Julia A. Scott

Early Folding Patterns and Asymmetries of the Normal Human Brain Detected from in Utero MRI

Early cortical folding and the emergence of structural brain asymmetries have been previously analyzed by neuropathology as well as qualitative analysis of magnetic resonance imaging (MRI) of fetuses and preterm neonates. In this study, we present a dedicated image analysis framework and its application for the detection of folding patterns during the critical period for the formation of many primary sulci (20-28 gestational weeks). Using structural information from in utero MRI, we perform morphometric analysis of cortical plate surface development and modeling of early folding in the normal fetal brain. First, we identify regions of the fetal brain surface that undergo significant folding changes during this developmental period and provide precise temporal staging of these changes for each region of interest. Then, we highlight the emergence of interhemispheric structural asymmetries that may be related to future functional specialization of cortical areas. Our findings complement previous descriptions of early sulcogenesis based on neuropathology and qualitative evaluation of 2D in utero MRI by accurate spatial and temporal mapping of the emergence of individual sulci as well as structural brain asymmetries. The study provides the missing starting point for their developmental trajectories and extends our understanding of normal cortical folding.

Local Tissue Growth Patterns Underlying Normal Fetal Human Brain Gyrification Quantified In Utero

Existing knowledge of growth patterns in the living fetal human brain is based upon in utero imaging studies by magnetic resonance imaging (MRI) and ultrasound, which describe overall growth and provide mainly qualitative findings. However, formation of the complex folded cortical structure of the adult brain requires, in part, differential rates of regional tissue growth. To better understand these local tissue growth patterns, we applied recent advances in fetal MRI motion correction and computational image analysis techniques to 40 normal fetal human brains covering a period of primary sulcal formation (20–28 gestational weeks). Growth patterns were mapped by quantifying tissue locations that were expanding more or less quickly than the overall cerebral growth rate, which reveal increasing structural complexity. We detected increased local relative growth rates in the formation of the precentral and postcentral gyri, right superior temporal gyrus, and opercula, which differentiated between the constant growth rate in underlying cerebral mantle and the accelerating rate in the cortical plate undergoing folding. Analysis focused on the cortical plate revealed greater volume increases in parietal and occipital regions compared to the frontal lobe. Cortical plate growth patterns constrained to narrower age ranges showed that gyrification, reflected by greater growth rates, was more pronounced after 24 gestational weeks. Local hemispheric volume asymmetry was located in the posterior peri-Sylvian area associated with structural lateralization in the mature brain. These maps of fetal brain growth patterns construct a spatially specific baseline of developmental biomarkers with which to correlate abnormal development in the human.

Growth trajectories of the human fetal brain tissues estimated from 3D reconstructed in utero MRI

In the latter half of gestation (20–40 gestational weeks), human brain growth accelerates in conjunction with cortical folding and the deceleration of ventricular zone progenitor cell proliferation. These processes are reflected in changes in the volume of respective fetal tissue zones. Thus far, growth trajectories of the fetal tissue zones have been extracted primarily from 2D measurements on histological sections and magnetic resonance imaging (MRI). In this study, the volumes of major fetal zones—cortical plate (CP), subplate and intermediate zone (SP + IZ), germinal matrix (GMAT), deep gray nuclei (DG), and ventricles (VENT)—are calculated from automatic segmentation of motion‐corrected, 3D reconstructed MRI. We analyzed 48 T2‐weighted MRI scans from 39 normally developing fetuses in utero between 20.57 and 31.14 gestational weeks (GW). The supratentorial volume (STV) increased linearly at a rate of 15.22% per week. The SP + IZ (14.75% per week) and DG (15.56% per week) volumes increased at similar rates. The CP increased at a greater relative rate (18.00% per week), while the VENT (9.18% per week) changed more slowly. Therefore, CP increased as a fraction of STV and the VENT fraction declined. The total GMAT volume slightly increased then decreased after 25 GW. We did not detect volumetric sexual dimorphisms or total hemispheric volume asymmetries, which may emerge later in gestation. Further application of the automated fetal brain segmentation to later gestational ages will bridge the gap between volumetric studies of premature brain development and normal brain development in utero.

