¿Podría contribuir la resonancia magnética a detectar la ventriculomegalia fetal aislada aparte de otras anormalidades?

Objetivo. Determinar el papel de la resonancia magnética (RM) cerebral en fetos que presentan ventriculomegalia aislada (VMA) en la evaluación ecográfica del cerebro fetal. Métodos. Se evaluaron retrospectivamente los hallazgos por ecografía y RM de 197 fetos diagnosticados con VMA entre noviembre de 2018 y noviembre de 2020. Se excluyeron los fetos con cariotipos anormales, anomalías adicionales o etiologías relacionadas a ventriculomegalia. Se comparó los resultados de ecografía y RM tanto en términos de medidas ventriculares medias como de grado de VMA. Resultados. Las mediciones de la RM fueron significativamente mayores en la VMA leve (10,33±0,38 mm frente a 11,11±0,51 mm, p<0,001) en comparación con la ecografía. En la VMA leve, la RM midió los ventrículos más anchos que la ecografía, con una diferencia media de 0,78 mm. No hubo diferencias significativas en las mediciones por ecografía y RM en cuanto a los valores medios de la VMA moderada y grave. Hubo buena concordancia entre la ecografía y la RM en la detección de la gravedad de la VMA derecha, izquierda y la media (Κ=0,265, Κ=0,324 y Κ=0,261, respectivamente). Los análisis de regresión lineal revelaron una relación estadísticamente significativa entre las mediciones de ecografía y RM de la VMA derecha, izquierda y la media (p<0,001, p<0,001 y p<0,001, respectivamente). La RM mostró una concordancia perfecta con la ecografía en detectar la lateralidad de la VMA (Κ=1,0, p<0,001). Conclusiones. En fetos con VMA leve detectada por ecografía se debe considerar la evaluación por RM del cerebro fetal para un diagnóstico preciso. Este enfoque puede proporcionar una estrategia eficaz en el manejo prenatal y el asesoramiento de estos embarazos.

Objective: To assess the role of brain magnetic resonance imaging (MRI) in fetuses presenting with isolated ventriculomegaly (IVM) in the ultrasound (US) evaluation of the fetal brain. Methods: US and MRI findings of 197 fetuses diagnosed with IVM between November 2018 and November 2020 were retrospectively evaluated. Fetuses with abnormal karyotypes, additional anomalies, or known etiologies for ventriculomegaly were excluded. US and MRI findings were compared both in terms of mean ventricular measurements and IVM grade. Results: MRI measurements were significantly higher in mild IMV (10.33 ± 0.38 mm vs. 11.11 ± 0.51 mm, p< 0.001) compared to US. In mild IVM, MRI measured ventricles larger than US with a mean difference of 0.78 mm. There was no significant difference in US and MRI measurements in terms of mean values in moderate and severe IVM. There was good agreement between US and MRI in detecting right, left and mean IVM severity (Κ=0.265, Κ=0.324, and Κ=0.261, respectively). Linear regression analyses revealed a statistically significant relationship between US and MRI measurements of the right, left, and mean IVM (p<0.001, p<0.001, and p<0.001, respectively). MRI showed perfect agreement with US in detecting IVM laterality (Κ=1.0, p<0.001). Conclusions: In fetuses with mild IVM detected by US, fetal brain MRI evaluation should be considered for accurate diagnosis. This approach may provide effective strategies in the antenatal management and counseling of these pregnancies.

Identification of Down syndrome fetal encephalopathy related genes and signaling pathways via bioinformatics analysis / 中华实用儿科临床杂志

Objective:To identify Down syndrome (DS) fetal encephalopathy related genes and signaling pathways via bioinformatics analysis, and to explore their potential mechanisms underlying the occurrence and development of DS neuropathology.Methods:Retrospective study.In December 2021, dataset GSE59630 was downloaded from the gene expression omnibus (GEO), and differentially expressed genes (DEGs) between DS and normal fetal brain tissue were identified by R software.Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and gene set enrichment analysis (GSEA) were performed on the genes identified.The protein-protein interaction (PPI) network was constructed based on search tool for the retrieval of interacting genes online database and Cytoscape software, and key modules and hub DEGs were identified.Real-time quantitative polymerase chain reaction technique was used to verify the expression of hub genes related to neurodegeneration in brain tissue of 3 pairs of DS and normal fetuses at the gestational age of 22-33 weeks.Results:A total of 225 DEGs were screened out from DS and normal fetal brain tissue, including 18 up-regulated genes and 207 down-regulated genes.GO functional enrichment analysis showed that DEGs were mainly enriched in neurogenesis, neuronal apoptosis, transcriptional regulation, mitochondrial energy metabolism, etc.KEGG pathway enrichment analysis revealed that DEGs were associated with a variety of neurodegenerative diseases.GSEA suggested that apoptosis and inflammatory responses play a vital part in the occurrence of DS neuropathology.Ten hub genes were identified by the PPI network established, and they were mainly related to histone acetylation and transcriptional regulation.According to the tissue verification result, the variations of RAB8A, TBP and TAF6 expression conformed to the microarray data. Conclusions:The key genes and signaling pathways identified by transcriptome analysis of fetal brain tissue facilitate the comprehensive understanding of the molecular mechanism of DS neuropathology.This study provides a novel insight into the clinical diagnosis and treatment of neurodevelopmental abnormalities and mental retardation in DS.

