scholarly journals Age-specific Structural Fetal Brain Atlases Construction and Cortical Development Quantification for Chinese Population

NeuroImage ◽  
2021 ◽  
pp. 118412
Author(s):  
Jiangjie Wu ◽  
Taotao Sun ◽  
Boliang Yu ◽  
Zhenghao Li ◽  
Qing Wu ◽  
...  
Keyword(s):  
Chinese Population ◽  
Cortical Development ◽  
Fetal Brain ◽  
Brain Atlases

P–766 Neurodevelopment in fetuses conceived by assisted reproductive technologies following fresh and frozen embryo transfer

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M L Boutet ◽  
E Eixarch ◽  
P Ahumada-Droguett ◽  
F Crovetto ◽  
M S Cívico ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Gestational Age ◽  
Maternal Age ◽  
Assisted Reproductive Technologies ◽  
Cortical Development ◽  
Multiple Pregnancy ◽  
Fetal Brain ◽  
Reproductive Technologies ◽  
Fine Motor ◽  
Problem Solving Skills

Abstract Study question Do in vitro fertilization (IVF) offspring present different neurodevelopment assessed by fetal neurosonography and infant neurobehavioral tests as compared to those spontaneously conceived (SC)? Summary answer IVF offspring, especially those obtained after fresh embryo-transfer (ET), showed subtle structural differences in fetal neurosonography and poorer neurobehavioral scores at twelve months of age. What is known already The number of pregnancies following assisted reproductive technologies (ART) is currently increasing worldwide. Concerns about the neurodevelopment of subjects conceived by IVF have been rising and mostly studied in children and adolescents with inconsistent results. Many of the identified risk associations were only observed in subgroups or disappeared after adjustment for covariates, mainly multiple pregnancy and gestational age at birth. It is unknown whether fetal brain development and cortical folding differ prenatally in IVF fetuses as compared to SC. Study design, size, duration This is the first study examining fetal neurodevelopment by neurosonography in IVF fetuses. A prospective cohort study of 210 singleton pregnancies recruited from 2017 to 2020, including 70 SC gestations, 70 conceived by IVF following frozen ET (FET) and 70 IVF after fresh ET. Fetal neurosonography was performed in all pregnancies. Additionally, Ages & Stages Questionnaires (ASQ) were obtained at 12 months of corrected age. Participants/materials, setting, methods IVF pregnancies were recruited from a single Assisted Reproduction Center, ensuring homogeneity in IVF stimulation protocols, endometrial preparation, laboratory procedures and embryo culture conditions. SC pregnancies were randomly selected from low-risk fertile couples and paired to IVF by maternal age. Fetal neurosonography including transvaginal approach was performed at 32±2 weeks of gestation, measured off-line by a single investigator and normalized by biparietal or occipitofrontal diameter. ASQ were obtained postnatally, at 12 months of corrected age. Main results and the role of chance Study groups were similar and comparable regarding maternal age, body mass index, study level and employment rate together with exposure to smoke, alcohol, aspirin and corticoids during pregnancy, gestational age (32±2 weeks) and estimated fetal weight (1700±400g) at neurosonography. As compared to SC pregnancies, both IVF populations showed differences in cortical development with reduced parieto-occipital (fresh ET 12.5mm [SD 2.5] vs FET 13.4 [2.6] vs SC 13.4 [2.6]), cingulate (fresh ET 5.8 [IQR 4.2–7.4] vs FET 5.8 [4.1–7.5] vs SC 6.5 [4.8–7.8]) and calcarine (fresh ET 13.5 [IQR 10.1–16.1] vs FET 14.5 [12.1–15.8] vs SC 16.4 [14.3–17.9]) sulci depth together with lower Sylvian fissure grading. Cortical development changes were more pronounced in the fresh ET group as compared to FET. Corpus callosum length and insula depth were lower in FET and fresh ET groups, respectively. Neurosonographic changes remained statistically significant after adjustment by ethnicity, gender, gestational age and weight centile at scan. IVF infants showed worse ASQ scores, especially in fresh ET for communication, personal-social, fine-motor and problem-solving skills. Gross-motor scores were significantly lower in FET as compared to SC and fresh ET. Differences were statistically significant after adjustment by maternal ethnicity, study level, employment status, breastfeeding, gender and corrected age. Limitations, reasons for caution The reported neurodevelopmental differences are subtle, with most neurosonographic findings lying within normal ranges. Infertility factors contribution to the outcome cannot be unraveled from the ART procedure itself. The milder features found in FET individuals cannot condition the techniqués choice and must be considered together with their global perinatal results. Wider implications of the findings: Neurosonography is an appropriate tool to identify subtle brain differences between fetuses exposed and not exposed to ART. Prenatal features were consistent with postnatal neurobehavioral findings. These results support the relevance of a neurodevelopmental follow-up in IVF patients. Further studies are warranted to assess the long-term performance in these subjects. Trial registration number Not applicable

