RESUMO
Normal cortical growth and the resulting folding patterns are crucial for normal brain function. Although cortical development is largely influenced by genetic factors, environmental factors in fetal life can modify the gene expression associated with brain development. As the placenta plays a vital role in shaping the fetal environment, affecting fetal growth through the exchange of oxygen and nutrients, placental oxygen transport might be one of the environmental factors that also affect early human cortical growth. In this study, we aimed to assess the placental oxygen transport during maternal hyperoxia and its impact on fetal brain development using MRI in identical twins to control for genetic and maternal factors. We enrolled 9 pregnant subjects with monochorionic diamniotic twins (30.03 ± 2.39 gestational weeks [mean ± SD]). We observed that the fetuses with slower placental oxygen delivery had reduced volumetric and surface growth of the cerebral cortex. Moreover, when the difference between placenta oxygen delivery increased between the twin pairs, sulcal folding patterns were more divergent. Thus, there is a significant relationship between placental oxygen transport and fetal brain cortical growth and folding in monochorionic twins.
Assuntos
Placenta , Gêmeos Monozigóticos , Feminino , Humanos , Gravidez , Desenvolvimento Fetal , Retardo do Crescimento Fetal/metabolismo , Oxigênio/metabolismo , Placenta/diagnóstico por imagem , Placenta/metabolismoRESUMO
Congenital heart disease affects 1% of infants and is associated with impaired neurodevelopment. Right- or left-sided sulcal features correlate with executive function among people with Tetralogy of Fallot or single ventricle congenital heart disease. Studies of multiple congenital heart disease types are needed to understand regional differences. Further, sulcal pattern has not been studied in people with d-transposition of the great arteries. Therefore, we assessed the relationship between sulcal pattern and executive function, general memory, and processing speed in a meta-regression of 247 participants with three congenital heart disease types (114 single ventricle, 92 d-transposition of the great arteries, and 41 Tetralogy of Fallot) and 94 participants without congenital heart disease. Higher right hemisphere sulcal pattern similarity was associated with improved executive function (Pearson r = 0.19, false discovery rate-adjusted P = 0.005), general memory (r = 0.15, false discovery rate P = 0.02), and processing speed (r = 0.17, false discovery rate P = 0.01) scores. These positive associations remained significant in for the d-transposition of the great arteries and Tetralogy of Fallot cohorts only in multivariable linear regression (estimated change ß = 0.7, false discovery rate P = 0.004; ß = 4.1, false discovery rate P = 0.03; and ß = 5.4, false discovery rate P = 0.003, respectively). Duration of deep hypothermic circulatory arrest was also associated with outcomes in the multivariate model and regression tree analysis. This suggests that sulcal pattern may provide an early biomarker for prediction of later neurocognitive challenges among people with congenital heart disease.
Assuntos
Cardiopatias Congênitas , Criança , Feminino , Humanos , Masculino , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Córtex Cerebral/crescimento & desenvolvimento , Função Executiva/fisiologia , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/patologia , Imageamento por Ressonância Magnética , Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/patologia , Adolescente , Adulto JovemRESUMO
The human cerebral cortex is distinguished by its large size and abundant gyrification, or folding. However, the evolutionary mechanisms that drive cortical size and structure are unknown. Although genes that are essential for cortical developmental expansion have been identified from the genetics of human primary microcephaly (a disorder associated with reduced brain size and intellectual disability) 1 , studies of these genes in mice, which have a smooth cortex that is one thousand times smaller than the cortex of humans, have provided limited insight. Mutations in abnormal spindle-like microcephaly-associated (ASPM), the most common recessive microcephaly gene, reduce cortical volume by at least 50% in humans2-4, but have little effect on the brains of mice5-9; this probably reflects evolutionarily divergent functions of ASPM10,11. Here we used genome editing to create a germline knockout of Aspm in the ferret (Mustela putorius furo), a species with a larger, gyrified cortex and greater neural progenitor cell diversity12-14 than mice, and closer protein sequence homology to the human ASPM protein. Aspm knockout ferrets exhibit severe microcephaly (25-40% decreases in brain weight), reflecting reduced cortical surface area without significant change in cortical thickness, as has been found in human patients3,4, suggesting that loss of 'cortical units' has occurred. The cortex of fetal Aspm knockout ferrets displays a very large premature displacement of ventricular radial glial cells to the outer subventricular zone, where many resemble outer radial glia, a subtype of neural progenitor cells that are essentially absent in mice and have been implicated in cerebral cortical expansion in primates12-16. These data suggest an evolutionary mechanism by which ASPM regulates cortical expansion by controlling the affinity of ventricular radial glial cells for the ventricular surface, thus modulating the ratio of ventricular radial glial cells, the most undifferentiated cell type, to outer radial glia, a more differentiated progenitor.
