl was given throughout pregnancy at levels of 0 (control), 3,000, 6,000, or 12,000 mg/liter as drinking water, ad libitum. Mean litter size and live fetus per dam at birth were not significantly different among the four groups. The frequency of gross brain abnormalities in live fetus at birth such as hemorrhages, delayed ossification in cranium, hydrocephaly, exencephaly, and microcephaly increased with increasing levels of the drug. Microscopically, disorganization of neuronal cell layers, spongiform changes in white matter, and reduced myelin development were noted in the coronally sectioned cerebrum from Trien-2HCl-treated fetus. These abnormal findings increased dose-dependently in regard to the extent and severity at the levels of 6,000 and 12,000 mg/liter. No such changes were observed in the cerebrum of controls. These results suggest that microscopic changes in fetal brain caused by Trien-2HCl may be in part similar to those in brindled mutant mouse. Special attention should be paid to the developing fetal brain when Trien-2HCl is used during pregnancy.