Antenatal diagnosis of alobar holoprosencephaly: a case report

'Holoprosencephaly (HPE) is a structural malformation of the brain that results from the complete or incomplete noncleavage of the forebrain/ prosencephalon of the embryo into 2 hemispheres1. We present a case of twenty-five year-old primigravida presented to the Outpatient department of Obstetrics for routine checkup and diagnosed with Alobar holoprosencephaly on 2nd level USG. Fetal MRI was performed and the findings were confirmed. Even though ultrasonography is diagnostic in the detection of fetal anomalies, MRI plays a vital role due to its multiplanar capability and excellent soft tissue resolution. The purpose of publishing this case is to sensitize the clinicians to the classical features of holoprosencephaly on various imaging modalities and to stress the importance of its detection before 20 weeks of gestation so as to allow for legal medical termination and alleviate maternal psychological trauma of bearing a deformed fetus.

Biometría del cráneo y sistema ventricular cerebral fetal: tablas de normalidad a través de pruebas no paramétricas

Objetivos: Realizar tablas de referencia a través de estadística no paramétrica para definir en percentiles los rangos de normalidad del diámetro biparietal, la circunferencia cefálica, el atrio ventricular cerebral, la cisterna magna, el cavum septum pellucidum y los ventrículos laterales, según recomendaciones de la International Society of Ultrasound in Obstetrics and Gynecology de evaluación y medida. Métodos: Estudio transversal realizado desde enero 2014 a enero 2016. Se evaluaron 1004 embarazadas normales, en diferentes edades gestacionales, y de manera previamente estandarizada se midieron las estructuras mencionadas. El análisis estadístico se realizó con el software libre PAST 3.04 para la organización de los datos de cada edad gestacional en percentiles. Se presentaron en gráficos tipo nomogramas y en modelo de regresión polinómica de primer orden. Cada gráfico fue evaluado con significancia estadística con P<0,05. Resultados: Las estructuras intracraneales pudieron medirse en su totalidad en 864 casos (86 % de los exámenes). Los diámetros biparietal y las circunferencias cefálica pudieron obtenerse en todos los casos, se observó un crecimiento directamente proporcional a la edad gestacional (P< 0,05). La medida del atrio ventricular resultó estable lo largo del embarazo. Se presentan las medidas de la cisterna magna, del cavum septum pellucidum y de los ventrículos laterales. Conclusiones: Los rangos de normalidad se representaron en tablas para correcto uso clínico y de investigación, no difieren de investigaciones previas realizadas en otros países. Se presentan valores de referencia utilizables en la consulta prenatal, a través de estadística no gaussiana.

Objectives: To carry out reference tables through non-parametric statistics to define in percentile ranges of normality of the biparietal diameter, head circumference, the cerebral ventricular atrium, the cisterna magna, cavum septum pellucidum, and the lateral ventricles, according to the recommendations of the International Society of Ultrasound in Obstetrics and Gynecology of evaluation and measurement. Methods: A cross-sectional study was carried out from January 2014 to January 2016; 1004 normal pregnant women, in different gestational ages, were evaluated, and the mentioned structures, previously standardized, were measured. The statistical analysis was performed with the FOSS PAST 3.04 for the organization of the data at each gestational age, in percentiles. They arose in graphic type nomograms and first-order polynomial regression model. Each graphic was evaluated with statistics significance with P < 0.05. Results: The intracranial structures could be measured entirely in 864 cases (86% of the tests). Biparietal diameter and head circumferences were obtained in all cases; it was observed a directly proportional growth to gestational age (P < 0.05). The measurement of the ventricular Atrium was stable throughout the pregnancy. Measures of the cisterna magna, cavum septum pellucidum and of the lateral ventricles are represented. Conclusions: Normal ranges are represented in tables for correct clinical use and research, the results are not different from previous research conducted in other countries. Usable reference values, in the prenatal consultation, through non-Gaussian statistics are presented.

