| Part 1 Fetal and perinatal human brain template:Application to early microstructural development of cerebral cortex and white matterObjective:During the 2nd half of gestation, fetal brain undergoes immensely complicated microstructural changes. Several paralleling biological events, such as dendritic growth, synaptogenesis, development of white matter tracts, make brain to be an assemble of cortical regions with distinctive cytoarchitecture and function connected by white matter tracts. Therefore, the research on the microstructural changes of fetal brain development during the 2nd half of gestation will help better understanding the maturation of higher-order cognitive function and mechanism of psychiatric disorders. Diffusion tensor imaging (DTI) is a unique tool which can non-invasively observe the microstructural changese in in vivo fetal brain. Diffusional measurements based on high-quality, high resolution averaged DTI template could reflect the microstructural changes of fetal brain more accurately. So the aims of our research are:● To create a set of high-resolution, high SNR averaged DTI fetal brain templates;● To quantify the microstructural changes of cerebral cortex development during the 2nd half of gestation based on averaged DTI templates;● To quantify the microstructural changes of major white matter tracts development during the 2nd half of gestation based on averaged DTI templates.Methods:We acquired high resolution and high SNR DTI dataset from 36 subjects, including 10 ex vivo postmortem fetal brain at 19-20 weeks of gestation,13 neonates at 35 and 40 weeks of gestation separately.The creation of averaged DTI templates at 3 time points:after DTI data of all subjects were affine tranformed into template space, one subject from each time group was selected as the single-subject template. FA and b0 images of other subjects were registrated to the single-subject template with LDDMM, and then the averaged DTI templates at each time points were generated by all images of each subject.Measuring the development of cerebral cortex:after segmented, the cerebral cortex was 3D reconstructed by Amira and FA was mapped all over the brain.12 ROIs were directly put on the surface of cortex, including auditory cortex (A1C), anterior limbic cortex (ALC), Broca’s area (BA), dorsolateral prefrontal cortex (PFC), inferior parietal cortex (IPC), motor cortex (M1C), orbital PFC (OPC), medial PFC (MFC), somatosensory cortex (SIC), superior occipital cortex (SOC), superior temporal cortex (STC) and ventral PFC (VFC). Mean FA was obtained by averaging the FA values of all voxels within the mask.Measuring the development of major white matter tracts:DTIStudion was applied to track the white matter tracts, including cingulum cingulate gyrus part part (CGC), cingulum hippocampal part (CGH), cortico-spinal tract (CST), superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFO), uncinate fasciculus (UNC), forceps major (Fmajor) and forceps minor (Fminor) of corpus callosum. The white matter skeleton derived from template was transformed to native space. After overlapping the skeleton mask with white matter tracts mask, mean FA of each tracts was obtained by averaging the FA values of each voxel within tract’s mask.Results:● Fetal brain averaged DTI templates at 19-20,35 and 40 weeks of gestation were established.● The decrease of FA values all over the brain during the 2nd half of gestation indicates the process of maturation.● FA measurements of ROIs:the accelerated FA drop on most cortical regions except somatosensory, motor and Broca’s area from 35 to 40 weeks of gestation indicates accelerated maturing of cerebral cortex. The lower FA on somatosensory and motor area, and the higher FA on Broca’s area may suggest that the asynchronous development of cerebral cortex may be drove by functional development:somatosensory and motor develop earlier and Broca’s area develop later.●Tracking results show the early appearance of fibers including cingulum cingulate gyrus part part, cortico-spinal tract, forceps minor of corpus callosum, inferior fronto-occipital fasciculus and uncinate fasciculus.● Dramatic FA increase was found in all tracts from 19 to 35 weeks of gestation. From 35 to 40 weeks of gestation, the FA of projection, limbic and corpus callosum reached to a platuea, while FA of association fibers still increased significantly.Conclusions:During the 2nd half of gestation, cerebral cortex development shows the spatio-temporal pattern. The heterogeneous development of different cortical regions may be related to the regionalization of synaptogenesis and disintegration of radial glial scaffold. In the term of brain function, the heterogeneous development of cortical regions may be drove by the development of function. Although there is no process of myelination in the fetal stage, the heterogeneous development of major white matter tracts were still found:projection, limbic and corpus callosum fiber develop earlier while association fibers which is related to higher-order function have a lag development, suggesting the vulnerability of white matter in preterm.Part 2 Length, microstructure and connection of limbic fibers in normal brain developmentObjective:Limbic system fibers, including cingulum and fornix, are the major connection between cerebral cortex and limbic cortex. Since related to memory and attention function, the abnormal development of limbic system fibers result psychiatric disorders such as schizophrenia and depression. Systematic research on the morphological, micro structural and functional development could help understanding related function and mental disorders. Therefore, our aims are● To describe the morphological development of limbic system fibers through measuring the length changes during development.