Preterm Birth Alters the Regional Development and Structural Covariance of Cerebellum at Term-Equivalent Age.

Preterm birth is associated with increased risk for a spectrum of neurodevelopmental disabilities. The cerebellum is implicated in a wide range of cognitive functions extending beyond sensorimotor control and plays an increasingly recognized role in brain development. Morphometric studies based on volume analyses have revealed impaired cerebellar development in preterm infants. However, the structural covariance between the cerebellum and cerebral cortex has not been studied during the neonatal period, and the extent to which structural covariance is affected by preterm birth remains unknown. In this study, using the structural MR images of 52 preterm infants scanned at term-equivalent age and 312 full-term controls from the Developing Human Connectome Project, we compared volumetric growth, local cerebellum shape development and cerebello-cerebral structural covariance between the two groups. We found that although there was no significant difference in the overall volume measurements between preterm and full-term infants, the shape measurements were different. Compared with the control infants, preterm infants had significantly larger thickness in the vermis and lower thickness in the lateral portions of the bilateral cerebral hemispheres. The structural covariance between the cerebellum and frontal and parietal lobes was significantly greater in preterm infants than in full-term controls. The findings in this study suggested that cerebellar development and cerebello-cerebral structural covariance may be affected by premature birth.

High-intensity interval training ameliorates postnatal immune activation-induced mood disorders through KDM6B-regulated glial activation.

Postnatal immune activation (PIA) induces persistent glial activation in the brain and causes various neuropathologies in adults. Exercise training improves stress-related mood disorders; however, the role of exercise in psychiatric disorders induced by early-life immune activation and the association between exercise training and glial activation remain unclear. We compared the effects of different exercise intensities on the PIA model, including high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT). Both HIIT and MICT in adolescent mice inhibited neuroinflammation, remodeled synaptic plasticity, and improved PIA-induced mood disorders in adulthood. Importantly, HIIT was superior to MICT in terms of reducing inflammation and increasing body weight. RNA-seq of prefrontal cortex (PFC) tissues revealed a gene expression pattern, confirming that HIIT was more effective than MICT in improving brain glial cell activation through epigenetic modifications of KDM6B. We investigated the role of KDM6B, a specific histone lysine demethylation enzyme - histone 3 lysine 27 demethylase, in inhibiting glial activation against PIA-induced depression and anxiety by regulating the expression of IL-4 and brain-derived neurotrophic factor (BDNF). Overall, our data support the idea that HIIT improves PIA-induced mood disorders by regulating KDM6B-mediated epigenetic mechanisms and indicate that HIIT might be superior to MICT in improving mood disorders with PIA in mice. Our findings provide new insights into the treatment of anxiety and depression disorders.

Altered cortical microstructure in preterm infants at term-equivalent age relative to term-born neonates.

Preterm (PT) birth is a potential factor for abnormal brain development. Although various alterations of cortical structure and functional connectivity in preterm infants have been reported, the underlying microstructural foundation is still undetected thoroughly in PT infants relative to full-term (FT) neonates. To detect the very early cortical microstructural alteration noninvasively with advanced neurite orientation dispersion and density imaging (NODDI) on a whole-brain basis, we used multi-shell diffusion MRI of healthy newborns selected from the Developing Human Connectome Project. 73 PT infants and 69 FT neonates scanned at term-equivalent age were included in this study. By extracting the core voxels of gray matter (GM) using GM-based spatial statistics (GBSS), we found that comparing to FT neonates, infants born preterm showed extensive lower neurite density in both primary and higher-order association cortices (FWE corrected, P < 0.025). Higher orientation dispersion was only found in very preterm subgroup in the orbitofrontal cortex, fronto-insular cortex, entorhinal cortex, a portion of posterior cingular gyrus, and medial parieto-occipital cortex. This study provided new insights into exploring structural MR for functional and behavioral variations in preterm population, and these findings may have marked clinical importance, particularly in the guidance of ameliorating the development of premature brain.

Evaluating the Impact of Intracranial Volume Correction Approaches on the Quantification of Intracranial Structures in MRI: A Systematic Analysis.