Impacts of Preeclampsia on the Brain of the Offspring / Impactos da pré-eclâmpsia no cérebro de nascituros

Abstract Preeclampsia (PE) is a significant gestational disorder that causes complications in 3- 5% of all human pregnancies. Apart from the immediate risks and complications for mother and fetus, both additionally carry elevated lifelong risks for specific complications. Offspring of PE pregnancies (PE-F1) have higher risks for hypertension, stroke and cognitive impairment compared with well-matched offspring (F1) fromuncomplicated pregnancies. Prior to the clinical onset of PE, placental angiokines secreted into the maternal plasma are deviated. In many PE patients this includes deficits in placental growth factor (PGF). Our laboratory found that mice genetically-deleted for PGF (PGF - / -) have altered cerebrovascular and brain neurological development detectable from midgestation to adulthood. We hypothesized that the PGF deficits seen in human PE, deviate fetal cerebrovascular and neurological development in a manner that impairs cognitive functions and elevates stroke risk. Here we summarize the initial analytical outcomes from a pilot study of 8-10 year old male and female PE-F1s and matched controls. Our studies were the first to report magnetic resonance imaging (MRI), magnetic resonance angiography (MRA) and functional brain region assessment by eyemovement control and clinical psychometric testing in PE-F1s. Further studies in larger cohorts are essential to define whether there are image-based biomarkers that describe unique anatomical features in PE-F1 brains.

Resumo A pré-eclampsia (PE) é importante doença gravídica complicando 3-5% de todas as gestações humanas. Além dos riscos imediatos e complicações para a mãe e o feto, a PE associa-se a outros riscos materno-fetais elevados em longo prazo. Nascituros de gestações complicadas por PE (PE-F1) apresentam maiores riscos de desenvolver hipertensão, acidente vascular cerebral e disfunção cognitiva em comparação com prole (F1) de gestações sem complicações. Antes do aparecimento clínico da PE, angiocitocinas placentárias secretadas no plasma materno apresentam-se alteradas. Em muitos pacientes com PE, isso inclui valores plasmáticos reduzidos de Fator de Crescimento Placentário (PGF). Nosso laboratório identificou que camundongos geneticamente não produtores de PGF (PGF- / - ) apresentam alterações vasculares e de desenvolvimento cerebral detectáveis do período gestacional à idade adulta. Nossa hipótese é que os déficits de PGF identificados em mulheres que desenvolveram PE podem desviar o desenvolvimento neurológico e vascular cerebral fetal, de maneira a prejudicar funções cognitivas, elevando o risco de AVC. Aqui resumimos os resultados analíticos iniciais de um estudo piloto comcrianças do sexomasculino e feminino de 8- 10 anos de idade nascidas de mães que tiveram PE (PE-F1s) comparadas com crianças controle pareadas por idade e sexo. Nossos estudos são os primeiros a relatar a ressonância magnética (RNM), a angiorressonância e a avaliação funcional do cérebro pelo controle de movimento dos olhos e pelo teste clínico psicotécnico em PE-F1s. Estudos adicionais em coortes maiores são essenciais para definir se há biomarcadores com base em imagens que possam descrever características anatômicas únicas em cérebros de crianças PE-F1.

Factibilidade e reprodutibilidade da avaliação da restrição de difusão de água por meio da ressonância magnética no cérebro do feto na síndrome de transfusão feto-fetal / Feasibility and reproducibility of diffusion-weighted magnetic resonance imaging of the fetal brain in twin-twin transfusion syndrome