Assuntos
Evolução Biológica , Córtex Cerebral/anatomia & histologia , Córtex Cerebral/metabolismo , Furões , Deleção de Genes , Microcefalia/genética , Microcefalia/patologia , Proteínas do Tecido Nervoso/deficiência , Sequência de Aminoácidos , Animais , Proteínas de Ligação a Calmodulina/deficiência , Proteínas de Ligação a Calmodulina/metabolismo , Centrossomo/metabolismo , Córtex Cerebral/patologia , Modelos Animais de Doenças , Feminino , Furões/anatomia & histologia , Furões/genética , Edição de Genes , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Inativação de Genes , Mutação em Linhagem Germinativa , Humanos , Masculino , Camundongos , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/patologia , Tamanho do Órgão , Transcrição GênicaRESUMO
Human fetal brains show regionally different temporal patterns of sulcal emergence following a regular timeline, which may be associated with spatiotemporal patterns of gene expression among cortical regions. This study aims to quantify the timing of sulcal emergence and its temporal variability across typically developing fetuses by fitting a logistic curve to presence or absence of sulcus. We found that the sulcal emergence started from the central to the temporo-parieto-occipital lobes and frontal lobe, and the temporal variability of emergence in most of the sulci was similar between 1 and 2 weeks. Small variability (< 1 week) was found in the left central and postcentral sulci and larger variability (>2 weeks) was shown in the bilateral occipitotemporal and left superior temporal sulci. The temporal variability showed a positive correlation with the emergence timing that may be associated with differential contributions between genetic and environmental factors. Our statistical analysis revealed that the right superior temporal sulcus emerged earlier than the left. Female fetuses showed a trend of earlier sulcal emergence in the right superior temporal sulcus, lower temporal variability in the right intraparietal sulcus, and higher variability in the right precentral sulcus compared to male fetuses. Our quantitative and statistical approach quantified the temporal patterns of sulcal emergence in detail that can be a reference for assessing the normality of developing fetal gyrification.
Assuntos
Caracteres Sexuais , Lobo Temporal , Humanos , Masculino , Feminino , Lobo Temporal/diagnóstico por imagem , Feto , Lobo Parietal , Lobo Frontal , Imageamento por Ressonância Magnética , Córtex Cerebral/diagnóstico por imagemRESUMO
Intergenerational effects are described as the genetic, epigenetic, as well as pre- and postnatal environmental influence parents have on their offspring's behavior, cognition, and brain. During fetal brain development, the primary cortical sulci emerge with a distinctive folding pattern that are under strong genetic influence and show little change of this pattern throughout postnatal brain development. We examined intergenerational transmission of cortical sulcal patterns by comparing primary sulcal patterns between children (N = 16, age 5.5 ± 0.81 years, 8 males) and their biological mothers (N = 15, age 39.72 ± 4.68 years) as well as between children and unrelated adult females. Our graph-based sulcal pattern comparison method detected stronger sulcal pattern similarity for child-mother pairs than child-unrelated pairs, where higher similarity between child-mother pairs was observed mostly for the right lobar regions. Our results also show that child-mother versus child-unrelated pairs differ for daughters and sons with a trend toward significance, particularly for the left hemisphere lobar regions. This is the first study to reveal significant intergenerational transmission of cortical sulcal patterns, and our results have important implications for the study of the heritability of complex behaviors, brain-based disorders, the identification of biomarkers, and targets for interventions.