BACKGROUND: In neuroscience, accurately quantifying individual brain regions in large cohorts is a challenge. Differences in intracranial structures can suggest functional differences, but they also reflect the effects of other factors. However, there is currently no standardized method for the correction of intracranial structure measurements. PURPOSE: To identify the optimal method to counteract the influence of total intracranial volume (TIV) and gender on the measurement of intracranial structures. STUDY TYPE: Prospective. POPULATION/SUBJECTS: One hundred forty-one healthy adult volunteers (70 male, mean age 21.8 ± 1.7 years). FIELD STRENGTH/SEQUENCE: T1-weighted 3D gradient-echo sequence at 3.0 T. ASSESSMENT: A radiologist with 5 years of work experience screened the raw images to exclude poor-quality images. Freesurfer then performed automated segmentation to obtain measurements of intracranial structures. Male-only, female-only, and TIV-matched sub-samples were created separately. Comparisons between the original data and these sub-samples were used to assess the effects of gender and TIV. Comparison the consistency between TIV-matched sample and corrected data that corrected by four methods: Proportion method, power-corrected proportion method, covariate regression method, and residual method. STATISTICAL TESTS: Cohen's d for examining group distribution disparities, t-tests for probing mean differences, correlation coefficients to assess the relationships between intracranial substructure measurements and TIV. Multiple comparison corrections were applied to the results. RESULTS: The correlation coefficients between TIV and the volumes of intracranial structures ranged from 0.033 to 0.883, with an average of 0.467. Thirty significant volume differences were found among 36 structures in the original sample, while no differences were observed in the TIV-matched sample. Among the four correction methods, the residual method had highest consistency (similarity 94.4%) with the TIV-matched group. DATA CONCLUSION: The variation in intracranial structure sizes between genders was largely attributable to TIV. The residual method offers a more accurate and effective approach for correcting the effects of TIV on intracranial structures. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Morphological development of the human fetal striatum during the second trimester.

The morphological development of the fetal striatum during the second trimester has remained poorly described. We manually segmented the striatum using 7.0-T MR images of the fetal specimens ranging from 14 to 22 gestational weeks. The global development of the striatum was evaluated by volume measurement. The absolute volume (Vabs) of the caudate nucleus (CN) increased linearly with gestational age, while the relative volume (Vrel) showed a quadratic growth. Both Vabs and Vrel of putamen increased linearly. Through shape analysis, the changes of local structure in developing striatum were specifically demonstrated. Except for the CN tail, the lateral and medial parts of the CN grew faster than the middle regions, with a clear rostral-caudal growth gradient as well as a distinct "outside-in" growth gradient. For putamen, the dorsal and ventral regions grew obviously faster than the other regions, with a dorsal-ventral bidirectional developmental pattern. The right CN was larger than the left, whereas there was no significant hemispheric asymmetry in the putamen. By establishing the developmental trajectories, spatial heterochrony, and hemispheric dimorphism of human fetal striatum, these data bring new insight into the fetal striatum development and provide detailed anatomical references for future striatal studies.

Morphological Development Trajectory and Structural Covariance Network of the Human Fetal Cortical Plate during the Early Second Trimester.

During the early second trimester, the cortical plate, or "the developing cortex", undergoes immensely complex and rapid development to complete its major complement of neurons. However, morphological development of the cortical plate and the precise patterning of brain structural covariance networks during this period remain unexplored. In this study, we used 7.0 T high-resolution magnetic resonance images of brain specimens ranging from 14 to 22 gestational weeks to manually segment the cortical plate. Thickness, area expansion, and curvature (i.e., folding) across the cortical plate regions were computed, and correlations of thickness values among different cortical plate regions were measured to analyze fetal cortico-cortical structural covariance throughout development of the early second trimester. The cortical plate displayed significant increases in thickness and expansions in area throughout all regions but changes of curvature in only certain major sulci. The topological architecture and network properties of fetal brain covariance presented immature and inefficient organizations with low degree of integration and high degree of segregation. Altogether, our results provide novel insight on the developmental patterning of cortical plate thickness and the developmental origin of brain network architecture throughout the early second trimester.

A probabilistic atlas of locus coeruleus pathways to transentorhinal cortex for connectome imaging in Alzheimer's disease.