Introdução: As lesões neurológicas fetais são importante causa de morbimortalidade neonatal. Uma condição relativamente frequente que expõe os fetos a maior risco de lesão cerebral é a síndrome da transfusão feto-fetal grave (STFF). O tratamento de escolha para STFF consiste na ablação dos vasos placentários com laser (AVPL) e mesmo após a sua realização existe possibilidade de lesão neurológica fetal. A ultrassonografia (USG) é ainda o método de escolha para a avaliação de anormalidades encefálicas fetais, e a ressonância magnética (RNM) pode melhorar o diagnóstico em condições específicas. Entretanto, a USG e as imagens ponderadas T1 e T2 da RM não são apropriadas para a detecção de lesões isquêmicas. A Restrição de Difusão da ressonância magnética (RD-RNM) permite a detecção de eventos isquêmicos agudos no cérebro através da avaliação subjetiva e objetiva da difusão microscópica da água. Esta última pode ser obtida por meio da medida do coeficiente de difusão aparente (CDA) e sua reprodutibilidade no cérebro fetal normal, em gestações únicas, foi recentemente demonstrada. Objetivo: Testar a factibilidade e a reprodutibilidade da restrição de difusão da ressonância magnética nas avaliações do cérebro fetal em casos de síndrome de transfusão feto-fetal tratados com a ablação dos vasos placentários com laser. Materiais e Métodos: Este estudo foi realizado no período de maio de 2011 a junho de 2012, após aprovação pelo Comitê de Ética em Pesquisa da FCM/UNICAMP. Pacientes com STFF grave realizaram uma ressonância magnética para a avaliação do cérebro dos fetos antes e depois da AVPL. Os dados foram analisados off-line em imagens axiais da restrição de difusão (RD) e em mapas do coeficiente de difusão aparente por dois radiologistas. A avaliação subjetiva foi descrita como a ausência ou a presença de restrição de difusão da água...

Introduction: The fetal neurological injuries are an important cause of neonatal morbidity and mortality. Severe twin-twin transfusion syndrome (TTTS) is a relatively frequent condition that exposes the fetuses to a higher risk of brain injury. The treatment of choice for TTTS consists in laser ablation of placental vessels (LAPV) and even after its completion there is the possibility of fetal neurologic injury. Ultrasonography (USG) is still the method of choice for evaluation of fetal brain abnormalities, and magnetic resonance imaging (MRI) can improve the diagnostic in specific conditions. However, ultrasonography and the T1 and T2 weighted images of MRI are not suitable for detection of ischemic lesions. Diffusion-weighted (DW) MRI enables the detection of acute hypoxic-ischemic events in the brain through subjective and objective evaluation of the microscopic diffusion of water. An objective evaluation consists of measuring the apparent diffusion coefficient (ADC): the reproducibility of this method in the normal fetal brain in singleton pregnancies was recently demonstrated. Purpose: To test the feasibility and reproducibility of diffusion-weighted magnetic resonance imaging (DW-MRI) evaluations of fetal brains in cases of twin-twin transfusion syndrome treated with laser ablation of placental vessels. Materials and Methods: This study was conducted from May 2011 to June 2012, after approval by the Institutional Review Board of FCM/UNICAMP. Patients with severe TTTS received an MRI scan for the evaluation of fetal brain before and after LAPV. Datasets were analyzed offline on axial DW images and apparent diffusion coefficient (ADC) maps by two radiologists. The subjective evaluation was described as the absence or presence of water diffusion restriction...

Fetal central nervous system magnetic resonance imaging at the University Hospital of the West Indies, Jamaica / Imagen por resonancia magnética del sistema nervioso central fetalen el Hospital Universitario de West Indies, Jamaica

BACKGROUND: Compared with ultrasound, magnetic resonance imaging (MRI) offers superior visualization of the fetal brain. It confirms and characterizes brain abnormalities detected by prenatal ultrasound, particularly in late pregnancy when acoustic windows are difficult or fetal position is inaccessible. Prior to July 2008, only two studies were attempted at our institution as local technical expertise was unavailable. Following collaboration with a neuroradiologist at an expert centre, images of sufficient quality for diagnosis were obtained. OBJECTIVE: The study objective is to evaluate the initial experience with fetal brain MRI and its effects on patient counselling and management in a resource limited healthcare system. METHOD: In seven fetuses with abnormal ultrasound neuroimaging, fetal MRI was performed with T2- weighted single-shot fast spin-echo (SSFSE) sequences using a 1.5T magnet (GE Medical Systems, Milwaukee, WI). RESULTS: Magnetic resonance imaging did not alter ultrasound diagnosis in two patients (28%); however, it changed the diagnosis in three (43%), provided additional information in one (14%) and changed management in two (28%) patients. CONCLUSION: Magnetic resonance imaging availability further elucidated brain pathology, aided patient counselling, parental decision-making and multidisciplinary management.