Assuntos
Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/crescimento & desenvolvimento , Desenvolvimento Infantil/fisiologia , Imageamento por Ressonância Magnética/tendências , Relações Mãe-Filho , Adulto , Criança , Feminino , Humanos , MasculinoRESUMO
Neurodevelopmental disabilities are the most common noncardiac conditions in patients with congenital heart disease (CHD). Executive function skills have been frequently observed to be decreased among children and adults with CHD compared with peers, but a neuroanatomical basis for the association is yet to be identified. In this study, we quantified sulcal pattern features from brain magnetic resonance imaging data obtained during adolescence among 41 participants with tetralogy of Fallot (ToF) and 49 control participants using a graph-based pattern analysis technique. Among patients with ToF, right-hemispheric sulcal pattern similarity to the control group was decreased (0.7514 vs. 0.7553, P = 0.01) and positively correlated with neuropsychological testing values including executive function (r = 0.48, P < 0.001). Together these findings suggest that sulcal pattern analysis may be a useful marker of neurodevelopmental risk in patients with CHD. Further studies may elucidate the mechanisms leading to different alterations in sulcal patterning.
Assuntos
Função Executiva , Tetralogia de Fallot/diagnóstico por imagem , Tetralogia de Fallot/psicologia , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Estudos de Casos e Controles , Córtex Cerebral/diagnóstico por imagem , Criança , Deficiências do Desenvolvimento/fisiopatologia , Deficiências do Desenvolvimento/psicologia , Feminino , Cardiopatias Congênitas , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Adulto JovemRESUMO
The relationship between structural changes of the cerebral cortex revealed by Magnetic Resonance Imaging (MRI) and gene expression in the human fetal brain has not been explored. In this study, we aimed to test the hypothesis that relative regional thickness (a measure of cortical evolving organization) of fetal cortical compartments (cortical plate [CP] and subplate [SP]) is associated with expression levels of genes with known cortical phenotype. Mean regional SP/CP thickness ratios across age measured on in utero MRI of 25 healthy fetuses (20-33 gestational weeks [GWs]) were correlated with publicly available regional gene expression levels (23-24 GW fetuses). Larger SP/CP thickness ratios (more pronounced cortical evolving organization) was found in perisylvian regions. Furthermore, we found a significant association between SP/CP thickness ratio and expression levels of the FLNA gene (mutated in periventricular heterotopia, congenital heart disease, and vascular malformations). Further work is needed to identify early MRI biomarkers of gene expression that lead to abnormal cortical development.
Assuntos
Encéfalo/crescimento & desenvolvimento , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/embriologia , Malformações do Desenvolvimento Cortical/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/embriologia , Adulto , Encéfalo/diagnóstico por imagem , Córtex Cerebral/anormalidades , Feminino , Feto/diagnóstico por imagem , Feto/metabolismo , Filaminas/genética , Expressão Gênica/genética , Expressão Gênica/fisiologia , Idade Gestacional , Cabeça , Humanos , Imageamento por Ressonância Magnética , Rede Nervosa/metabolismo , Gravidez , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , TranscriptomaRESUMO
Down syndrome (DS) is the most common genetic cause of developmental disabilities. Advanced analysis of brain magnetic resonance imaging (MRI) has been used to find brain abnormalities and their relationship to neurocognitive impairments in children and adolescents with DS. Because genetic factors affect brain development in early fetal life, there is a growing interest in analyzing brains from living fetuses with DS. In this study, we investigated regional sulcal folding depth as well as global cortical gyrification from fetal brain MRIs. Nine fetuses with DS (29.1 ± 4.24 gestational weeks [mean ± standard deviation]) were compared with 17 typically developing [TD] fetuses (28.4 ± 3.44). Fetuses with DS showed lower whole-brain average sulcal depths and gyrification index than TD fetuses. Significant decreases in sulcal depth were found in bilateral Sylvian fissures and right central and parieto-occipital sulci. On the other hand, significantly increased sulcal depth was shown in the left superior temporal sulcus, which is related to atypical hemispheric asymmetry of cortical folding. Moreover, these group differences increased as gestation progressed. This study demonstrates that regional sulcal depth is a sensitive marker for detecting alterations of cortical development in DS during fetal life, which may be associated with later neurocognitive impairment.