According to the latest Braak staging of Alzheimer's disease (AD), tau pathology occurs earliest in the brain in the locus coeruleus (LC) of the brainstem, then propagates to the transentorhinal cortex (TEC), and later to other neocortical regions. Recent animal and in vivo human brain imaging research also support the trans-axonal propagation of tau pathology. In addition, neurochemical studies link norepinephrine to behavioral symptoms in AD. It is thus critical to examine the integrity of the LC-TEC pathway in studying the early development of the disease, but there has been limited work in this direction. By leveraging the high-resolution and multi-shell diffusion MRI data from the Human Connectome Project (HCP), in this work we develop a novel method for the reconstruction of the LC-TEC pathway in a cohort of 40 HCP subjects carefully selected based on rigorous quality control of the residual distortion artifacts in the brainstem. A probabilistic atlas of the LC-TEC pathway of both hemispheres is then developed in the MNI152 space and distributed publicly on the NITRC website. To apply our atlas on clinical imaging data, we develop an automated approach to calculate the medial core of the LC-TEC pathway for localized analysis of connectivity changes. In a cohort of 138 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we demonstrate the detection of the decreased fiber integrity in the LC-TEC pathways with increasing disease severity.

Morphometric development of the human fetal cerebellum during the early second trimester.

The protracted nature of development makes the cerebellum vulnerable to a broad spectrum of pathologic conditions, especially during the early fetal period. This study aims to characterize normal cerebellar growth in human fetuses during the early second trimester. We manually segmented the fetal cerebellum using 7.0-T high-resolution MR images obtained in 35 specimens with gestational ages ranging from 15 to 22 weeks. Volume measurements and shape analysis were performed to quantitatively evaluate global and regional cerebellar growth. The absolute volume of the fetal cerebellum showed a quadratic growth with increasing gestational age, while the pattern of relative volume changes revealed that the cerebellum grew at a greater pace than the cerebrum after 17 gestational weeks. Shape analysis was used to examine the distinctive development of subregions of the cerebellum. The extreme lateral portions of both cerebellar hemispheres showed the lowest rate of growth. The anterior lobe grew faster than most of the posterior lobe. These findings expand our understanding of the early growth pattern of the human cerebellum and could be further used to assess the developmental conditions of the fetal brain.

A probabilistic atlas of human brainstem pathways based on connectome imaging data.

The brainstem is a critical structure that regulates vital autonomic functions, houses the cranial nerves and their nuclei, relays motor and sensory information between the brain and spinal cord, and modulates cognition, mood, and emotions. As a primary relay center, the fiber pathways of the brainstem include efferent and afferent connections among the cerebral cortex, spinal cord, and cerebellum. While diffusion MRI has been successfully applied to map various brain pathways, its application for the in vivo imaging of the brainstem pathways has been limited due to inadequate resolution and large susceptibility-induced distortion artifacts. With the release of high-resolution data from the Human Connectome Project (HCP), there is increasing interest in mapping human brainstem pathways. Previous works relying on HCP data to study brainstem pathways, however, did not consider the prevalence (>80%) of large distortions in the brainstem even after the application of correction procedures from the HCP-Pipeline. They were also limited in the lack of adequate consideration of subject variability in either fiber pathways or region of interests (ROIs) used for bundle reconstruction. To overcome these limitations, we develop in this work a probabilistic atlas of 23 major brainstem bundles using high-quality HCP data passing rigorous quality control. For the large-scale data from the 500-Subject release of HCP, we conducted extensive quality controls to exclude subjects with severe distortions in the brainstem area. After that, we developed a systematic protocol to manually delineate 1300 ROIs on 20 HCP subjects (10 males; 10 females) for the reconstruction of fiber bundles using tractography techniques. Finally, we leveraged our novel connectome modeling techniques including high order fiber orientation distribution (FOD) reconstruction from multi-shell diffusion imaging and topography-preserving tract filtering algorithms to successfully reconstruct the 23 fiber bundles for each subject, which were then used to calculate the probabilistic atlases in the MNI152 space for public release. In our experimental results, we demonstrate that our method yielded anatomically faithful reconstruction of the brainstem pathways and achieved improved performance in comparison with an existing atlas of cerebellar peduncles based on HCP data. These atlases have been publicly released on NITRIC (https://www.nitrc.org/projects/brainstem_atlas/) and can be readily used by brain imaging researchers interested in studying brainstem pathways.

Brain structure differences between Chinese and Caucasian cohorts: A comprehensive morphometry study.

