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Auditory perception is established through experience-dependent stimuli exposure during sensitive developmental periods; however, little is known regarding the structural development of the central auditory pathway in humans. The present study characterized the regional developmental trajectories of the ascending auditory pathway from the brainstem to the auditory cortex from infancy through adolescence using a novel diffusion MRI-based tractography approach and along-tract analyses. We used diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) to quantify the magnitude and timing of auditory pathway microstructural maturation. We found spatially varying patterns of white matter maturation along the length of the tract, with inferior brainstem regions developing earlier than thalamocortical projections and left hemisphere tracts developing earlier than the right. These results help to characterize the processes that give rise to functional auditory processing and may provide a baseline for detecting abnormal development.
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Neocortical maturation is a dynamic process that proceeds in a hierarchical manner; however, the spatiotemporal organization of cortical microstructure with diffusion MRI has yet to be fully defined. This study characterized cortical microstructural maturation using diffusion MRI (fwe-diffusion tensor imaging [DTI] and neurite orientation dispersion and density imaging [NODDI] multicompartment modeling) in a cohort of 637 children and adolescents between 8 and 21 years of age. We found spatially heterogeneous developmental patterns broadly demarcated into functional domains where NODDI metrics increased, and fwe-DTI metrics decreased with age. By applying nonlinear growth models in a vertex-wise analysis, we observed a general posterior-to-anterior pattern of maturation, where the fwe-DTI measures mean diffusivity and radial diffusivity reached peak maturation earlier than the NODDI metrics neurite density index. Using non-negative matrix factorization, we found occipito-parietal cortical regions that correspond to lower order sensory domains mature earlier than fronto-temporal higher order association domains. Our findings corroborate previous histological and neuroimaging studies that show spatially varying patterns of cortical maturation that may reflect unique developmental processes of cytoarchitectonically determined regional patterns of change.
Assuntos
Imagem de Tensor de Difusão , Substância Branca , Criança , Humanos , Adolescente , Imagem de Tensor de Difusão/métodos , Imagem de Difusão por Ressonância Magnética , Neuritos , Neuroimagem , CabeçaRESUMO
Neocortical maturation is a dynamic process that proceeds in a hierarchical manner; however, the spatiotemporal organization of cortical microstructure with diffusion MRI has yet to be fully defined. This study characterized cortical microstructural maturation using diffusion MRI (fwe-DTI and NODDI multi-compartment modeling) in a cohort of 637 children and adolescents between 8 and 21 years of age. We found spatially heterogeneous developmental patterns broadly demarcated into functional domains where NODDI metrics increased and fwe-DTI metrics decreased with age. Using non-negative matrix factorization, we found cortical regions that correspond to lower-order sensory regions mature earlier than higher-order association regions. Our findings corroborate previous histological and neuroimaging studies that show spatially-varying patterns of cortical maturation that may reflect unique developmental processes of cytoarchitectonically-determined regional patterns of change.
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Enlarged perivascular spaces (PVS) are considered a biomarker for vascular pathology and are observed in normal aging and neurological conditions; however, research on the role of PVS in health and disease are hindered by the lack of knowledge regarding the normative time course of PVS alterations with age. To this end, we characterized the influence of age, sex and cognitive performance on PVS anatomical characteristics in a large cross-sectional cohort (â¼1400) of healthy subjects between 8 and 90 years of age using multimodal structural MRI data. Our results show age is associated with wider and more numerous MRI-visible PVS over the course of the lifetime with spatially-varying patterns of PVS enlargement trajectories. In particular, regions with low PVS volume fraction in childhood are associated with rapid age-related PVS enlargement (e.g., temporal regions), while regions with high PVS volume fraction in childhood are associated with minimal age-related PVS alterations (e.g., limbic regions). PVS burden was significantly elevated in males compared to females with differing morphological time courses with age. Together, these findings contribute to our understanding of perivascular physiology across the healthy lifespan and provide a normative reference for the spatial distribution of PVS enlargement patterns to which pathological alterations can be compared.
