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Population averaged diffusion atlases can be utilized to characterize complex microstructural changes with less bias than data from individual subjects. In this study, a fetal diffusion tensor imaging (DTI) atlas was used to investigate tract-based changes in anisotropy and diffusivity in vivo from 23 to 38 weeks of gestational age (GA). Healthy pregnant volunteers with typically developing fetuses were imaged at 3 T. Acquisition included structural images processed with a super-resolution algorithm and DTI images processed with a motion-tracked slice-to-volume registration algorithm. The DTI from individual subjects were used to generate 16 templates, each specific to a week of GA; this was accomplished by means of a tensor-to-tensor diffeomorphic deformable registration method integrated with kernel regression in age. Deterministic tractography was performed to outline the forceps major, forceps minor, bilateral corticospinal tracts (CST), bilateral inferior fronto-occipital fasciculus (IFOF), bilateral inferior longitudinal fasciculus (ILF), and bilateral uncinate fasciculus (UF). The mean fractional anisotropy (FA) and mean diffusivity (MD) was recorded for all tracts. For a subset of tracts (forceps major, CST, and IFOF) we manually divided the tractograms into anatomy conforming segments to evaluate within-tract changes. We found tract-specific, nonlinear, age related changes in FA and MD. Early in gestation, these trends appear to be dominated by cytoarchitectonic changes in the transient white matter fetal zones while later in gestation, trends conforming to the progression of myelination were observed. We also observed significant (local) heterogeneity in within-tract developmental trajectories for the CST, IFOF, and forceps major., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

The third trimester of pregnancy is a period of rapid development of fiber bundles in the fetal white matter. Using a recently developed motion-tracked slice-to-volume registration (MT-SVR) method, we aimed to quantify tract-specific developmental changes in apparent diffusion coefficient (ADC), fractional anisotropy (FA), and volume in third trimester healthy fetuses. To this end, we reconstructed diffusion tensor images from motion corrected fetal diffusion magnetic resonance imaging data. With an approved protocol, fetal MRI exams were performed on healthy pregnant women at 3 Tesla and included multiple (2-8) diffusion scans of the fetal head (1-2 b = 0 s/mm 2 images and 12 diffusion-sensitized images at b = 500 s/mm 2 ). Diffusion data from 32 fetuses (13 females) with median gestational age (GA) of 33 weeks 4 days were processed with MT-SVR and deterministic tractography seeded by regions of interest corresponding to 12 major fiber tracts. Multivariable regression analysis was used to evaluate the association of GA with volume, FA, and ADC for each tract. For all tracts, the volume and FA increased, and the ADC decreased with GA. Associations reached statistical significance for: FA and ADC of the forceps major; volume and ADC for the forceps minor; FA, ADC, and volume for the cingulum; ADC, FA, and volume for the uncinate fasciculi; ADC of the inferior fronto-occipital fasciculi, ADC of the inferior longitudinal fasciculi; and FA and ADC for the corticospinal tracts. These quantitative results demonstrate the complex pattern and rates of tract-specific, GA-related microstructural changes of the developing white matter in human fetal brain., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

Abstract Altered structural fetal brain development has been linked to neuro-developmental disorders. These structural alterations can be potentially detected in utero using diffusion tensor imaging (DTI). However, acquisition and reconstruction of in utero fetal brain DTI remains challenging. Until now, motion-robust DTI methods have been employed for reconstruction of in utero fetal DTIs. However, due to the unconstrained fetal motion and permissible in utero acquisition times, these methods yielded limited success and have typically resulted in noisy DTIs. Consequently, atlases and methods that could enable groupwise studies, multi-modality imaging, and computer-aided diagnosis from in utero DTIs have not yet been developed. This paper presents the first DTI atlas of the fetal brain computed from in utero diffusion-weighted images. For this purpose an algorithm for computing an unbiased spatiotemporal DTI atlas, which integrates kernel-regression in age with a diffeomorphic tensor-to-tensor registration of motion-corrected and reconstructed individual fetal brain DTIs, was developed. Our new algorithm was applied to a set of 67 fetal DTI scans acquired from healthy fetuses each scanned at a gestational age between 21 and 39 weeks. The neurodevelopmental trends in the fetal brain, characterized by the atlas, were qualitatively and quantitatively compared with the observations reported in prior ex vivo and in utero studies, and with results from imaging gestational-age equivalent preterm infants. Our major findings revealed early presence of limbic fiber bundles, followed by the appearance and maturation of projection pathways (characterized by an age related increase in FA) during late 2nd and early 3rd trimesters. During the 3rd trimester association fiber bundles become evident. In parallel with the appearance and maturation of fiber bundles, from 21 to 39 gestational weeks gradual disappearance of the radial coherence of the telencephalic wall was qualitatively identified. These results and analyses show that our DTI atlas of the fetal brain is useful for reliable detection of major neuronal fiber bundle pathways and for characterization of the fetal brain reorganization that occurs in utero. The atlas can also serve as a useful resource for detection of normal and abnormal fetal brain development in utero. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]