Assuntos
Córtex Cerebral/diagnóstico por imagem , Síndrome de Down/diagnóstico por imagem , Feto/diagnóstico por imagem , Adolescente , Adulto , Córtex Cerebral/embriologia , Desenvolvimento Fetal , Idade Gestacional , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Idade Materna , Neuroimagem , Adulto JovemRESUMO
Hypogenesis (hCC) and dysgenesis (dCC) of the corpus callosum (CC) are characterized by its smaller size or absence. The outcomes of these patients vary considerably and are unrelated to the size of the CC abnormality. The aim of the current study was to characterize the sulcal pattern in children with hCC and dCC and to explore its relation to clinical outcome. We used quantitative sulcal pattern analysis that measures deviation (similarity index, SI) of the composite or individual sulcal features (position, depth, area, and graph topology) compared to the control group. We calculated SI for each hemisphere and lobe in 11 children with CC disorder (hCC = 4, dCC = 7) and 15 controls. hCC and dCC had smaller hemispheric SI compared to controls. dCC subjects had smaller regional SI in the frontal and occipital lobes, which were driven by a smaller SI in a position or a graph topology. The significantly decreased SI gradient was found across groups only in the sulcal graph topology of the temporal lobes (controls > hCC > dCC) and was related to clinical outcome. Our results suggest that careful examination of sulcal pattern in hCC and dCC patients could be a useful biomarker of outcome.
Assuntos
Agenesia do Corpo Caloso/complicações , Agenesia do Corpo Caloso/patologia , Transtornos do Comportamento Infantil/etiologia , Transtornos do Neurodesenvolvimento/etiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , MasculinoRESUMO
Sulcal pits are thought to represent the first cortical folds of primary sulci during neurodevelopment. The uniform spatial distribution of sulcal pits across individuals is hypothesized to be predetermined by a human-specific protomap which is related to functional localization under genetic controls in early fetal life. Thus, it is important to characterize temporal and spatial patterns of sulcal pits in the fetal brain that would provide additional information of functional development of the human brain and crucial insights into abnormal cortical maturation. In this paper, we investigated temporal patterns of emergence and spatial distribution of sulcal pits using 48 typically developing fetal brains in the second half of gestation. We found that the position and spatial variance of sulcal pits in the fetal brain are similar to those in the adult brain, and they are also temporally uniform against dynamic brain growth during fetal life. Furthermore, timing of pit emergence shows a regionally diverse pattern that may be associated with the subdivisions of the protomap. Our findings suggest that sulcal pits in the fetal brain are useful anatomical landmarks containing detailed information of functional localization in early cortical development and maintaining their spatial distribution throughout the human lifetime.
