Sylvain Gouttard

A Structural MRI Study of Human Brain Development from Birth to 2 Years

Brain development in the first 2 years after birth is extremely dynamic and likely plays an important role in neurodevelopmental disorders, including autism and schizophrenia. Knowledge regarding this period is currently quite limited. We studied structural brain development in healthy subjects from birth to 2. Ninety-eight children received structural MRI scans on a Siemens head-only 3T scanner with magnetization prepared rapid gradient echo T1-weighted, and turbo spin echo, dual-echo (proton density and T2 weighted) sequences: 84 children at 2–4 weeks, 35 at 1 year and 26 at 2 years of age. Tissue segmentation was accomplished using a novel automated approach. Lateral ventricle, caudate, and hippocampal volumes were also determined. Total brain volume increased 101% in the first year, with a 15% increase in the second. The majority of hemispheric growth was accounted for by gray matter, which increased 149% in the first year; hemispheric white matter volume increased by only 11%. Cerebellum volume increased 240% in the first year. Lateral ventricle volume increased 280% in the first year, with a small decrease in the second. The caudate increased 19% and the hippocampus 13% from age 1 to age 2. There was robust growth of the human brain in the first two years of life, driven mainly by gray matter growth. In contrast, white matter growth was much slower. Cerebellum volume also increased substantially in the first year of life. These results suggest the structural underpinnings of cognitive and motor development in early childhood, as well as the potential pathogenesis of neurodevelopmental disorders.

Differences in White Matter Fiber Tract Development Present From 6 to 24 Months in Infants With Autism

OBJECTIVE Evidence from prospective studies of high-risk infants suggests that early symptoms of autism usually emerge late in the first or early in the second year of life after a period of relatively typical development. The authors prospectively examined white matter fiber tract organization from 6 to 24 months in high-risk infants who developed autism spectrum disorders (ASDs) by 24 months. METHOD The participants were 92 high-risk infant siblings from an ongoing imaging study of autism. All participants had diffusion tensor imaging at 6 months and behavioral assessments at 24 months; a majority contributed additional imaging data at 12 and/or 24 months. At 24 months, 28 infants met criteria for ASDs and 64 infants did not. Microstructural properties of white matter fiber tracts reported to be associated with ASDs or related behaviors were characterized by fractional anisotropy and radial and axial diffusivity. RESULTS The fractional anisotropy trajectories for 12 of 15 fiber tracts differed significantly between the infants who developed ASDs and those who did not. Development for most fiber tracts in the infants with ASDs was characterized by higher fractional anisotropy values at 6 months followed by slower change over time relative to infants without ASDs. Thus, by 24 months of age, those with ASDs had lower values. CONCLUSIONS These results suggest that aberrant development of white matter pathways may precede the manifestation of autistic symptoms in the first year of life. Longitudinal data are critical to characterizing the dynamic age-related brain and behavior changes underlying this neurodevelopmental disorder.

Fiber tract-oriented statistics for quantitative diffusion tensor MRI analysis

Diffusion tensor imaging (DTI) has become the major modality to study properties of white matter and the geometry of fiber tracts of the human brain. Clinical studies mostly focus on regional statistics of fractional anisotropy (FA) and mean diffusivity (MD) derived from tensors. Existing analysis techniques do not sufficiently take into account that the measurements are tensors, and thus require proper interpolation and statistics based on tensors, and that regions of interest are fiber tracts with complex spatial geometry. We propose a new framework for quantitative tract-oriented DTI analysis that includes tensor interpolation and averaging, using nonlinear Riemannian symmetric space. As a result, tracts of interest are represented by the geometry of the medial spine attributed with tensor statistics calculated within cross-sections. Examples from a clinical neuroimaging study of the early developing brain illustrate the potential of this new method to assess white matter fiber maturation and integrity.

Towards a shape model of white matter fiber bundles using diffusion tensor MRI

White matter fiber bundles of the human brain form a spatial pattern defined by the anatomical and functional architecture. Human brain atlases provide names for individual tracts and document that these patterns are comparable across subjects. Tractography applied to the tensor field in diffusion tensor imaging (DTI) results in sets of streamlines which can be associated with major fiber tracts. Comparison of fiber tract properties across subjects requires comparison at corresponding anatomical locations. As an alternative to linear and nonlinear registration of DTI images and voxel-based analysis, we propose a novel methodology that models the shape of white matter tracts. A clustering uses similarity of adjacent curves and an iterative processing scheme to group sets of curves to bundles and to reject outliers. Unlike previous work which models fiber tracts as sets of curves centered around a spine, we extend the notion of bundling towards a more general representation of manifolds. We describe tracts, represented as sets of curves of similar shape, by a shape prototype swept along a space trajectory. This approach can naturally describe white matter structures observed either as bundles dispersing towards the cortex or tracts defined as dense patterns of parallel fibers forming manifolds. Curves are parameterized by arc-length and represented by intrinsic local shape properties (curvature and torsion). Feasibility is demonstrated by modeling the left and right cortico-spinal tracts and a part of the transversal callosal tract.