P-766 Neurodevelopment in fetuses conceived by assisted reproductive technologies following fresh and frozen embryo transfer

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M L Boutet ◽  
E Eixarch ◽  
P Ahumada-Droguett ◽  
F Crovetto ◽  
M S Cívico ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Gestational Age ◽  
Maternal Age ◽  
Assisted Reproductive Technologies ◽  
Cortical Development ◽  
Multiple Pregnancy ◽  
Fetal Brain ◽  
Reproductive Technologies ◽  
Fine Motor ◽  
Problem Solving Skills

Abstract Study question Do in vitro fertilization (IVF) offspring present different neurodevelopment assessed by fetal neurosonography and infant neurobehavioral tests as compared to those spontaneously conceived (SC)? Summary answer IVF offspring, especially those obtained after fresh embryo-transfer (ET), showed subtle structural differences in fetal neurosonography and poorer neurobehavioral scores at twelve months of age. What is known already The number of pregnancies following assisted reproductive technologies (ART) is currently increasing worldwide. Concerns about the neurodevelopment of subjects conceived by IVF have been rising and mostly studied in children and adolescents with inconsistent results. Many of the identified risk associations were only observed in subgroups or disappeared after adjustment for covariates, mainly multiple pregnancy and gestational age at birth. It is unknown whether fetal brain development and cortical folding differ prenatally in IVF fetuses as compared to SC. Study design, size, duration This is the first study examining fetal neurodevelopment by neurosonography in IVF fetuses. A prospective cohort study of 210 singleton pregnancies recruited from 2017 to 2020, including 70 SC gestations, 70 conceived by IVF following frozen ET (FET) and 70 IVF after fresh ET. Fetal neurosonography was performed in all pregnancies. Additionally, Ages & Stages Questionnaires (ASQ) were obtained at 12 months of corrected age. Participants/materials, setting, methods IVF pregnancies were recruited from a single Assisted Reproduction Center, ensuring homogeneity in IVF stimulation protocols, endometrial preparation, laboratory procedures and embryo culture conditions. SC pregnancies were randomly selected from low-risk fertile couples and paired to IVF by maternal age. Fetal neurosonography including transvaginal approach was performed at 32±2 weeks of gestation, measured off-line by a single investigator and normalized by biparietal or occipitofrontal diameter. ASQ were obtained postnatally, at 12 months of corrected age. Main results and the role of chance Study groups were similar and comparable regarding maternal age, body mass index, study level and employment rate together with exposure to smoke, alcohol, aspirin and corticoids during pregnancy, gestational age (32±2 weeks) and estimated fetal weight (1700±400g) at neurosonography. As compared to SC pregnancies, both IVF populations showed differences in cortical development with reduced parieto-occipital (fresh ET 12.5mm [SD 2.5] vs FET 13.4 [2.6] vs SC 13.4 [2.6]), cingulate (fresh ET 5.8 [IQR 4.2-7.4] vs FET 5.8 [4.1-7.5] vs SC 6.5 [4.8-7.8]) and calcarine (fresh ET 13.5 [IQR 10.1-16.1] vs FET 14.5 [12.1-15.8] vs SC 16.4 [14.3-17.9]) sulci depth together with lower Sylvian fissure grading. Cortical development changes were more pronounced in the fresh ET group as compared to FET. Corpus callosum length and insula depth were lower in FET and fresh ET groups, respectively. Neurosonographic changes remained statistically significant after adjustment by ethnicity, gender, gestational age and weight centile at scan. IVF infants showed worse ASQ scores, especially in fresh ET for communication, personal-social, fine-motor and problem-solving skills. Gross-motor scores were significantly lower in FET as compared to SC and fresh ET. Differences were statistically significant after adjustment by maternal ethnicity, study level, employment status, breastfeeding, gender and corrected age. Limitations, reasons for caution The reported neurodevelopmental differences are subtle, with most neurosonographic findings lying within normal ranges. Infertility factors contribution to the outcome cannot be unraveled from the ART procedure itself. The milder features found in FET individuals cannot condition the techniqués choice and must be considered together with their global perinatal results. Wider implications of the findings Neurosonography is an appropriate tool to identify subtle brain differences between fetuses exposed and not exposed to ART. Prenatal features were consistent with postnatal neurobehavioral findings. These results support the relevance of a neurodevelopmental follow-up in IVF patients. Further studies are warranted to assess the long-term performance in these subjects. Trial registration number not applicable