Assuntos
Sistema Glinfático , Masculino , Feminino , Humanos , Longevidade , Estudos Transversais , Imageamento por Ressonância Magnética/métodos , EnvelhecimentoRESUMO
White matter hyperintensities (WMHs) frequently occur in Alzheimer's Disease (AD) and have a contribution from ischemia, though their relationship with ß-amyloid and cardiovascular risk factors (CVRFs) is not completely understood. We used AT classification to categorize individuals based on their ß-amyloid and tau pathologies, then assessed the effects of ß-amyloid and tau on WMH volume and number. We then determined regions in which ß-amyloid and WMH accumulation were related. Last, we analyzed the effects of various CVRFs on WMHs. As secondary analyses, we observed effects of age and sex differences, atrophy, cognitive scores, and APOE genotype. PET, MRI, FLAIR, demographic, and cardiovascular health data was collected from the Alzheimer's Disease Neuroimaging Initiative (ADNI-3) (N = 287, 48 % male). Participants were categorized as A + and T + if their Florbetapir SUVR and Flortaucipir SUVR were above 0.79 and 1.25, respectively. WMHs were mapped on MRI using a deep convolutional neural network (Sepehrband et al., 2020). CVRF scores were based on history of hypertension, systolic and diastolic blood pressure, pulse rate, respiration rate, BMI, and a cumulative score with 6 being the maximum score. Regression models and Pearson correlations were used to test associations and correlations between variables, respectively, with age, sex, years of education, and scanner manufacturer as covariates of no interest. WMH volume percent was significantly associated with global ß-amyloid (r = 0.28, p < 0.001), but not tau (r = 0.05, p = 0.25). WMH volume percent was higher in individuals with either A + or T + pathology compared to controls, particularly within in the A+/T + group (p = 0.007, Cohen's d = 0.4, t = -2.5). Individual CVRFs nor cumulative CVRF scores were associated with increased WMH volume. Finally, the regions where ß-amyloid and WMH count were most positively associated were the middle temporal region in the right hemisphere (r = 0.18, p = 0.002) and the fusiform region in the left hemisphere (r = 0.017, p = 0.005). ß-amyloid and WMH have a clear association, though the mechanism facilitating this association is still not fully understood. The associations found between ß-amyloid and WMH burden emphasizes the relationship between ß-amyloid and vascular lesion formation while factors like CVRFs, age, and sex affect AD development through various mechanisms. These findings highlight potential causes and mechanisms of AD as targets for future preventions and treatments. Going forward, a larger emphasis may be placed on ß-amyloid's vascular effects and the implications of impaired brain clearance in AD.
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Doença de Alzheimer , Disfunção Cognitiva , Substância Branca , Humanos , Masculino , Feminino , Doença de Alzheimer/patologia , Substância Branca/patologia , Proteínas tau/metabolismo , Disfunção Cognitiva/patologia , Peptídeos beta-Amiloides/metabolismo , Proteínas Amiloidogênicas , AmiloideRESUMO
PURPOSE: To develop a weakly supervised 3D perivascular spaces (PVS) segmentation model that combines the filter-based image processing algorithm and the convolutional neural network. METHODS: We present a weakly supervised learning method for PVS segmentation by combing a rule-based image processing approach Frangi filter with a canonical deep learning algorithm Unet using conditional random field theory. The weighted cross entropy loss function and the training patch selection were implemented for the optimization and to alleviate the class imbalance issue. The performance of the model was evaluated on the Human Connectome Project data. RESULTS: The proposed method increases the true positive rate compared to the rule-based method and reduces the false positive rate by 36% in the weakly supervised training experiment and 39.4% in the supervised training experiment compared to Unet, which results in superior overall performance. In addition, by training the model on manually quality controlled and annotated data which includes the subjects with the presence of white matter hyperintensities, the proposed method differentiates between PVS and white matter hyperintensities, which reduces the false positive rate by 78.5% compared to weakly supervised trained model. CONCLUSIONS: Combing the filter-based image processing algorithm and the convolutional neural network algorithm could improve the model's segmentation accuracy, while reducing the training dependence on the large scale annotated PVS mask data by the trained physician. Compared to the filter-based image processing algorithm, the data driven PVS segmentation model using quality-controlled data as the training target could differentiate the white matter hyperintensity from PVS resulting low false positive rate.