Assuntos
Córtex Cerebral/embriologia , Desenvolvimento Fetal/fisiologia , Adolescente , Adulto , Encéfalo/embriologia , Feminino , Feto , Humanos , Masculino , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Análise Espaço-Temporal , Adulto JovemRESUMO
Down syndrome (DS) is the most common liveborn autosomal chromosomal anomaly and is a major cause of developmental disability. Atypical brain development and the resulting intellectual disability originate during the fetal period. Perinatal interventions to correct such aberrant development are on the horizon in preclinical studies. However, we lack tools to sensitively measure aberrant structural brain development in living human fetuses with DS. In this study, we aimed to develop safe and precise neuroimaging measures to monitor fetal brain development in DS. We measured growth patterns of regional brain structures in 10 fetal brains with DS (29.1 ± 4.2, weeks of gestation, mean ± SD, range 21.7~35.1) and 12 control fetuses (25.2 ± 5.0, range 18.6~33.3) using regional volumetric analysis of fetal brain MRI. All cases with DS had confirmed karyotypes. We performed non-linear regression models to compare fitted regional growth curves between DS and controls. We found decreased growth trajectories of the cortical plate (P = 0.033), the subcortical parenchyma (P = 0.010), and the cerebellar hemispheres (P < 0.0001) in DS compared to controls. This study provides proof of principle that regional volumetric analysis of fetal brain MRI facilitates successful evaluation of brain development in living fetuses with DS.
Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/embriologia , Síndrome de Down/diagnóstico por imagem , Imageamento por Ressonância Magnética , Encéfalo/patologia , Mapeamento Encefálico/métodos , Síndrome de Down/patologia , Desenvolvimento Fetal , Idade Gestacional , Humanos , Diagnóstico Pré-NatalRESUMO
Neurodevelopmental abnormalities are the most common noncardiac complications in patients with congenital heart disease (CHD). Prenatal brain abnormalities may be due to reduced oxygenation, genetic factors, or less commonly, teratogens. Understanding the contribution of these factors is essential to improve outcomes. Because primary sulcal patterns are prenatally determined and under strong genetic control, we hypothesized that they are influenced by genetic variants in CHD. In this study, we reveal significant alterations in sulcal patterns among subjects with single ventricle CHD (n = 115, 14.7 ± 2.9 years [mean ± standard deviation]) compared with controls (n = 45, 15.5 ± 2.4 years) using a graph-based pattern-analysis technique. Among patients with CHD, the left hemisphere demonstrated decreased sulcal pattern similarity to controls in the left temporal and parietal lobes, as well as the bilateral frontal lobes. Temporal and parietal lobes demonstrated an abnormally asymmetric left-right pattern of sulcal basin area in CHD subjects. Sulcal pattern similarity to control was positively correlated with working memory, processing speed, and executive function. Exome analysis identified damaging de novo variants only in CHD subjects with more atypical sulcal patterns. Together, these findings suggest that sulcal pattern analysis may be useful in characterizing genetically influenced, atypical early brain development and neurodevelopmental risk in subjects with CHD.
Assuntos
Cérebro/patologia , Cardiopatias Congênitas/complicações , Transtornos do Neurodesenvolvimento/etiologia , Adolescente , Cérebro/diagnóstico por imagem , Feminino , Cardiopatias Congênitas/genética , Humanos , Imageamento por Ressonância Magnética , Masculino , Transtornos do Neurodesenvolvimento/patologia , Transtornos do Neurodesenvolvimento/psicologia , Testes NeuropsicológicosRESUMO
Seven unrelated individuals (four pediatric, three adults) with the TUBB3 E410K syndrome, harboring identical de novo heterozygous TUBB3 c.1228 G>A mutations, underwent neuropsychological testing and neuroimaging. Despite the absence of cortical malformations, they have intellectual and social disabilities. To search for potential etiologies for these deficits, we compared their brain's structural and white matter organization to 22 controls using structural and diffusion magnetic resonance imaging. Diffusion images were processed to calculate fractional anisotropy (FA) and perform tract reconstructions. Cortical parcellation-based network analysis and gyral topology-based FA analyses were performed. Major interhemispheric, projection and intrahemispheric tracts were manually segmented. Subjects had decreased corpus callosum volume and decreased network efficiency. While only pediatric subjects had diffuse decreases in FA predominantly affecting mid- and long-range tracts, only adult subjects had white matter volume loss associated with decreased cortical surface area. All subjects showed aberrant corticospinal tract trajectory and bilateral absence of the dorsal language network long segment. Furthermore, pediatric subjects had more tracts with decreased FA compared with controls than did adult subjects. These findings define a TUBB3 E410K neuroimaging endophenotype and lead to the hypothesis that the age-related changes are due to microscopic intrahemispheric misguided axons that are pruned during maturation.
