Zhonghe Zhang

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.

Development of fetal brain of 20 weeks gestational age: Assessment with post-mortem Magnetic Resonance Imaging

BACKGROUND The 20th week gestational age (GA) is at mid-gestation and corresponds to the age at which the termination of pregnancy in several countries and the first Magnetic Resonance Imaging (MRI) can be performed, and at which the premature babies may survive. However, at present, very little is known about the exact anatomical character at this GA. OBJECTIVE To delineate the developing fetal brain of 20 weeks GA and obtain the three dimensional visualization model. MATERIALS AND METHODS 20 fetal specimens were scanned by 3.0 T and 7.0 T post-mortem MRI, and the three dimensional visualization model was obtained with Amira 4.1. RESULTS Most of the sulci or their anlage, except the postcentral sulcus and intraparietal sulcus, were present. The laminar organization, described as layers with different signal intensities, was most clearly distinguished at the parieto-occipital lobe and peripheral regions of the hippocampus. The basal nuclei could be clearly visualized, and the brain stem and cerebellum had formed their common shape. On the visualization model, the shape and relative relationship of the structures could be appropriately delineated. The ranges of normal values of the brain structures were obtained, but no sexual dimorphisms or cerebral asymmetries were found. CONCLUSIONS The developing fetal brain of 20 weeks GA can be clearly delineated on 3.0 T and 7.0 T post-mortem MRIs, and the three dimensional visualization model supplies great help in precise cognition of the immature brain. These results may have positive influences on the evaluation of the fetal brain in the uterus.

Development of the Fetal Cerebral Cortex in the Second Trimester: Assessment with 7T Postmortem MR Imaging

BACKGROUND AND PURPOSE: Few investigators have analyzed the fetal cerebral cortex with MR imaging of high magnetic strength. Our purpose was to document the sulcal development and obtain quantitative measurements of the fetal brain in the second trimester. MATERIALS AND METHODS: The brains of 69 fetal specimens, with GA 12–22 weeks, were first scanned on a 7T MR imaging scanner. Then the sequential development of the different fissures and sulci was analyzed, and quantitative measurements of the cerebral cortex were obtained. RESULTS: A new chronology of sulcal development during 12–22 weeks GA was summarized. Before 12 weeks, few sulci were present; by 16 weeks, many sulci were present. The 16th week could be considered the most intensive time point for sulcal emergence. Most sulci, except for the postcentral sulcus and intraparietal sulcus, were present by 22 weeks GA. Measurements of the fetal brains, each with different growth rates, linearly increased with GA, but no sexual dimorphisms or cerebral asymmetries were detected. CONCLUSIONS: The second trimester is the most important phase, during which most sulci are present and can be clearly shown on 7T postmortem MR imaging. It is apparent that the specific time during which neuropathologic features of sulci appear, previously thought to be well understood, should be redefined. Quantitative data provide assistance in the precise understanding of the immature brain. The present results are valuable in anatomic education, research, and assessment of normal brain development in the uterus.

Development of the human fetal cerebellum in the second trimester: a post mortem magnetic resonance imaging evaluation

The cerebellum is one of the most important structures in the posterior cranial fossa, but the characterization of its development by magnetic resonance imaging (MRI) is incomplete. We scanned 40 fetuses that had no morphological brain disorder at 14–22 weeks of gestation using 7.0 T MRI. Amira 4.1 software was used to determine morphological parameters of the fetal cerebellum, which included the cerebellar volume (CV), transverse cerebellar diameter (TCD), and the length and width of the vermis. The relationship between these measurements and gestational age (GA) was analysed. We found that the primary fissure was visible at week 14 of gestation. From week 16, the prepyramidal fissure, the secondary fissure and the dentate nucleus could be identified. The posterolateral fissure and the fourth ventricle were recognized at week 17, whereas the tentorium of the cerebellum was visible at week 20. The relationships between GA and CV, TCD, and the width and length of the vermis were described adequately by second‐order polynomial regression curves. The ratios between TCD and vermis length and between TCD and vermis width decreased with GA. These results show that 7.0 T MRI can show the trajectory of cerebellar development clearly. They increase our understanding of normal cerebellar development in the fetus, and will facilitate the diagnosis of pathological intrauterine changes in the cerebellum.

