Faculty Bibliography

Shape analysis has become of increasing interest to the neuroimaging community due to its potential to precisely locate morphological changes between healthy and pathological structures. This manuscript presents a C comprehensive set of tools for the computation of 3D structural statistical shape analysis. It has been applied in several studies on brain morphometry, but can potentially be employed in other 3D shape problems. Its main limitations is the necessity of spherical topology. The input of the proposed shape analysis is a set of binary segmentation of a single brain structure, such as the hippocampus or caudate. These segmentations are converted into a corresponding spherical harmonic description (SPHARM), which is then sampled into a triangulated surfaces (SPHARM-PDM). After alignment, differences between groups of surfaces are computed using the Hotelling T(2) two sample metric. Statistical p-values, both raw and corrected for multiple comparisons, result in significance maps. Additional visualization of the group tests are provided via mean difference magnitude and vector maps, as well as maps of the group covariance information. The correction for multiple comparisons is performed via two separate methods that each have a distinct view of the problem. The first one aims to control the family-wise error rate (FWER) or false-positives via the extrema histogram of non-parametric permutations. The second method controls the false discovery rate and results in a less conservative estimate of the false-negatives. Prior versions of this shape analysis framework have been applied already to clinical studies on hippocampus and lateral ventricle shape in adult schizophrenics. The novelty of this submission is the use of the Hotelling, T2 two-sample group difference metric for the computation of a template free statistical shape analysis. Template free group testing allowed this framework to become independent of any template choice. as well as it improved the sensitivity of our method considerably. In addition to our existing correction methodology for the multiple comparison problem using non-parametric permutation tests, we have extended the testing framework to include False Discovery Rate (FDR). FDR provides a significance correction with higher sensitivity while allowing a expected minimal amount of false-positives compared to our prior testing scheme.

OBJECTIVE: The corpus callosum is the primary anatomical substrate for interhemispheric communication, which is important for a range of adaptive and cognitive behaviors in early development. Previous studies that have measured the corpus callosum in developmental populations have been limited by the use of rather arbitrary methods of subdividing the corpus callosum. The purpose of this study was to measure the corpus callosum in a clinical group of developmentally delayed children using a subdivision that more accurately reflected the anatomical properties of the corpus callosum. METHOD: The authors applied tractography to subdivide the corpus callosum into regions corresponding to the cortical regions to and from which its fibers travel in a clinical group of very young children with developmental delay, a precursor to general mental retardation, in comparison with typically developing children. RESULTS: The data demonstrate that the midsagittal area of the entire corpus callosum is reduced in children presenting with developmental delay, reflected in the smaller area of each of the fiber-based callosal subdivisions. In addition, while the area of each subdivision was strongly and significantly correlated with the corresponding cortical white matter volume in comparison subjects, this correlation was prominently absent in the developmentally delayed group. CONCLUSIONS: A fiber-based subdivision successfully separates lobar regions of the corpus callosum, and the areas of these regions distinguish a developmentally delayed clinical group from the comparison group. This distinction was evident both in the area measurements themselves and in their correlation to the white matter volumes of the corresponding cortical lobes.

Quantitative diffusion tensor imaging (DTI) has become the major imaging 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 of 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 systematically includes tensor interpolation and averaging, using nonlinear Riemannian symmetric space. A new measure of tensor anisotropy, called geodesic anisotropy (GA) is applied and compared with FA. As a result, tracts of interest are represented by the geometry of the medial spine attributed with tensor statistics (average and variance) calculated within cross-sections. Feasibility of our approach is demonstrated on various fiber tracts of a single data set. A validation study, based on six repeated scans of the same subject, assesses the reproducibility of this new DTI data analysis framework.

Active contour segmentation and its robust implementation using level set methods are well-established theoretical approaches that have been studied thoroughly in the image analysis literature. Despite the existence of these powerful segmentation methods, the needs of clinical research continue to be fulfilled, to a large extent, using slice-by-slice manual tracing. To bridge the gap between methodological advances and clinical routine, we developed an open source application called ITK-SNAP, which is intended to make level set segmentation easily accessible to a wide range of users, including those with little or no mathematical expertise. This paper describes the methods and software engineering philosophy behind this new tool and provides the results of validation experiments performed in the context of an ongoing child autism neuroimaging study. The validation establishes SNAP intrarater and interrater reliability and overlap error statistics for the caudate nucleus and finds that SNAP is a highly reliable and efficient alternative to manual tracing. Analogous results for lateral ventricle segmentation are provided.

In this paper, we present a Bayesian framework for both generating inter-subject large deformation transformations between two multi-modal image sets of the brain and for forming multi-class brain atlases. In this framework, the estimated transformations are generated using maximal information about the underlying neuroanatomy present in each of the different modalities. This modality independent registration framework is achieved by jointly estimating the posterior probabilities associated with the multi-modal image sets and the high-dimensional registration transformations mapping these posteriors. To maximally use the information present in all the modalities for registration, Kullback-Leibler divergence between the estimated posteriors is minimized. Registration results for image sets composed of multi-modal MR images of healthy adult human brains are presented. Atlas formation results are presented for a population of five infant human brains.