Assuntos
Transtorno do Espectro Autista/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Corpo Caloso/diagnóstico por imagem , Deficiência Intelectual/diagnóstico por imagem , Tratos Piramidais/diagnóstico por imagem , Tubulina (Proteína)/genética , Substância Branca/diagnóstico por imagem , Adulto , Fatores Etários , Anisotropia , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/patologia , Transtorno do Espectro Autista/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Estudos de Casos e Controles , Córtex Cerebral/patologia , Criança , Corpo Caloso/patologia , Imagem de Difusão por Ressonância Magnética , Imagem de Tensor de Difusão , Endofenótipos , Feminino , Fibrose/diagnóstico por imagem , Fibrose/genética , Fibrose/patologia , Fibrose/fisiopatologia , Heterozigoto , Humanos , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Deficiência Intelectual/fisiopatologia , Síndrome de Kallmann/diagnóstico por imagem , Síndrome de Kallmann/genética , Síndrome de Kallmann/patologia , Síndrome de Kallmann/fisiopatologia , Masculino , Mutação , Vias Neurais/diagnóstico por imagem , Vias Neurais/patologia , Testes Neuropsicológicos , Oftalmoplegia/diagnóstico por imagem , Oftalmoplegia/genética , Oftalmoplegia/patologia , Oftalmoplegia/fisiopatologia , Tamanho do Órgão , Tratos Piramidais/patologia , Síndrome , Substância Branca/patologia , Adulto JovemRESUMO
Fetuses with congenital heart disease (CHD) have third trimester alterations in cortical development on brain magnetic resonance imaging (MRI). However, the intersulcal relationships contributing to global sulcal pattern remain unknown. This study applied a novel method for examining the geometric and topological relationships between sulci to fetal brain MRIs from 21-30 gestational weeks in CHD fetuses (n = 19) and typically developing (TD) fetuses (n = 17). Sulcal pattern similarity index (SI) to template fetal brain MRIs was determined for the position, area, and depth for corresponding sulcal basins and intersulcal relationships for each subject. CHD fetuses demonstrated altered global sulcal patterns in the left hemisphere compared with TD fetuses (TD [SI, mean ± SD]: 0.822 ± 0.023, CHD: 0.795 ± 0.030, P = 0.002). These differences were present in the earliest emerging sulci and were driven by differences in the position of corresponding sulcal basins (TD: 0.897 ± 0.024, CHD: 0.878 ± 0.019, P = 0.006) and intersulcal relationships (TD: 0.876 ± 0.031, CHD: 0.857 ± 0.018, P = 0.033). No differences in cortical gyrification index, mean curvature, or surface area were present. These data suggest our methods may be more sensitive than traditional measures for evaluating cortical developmental alterations early in gestation.
Assuntos
Córtex Cerebral/diagnóstico por imagem , Feto/diagnóstico por imagem , Cardiopatias Congênitas , Encéfalo/diagnóstico por imagem , Encéfalo/embriologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Imageamento Tridimensional , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Lobo Occipital/diagnóstico por imagem , Lobo Parietal/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Estudos Prospectivos , Lobo Temporal/diagnóstico por imagemRESUMO
Spatial distribution and specific geometric and topological patterning of early sulcal folds have been hypothesized to be under stronger genetic control and are more associated with optimal organization of cortical functional areas and their white matter connections, compared to later developing sulci. Several previous studies of sulcal pit (putative first sulcal fold) distribution and sulcal pattern analyses using graph structures have provided evidence of the importance of sulcal pits and patterns as remarkable anatomical features closely related to human brain function, suggesting additional insights concerning the anatomical and functional development of the human brain. Recently, early sulcal folding patterns have been observed in healthy fetuses and fetuses with brain abnormalities such as polymicrogyria and agenesis of corpus callosum. Graph-based quantitative sulcal pattern analysis has shown high sensitivity in detecting emerging subtle abnormalities in cerebral cortical growth in early fetal stages that are difficult to detect via qualitative visual assessment or using traditional cortical measures such as gyrification index and curvature. It has proven effective for characterizing genetically influenced early cortical folding development. Future studies will be aimed at better understanding a comprehensive map of spatio-temporal dynamics of fetal cortical folding in a large longitudinal cohort in order to examine individual clinical fetal MRIs and predict postnatal neurodevelopmental outcomes from early fetal life.