Volumetric and surface-based 3D MRI analyses of fetal isolated mild ventriculomegaly

Diagnosis of fetal isolated mild ventriculomegaly (IMVM) is the most common brain abnormality on prenatal ultrasound. We have set to identify potential alterations in brain development specific to IMVM in tissue volume and cortical and ventricular local surface curvature derived from in utero magnetic resonance imaging (MRI). Multislice 2D T2-weighted MRI were acquired from 32 fetuses (16 IMVM, 16 controls) between 22 and 25.5 gestational weeks. The images were motion-corrected and reconstructed into 3D volumes for volumetric and curvature analyses. The brain images were automatically segmented into cortical plate, cerebral mantle, deep gray nuclei, and ventricles. Volumes were compared between IMVM and control subjects. Surfaces were extracted from the segmentations for local mean surface curvature measurement on the inner cortical plate and the ventricles. Linear models were estimated for age-related and ventricular volume-associated changes in local curvature in both the inner cortical plate and ventricles. While ventricular volume was enlarged in IMVM, all other tissue volumes were not different from the control group. Ventricles increased in curvature with age along the atrium and anterior body. Increasing ventricular volume was associated with reduced curvature over most of the ventricular surface. The cortical plate changed in curvature with age at multiple sites of primary sulcal formation. Reduced cortical folding was detected near the parieto-occipital sulcus in IMVM subjects. While tissue volume appears to be preserved in brains with IMVM, cortical folding may be affected in regions where ventricles are dilated.

3D Morphometric Analysis of Human Fetal Cerebellar Development

To date, growth of the human fetal cerebellum has been estimated primarily from linear measurements from ultrasound and 2D magnetic resonance imaging (MRI). In this study, we use 3D analytical methods to develop normative growth trajectories for the cerebellum in utero. We measured cerebellar volume, linear dimensions, and local surface curvature from 3D reconstructed MRI of the human fetal brain (N = 46). We found that cerebellar volume increased approximately 7-fold from 20 to 31 gestational weeks. The better fit of the exponential curve (R2 = 0.96) compared to the linear curve (R2 = 0.92) indicated acceleration in growth. Within-subject cerebellar and cerebral volumes were highly correlated (R2 = 0.94), though the cerebellar percentage of total brain volume increased from approximately 2.4% to 3.7% (R2 = 0.63). Right and left hemispheric volumes did not significantly differ. Transcerebellar diameter, vermal height, and vermal anterior to posterior diameter increased significantly at constant rates. From the local curvature analysis, we found that expansion along the inferior and superior aspects of the hemispheres resulted in decreased convexity, which is likely due to the physical constraints of the dura surrounding the cerebellum and the adjacent brainstem. The paired decrease in convexity along the inferior vermis and increased convexity of the medial hemisphere represents development of the paravermian fissure, which becomes more visible during this period. In this 3D morphometric analysis of the human fetal cerebellum, we have shown that cerebellar growth is accelerating at a greater pace than the cerebrum and described how cerebellar growth impacts the shape of the structure.

Bias Field Inconsistency Correction of Motion-Scattered Multislice MRI for Improved 3D Image Reconstruction

A common solution to clinical MR imaging in the presence of large anatomical motion is to use fast multislice 2D studies to reduce slice acquisition time and provide clinically usable slice data. Recently, techniques have been developed which retrospectively correct large scale 3D motion between individual slices allowing the formation of a geometrically correct 3D volume from the multiple slice stacks. One challenge, however, in the final reconstruction process is the possibility of varying intensity bias in the slice data, typically due to the motion of the anatomy relative to imaging coils. As a result, slices which cover the same region of anatomy at different times may exhibit different sensitivity. This bias field inconsistency can induce artifacts in the final 3D reconstruction that can impact both clinical interpretation of key tissue boundaries and the automated analysis of the data. Here we describe a framework to estimate and correct the bias field inconsistency in each slice collectively across all motion corrupted image slices. Experiments using synthetic and clinical data show that the proposed method reduces intensity variability in tissues and improves the distinction between key tissue types.