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Imageamento por Ressonância Magnética , Redes Neurais de Computação , Humanos , Imageamento por Ressonância Magnética/métodos , Processamento de Imagem Assistida por Computador/métodos , AlgoritmosRESUMO
In this article, we provide an overview of current neuroimaging methods for studying perivascular spaces (PVS) in humans using brain MRI. In recent years, an increasing number of studies highlighted the role of PVS in cerebrospinal/interstial fluid circulation and clearance of cerebral waste products and their association with neurological diseases. Novel strategies and techniques have been introduced to improve the quantification of PVS and to investigate their function and morphological features in physiological and pathological conditions. After a brief introduction on the anatomy and physiology of PVS, we examine the latest technological developments to quantitatively analyze the structure and function of PVS in humans with MRI. We describe the applications, advantages, and limitations of these methods, providing guidance and suggestions on the acquisition protocols and analysis techniques that can be applied to study PVS in vivo. Finally, we review the human neuroimaging studies on PVS across the normative lifespan and in the context of neurological disorders.
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Sistema Glinfático , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Sistema Glinfático/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodosRESUMO
Prior epidemiological studies have found that in utero exposure to gestational diabetes mellitus (GDM) is associated with increased risk for neurodevelopmental disorders. However, brain alterations associated with GDM are not known. The hippocampus is pivotal for cognition and emotional regulation. Therefore, we assessed relationships between in utero exposure to GDM and hippocampal morphology and subfield structure during childhood. One hundred seventeen children aged 7-11 years (57% girls, 57% exposed to GDM), born at Kaiser Permanente Southern California, participated in the BrainChild Study. Maternal GDM status was determined from electronic medical records. Children underwent brain magnetic resonance imaging. Freesurfer 6.0 was used to measure hippocampal and individual hippocampal subfield gray matter volume (mm3 ). Morphological analyses on the hippocampal surface were carried out using shape analysis. GDM-exposed children exhibited reduced radial thickness in a small, spatially-restricted portion of the left inferior body of the hippocampus that corresponds to the CA1 subfield. There was a significant interaction between GDM-exposure and sex on the right hippocampal CA1 subfield. GDM-exposed boys had reduced right CA1 volume compared to unexposed boys, but this association was no longer significant after controlling for age. No significant group differences were observed in girls. Our results suggest that GDM-exposure impacts shape of the left hippocampal CA1 subfield in both boys and girls and may reduce volume of right hippocampal CA1 only in boys. These in-depth findings illuminate the unique properties of the hippocampus impacted by prenatal GDM-exposure and could have important implications for hippocampal-related functions.
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Diabetes Gestacional , Hipocampo/patologia , Efeitos Tardios da Exposição Pré-Natal/patologia , Região CA1 Hipocampal/diagnóstico por imagem , Região CA1 Hipocampal/patologia , Criança , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/diagnóstico por imagem , Fatores SexuaisRESUMO
Vascular contributions to early cognitive decline are increasingly recognized, prompting further investigation into the nature of related changes in perivascular spaces (PVS). Using magnetic resonance imaging, we show that, compared to a cognitively normal sample, individuals with early cognitive dysfunction have altered PVS presence and distribution, irrespective of Amyloid-ß. Surprisingly, we noted lower PVS presence in the anterosuperior medial temporal lobe (asMTL) (1.29 times lower PVS volume fraction in cognitively impaired individuals, p < 0.0001), which was associated with entorhinal neurofibrillary tau tangle deposition (beta (standard error) = -0.98 (0.4); p = 0.014), one of the hallmarks of early Alzheimer's disease pathology. We also observed higher PVS volume fraction in centrum semi-ovale of the white matter, but only in female participants (1.47 times higher PVS volume fraction in cognitively impaired individuals, p = 0.0011). We also observed PVS changes in participants with history of hypertension (higher in the white matter and lower in the asMTL). Our results suggest that anatomically specific alteration of the PVS is an early neuroimaging feature of cognitive impairment in aging adults, which is differentially manifested in female.