scholarly journals Transcriptome and epigenome landscape of human cortical development modeled in organoids

Science ◽  
2018 ◽  
Vol 362 (6420) ◽  
pp. eaat6720 ◽  
Author(s):  
Anahita Amiri ◽  
Gianfilippo Coppola ◽  
Soraya Scuderi ◽  
Feinan Wu ◽  
Tanmoy Roychowdhury ◽  
...  
Keyword(s):  
Molecular Level ◽  
Cortical Development ◽  
Disease Onset ◽  
Fetal Brain ◽  
Human Fetal Brain ◽  
Pluripotent Cells ◽  
Genomic Variants ◽  
Human Brain Development ◽  
Early Human ◽  
Active Genes

Genes implicated in neuropsychiatric disorders are active in human fetal brain, yet difficult to study in a longitudinal fashion. We demonstrate that organoids from human pluripotent cells model cerebral cortical development on the molecular level before 16 weeks postconception. A multiomics analysis revealed differentially active genes and enhancers, with the greatest changes occurring at the transition from stem cells to progenitors. Networks of converging gene and enhancer modules were assembled into six and four global patterns of expression and activity across time. A pattern with progressive down-regulation was enriched with human-gained enhancers, suggesting their importance in early human brain development. A few convergent gene and enhancer modules were enriched in autism-associated genes and genomic variants in autistic children. The organoid model helps identify functional elements that may drive disease onset.

scholarly journals Mapping fetal brain development based on automated segmentation and 4D brain atlasing

2020 ◽  
Author(s):  
Haotian Li ◽  
Guohui Yan ◽  
Wanrong Luo ◽  
Tintin Liu ◽  
Yan Wang ◽  
...  
Keyword(s):  
Quantitative Analysis ◽  
Brain Development ◽  
Chinese Population ◽  
Brain Mri ◽  
Fetal Brain ◽  
In Utero ◽  
Brain Atlas ◽  
Morphological Development ◽  
Brain Extraction ◽  
Fetal Brain Development

AbstractFetal brain MRI has become an important tool for in utero assessment of brain development and disorders. However, quantitative analysis of fetal brain MRI remains difficult, partially due to the limited tools for automated preprocessing and the lack of normative brain templates. In this paper, we proposed an automated pipeline for fetal brain extraction, super-resolution reconstruction, and fetal brain atlasing to quantitatively map in utero fetal brain development during mid-to-late gestation in a Chinese population. First, we designed a U-net convolutional neural network for automated fetal brain extraction, which achieved an average accuracy of 97%. We then generated a developing fetal brain atlas, using an iterative linear and nonlinear registration approach. Based on the 4D spatiotemporal atlas, we quantified the morphological development of the fetal brain between 23-36 weeks of gestation. The proposed pipeline enabled the fully-automated volumetric reconstruction for clinically available fetal brain MRI data, and the 4D fetal brain atlas provided normative templates for quantitative analysis of potential fetal brain abnormalities, especially in the Chinese population.