ANTECEDENTES: A diferencia del ultrasonido, la imagen por resonancia magnética (IRM) ofrece una visualización superior del cerebro fetal. Mediante ella, se hace posible confirmar y caracterizar las anormalidades detectadas por el ultrasonido prenatal, particularmente en la última etapa del embarazo, cuando las ventanas acústicas son difíciles, o la posición fetal es inaccesible. Antes del 2008 de julio, se intentaron sólo dos estudios en nuestra institución, ya que a nivel local no se disponía de conocimientos técnicos especializados. Tras la colaboración con un neuroradiólogo en un centro especializado, se obtuvieron imágenes de calidad suficiente para realizar el diagnóstico. OBJETIVO: El objetivo del estudio es evaluar la experiencia inicial con el IRM del cerebro fetal y sus efectos en cuanto a brindar consejos y tratamiento a los pacientes en un sistema de atención a la salud con recursos limitados. MÉTODO: En siete fetos con neuroimágenes de ultrasonido anormales, se llevó a cabo un IRM fetal con secuencias potenciadas en T2 como single-shot fast spin-echo (SSFSE), usando un imán 1.5T (GE Medical Systems, Milwaukee, WI). RESULTADOS: La imagen por resonancia magnética (IRM) no alteró el diagnóstico del ultrasonido en dos pacientes (28%). Sin embargo, cambió el diagnóstico en tres (43%), dio información adicional en uno (14%), y cambió el tratamiento en dos (28%) pacientes. CONCLUSIÓN: Poder contar con la imagen de resonancia magnética permitió dilucidar aún más la patología del cerebro, ayudar a dar consejos al paciente, tomar decisiones a los padres, y alcanzar un tratamiento multidisciplinario.

Neurosonografía y resonancia magnética en patología cerebral fetal severa / Ultrasound and magnetic resonance imaging in the prenatal evaluation of brain pathology

Abnormalities of the brain are among the most frequent congenital malformations and its incidence is probably higher than reported as many of the anomalies are only recognized postnatally. Fetal neurosonography performed transvaginally has become an important imaging technique based on its improved resolution and resulting better sensibility. Nevertheless, there are several maternal and fetal factors that can affect visualization rate and, therefore, it has been recommended that US should be complemented with 3D ultrasound and magnetic resonance imaging (MRI) in the prenatal evaluation of brain pathology. In the last years, the incorporation of ultrafast MRI has allowed to obtain high-quality images from the fetal lungs and brain. In this collaborative work from 2 public hospitals, we compare the diagnostic performance of fetal neurosonography and MRI in 17 cases of severe fetal brain abnormalities. MRI was able to confirm the diagnosis in 100 percent of the cases, adding important clinical information in 17 percent, although missed diagnoses were documented in 12 percent of them. These results are comparable to other published series, highlighting the diagnostic correlation between the 2 techniques. Nevertheless, ultrasound has the advantages of its wider availability and lower costs than MRI, which make it the prefered imaging modality when a fetal brain malformation is suspected.

Las malformaciones congénitas cerebrales son muy frecuentes y probablemente tengan una incidencia mayor aun a la descrita, pues muchas de ellas solo son reconocidas en la etapa postnatal. La neurosonografía fetal dirigida por vía transvaginal se ha incorporado los últimos años como el estándar de referencia en el diagnostico de estas malformaciones, especialmente por la mayor sensibilidad y una mejor resolución. Aun así, pueden existir condiciones maternas o fetales que obligan a complementar el estudio con otras tecnologías como el ultrasonido 3D y la resonancia magnética (RM). Con la incorporación de secuencias ultrarrápidas, la RM ha permitido obtener imágenes prenatales de calidad diagnostica donde destacan el estudio de malformaciones de tórax y del cerebro fetal. Este trabajo colaborativo de 2 centros públicos compara los resultados diagnósticos entre la neurosonografía y RM en 17 casos de patología neurológica fetal. La RM confirma el 100 por ciento de los diagnósticos, pero además entrega información adicional en un 17 por ciento pero omite información parcial en un 12 por ciento de los casos. Estos resultados son comparables a lo publicado en series extranjeras, destacando la alta correlación diagnostica entre los 2 métodos. Sin embargo, los beneficios que tiene el US en comparación con la RM, como la alta disponibilidad y el bajo costo, aconsejan su uso preferente en nuestro medio.

