Faculty Bibliography

BACKGROUND: Many psychiatric and neurodevelopmental disorders are associated with mild enlargement of the lateral ventricles thought to have origins in prenatal brain development. Little is known about development of the lateral ventricles and the relationship of prenatal lateral ventricle enlargement with postnatal brain development. METHODS: We performed neonatal magnetic resonance imaging on 34 children with isolated mild ventriculomegaly (MVM; width of the atrium of the lateral ventricle >/= 1.0 cm) on prenatal ultrasound and 34 age- and sex-matched control subjects with normal prenatal ventricle size. Lateral ventricle and cortical gray and white matter volumes were assessed. Fractional anisotropy (FA) and mean diffusivity (MD) in corpus callosum and corticospinal white matter tracts were determined obtained using quantitative tractography. RESULTS: Neonates with prenatal MVM had significantly larger lateral ventricle volumes than matched control subjects (286.4%; p < .0001). Neonates with MVM also had significantly larger intracranial volumes (ICV; 7.1%, p = .0063) and cortical gray matter volumes (10.9%, p = .0004) compared with control subjects. Diffusion tensor imaging tractography revealed a significantly greater MD in the corpus callosum and corticospinal tracts, whereas FA was significantly smaller in several white matter tract regions. CONCLUSIONS: Prenatal enlargement of the lateral ventricle is associated with enlargement of the lateral ventricles after birth, as well as greater gray matter volumes and delayed or abnormal maturation of white matter. It is suggested that prenatal ventricle volume is an early structural marker of altered development of the cerebral cortex and may be a marker of risk for neuropsychiatric disorders associated with ventricle enlargement.

BACKGROUND: A reduction in interhemispheric connectivity is thought to contribute to the etiology of schizophrenia. Diffusion Tensor Imaging (DTI) measures the diffusion of water and can be used to describe the integrity of the corpus callosum white matter tracts, thereby providing information concerning possible interhemispheric connectivity abnormalities. Previous DTI studies in schizophrenia are inconsistent in reporting decreased Fractional Anisotropy (FA), a measure of anisotropic diffusion, within different portions of the corpus callosum. Moreover, none of these studies has investigated corpus callosum systematically, using anatomical subdivisions. METHODS: DTI and structural MRI scans were obtained from 32 chronic schizophrenic subjects and 42 controls. Corpus callosum cross sectional area and its probabilistic subdivisions were determined automatically from structural MRI scans using a model based deformable contour segmentation. These subdivisions employ a previously generated probabilistic subdivision atlas, based on fiber tractography and anatomical lobe subdivision. The structural scan was then co-registered with the DTI scan and the anatomical corpus callosum subdivisions were propagated to the associated FA map. RESULTS: Results revealed decreased FA within parts of the corpus interconnecting frontal regions in schizophrenia compared with controls, but no significant changes for callosal fibers interconnecting parietal and temporo-occipital brain regions. In addition, integrity of the anterior corpus was statistically significantly correlated with negative as well as positive symptoms, while posterior measures correlated with positive symptoms only. CONCLUSIONS: This study provides quantitative evidence for a reduction of interhemispheric brain connectivity in schizophrenia, involving corpus callosum, and further points to frontal connections as possibly disrupted in schizophrenia.

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.

BACKGROUND AND PURPOSE: Unlike conventional functional MR imaging where external sensory/cognitive paradigms are needed to specifically activate different regions of the brain, resting functional connectivity MR imaging acquires images in the absence of cognitive demands (a resting condition) and detects brain regions, which are highly temporally correlated. Therefore, resting functional MR imaging is highly suited for the study of brain functional development in pediatric subjects. This study aimed to determine the temporal and spatial patterns of rfc in healthy pediatric subjects between 2 weeks and 2 years of age. MATERIALS AND METHODS: Rfc studies were performed on 85 children: 38 neonates (2-4 weeks of age), 26 one-year-olds, and 21 two-year-olds. All subjects were imaged while asleep; no sedation was used. Six regions of interest were chosen, including the primary motor, sensory, and visual cortices in each hemisphere. Mean signal intensity of each region of interest was used to perform correlation analysis pixel by pixel throughout the entire brain, identifying regions with high temporal correlation. RESULTS: Functional connectivity was observed in all subjects in the sensorimotor and visual areas. The percent brain volume exhibiting rfc and the strength of rfc continued to increase from 2 weeks to 2 years. The growth trajectories of the percent brain volume of rfc appeared to differ between the sensorimotor and visual areas, whereas the z-score was similar. The percent brain volume of rfc in the sensorimotor area was significantly larger than that in the visual area for subjects 2 weeks of age (P = .008) and 1-year-olds (P = .017) but not for the 2-year-olds. CONCLUSIONS: These findings suggest that rfc in the sensorimotor precedes that in the visual area from 2 weeks to 1 year but becomes comparable at 2 years. In contrast, the comparable z-score values between the sensorimotor and visual areas for all age groups suggest a disassociation between percent brain volume and the strength of cortical rfc.