Development of fetal cerebral cortex: assessment of the folding conditions with post-mortem Magnetic Resonance Imaging

Quantitative data of fetal cortical folding and its developmental changes supply important information in the estimation of fetal age and assessment of brain maturation, so the increasing tendencies of cortical growth and its folding conditions at the beginning of the second and third trimesters with post‐mortem Magnetic Resonance Imaging (MRI) were analyzed. 131 fetal specimens of 14–40 weeks gestational age (GA) were selected and scanned with 3.0 T MR. Then the length of folded cortical margin (LFCM) and length of unfolded cortical margin (LUCM) were measured by Photoshop and ZoomMagic software. Degrees of cortical folding (DCF) were calculated by means of (LFCM − LUCM)/LFCM. Growth curves were obtained between the 3 above values and GA, and significant differences in age stages, hemispheres and genders were analyzed. The relationship between LFCM in centimeters, DCF and GA in weeks was described by two exponential growth curves [LFCM = 5.325 exp(0.079GA); DCF = 11.890 exp(0.043GA)]. The curves increased rapidly after 26 weeks GA, which could be recognized as a cut‐off point of fetal cortical and sulcal development. LUCM and GA were described by a logarithmic growth curve which slowed down after 26 weeks GA [LUCM = 30.580 Ln(GA) − 72.490]. Significant differences of the 3 values before and after 26 weeks GA (p < 0.01), but not any in hemispheres and genders were noticed. These results, which may be valuable in assessing normal brain development and can serve as a model in clinical settings, indicate that the cerebral volume first increases and is then followed by increases of the surface area.

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.

Measurements using 7.0 T post-mortem magnetic resonance imaging of the scalar dimensions of the fetal brain between 12 and 20 weeks gestational age

In this study, scalar values for the fetal brain from 12 to 20 weeks gestational age were obtained. Fifty‐two fetal specimens of 12–20 weeks gestational age with an anatomically normal and developmentally appropriate central nervous system (CNS) were scanned using a 7.0 T magnetic resonance imaging (MRI) scanner. The linear biometric measurements of the brain were then determined. All the measurements (except for the interhemispheric distance) were found to increase linearly with gestational age, although each increased at a different growth rates. The 95% confidence interval for each value was obtained. These data may be considered to be a valuable reference for the assessment of normal fetal brain development in clinical settings and as a supplement to post‐mortem MRI or anatomical investigations.

Fetal Adrenal Gland in the Second Half of Gestation: Morphometrical Assessment with 3.0T Post-Mortem MRI

Background The morphometry of fetal adrenal gland is rarely described with MRI of high magnetic field. The purpose of this study is to assess the normal fetal adrenal gland length (AL), width (AW), height (AH), surface area (AS) and volume (AV) in the second half of gestation with 3.0T post-mortem MRI. Methods and Findings Fifty-two fetal specimens of 23–40 weeks gestational age (GA) were scanned by 3.0T MRI. Morphological changes and quantitative measurements of the fetal adrenal gland were analyzed. Asymmetry and sexual dimorphism were also obtained. The shape of the fetal adrenal gland did not change substantially from 23 to 40 weeks GA. The bilateral adrenal glands appeared as a ‘Y’, pyramidal or half-moon shape after reconstruction. There was a highly linear correlation between AL, AW, AH, AS, AV and GA. AW, AH, AS and AV were larger for the left adrenal gland than the right. No sexual dimorphism was found. Conclusions Our data delineated the normal fetal adrenal gland during the second half of gestation, and can serve as a useful precise reference for anatomy or in vivo fetus.

Fetal cerebral lobes development between 20 and 28 weeks gestational age: a postmortem MR study.

To investigate the fetal cerebral lobes development between 20 and 28 weeks gestational age, 36 fetus specimen without CNS abnormality, with 4 fetuses in each gestation week, were scanned with 3.0 T MR. Lobular parameters were measured, including the parenchyma thickness of the frontoparietal and the temporal lobes, the margin length of frontoparietal, the insula and the temporal lobes, the Sylvian fissure and the perimeter of hippocampus, on the plane perpendicular to the longitudinal axis of hippocampus body across the base of cerebral peduncle. The relative value of parenchyma thickness and the lobes’ length ratios to the same side hemisphere were calculated and their correlation with gestational weeks was analyzed. All measured parameters were positively correlated with gestational age. No significant tendency was found for relative value of the parenchyma thickness (P > 0.05). The temporal lobe length ratio increased while the frontoparietal ratio decreased before 24 weeks GA and then the two reversed. The Sylvian fissure length ratio increased (P < 0.001) and the hippocampus decreased (P < 0.001) throughout this period. In conclusion, the early fetal cerebrum lobes developed asynchronously during this period, the 24 weeks GA could be a turning point for cerebrum development pattern changing from primitive to mature.

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.