Análise da reprodutibilidade do Doppler de amplitude tridimensional na avaliação da circulação do cérebro fetal / Analysis of three-dimensional power Doppler sonography reproducibility in the assessment of fetal brain circulation

OBJETIVO: Avaliar a reprodutibilidade intra e interobservador do Doppler de amplitude tridimensional (3D power Doppler) na avaliação do fluxo sanguíneo cerebral do território da artéria cerebral média. MATERIAIS E MÉTODOS: Foi realizado estudo transversal com 20 gestantes normais entre 26 e 34 semanas. O território da artéria cerebral média mais próximo ao transdutor foi selecionado e o volume foi calculado utilizando-se o método Virtual Organ Computer-aided AnaLysis. Posteriormente, obtiveram-se os índices do 3D power Doppler: índice de vascularização (VI), índice de fluxo (FI) e índice de vascularização-fluxo (VFI). Utilizaram-se, para os cálculos, o coeficiente de correlação intraclasse (CCI) e gráficos de Bland-Altman. RESULTADOS: Foi observada boa concordância intra e interobservador, com CCI > 0,90 para todos os índices do 3D power Doppler: VI [CCI = 0,992 (IC 95 por cento: 0,981-0,997)], FI [CCI = 0,999 (IC 95 por cento: 0,998-0,999)], VFI [CCI = 0,995 (IC 95 por cento: 0,987-0,998)]. Reprodutibilidade interobservador: VI [CCI = 0,988 (IC 95 por cento: 0,970-0,995)], FI [CCI = 0,999 (IC 95 por cento: 0,997-1,000)], VFI [CCI = 0,994 (IC 95 por cento: 0,994-0,998)]. CONCLUSÃO: O 3D power Doppler mostrou-se um método prático, fácil e com boa reprodutibilidade intra e interobservador, com o IF evidenciando a melhor concordância intra e interobservador.

OBJECTIVE: To evaluate the intra- and interobserver reproducibility of three-dimensional power Doppler sonography (3D power Doppler) in the assessment of fetal brain blood flow in the middle cerebral artery territory. MATERIALS AND METHODS: A cross-sectional study was developed with 20 healthy pregnant women between 26 and 34 gestational weeks. The middle cerebral artery territory closest to the transducer was scanned and the blood flow volume was calculated with the method Virtual Organ Computer-aided AnaLysis. The following 3D power Doppler indices were later obtained: vascularization index (VI), flow index (FI) and vascularization-flow index (VFI). The intraclass correlation coefficient (ICC) and Bland-Altman plots were utilized for calculating the intra- and interobserver variability. RESULTS: A good intra- and interobserver agreement was observed, with ICC > 0.90 for all the 3D power Doppler indices: VI [ICC = 0.992 (CI 95 percent: 0.981-0.997)], FI [ICC = 0.999 (CI 95 percent: 0.998-0.999)], VFI [ICC = 0.995 (CI 95 percent: 0.987-0.998)]. Interobserver reproducibility: VI [ICC = 0.988 (CI 95 percent: 0.970-0.995)], FI [ICC = 0.999 (CI 95 percent: 0.997- 1.000)], VFI [ICC = 0.994 (CI 95 percent: 0.994-0.998)]. CONCLUSION: 3D power Doppler has shown to be a practical and easy method in the assessment of fetal brain blood flow, with good intra- and interobserver reproducibility. The FI presented the best intra- and interobserver agreement.

Evaluation of the Antenatal Fetal Brain Metabolites using Proton Magnetic Resonance Spectroscopy / 대한주산의학회잡지

OBJECTIVE:The purpose of this study was to compare the sensitivity of proton Magnetic Resonance Spectrography (MRS) for estimating absolute metabolite concentrations and ratio of fetal brains. METHODS:Between September 2005 and August 2006, our study was prospective single center trial and included 39 healthy women (Group 1: fetuses with risk factor of fetal distress or hypoxic damage [n=15], Group 2: fetal CNS anomalies on ultrasound [n=12], Group 3: normal fetuses [n=12]). We quantified resonances for the main proton MRS-detectable brain and calculated metabolite ratios of the three groups. We compared the obtained metabolite levels of the three groups with electronic fetal cardiotocography, Doppler ultrasound examination, Apgar score, and umbilical artery blood gas analysis. RESULTS:Abnormal amniotic fluid, abnormal Doppler studies, and abnormal cardiotocograms were significantly more prevalent in Group 1 compared with those of Group 2 and 3. In Group 1, choline (Cho) levels (7.86+/-3.51mmol/L) were significantly higher than in Group 2 or 3 (p=0.024). The ratios of N-acetylasparate (NAA)/creatinine-phosphocreatine (Cr) and Cho/Cr were increased whereas the ratios of NAA/Cho, lactate (Lac)/Cho, Lac/NAA, and Lac/Cr were decreased; however, there was no statistical significance. In patients who have oligohydramnios and absence of umbilical diastolic flow, choline and N-acetylasparate levels were significantly elevated (p<0.05, p<0.05, respectively). But, MRS metabolites and ratios showed no significant differences for low Apgar scores, umbilical arterial academia, uterine artery notching, maternal blood pressure or abnormal fetal cardiotocograms. CONCLUSION:This study demonstrates the possibility of performing proton MRS to assess the metabolic information of the fetal brain. Further technical progress may be useful of improving the degree of detection of hypoxic changes or an impending hypoxic state for prenatal diagnosis.