Numerous behavioral observations and brain function studies have demonstrated that neurological differences exist between East Asians and Westerners. However, the extent to which these factors relate to differences in brain structure is still not clear. As the basis of brain functions, the anatomical differences in brain structure play a primary and critical role in the origination of functional and behavior differences. To investigate the underlying differences in brain structure between the two cultural/ethnic groups, we conducted a comparative study on education-matched right-handed young male adults (age = 22-29 years) from two cohorts, Han Chinese (n = 45) and Caucasians (n = 45), using high-dimensional structural magnetic resonance imaging (MRI) data. Using two well-validated imaging analysis techniques, surface-based morphometry (SBM) and voxel-based morphometry (VBM), we performed a comprehensive vertex-wise morphometric analysis of the brain structures between Chinese and Caucasian cohorts. We identified consistent significant between-group differences in cortical thickness, volume, and surface area in the frontal, temporal, parietal, occipital, and insular lobes as well as the cingulate cortices. The SBM analyses revealed that compared with Caucasians, the Chinese population showed larger cortical structures in the temporal and cingulate regions, and smaller structural measures in the frontal and parietal cortices. The VBM data of the same sample was well-aligned with the SBM findings. Our findings systematically revealed comprehensive brain structural differences between young male Chinese and Caucasians, and provided new neuroanatomical insights to the behavioral and functional distinctions in the two cultural/ethnic populations.

Breast masses in mammography classification with local contour features.

BACKGROUND: Mammography is one of the most popular tools for early detection of breast cancer. Contour of breast mass in mammography is very important information to distinguish benign and malignant mass. Contour of benign mass is smooth and round or oval, while malignant mass has irregular shape and spiculated contour. Several studies have shown that 1D signature translated from 2D contour can describe the contour features well. METHODS: In this paper, we propose a new method to translate 2D contour of breast mass in mammography into 1D signature. The method can describe not only the contour features but also the regularity of breast mass. Then we segment the whole 1D signature into different subsections. We extract four local features including a new contour descriptor from the subsections. The new contour descriptor is root mean square (RMS) slope. It can describe the roughness of the contour. KNN, SVM and ANN classifier are used to classify benign breast mass and malignant mass. RESULTS: The proposed method is tested on a set with 323 contours including 143 benign masses and 180 malignant ones from digital database of screening mammography (DDSM). The best accuracy of classification is 99.66% using the feature of root mean square slope with SVM classifier. CONCLUSION: The performance of the proposed method is better than traditional method. In addition, RMS slope is an effective feature comparable to most of the existing features.

Neuroplastin 65 mediates cognitive functions via excitatory/inhibitory synapse imbalance and ERK signal pathway.

Neuroplastin 65 (NP65) is a brain-specific glycoprotein component of synaptic membrane, which is predominantly located in the forebrain such as the cortex, amygdala and striatum and hippocampus. Previous studies have shown that NP65 is implicated in synaptic plasticity, so it was hypothesized to play roles in cognitive functions. To test this hypothesis, we generated NP65 knock-out (KO) mice and found that the null mice exhibited enhanced hippocampus-dependent learning and memory as manifested by Morris water maze test and step-through passive avoidance test, but showed anxiety-like behaviors as manifested by open field test and light/dark exploration test. In addition, molecular and cellular studies revealed several alterations including: (1) the enhanced ratio of excitatory to inhibitory synapses; (2) increased expression of NMDA receptors NR2A; (3) enhanced activation of ERK signaling; (4) lowered number of the mushroom- and bifurcate-shaped dendritic spines in NP65 KO mice. Together, our findings suggest that NP65 may mediate cognitive functions.

Development of the human fetal hippocampal formation during early second trimester.

Development of the fetal hippocampal formation has been difficult to fully describe because of rapid changes in its shape during the fetal period. The aims of this study were to: (1) segment the fetal hippocampal formation using 7.0 T MR images from 41 specimens with gestational ages ranging from 14 to 22 weeks and (2) reveal the developmental course of the fetal hippocampal formation using volume and shape analyses. Differences in hemispheric volume were observed, with the right hippocampi being larger than the left. Absolute volume changes showed a linear increase, while relative volume changes demonstrated an inverted-U shape trend during this period. Together these exhibited a variable developmental rate among different regions of the fetal brain. Different sub-regional growth of the fetal hippocampal formation was specifically observed using shape analysis. The fetal hippocampal formation possessed a prominent medial-lateral bidirectional shape growth pattern during its rotation process. Our results provide additional insight into 3D hippocampal morphology in the assessment of fetal brain development and can be used as a reference for future hippocampal studies.

Sectional anatomy of the abducens nerve: according to 3D-SPACE magnetic resonance sequences correlated with cryosectional specimens.