Assuntos
Encéfalo/embriologia , Feto/embriologia , HumanosRESUMO
Accurate parcellation and labeling of primary cortical sulci in the human fetal brain is useful for regional analysis of brain development. However, human fetal brains show large spatio-temporal changes in brain size, cortical folding patterns, and relative position/size of cortical regions, making accurate automatic sulcal labeling challenging. Here, we introduce a novel sulcal labeling method for the fetal brain using spatio-temporal gyrification information from multiple fetal templates. First, spatial probability maps of primary sulci are generated on the templates from 23 to 33 gestational weeks and registered to an individual brain. Second, temporal weights, which determine the level of contribution to the labeling for each template, are defined by similarity of gyrification between the individual and the template brains. We combine the weighted sulcal probability maps from the multiple templates and adopt sulcal basin-wise approach to assign sulcal labels to each basin. Our labeling method was applied to 25 fetuses (22.9-29.6 gestational weeks), and the labeling accuracy was compared to manually assigned sulcal labels using the Dice coefficient. Moreover, our multi-template basin-wise approach was compared to a single-template approach, which does not consider the temporal dynamics of gyrification, and a fully-vertex-wise approach. The mean accuracy of our approach was 0.958 across subjects, significantly higher than the accuracies of the other approaches. This novel approach shows highly accurate sulcal labeling and provides a reliable means to examine characteristics of cortical regions in the fetal brain.
Assuntos
Córtex Cerebral/anatomia & histologia , Córtex Cerebral/crescimento & desenvolvimento , Desenvolvimento Fetal , Feto/anatomia & histologia , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Adolescente , Adulto , Feminino , Idade Gestacional , Humanos , Pessoa de Meia-Idade , Gravidez , Análise Espaço-Temporal , Adulto JovemRESUMO
Fetuses with isolated agenesis of the corpus callosum (ACC) are associated with a broad spectrum of neurodevelopmental disability that cannot be specifically predicted in prenatal neuroimaging. We hypothesized that ACC may be associated with aberrant cortical folding. In this study, we determined altered patterning of early primary sulci development in fetuses with isolated ACC using novel quantitative sulcal pattern analysis which measures deviations of regional sulcal features (position, depth, and area) and their intersulcal relationships in 7 fetuses with isolated ACC (27.1 ± 3.8 weeks of gestation, mean ± SD) and 17 typically developing (TD) fetuses (25.7 ± 2.0 weeks) from normal templates. Fetuses with ACC showed significant alterations in absolute sulcal positions and relative intersulcal positional relationship compared to TD fetuses, which were not detected by traditional gyrification index. Our results reveal altered sulcal positional development even in isolated ACC that is present as early as the second trimester and continues throughout the fetal period. It might originate from altered white matter connections and portend functional variances in later life.