Changing characteristics of neural stem cells in the temporal lobe of cortex from human fetal brain at different age / 医学研究生学报

Objective:To investigate the changing characteristics of neural stem cells(NSC) in the temporal lobe of cortex from human fetal brain at different age.Methods:Ninety embryos delivered by induction labor with water bag at gestational age 16-36 w were collected,distribution,Shapes,growth modes and the number of NSC in the temporal lobe of cortex were determined with immunohistochemical method under light microscope. Results:NSC existed in the temporal lobe of cortex from human fetal brain and were round,elliptic or polygonal in shape,especially small round,NSC distributed mainly in cone cell and inner granule cell layers.NSC had enations from 0 to 2,nucleoli from 1 to 2 and rarefactive chromatin,nucli were large.Most NSC distributed in clones with a few NSC existed in a single mode among other nerve cells.There were no differences between groups in the distribution,shapes,species and growth modes of NSC in the temporal lobe of cortex,but the numbers of NSC gradually decreased with increase of age.Conclusion:There were no differences on the distribution,shapes,species and growth modes of NSCs in the temporal lobe of cortex from different gestational age,the number of NSC decreased with increase of age.

EXPRESSION OF THYROID HORMONE RECEPTOR mRNA DURING THE HUMAN BRAIN DEVELOPMENT / 解剖学报

Objective To observe the variations of thyroid hormone receptors(RTs) mRNA experession during the human brain devlopment. Methods We investigated the ontogeny of TR isoforms in the first and second trimester human fetal different brain areas by semi-quantitative reverse transcriptase-polymerase chain reaction analysis. When we amplified the TR? 2 by PCR, the other sequence was amplified at the same time, it is about 100pb less than the RT? 2, so we cloned it into pGEM-T easy vector to determine its sequence. Results In the first and second trimester human fatal brain, RTs mRNAs were detected in cerebrum, cerebellum, brain, stem, hippocampus, spinal cord, thalamus. TRs mRNAs were relatively higher in cerebrum, cerebellum, hippocampus. In the first trimester human fatal brain, the TR? isoforms mRNAs were higher than TR? 1, In the second trimester human fatal brain, the TR? 2 and TR? 1 were higher than TR? 1. An additional truncated species was detected with the TR? 2 primer set. We submitted its sequencing results to Genbank, comparing it with TR? 2 by BLAST software, the results showed that it is identical to TR? 2 with the exception that it is missing 42 amino acids at 371-412 of TR? 2 sequence, so it is the human TR? 3. At the same time we acquired the Genbank accession number AF522368. Conclusion The spatial and temporal expressions of TR isoforms mRNAs exist in CNS development. We firstly assure the different sequence between human TR?2 and TR?3.

The Apoptosis and Expression of Bcl-2, Bcl-xS, Bax Proteins in Fetal Brain after Treating Pregnant Mice with Endotoxin

PURPOSE: Apoptosis is active cell death which plays an important role in developing normal tissues. Various conditions such as genetic defects, drugs, ischemia or infections are known to induce apoptosis. We studied the effect of maternal infection on fetal brain development during pregnancy. METHODS: We treated 46 C3H pregnant mice with lipopolysaccharide (LPS) or phosphat-buffered saline and observed the changes in apoptosis and expression of bcl-2, bcl-xS, bax. The fetal brain tissues were removed 1-48 hours after LPS treatment. The number of apoptosis per 100 neurons and glial cells was counted in H&E stained tissue and was analyzed statistically. Immunohistochemical staining with primary antibodies of bcl-2, bcl-xS, bax was done and their expression was classified by the degree of staining. RESULTS: The number of apoptosis was increased significantly in both neurons and glial cells of LPS-treated group and its degree of staining was more remarkable in glial cells. Immunohisto chemistry for bcl-2, bcl-xS, bax oncoprotein revealed mildly decreased expression of bcl-2 and markedly increased expression of bax in both neurons and glial cells, but it was more remarkable in glial cells. Immunochemistry for bcl-xS revealed no expression in neurons and minimal expression of bcl-xS in glial cells in both study groups. CONCLUSOIN: We observed an increase in the number of apoptosis, mildly decreased expression of bcl-2 and markedly increased expression of bax in both neurons and glial cells of fetal brain after treating pregnant mice with LPS. Maternal infection during pregnancy may have profound effects on developing fetal brain.