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Disfunção Cognitiva/patologia , Sistema Glinfático/patologia , Envelhecimento/patologia , Amiloide/metabolismo , Feminino , Sistema Glinfático/diagnóstico por imagem , Sistema Glinfático/metabolismo , Humanos , Hipertensão/patologia , Imageamento por Ressonância Magnética , Masculino , Emaranhados Neurofibrilares/metabolismo , Neuroimagem , Tamanho do Órgão , Caracteres Sexuais , Substância Branca/patologia , Proteínas tau/metabolismoRESUMO
Childhood obesity is associated with negative physiological and cognitive health outcomes. The hippocampus is a diverse subcortical structure involved in learned feeding behaviors and energy regulation, and research has shown that the hippocampus is vulnerable to the effects of excess adiposity. Previous studies have demonstrated reduced hippocampal volume in overweight and obese children; however, it is unclear if certain subregions are selectively affected. The purpose of this study was to determine how excess body weight influences regional hippocampal surface morphology and memory performance in a large cross-sectional cohort of 588 children and adolescents between 8.33 and 19.92 years of age using body mass index expressed as a percentage of the 95th percentile cutoff (%BMIp95). We demonstrate %BMIp95 is associated with reduced radial thickness in the superior anterior region of the left hippocampus, and this relationship is predominantly driven by children younger than 14 years. We also found %BMIp95 was associated with worse performance on a spatial episodic memory task and this relationship was partially mediated by the radial thickness of the significant shape cluster. These results demonstrate the differential influence of excess body weight on regional hippocampal structure and hippocampal-dependent behavior in children and adolescents.
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Obesidade Infantil , Adolescente , Índice de Massa Corporal , Criança , Cognição , Estudos Transversais , Hipocampo/fisiologia , Humanos , Obesidade Infantil/diagnóstico por imagem , Obesidade Infantil/psicologiaRESUMO
White matter maturation is a nonlinear and heterogeneous phenomenon characterized by axonal packing, increased axon caliber, and a prolonged period of myelination. While current in vivo diffusion MRI (dMRI) methods, like diffusion tensor imaging (DTI), have successfully characterized the gross structure of major white matter tracts, these measures lack the specificity required to unravel the distinct processes that contribute to microstructural development. Neurite orientation dispersion and density imaging (NODDI) is a dMRI approach that probes tissue compartments and provides biologically meaningful measures that quantify neurite density index (NDI) and orientation dispersion index (ODI). The purpose of this study was to characterize the magnitude and timing of major white matter tract maturation with NODDI from infancy through adolescence in a cross-sectional cohort of 104 subjects (0.6-18.8 years). To probe the regional nature of white matter development, we use an along-tract approach that partitions tracts to enable more fine-grained analysis. Major white matter tracts showed exponential age-related changes in NDI with distinct maturational patterns. Overall, analyses revealed callosal fibers developed before association fibers. Our along-tract analyses elucidate spatially varying patterns of maturation with NDI that are distinct from those obtained with DTI. ODI was not significantly associated with age in the majority of tracts. Our results support the conclusion that white matter tract maturation is heterochronous process and, furthermore, we demonstrate regional variability in the developmental timing within major white matter tracts. Together, these results help to disentangle the distinct processes that contribute to and more specifically define the time course of white matter maturation.