Assuntos
Agenesia do Corpo Caloso/patologia , Córtex Cerebral/patologia , Feminino , Feto , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética , Masculino , Neuroimagem/métodosRESUMO
Developmental dyslexia (DD) is highly heritable and previous studies observed reduced cortical volume, white matter integrity, and functional alterations in left posterior brain regions in individuals with DD. The primary sulcal pattern has been hypothesized to relate to optimal organization and connections of cortical functional areas. It is determined during prenatal development and may reflect early, genetically influenced, brain development. We characterize the sulcal pattern using graph-based pattern analysis and investigate whether sulcal patterns in parieto-temporal and occipito-temporal regions are atypical in elementary school-age children with DD and pre-readers/beginning readers (preschoolers/kindergarteners) with a familial risk (elementary school-age children: n [males/females], age range = 17/11, 84-155 months; preschoolers/kindergarteners: 16/15, 59-84 months). The pattern of sulcal basin area in left parieto-temporal and occipito-temporal regions was significantly atypical (more sulcal basins of smaller size) in children with DD and further correlated with reduced reading performance on single- and nonword reading measures. A significantly atypical sulcal area pattern was also confirmed in younger preschoolers/kindergarteners with a familial risk of DD. Our results provide further support for atypical early brain development in DD and suggest that DD may originate from altered organization or connections of cortical areas in the left posterior regions.
Assuntos
Córtex Cerebral/patologia , Dislexia/patologia , Córtex Cerebral/crescimento & desenvolvimento , Criança , Pré-Escolar , Família , Feminino , Predisposição Genética para Doença , Humanos , Imageamento por Ressonância Magnética , MasculinoRESUMO
Tuberous sclerosis complex (TSC) is characterized by benign hamartomas in multiple organs including the brain and its clinical phenotypes may be associated with abnormal neural connections. We aimed to provide the first detailed findings on disrupted structural brain networks in TSC patients. Structural whole-brain connectivity maps were constructed using structural and diffusion MRI in 20 TSC (age range: 3-24 years) and 20 typically developing (TD; 3-23 years) subjects. We assessed global (short- and long-association and interhemispheric fibers) and regional white matter connectivity, and performed graph theoretical analysis using gyral pattern- and atlas-based node parcellations. Significantly higher mean diffusivity (MD) was shown in TSC patients than in TD controls throughout the whole brain and positively correlated with tuber load severity. A significant increase in MD was mainly influenced by an increase in radial diffusivity. Furthermore, interhemispheric connectivity was particularly reduced in TSC, which leads to increased network segregation within hemispheres. TSC patients with developmental delay (DD) showed significantly higher MD than those without DD primarily in intrahemispheric connections. Our analysis allows non-biased determination of differential white matter involvement, which may provide better measures of "lesion load" and lead to a better understanding of disease mechanisms.
Assuntos
Neoplasias Encefálicas/patologia , Encéfalo/patologia , Esclerose Tuberosa/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Masculino , Vias Neurais/patologia , Substância Branca/patologia , Adulto JovemRESUMO
Polymicrogyria (PMG) is a cortical malformation characterized by multiple small gyri and altered cortical lamination, which may be associated with disrupted white matter connectivity. However, little is known about the topological patterns of white matter networks in PMG. We examined structural connectivity and network topology using individual primary gyral pattern-based nodes in PMG patients, overcoming the limitations of an atlas-based approach. Structural networks were constructed from structural and diffusion magnetic resonance images in 25 typically developing and 14 PMG subjects. The connectivity analysis for different fiber groups divided based on gyral topology revealed severely reduced connectivity between neighboring primary gyri (short U-fibers) in PMG, which was highly correlated with the regional involvement and extent of abnormal gyral folding. The patients also showed significantly reduced connectivity between distant gyri (long association fibers) and between the two cortical hemispheres. In relation to these results, gyral node-based graph theoretical analysis revealed significantly altered topological organization of the network (lower clustering and higher modularity) and disrupted network hub architecture in cortical association areas involved in cognitive and language functions in PMG patients. Furthermore, the network segregation in PMG patients decreased with the extent of PMG and the degree of language impairment. Our approach provides the first detailed findings and interpretations on altered cortical network topology in PMG related to abnormal cortical structure and brain function, and shows the potential for an individualized method to characterize network properties and alterations in connections that are associated with malformations of cortical development.