● To describe the microstructural development of limbic system fibers through measuring the diffusional indices changes during development.● To observe the developmental relationship between cingulum cingulate gyrus part part and posterior cingulate cortex-medial prefrontal cortex (PCC-mPFC) functional connectivity.Methods:We acquired DTI data from 59 health volunteers aged from birth to 25 years old and fMRI data from 6 volunteer (3 neonates and 3 adults selected from 59 volunteers).● Limbic system fibers of all subjects were tracked and reconstructed.● The averaged value of longest 10% fibers of the entire tract was defined as the averaged length of entire tract, also called original fiber length. The longest distence between most anterior and posterior of saggital brain was used to normalize fiber length. The fiber length after normalization is called normalized fiber length.● The mean values of diffusional measurements (FA, AD, RD, MD) were obtained by averaging values of all voxels in tract masks were called uncorrected diffusional measurements. Free water elimination was applied to correct the bias of measurements from free water diffusoin. Then the averaged diffusional measurements were called corrected diffusional meansurements. The cingulum cingulate gyrus part part were evenly divided into 3 segments by trisection point of line from most anterior to most posterior in saggital cingulum cingulate gyrus part part’s trunck. The corrected diffusional measurements from each segment were also measured.● After the pre-processing procedures such as motion correction, spatial smooth, intensity normalization and high-pass temporal filtering with a cut-off, ICA was applied to analyze the fMRI data and the well-fitted default-mode network was selected by hand. Default mode network was registrated to DTI space and was reconstructed with cingulum cingulate gyrus part part fibers.Results:● The original fier length of limbic fiber showed the increasing with age. However, the increasing trend of fiber length in cingulum cingulate gyrus part part fibers but not cingulum hippocampal part and fornix.● There are significant differences between corrected and uncorrected diffusional measurements. Moreover, the extent of difference is related to the location of tracts and the selection of indices. The overlapping between corrected and uncorrected cingulum FA curves may suggest that water content in brain becomes stable at about 20 year old.● The diffusional measurements of cingulum show the age-related changes which can be well fitted by expotential curves. Only the age-related changes of corrected RD in fornix is more suitable for polynomial curve. By showing the smallest value at about 15 years old, corrected RD suggests the early maturation of fornix. However, there is no relationship of corrected and uncrrected AD and MD of fornix with age.● Three segments of cingulum cingulate gyrus part shows the significant differences among diffusional measurements:segment 2 has the highest FA and lowest AD, RD and MD. On the contrary, the AD, RD and MD are highest in segment 1.● cingulum cingulate gyrus part shows the left-is-greater-than-right fiber length and diffusional measurements. Further comparing 3 segments of left and right, significant higher FA and lower AD, RD and MD are shown in the left side segment 1 and 2 but not 3. No differences are found neither in length nor diffusional measurements of cingulum hippocampal part.● The PCC-mPFC anatomical and functional connectivity has been established in neonate, which has a similar pattern with that of adult, suggesting that the immature cingulum cingulate gyrus part has played an important role in default mode network in neonate.Conclusion:Heterogeneous development of limbic system fibers are found:fornix developments earlier than cingulum. Although there is no significant differences in diffusional measurements, cingulum cingulate gyrus part shows a lag development by showing the dramatic increasing of fiber length. Further within cingulum cingulate gyrus part, the heterogeneous development is also found by the lag development of segment 1. Moreover, the lateralization of cingulum cingulate gyrus part is mainlu shown in the anterior part, which may explain the injury of anterior part of left cingulum cingulate gyrus part causing the deficit attention and memory function. The establishment of PCC-mPFC anatomical and functional connectivity may suggest that the immature cingulum cingulate gyrus part has played an important role in default mode network.in neonate. |
PDF Full Text Request