Prenatal Development Of The Cerebral Cortex: Assessment With MRI Of High Magnetic Strength

Systematic and complete imaging knowledge of the fetal cortical development is lacking for a long period. At present, ultrasonograph (US) is the main method to exam the fetus in vivo, and the fetal MRI is considered when the US result is inconclusive or inadequate. So, Most of our imaging knowledge about fetal cortical development is from the US and in vivo fetal MRI. The US is now the first choice to assess the fetal development, and its superiorities are safe, low-cost, convenient and real-time imaging. But it has some obvious limitations, such as the low space and tissue resolution, low image quality for obesity, oligohydramnion and the imaging area with gas around. In the late period of pregnancy, its penetrativity is easily influenced by the fetal crinial bones or maternal pelvic bones. The US also does not have specificities for some deformities. With the development of MRI techniques, especially the application of rapid acquisition with relaxation enhancement sequence, image quality of in vivo fetal MRI is greatly improved, and in vivo fetal MRI has become the most effective supplementary examination after the US. But the magnetic strength of in vivo fetal MRI is commonly 1.5T, and it is also limited by the special scanning sequence and thickness, and it is also influenced by fetal movement, maternal structures and pulse of the maternal artery. So the in vivo fetal MRI may not sufficiently demonstrate the developing feta brain. Compared with the in vivo fetal MRI, the in vitro post-mortem MRI is free from the limitations above, and the image quality is improved. The previous research of post-mortem MRI confirms its value in autopsy and contributions to fetal brain development. During fetal cortical development, complex events take place including the rapid growing process of the exterior morphology and internal cells. The sulci on the cortical surface, the laminar organization, the cortical folding, its surface area, volume and various diameters can all be considered as good markers of fetal brain maturation, and they are significant for the assessment of fetal brain physical conditions.So, it will be a breakthough to analyze the developmental changes of human fetal cerebral cortex on post-mortem MRIs of high magnetic strgenth with specimens of large sample and great GA span, and it will be also a breakthough to obtain the developmental regularities of the sulci and the lamination, and the accurate measurements of the cortical folding, surface area, volume and various diameters. This study aims to rich our embryological and radiological knowledge about human fetal brain development and supplies guidance for the diagnosis and assessment of fetal brain development in the uterus in clinical settings. The results of this study can benefit the diagnosis of abnormal fetuses, the increase of healthy newboms, and the improvement of survival rate of prematures.This study is divided into 4 parts:1. The prenatal development of the sulci; 2. The development of the cortical folding; 3. The development of the cortical laminar organization; 4. The quantitative study of fetal cortical development in the second trimester.Part 1:The development of the sulciObjectives:To document the emergence time of the fetal sulci and their branches.Materials and methods:The brains of 251 fetal specimens of 12-40 weeks GA were scanned by 3.0T MR,70 of 12-26 week GA were scanned by 7.0T MR. The sequential development of the different sulci and their branches was analyzed on MRIs of different Tesla and position.Results:A new chronology in GA about the sulcal development was summarized. Before 12 weeks GA, no sulci had been present except the lateral sulcus. By 16 weeks GA, many sulci had been present, such as the parietooccipital sulcus, the calacarine sulcus and the central sulcus. The superior frontal sulcus, inferior temporal sulcus, precentral sulcus, orbital sulcus and olfactory sulcus were present till 18 weeks GA, and the 16-18 weeks GA could be considered as the most intensive period for the sulcal emergence. Most of the sulci were'sulcal roots'now. After 24 weeks GA, the postcentral sulcus and the intraparietal sulcus could be distinguished. The 26-27 weeks GA could be considered as the starting point when the sulci quickly became deeper, curved and sent out branches. The secondary branch of the cingular sulcus could be delineated as early as 26 weeks GA. After 30 week GA, the secondary branch of the parietooccipital sulcus and the calacarine sulcus could be described, while their tertiary branch could be observed after 37 weeks GA.Conclusions:The neuropathologic present time of sulci, widely accepted previously, may should be reconsidered. Development of the fetal sulci follows a specific spatiotemporal schedule, and post-mortem MRI could delineate their changes precisely. Our results could be considered as a reference to determine whether the fetal sulci were developing normally or not.Part 2:The development of the cortical foldingObjectives:The increasing tendencies of cortical growth and its folding conditions at the second and third trimesters were quantitatively analyzed with 3.0T post-mortem MRI.Materials and methods:131 fetal specimens of 14-40 weeks GA were selected and scanned with 3.0T MR. The horizontal image, which was through the genu and splenium below of the corpus callosum was chosen to obtain the measurements. The length of folded cortical margin (LFCM) and length of unfolded cortical margin (LUCM) were measured by Photoshop and ZoomMagic softwares. 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.Results: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 (0.043 GA)]. 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 detected.Conclusions:The cerebral volume first increased before 26 weeks GA, when all the sulci had been present, and is then followed by increase of the surface area after 26 weeks GA, when the sulci quickly and intensively folded. These results, which may be valuable in assessing normal brain development, could serve as a model in clinical settings.Part 3:The development of the laminar organizationObjective:To show the demonstrating condition of laminar organization on 3.0T and 7.0T post-mortem MRI and analyze the developmental changes during the second and third trimesters.Materials and methods:Heads of 131 fetal specimens of 14-40 weeks GA were scanned by 3.0T MR.11 of 14-27 weeks GA were scanned by 7.0T MR. Clear images were chosen for analysis. The sequential development of the laminar organization was analyzed on MRIs of different position.Results:On T1-weighted 3.0T MRI, layers could be visualized at 14 weeks GA, and became clearer after 18 weeks GA. On 7.0T MRI,4 zones could be recognized at 14 weeks GA, and 6 zones could be recognized at 16 weeks GA. During 18-23 weeks GA, when laminar organization was typical,7 layers including the periventricular zone and external capsule fibers could be differentiated, which corresponded to 7 zones in histologcial stained sections. At 24-28 weeks GA, laminar organization became less typical and borderlines among them were obscured. After 30 weeks GA, it disappeared and turned into mature-like. The developing lamination was the most distinguishable at the parieto-occipital part of brain and peripheral regions of hippocampus. The migrating thalamocortical afferents appeared as a high signal layer located at the lower, middle, and upper part of the subplate zone respectively at 16-28 weeks GA on T1-weighted 3.0T MRI.Conclusions:T1-weighted 3.0T MRI and T2-weighted 7.0T MRI could demonstrate the laminar organization well. Development of the lamination followed a specific spatio-temporal regularity and postmortem MRI of the parieto-occipital part of brain obtained with 3.0T or 7.0T was an effective way to show the developmental changes.Part 4:Quantitative study of fetal cortical development in the second trimesterObjectives:To delineate the fetal cerebral cortex development in the second trimester with 7.0T post-mortem MRI, and obtain the three dimensional visualization model and quantitative measurements of fetal cerebral cortex, and then analyze the relationship between the measurements and GA.Materials and methods:The brains of 69 fetal specimens of 12-22 weeks GA were scanned by 7.0T MR. The segmentation was performed on the transverse, sagittal and coronal T2-weighted MRIs with Amira 4.1 software, and then the three dimensional visualization model was obtained.Results:The three dimensional visualization model could precisely delineate the total cortical surface, the sulci on the cerebral cortex and their location relationship among each other. Measurements of the fetal brain, with different growth rates among each other, linearly increased with GA, but no sexual dimorphisms or cerebral asymmetries were detected.Conclusions:The 7.0T post-mortem MRI could well describe the developing fetal cerebral cortex. The three dimensional visualization model and quantitative data supply great help in the precise cognition of the immature brain.