PURPOSE: To identify and justify the best section to reveal each segment of the abducens nerve according to 3D-SPACE magnetic resonance sequences and correlate with cryosectional specimens. METHODS: Thirty-four healthy adults were recruited for MRI using a 3D-SPACE sequence. Eighteen adult head specimens were cut into serial transverse, sagittal and coronal section using an electric band saw after the specimens were frozen. The MRI characteristics and the anatomical features of the abducens nerve were analyzed by correlation with the cryosection. RESULTS: We divided the abducens nerve into five segments, the cisternal segment, Dorello canal (DC) segment, cavernous sinus (CS) segment, superior orbital fissure (SOF) segment and intraorbital segment. In the transverse sections, the detection rates for the cisternal and Dorello canal segments of the abducens nerve were 97.06 and 94.12 %, respectively, on 3D-SPACE MR images. In the sagittal section of the frozen specimens, only the cisternal segment of the abducens nerve could be observed, and its detection rate was 51.50 %. In the coronal section, the CS segment of the abducens nerve was located inferior lateral to the ICA as well as, inferior to the oculomotor and trochlear nerves, and the detection rate of the CS segment was 42.60 % on 3D-SPACE MR images. CONCLUSION: 3D-SPACE sequence MR scanning was a useful method for observing the cisternal and DC segment of the abducens nerve in a transverse section, observing the cisternal segment in a sagittal section and observing the CS segment in a coronal section.

Peroxides as "switches" of dialkyl H-phosphonate: two mild and metal-free methods for preparation of 2-acylbenzothiazoles and dialkyl benzothiazol-2-ylphosphonates.

Two mild and metal-free methods for the preparation of two kinds of important benzothiazole derivatives, 2-acylbenzothiazoles and dialkyl benzothiazol-2-ylphosphonates, respectively, were developed. The dialkyl H-phosphonate (RO)2P(O)H exists in equilibrium with its tautomer dialkyl phosphite (RO)2POH. TBHP triggered α-carbon-centered phosphite radical formation, whereas DTBP triggered phosphorus-centered phosphonate radical formation. The two types of radicals led respectively to two different reaction processes, the direct C2-acylation of benzothiazoles and C2-phosphonation of benzothiazoles.

Increasing breadth of the frontal lobe but decreasing height of the human brain between two Chinese samples from a Neolithic site and from living humans.

Morphological observation and measurements of endocasts have played a vital role in research on the evolution of the human brain. However, endocasts have never been used to investigate how the human brain has evolved since the Neolithic period. We investigated the evolution of the human brain during the Holocene by comparing virtual endocasts from Beiqian site (a Neolithic Chinese site) and a sample of Chinese modern-day humans. Standardized measurements and indices were taken to provide quantification of the overall endocast shape, including the length, breadth, height, frontal breadth, and the ratio of frontal breadth to breadth, as well as the cranial capacity. We found that the height of the endocasts and cranial capacity have decreased between our two samples, whereas the frontal breadth and sexual dimorphism have increased. We argue that these changes can be caused by random genetic mutation and epigenetic change in response to changes in the environment.

Harpagide inhibits the TNF-α-induced inflammatory response in rat articular chondrocytes by the glycolytic pathways for alleviating osteoarthritis.

Osteoarthritis (OA) causes severe and functional dysfunction due to abnormal inflammation. The objective of this study was to evaluate the effect of Harpagide (HPG) on TNF-α-induced inflammation in vitro and in vivo. The effect of HPG on the proliferation of rat chondrocytes was studied. The anti-inflammatory effect of HPG and its molecular mechanisms were elucidated by qPCR, Western blotting, flow cytometry, metabolome analysis in vitro. In addition, the OA rat model was established, and the effect of HPG on OA was verified in vivo. We revealed 10 µM HPG demonstrated biocompatibility. The results demonstrated that HPG restored the upregulation of MMP-13, COX2, IL-1ß and IL-6 induced by TNF-α. Moreover, HPG reversed TNF-α induced degradation of the extracellular matrix of chondrocytes. TNF-α treatment induced down-regulation of the mRNA/protein levels of proliferative markers Bcl2, CDK1 and Cyclin D1 were also recovered. HPG can inhibit TNF-α-induced inflammatory response through glycolytic metabolic pathways. HPG can restore TNF-α-induced upregulation of GRP78/IRE1α, and downregulation of AMPK proteins. In vivo experiments demonstrated that after HPG treatment, the appearance and physiological structure of articular cartilage were more integrated with highly organized chondrocytes and rich cartilage matrix compared with OA group. Finally, the molecular docking of HPG and selected key factors in glycolysis results showed that HPG had good binding potential with PFKM, PFKP, PFKFB3, PKM, HK2, and PFKL. In conclusion, the results shown HPG protects and activates chondrocytes, inhibits TNF-α-induced inflammatory response by glycolysis pathway in rat articular chondrocytes, and plays a role in the treatment of OA.