Quantitative tract-based white matter development from birth to age 2years

Few large-scale studies have been done to characterize the normal human brain white matter growth in the first years of life. We investigated white matter maturation patterns in major fiber pathways in a large cohort of healthy young children from birth to age two using diffusion parameters fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (RD). Ten fiber pathways, including commissural, association and projection tracts, were examined with tract-based analysis, providing more detailed and continuous spatial developmental patterns compared to conventional ROI based methods. All DTI data sets were transformed to a population specific atlas with a group-wise longitudinal large deformation diffeomorphic registration approach. Diffusion measurements were analyzed along the major fiber tracts obtained in the atlas space. All fiber bundles show increasing FA values and decreasing radial and axial diffusivities during development in the first 2years of life. The changing rates of the diffusion indices are faster in the first year than the second year for all tracts. RD and FA show larger percentage changes in the first and second years than AD. The gender effects on the diffusion measures are small. Along different spatial locations of fiber tracts, maturation does not always follow the same speed. Temporal and spatial diffusion changes near cortical regions are in general smaller than changes in central regions. Overall developmental patterns revealed in our study confirm the general rules of white matter maturation. This work shows a promising framework to study and analyze white matter maturation in a tract-based fashion. Compared to most previous studies that are ROI-based, our approach has the potential to discover localized development patterns associated with fiber tracts of interest.

Quality Control of Diffusion Weighted Images

Diffusion Tensor Imaging (DTI) has become an important MRI procedure to investigate the integrity of white matter in brain in vivo. DTI is estimated from a series of acquired Diffusion Weighted Imaging (DWI) volumes. DWI data suffers from inherent low SNR, overall long scanning time of multiple directional encoding with correspondingly large risk to encounter several kinds of artifacts. These artifacts can be too severe for a correct and stable estimation of the diffusion tensor. Thus, a quality control (QC) procedure is absolutely necessary for DTI studies. Currently, routine DTI QC procedures are conducted manually by visually checking the DWI data set in a gradient by gradient and slice by slice way. The results often suffer from low consistence across different data sets, lack of agreement of different experts, and difficulty to judge motion artifacts by qualitative inspection. Additionally considerable manpower is needed for this step due to the large number of images to QC, which is common for group comparison and longitudinal studies, especially with increasing number of diffusion gradient directions. We present a framework for automatic DWI QC. We developed a tool called DTIPrep which pipelines the QC steps with a detailed protocoling and reporting facility. And it is fully open source. This framework/tool has been successfully applied to several DTI studies with several hundred DWIs in our lab as well as collaborating labs in Utah and Iowa. In our studies, the tool provides a crucial piece for robust DTI analysis in brain white matter study.

DTI registration in atlas based fiber analysis of infantile Krabbe disease.

In recent years, diffusion tensor imaging (DTI) has become the modality of choice to investigate white matter pathology in the developing brain. To study neonate Krabbe disease with DTI, we evaluate the performance of linear and non-linear DTI registration algorithms for atlas based fiber tract analysis. The DTI scans of 10 age-matched neonates with infantile Krabbe disease are mapped into an atlas for the analysis of major fiber tracts - the genu and splenium of the corpus callosum, the internal capsules tracts and the uncinate fasciculi. The neonate atlas is based on 377 healthy control subjects, generated using an unbiased diffeomorphic atlas building method. To evaluate the performance of one linear and seven nonlinear commonly used registration algorithms for DTI we propose the use of two novel evaluation metrics: a regional matching quality criterion incorporating the local tensor orientation similarity, and a fiber property profile based metric using normative correlation. Our experimental results indicate that the whole tensor based registration method within the DTI-ToolKit (DTI-TK) shows the best performance for our application.

The DTI Challenge: Toward Standardized Evaluation of Diffusion Tensor Imaging Tractography for Neurosurgery

Diffusion tensor imaging (DTI) tractography reconstruction of white matter pathways can help guide brain tumor resection. However, DTI tracts are complex mathematical objects and the validity of tractography‐derived information in clinical settings has yet to be fully established. To address this issue, we initiated the DTI Challenge, an international working group of clinicians and scientists whose goal was to provide standardized evaluation of tractography methods for neurosurgery. The purpose of this empirical study was to evaluate different tractography techniques in the first DTI Challenge workshop.

Asymmetrical lateral ventricular enlargement in Parkinson’s disease

Background:  A recent case report suggested the presence of asymmetrical lateral ventricular enlargement associated with motor asymmetry in Parkinson’s disease (PD). The current study explored these associations further.

Multi-atlas segmentation of subcortical brain structures via the AutoSeg software pipeline

Automated segmenting and labeling of individual brain anatomical regions, in MRI are challenging, due to the issue of individual structural variability. Although atlas-based segmentation has shown its potential for both tissue and structure segmentation, due to the inherent natural variability as well as disease-related changes in MR appearance, a single atlas image is often inappropriate to represent the full population of datasets processed in a given neuroimaging study. As an alternative for the case of single atlas segmentation, the use of multiple atlases alongside label fusion techniques has been introduced using a set of individual “atlases” that encompasses the expected variability in the studied population. In our study, we proposed a multi-atlas segmentation scheme with a novel graph-based atlas selection technique. We first paired and co-registered all atlases and the subject MR scans. A directed graph with edge weights based on intensity and shape similarity between all MR scans is then computed. The set of neighboring templates is selected via clustering of the graph. Finally, weighted majority voting is employed to create the final segmentation over the selected atlases. This multi-atlas segmentation scheme is used to extend a single-atlas-based segmentation toolkit entitled AutoSeg, which is an open-source, extensible C++ based software pipeline employing BatchMake for its pipeline scripting, developed at the Neuro Image Research and Analysis Laboratories of the University of North Carolina at Chapel Hill. AutoSeg performs N4 intensity inhomogeneity correction, rigid registration to a common template space, automated brain tissue classification based skull-stripping, and the multi-atlas segmentation. The multi-atlas-based AutoSeg has been evaluated on subcortical structure segmentation with a testing dataset of 20 adult brain MRI scans and 15 atlas MRI scans. The AutoSeg achieved mean Dice coefficients of 81.73% for the subcortical structures.