Mapping directionality specific volume changes using tensor based morphometry: an application to the study of gyrogenesis and lateralization of the human fetal brain.

Tensor based morphometry (TBM) is a powerful approach to analyze local structural changes in brain anatomy. However, conventional scalar TBM methods do not completely capture all direction specific volume changes required to model complex changes such as those during brain growth. In this paper, we describe novel TBM descriptors for studying direction-specific changes in a subject population which can be used in conjunction with scalar TBM to analyze local patterns in directionality of volume change during brain development. We also extend the methodology to provide a new approach to mapping directional asymmetry in deformation tensors associated with the emergence of structural asymmetry in the developing brain. We illustrate the use of these methods by studying developmental patterns in the human fetal brain, in vivo. Results show that fetal brain development exhibits a distinct spatial pattern of anisotropic growth. The most significant changes in the directionality of growth occur in the cortical plate at major sulci. Our analysis also detected directional growth asymmetry in the peri-Sylvian region and the medial frontal lobe of the fetal brain.

Spatiotemporal morphometry of adjacent tissue layers with application to the study of sulcal formation

The process of brain growth involves the expansion of tissue at different rates at different points within the brain. As the layers within the developing brain evolve they can thicken or increase in area as the brain surface begins to fold. In this work we propose a new spatiotemporal formulation of tensor based volume morphometry that is derived in relation to tissue boundaries. This allows the study of the directional properties of tissue growth by separately characterizing the changes in area and thickness of the adjacent layers. The approach uses temporally weighted, local regression across a population of anatomies with different ages to model changes in components of the growth radial and tangential to the boundary between tissue layers. The formulation is applied to the study of sulcal formation from in-utero MR imaging of human fetal brain anatomy. Results show that the method detects differential growth of tissue layers adjacent to the cortical surface, particularly at sulcal locations, as early as 22 gestational weeks.

Non-iterative relative bias correction for 3D reconstruction of in utero fetal brain MR imaging

The slice intersection motion correction (SIMC) method is a powerful tool to compensate for motion that occurs during in utero acquisition of the multislice magnetic resonance (MR) images of the human fetal brain. The SIMC method makes use of the slice intersection intensity profiles of orthogonally planned slice pairs to simultaneously correct for the relative motion occurring between all the acquired slices. This approach is based on the assumption that the bias field is consistent between slices. However, for some clinical studies where there is a strong bias field combined with significant fetal motion relative to the coils, this assumption is broken and the resulting motion estimate and the reconstruction to a 3D volume can both contain errors. In this work, we propose a method to correct for the relative differences in bias field between all slice pairs. For this, we define the energy function as the mean square difference of the intersection profiles, that is then minimized with respect to the bias field parameters of the slices. A non iterative method which considers the relative bias between each slice simultaneously is used to efficiently remove inconsistencies. The method, when tested on synthetic simulations and actual clinical imaging studies where bias was an issue, brought a significant improvement to the final reconstructed image.

SLIMMER: SLIce MRI motion estimation and reconstruction tool for studies of fetal anatomy

We describe a free software tool which combines a set of algorithms that provide a framework for building 3D volumetric images of regions of moving anatomy using multiple fast multi-slice MRI studies. It is specifically motivated by the clinical application of unsedated fetal brain imaging, which has emerged as an important area for image analysis. The tool reads multiple DICOM image stacks acquired in any angulation into a consistent patient coordinate frame and allows the user to select regions to be locally motion corrected. It combines algorithms for slice motion estimation, bias field inconsistency correction and 3D volume reconstruction from multiple scattered slice stacks. The tool is built onto the RView (http://rview.colin-studholme.net) medical image display software and allows the user to inspect slice stacks, and apply both stack and slice level motion estimation that incorporates temporal constraints based on slice timing and interleave information read from the DICOM data. Following motion estimation an algorithm for bias field inconsistency correction provides the user with the ability to remove artifacts arising from the motion of the local anatomy relative to the imaging coils. Full 3D visualization of the slice stacks and individual slice orientations is provided to assist in evaluating the quality of the motion correction and final image reconstruction. The tool has been evaluated on a range of clinical data acquired on GE, Siemens and Philips MRI scanners.