Human genomic DNA isolation and chromosomal localization of fetal brain cDNA (FB174) / 대한해부학회지

Eventhough surmountable amounts of genes are being cloned and a number of methods are being developed by human genome project, it's not easy to predict possible functions of genes and determine the chromosomal locations of genes. In this experiment, cDNA pool was made from 18 weeks old human fetal brain and analyzed the sequences. FB174 clone was chosen, in situ hybridization histochemistry was performed on developing and adult rat tissue section to observe the tissue specificity and developmental expression of this gene. To observe the chromosomal location of FB174 clone, the genomic DNA from human genomic library was isolated and fluorescence in situ hybridization was carried out. By sequencing and sequence search with GenBank data it was revealed that cloned FB174 cDNA was quite similar to translationally controlled tumor protein which is known to locate to human chromosome 13q14. The expression of FB174 mRNA was not detected in rat tissue sections by in situ hybridization histochemistry. Fluorescence in situ hybridization using biotin labeled FB174 probe resulted in specific labeling of human chromosome 7q22. These results and high sequence homology of FB174 to known translationally controlled tumor protein suggest that FB174 clone may be a new translationally controlled tumor protein-related gene.

A Study on the Formation of Organotypic Spheroids from Early Human Fetal Brain

The present study investigated whether organotypic spheroids derived from human fetal brain tissue, cultured at agarose-overlay media, may serve as an optimal invitro model for multidisciplinary studies in human neurobiology, particularly in the fields of tumor invasiveness and its biochemical mechanism, using light microscopy, electron microscopy and immunohistochemical staining. Eight fetal brain tissues of 8-9 weeks of gestation were minced and explanted into agarose-coated culture wells. After three to five days these human fetal brain tissue fragments emerged as spheroids and could be maintained as organotypic spheroids for up to seven weeks. Light and electron microscopic studies of sphereoids demonstrated that most cells were poorly differentiated and there were no definite mature neurons or glial cells after enough culture time, but some cells showed certain evidence suggestive of differentiation to neurons or glial cells. Immunohistochemical staining for glial fibrillary acidic protein(GFAP) and neur on specific enolase(NSE) demonstrated that NSE-positive cells were oval or spherical cells containing abundant cytoplasm and GFAP-positive cells were fibrillary cytoplasma-containing cells which showed some evidence suggestive of differentiation to glial cells by light microscopy. In future, adding some modifications in culture, this organotypic spheroids derived from the human fetal brain may serve as an optimal in vitro model for neurobiology especially in the field of studies on tumor invasiveness through co-culture with microtumor spheroids.

Changes of Malondialdehyde,Myeloperoxidase and Intracellular Free Calcium Contents in Brain Tissue of Fetal Rats Induced by Intrauterine Infection / 实用儿科临床杂志

Objective To establish a model, fetal rat brain damage made by lipopolysaccharide (LPS)-induced intrauterine infection and explore content change and significance of malondialdehyde(MDA),myeloperoxidase(MPO),intracellular free calcium in the development of fetal brain damage.Methods Twenty-eight pregnant rats were injected with LPS(500 ?g/kg)on gestation d20 intraperitoneally in experimental group rats;the same volume of normal saline was injected to 28 rats as control group;there were 8 pregnant rats as blank control rat. Fetal brain water,MDA,MPO,Ca~(2+) contents were measured, fetal brain,placenta for pathological check after injection 2,6,12,24 hours,respectively.Results Brain water,MDA,MPO contents of LPS group were higher than those of controls at 2 h,and Ca~(2+) content of LPS group was higher than that of controls at 6 h,they were continued to be on high level until 24 h.There were histopathological inflammation changes of placenta, edema,inflammation in fetal brain at 6 h ,degeneration and necrosis of nerve cell at 12 h.Conclusions Fetal rat brain damage is made by LPS-induced intrauterine infection.MDA,MPO,Ca~(2+) content increasing in fetal brain tissue that indicates there is lipid peroxidation damage in fetal rat brain damage due to intrauterine infection; damage of free radical,persistent activation of polymorphonuclear,calcium overlord are mechanisms of fetal brain damage .