Aging pattern of the brainstem based on volumetric measurement and optimized surface shape analysis.

The brainstem, a small and crucial structure, is connected to the cerebrum, spinal cord, and cerebellum, playing a vital role in regulating autonomic functions, transmitting motor and sensory information, and modulating cognitive processes, emotions, and consciousness. While previous research has indicated that changes in brainstem anatomy can serve as a biomarker for aging and neurodegenerative diseases, the structural changes that occur in the brainstem during normal aging remain unclear. This study aimed to examine the age- and sex-related differences in the global and local structural measures of the brainstem in 187 healthy adults (ranging in age from 18 to 70 years) using structural magnetic resonance imaging. The findings showed a significant negative age effect on the volume of the two major components of the brainstem: the medulla oblongata and midbrain. The shape analysis revealed that atrophy primarily occurs in specific structures, such as the pyramid, cerebral peduncle, superior and inferior colliculi. Surface area and shape analysis showed a trend of flattening in the aging brainstem. There were no significant differences between the sexes or sex-by-age interactions in brainstem structural measures. These findings provide a systematic description of age associations with brainstem structures in healthy adults and may provide a reference for future research on brain aging and neurodegenerative diseases.

Morphological changes in the cerebellum during aging: evidence from convolutional neural networks and shape analysis.

The morphology and function of the cerebellum are associated with various developmental disorders and healthy aging. Changes in cerebellar morphology during the aging process have been extensively investigated, with most studies focusing on changes in cerebellar regional volume. The volumetric method has been used to quantitatively demonstrate the decrease in the cerebellar volume with age, but it has certain limitations in visually presenting the morphological changes of cerebellar atrophy from a three-dimensional perspective. Thus, we comprehensively described cerebellar morphological changes during aging through volume measurements of subregions and shape analysis. This study included 553 healthy participants aged 20-80 years. A novel cerebellar localized segmentation algorithm based on convolutional neural networks was utilized to analyze the volume of subregions, followed by shape analysis for localized atrophy assessment based on the cerebellar thickness. The results indicated that out of the 28 subregions in the absolute volume of the cerebellum, 15 exhibited significant aging trends, and 16 exhibited significant sex differences. Regarding the analysis of relative volume, only 11 out of the 28 subregions of the cerebellum exhibited significant aging trends, and 4 exhibited significant sex differences. The results of the shape analysis revealed region-specific atrophy of the cerebellum with increasing age. Regions displaying more significant atrophy were predominantly located in the vermis, the lateral portions of bilateral cerebellar hemispheres, lobules I-III, and the medial portions of the posterior lobe. This atrophy differed between sexes. Men exhibited slightly more severe atrophy than women in most of the cerebellar regions. Our study provides a comprehensive perspective for observing cerebellar atrophy during the aging process.

Spatial-temporal atlas of human fetal brain development during the early second trimester.

During the second trimester, the human fetal brain undergoes numerous changes that lead to substantial variation in the neonatal in terms of its morphology and tissue types. As fetal MRI is more and more widely used for studying the human brain development during this period, a spatiotemporal atlas becomes necessary for characterizing the dynamic structural changes. In this study, 34 postmortem human fetal brains with gestational ages ranging from 15 to 22 weeks were scanned using 7.0 T MR. We used automated morphometrics, tensor-based morphometry and surface modeling techniques to analyze the data. Spatiotemporal atlases of each week and the overall atlas covering the whole period with high resolution and contrast were created. These atlases were used for the analysis of age-specific shape changes during this period, including development of the cerebral wall, lateral ventricles, Sylvian fissure, and growth direction based on local surface measurements. Our findings indicate that growth of the subplate zone is especially striking and is the main cause for the lamination pattern changes. Changes in the cortex around Sylvian fissure demonstrate that cortical growth may be one of the mechanisms for gyration. Surface deformation mapping, revealed by local shape analysis, indicates that there is global anterior-posterior growth pattern, with frontal and temporal lobes developing relatively quickly during this period. Our results are valuable for understanding the normal brain development trajectories and anatomical characteristics. These week-by-week fetal brain atlases can be used as reference in in vivo studies, and may facilitate the quantification of fetal brain development across space and time.