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Encéfalo/crescimento & desenvolvimento , Vias Neurais/crescimento & desenvolvimento , Neuritos , Neuroimagem/métodos , Substância Branca/crescimento & desenvolvimento , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Lactente , Imageamento por Ressonância Magnética , Masculino , NeurogêneseRESUMO
The hippocampus is a subcortical structure critical for learning and memory, and a thorough understanding of its neurodevelopment is important for studying these processes in health and disease. However, few studies have quantified the typical developmental trajectory of the structure in childhood and adolescence. This study examined the cross-sectional age-related changes and sex differences in hippocampal shape in a multisite, multistudy cohort of 1676 typically developing children (age 1-22 years) using a novel intrinsic brain mapping method based on Laplace-Beltrami embedding of surfaces. Significant age-related expansion was observed bilaterally and nonlinear growth was observed primarily in the right head and tail of the hippocampus. Sex differences were also observed bilaterally along the lateral and medial aspects of the surface, with females exhibiting relatively larger surface expansion than males. Additionally, the superior posterior lateral surface of the left hippocampus exhibited an age-sex interaction with females expanding faster than males. Shape analysis provides enhanced sensitivity to regional changes in hippocampal morphology over traditional volumetric approaches and allows for the localization of developmental effects. Our results further support evidence that hippocampal structures follow distinct maturational trajectories that may coincide with the development of learning and memory skills during critical periods of development.
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Hipocampo/anatomia & histologia , Hipocampo/crescimento & desenvolvimento , Adolescente , Desenvolvimento do Adolescente/fisiologia , Adulto , Criança , Desenvolvimento Infantil/fisiologia , Pré-Escolar , Estudos Transversais , Humanos , Lactente , Imageamento por Ressonância Magnética , Tamanho do Órgão , Caracteres Sexuais , Adulto JovemRESUMO
Exploring neuroanatomical sex differences using a multivariate statistical learning approach can yield insights that cannot be derived with univariate analysis. While gross differences in total brain volume are well-established, uncovering the more subtle, regional sex-related differences in neuroanatomy requires a multivariate approach that can accurately model spatial complexity as well as the interactions between neuroanatomical features. Here, we developed a multivariate statistical learning model using a support vector machine (SVM) classifier to predict sex from MRI-derived regional neuroanatomical features from a single-site study of 967 healthy youth from the Philadelphia Neurodevelopmental Cohort (PNC). Then, we validated the multivariate model on an independent dataset of 682 healthy youth from the multi-site Pediatric Imaging, Neurocognition and Genetics (PING) cohort study. The trained model exhibited an 83% cross-validated prediction accuracy, and correctly predicted the sex of 77% of the subjects from the independent multi-site dataset. Results showed that cortical thickness of the middle occipital lobes and the angular gyri are major predictors of sex. Results also demonstrated the inferential benefits of going beyond classical regression approaches to capture the interactions among brain features in order to better characterize sex differences in male and female youths. We also identified specific cortical morphological measures and parcellation techniques, such as cortical thickness as derived from the Destrieux atlas, that are better able to discriminate between males and females in comparison to other brain atlases (Desikan-Killiany, Brodmann and subcortical atlases).
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Encéfalo/anatomia & histologia , Interpretação de Imagem Assistida por Computador/métodos , Caracteres Sexuais , Máquina de Vetores de Suporte , Adolescente , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Adulto JovemRESUMO
Arginine vasopressin (AVP) has previously been shown to promote disruption of the blood-brain barrier, exacerbate edema, and augment the loss of neural tissue in various forms and models of brain injury. However, the mechanisms underlying these AVP actions are not well understood. These mechanisms were studied in AVP-deficient Brattleboro rats (Avp(di/di)), and their parental Long-Evans strain, using a controlled cortical impact model of traumatic brain injury (TBI). The increased influx of inflammatory cells into the injured cortex in wild-type versus Avp(di/di) rats was associated with higher levels of cortical synthesis of the CXC and CC chemokines found in wild-type versus Avp(di/di) rats. These chemokines were predominantly produced by the cerebrovascular endothelium and astrocytes. In astrocyte and brain endothelial cell cultures, AVP acted synergistically with tumor necrosis factor-alpha (TNF-alpha) to increase the TNF-alpha-dependent production of CXC and CC chemokines. These AVP actions were mediated by c-Jun N-terminal kinase (JNK), as shown by Western blotting and pharmacological inhibition of JNK activity. The activity of JNK was increased in response to injury, and the differences in the magnitude of its post-traumatic activation between Avp(di/di) and wild-type rats were observed. These data demonstrate that AVP plays an important role in exacerbating the brain inflammatory response to injury.