Severity of Fetal Brain Abnormalities in Congenital Heart Disease in Relation to the Main Expected Pattern of in utero Brain Blood Supply

2015 ◽  
Vol 39 (4) ◽  
pp. 269-278 ◽  
Author(s):  
Narcís Masoller ◽  
Magda Sanz-Cortés ◽  
Fàtima Crispi ◽  
Olga Gómez ◽  
Mar Bennasar ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Blood Supply ◽  
Congenital Heart ◽  
Cortical Development ◽  
Fetal Brain ◽  
Fetal Mri ◽  
In Utero ◽  
Class A ◽  
Severe Reduction

Objectives: We evaluated the hypothesis that in fetuses with congenital heart disease (CHD) there is a correlation between the expected pattern of in utero brain blood supply and the severity of neurodevelopmental impairment. Methods: A total of 58 fetuses with CHD and 58 controls underwent a Doppler ultrasound and fetal MRI at 36-38 weeks. Fetuses with CHD were divided into two functional classes: class A with an expected severe reduction in oxygenated brain blood supply (left outflow tract obstruction and transposition of great vessels) and class B with theoretically near-normal or mildly impaired oxygenated brain blood supply (other CHD). Head biometry and cerebroplacental Doppler were assessed by ultrasound, and brain volumetry, cortical development and metabolism by MRI. Results: Both class A and B CHD fetuses had significant differences in head biometry, brain perfusion, cortical development and brain metabolism compared with controls. However, there was a significant linear tendency for head biometry, cerebral Doppler, volumes, cortical sulcation and metabolic ratios across the three clinical groups, with signs of more severe brain alterations in type A CHD fetuses. Conclusions: All fetuses with CHD showed significant brain developmental changes, but differences were more pronounced in CHD associated with an expected severe reduction in oxygenated blood supply to the brain.

scholarly journals Cerebral organoid proteomics reveals signatures of dysregulated cortical development associated with human trisomy 21

2018 ◽  
Author(s):  
Tristan D. McClure-Begley ◽  
Christopher C. Ebmeier ◽  
Kerri E. Ball ◽  
Jeremy R. Jacobsen ◽  
Igor Kogut ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Intellectual Disability ◽  
Trisomy 21 ◽  
Cortical Development ◽  
Fetal Brain ◽  
Chromosome 21 ◽  
Response To Treatment ◽  
Causative Role ◽  
Matrix Remodeling ◽  
Label Free

SUMMARYHuman trisomy 21 (Down syndrome) is the most common genetic cause of intellectual disability, and is associated with complex perturbations in protein expression during development. Brain region-specific alterations in neuronal density and composition originate prenatally in trisomy 21 individuals, and are presumed to underlie the intellectual disability and early onset neurodegeneration that characterizes Down syndrome. However, the mechanisms by which chromosome 21 aneuploidy drives alterations in the central nervous system are not well understood, particularly in brain regions that are uniquely human and thus inaccessible to established animal models. Cerebral organoids are pluripotent stem cell derived models of prenatal brain development that have been used to deepen our understanding of the atypical processes associated with human neurobiological disorders, and thus provide a promising avenue to explore the molecular basis for neurodevelopmental alterations in trisomy 21. Here, we employ high-resolution label-free mass spectrometry to map proteomic changes over the course of trisomy 21 cerebral organoid development, and evaluate the proteomic alterations in response to treatment with harmine, a small molecule inhibitor of the chromosome 21 encoded protein kinase DYRK1A. Our results reveal trisomy 21 specific dysregulation of networks associated with neurogenesis, axon guidance and extracellular matrix remodeling. We find significant overlap of these networks show significant overlap with previously identified dysregulated gene expression modules identified in trisomy 21 fetal brain tissue. We show that harmine leads to partial normalization of key regulators of cortical development, including WNT7A and the transcription factors TBR1, BCL11A, and POU3F2, pointing to a causative role for DYRK1A over-expression in neurodevelopmental effects of human trisomy 21.

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