Data sharing in autism neuroimaging presents scientific, technical, and social obstacles. We outline the desiderata for a data-sharing scheme that combines imaging with other measures of phenotype and with genetics, defines requirements for comparability of derived data and recommendations for raw data, outlines a core protocol including multispectral structural and diffusion-tensor imaging and optional extensions, provides for the collection of prospective, confound-free normative data, and extends sharing and collaborative development not only to data but to the analytical tools and methods applied to these data. A theme in these requirements is the need to preserve creative approaches and risk-taking within individual laboratories at the same time as common standards are provided for these laboratories to build on.

This paper describes a framework for quantitative analysis of neuroimaging data of traveling human phantoms used for cross-site validation. We focus on the analysis of magnetic resonance image data including intra- and inter-site comparison. Locations and magnitude of geometric deformation is studied via unbiased atlas building and metrics on deformation fields. Variability of tissue segmentation is analyzed by comparison of volumes, overlap of tissue maps, and a new Kullback-Leibler divergence on tissue probabilities, with emphasis on comparing probabilistic rather than binary segmentations. We show that results from this information theoretic measure are highly correlated with overlap. Reproducibility of automatic, atlas-based segmentation of subcortical structures is examined by comparison of volumes, shape overlap and surface distances. Variability among scanners of the same type but also differences to a different scanner type are discussed. The results demonstrate excellent reliability across multiple sites that can be achieved by the use of the today's scanner generation and powerful automatic analysis software. Knowledge about such variability is crucial for study design and power analysis in new multi-site clinical studies.

We present a framework for hypothesis testing of differences between groups of DTI fiber tracts. An anatomical, tract-oriented coordinate system provides a basis for estimating the distribution of diffusion properties. The parametrization of sampled, smooth functions is normalized across a population using DTI atlas building. Functional data analysis, an extension of multivariate statistics to continuous functions is applied to the problem of hypothesis testing and discrimination. B-spline models of fractional anisotropy (FA) and Frobenius norm measures are analyzed jointly. Plots of the discrimination direction provide a clinical interpretation of the group differences. The methodology is tested on a pediatric study of subjects aged one and two years.

The topic of studying the growth of human brain development has become of increasing interest in the neuroimaging community. Cross-sectional studies may allow comparisons between means of different age groups, but they do not provide a growth model that integrates the continuum of time, nor do they present any information about how individuals/population change over time. Longitudinal data analysis method arises as a strong tool to address these questions. In this paper, we use longitudinal analysis methods to study tissue development in early brain growth. A novel approach of multivariate longitudinal analysis is applied to study the associations between the growth of different brain tissues. In this paper, we present the methodologies to statistically study scalar (univariate) and vector (multivariate) longitudinal data, and demonstrate exploratory results in a neuroimaging study of early brain tissue development. We obtained growth curves as a quadratic function of time for all three tissues. The quadratic terms were tested to be statistically significant, showing that there was indeed a quadratic growth of tissues in early brain development. Moreover, our result shows that there is a positive correlation between repeated measurements of any single tissue, and among those of different tissues. Our approach is generic in natural and thus can be applied to any longitudinal data with multiple outcomes, even brain structures. Also, our joint mixed model is flexible enough to allow incomplete and unbalanced data, i.e. subjects do not need to have the same number of measurements, or be measured at the exact time points.

Establishing optimal correspondence across object populations is essential to statistical shape analysis. Minimizing the description length (MDL) is a popular method for finding correspondence. In this work, we extend the MDL method by incorporating various local curvature metrics. Using local curvature can improve performance by ensuring that corresponding points exhibit similar local geometric characteristics that can't always be captured by mere point locations. We illustrate results on a variety of anatomical structures. The MDL method with a combination of point locations and curvature outperforms all the other methods we analyzed, including traditional MDL and spherical harmonics (SPHARM) correspondence, when the analyzed object population exhibits complex structure. When the objects are of simple nature, however, there's no added benefit to using the local curvature. In our experiments, we did not observe a significant difference in the correspondence quality when different curvature metrics (e.g. principal curvatures, mean curvature, Gaussian curvature) were used.