Unified Heat Kernel Regression for Diffusion, Kernel Smoothing and Wavelets on Manifolds and Its Application to Mandible Growth Modeling in CT Images

We present a novel kernel regression framework for smoothing scalar surface data using the Laplace-Beltrami eigenfunctions. Starting with the heat kernel constructed from the eigenfunctions, we formulate a new bivariate kernel regression framework as a weighted eigenfunction expansion with the heat kernel as the weights. The new kernel regression is mathematically equivalent to isotropic heat diffusion, kernel smoothing and recently popular diffusion wavelets. Unlike many previous partial differential equation based approaches involving diffusion, our approach represents the solution of diffusion analytically, reducing numerical inaccuracy and slow convergence. The numerical implementation is validated on a unit sphere using spherical harmonics. As an illustration, we have applied the method in characterizing the localized growth pattern of mandible surfaces obtained in CT images from subjects between ages 0 and 20 years by regressing the length of displacement vectors with respect to the template surface.Comment: Accepted in Medical Image Analysi

Nonparametric tests of structure for high angular resolution diffusion imaging in Q-space

High angular resolution diffusion imaging data is the observed characteristic function for the local diffusion of water molecules in tissue. This data is used to infer structural information in brain imaging. Nonparametric scalar measures are proposed to summarize such data, and to locally characterize spatial features of the diffusion probability density function (PDF), relying on the geometry of the characteristic function. Summary statistics are defined so that their distributions are, to first-order, both independent of nuisance parameters and also analytically tractable. The dominant direction of the diffusion at a spatial location (voxel) is determined, and a new set of axes are introduced in Fourier space. Variation quantified in these axes determines the local spatial properties of the diffusion density. Nonparametric hypothesis tests for determining whether the diffusion is unimodal, isotropic or multi-modal are proposed. More subtle characteristics of white-matter microstructure, such as the degree of anisotropy of the PDF and symmetry compared with a variety of asymmetric PDF alternatives, may be ascertained directly in the Fourier domain without parametric assumptions on the form of the diffusion PDF. We simulate a set of diffusion processes and characterize their local properties using the newly introduced summaries. We show how complex white-matter structures across multiple voxels exhibit clear ellipsoidal and asymmetric structure in simulation, and assess the performance of the statistics in clinically-acquired magnetic resonance imaging data.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS441 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Dynamic Decomposition of Spatiotemporal Neural Signals

Neural signals are characterized by rich temporal and spatiotemporal dynamics that reflect the organization of cortical networks. Theoretical research has shown how neural networks can operate at different dynamic ranges that correspond to specific types of information processing. Here we present a data analysis framework that uses a linearized model of these dynamic states in order to decompose the measured neural signal into a series of components that capture both rhythmic and non-rhythmic neural activity. The method is based on stochastic differential equations and Gaussian process regression. Through computer simulations and analysis of magnetoencephalographic data, we demonstrate the efficacy of the method in identifying meaningful modulations of oscillatory signals corrupted by structured temporal and spatiotemporal noise. These results suggest that the method is particularly suitable for the analysis and interpretation of complex temporal and spatiotemporal neural signals

Higher-Order Tensors and Differential Topology in Diffusion MRI Modeling and Visualization

Diffusion Weighted Magnetic Resonance Imaging (DW-MRI) is a noninvasive method for creating three-dimensional scans of the human brain. It originated mostly in the 1970s and started its use in clinical applications in the 1980s. Due to its low risk and relatively high image quality it proved to be an indispensable tool for studying medical conditions as well as for general scientific research. For example, it allows to map fiber bundles, the major neuronal pathways through the brain. But all evaluation of scanned data depends on mathematical signal models that describe the raw signal output and map it to biologically more meaningful values. And here we find the most potential for improvement. In this thesis we first present a new multi-tensor kurtosis signal model for DW-MRI. That means it can detect multiple overlapping fiber bundles and map them to a set of tensors. Compared to other already widely used multi-tensor models, we also add higher order kurtosis terms to each fiber. This gives a more detailed quantification of fibers. These additional values can also be estimated by the Diffusion Kurtosis Imaging (DKI) method, but we show that these values are drastically affected by fiber crossings in DKI, whereas our model handles them as intrinsic properties of fiber bundles. This reduces the effects of fiber crossings and allows a more direct examination of fibers. Next, we take a closer look at spherical deconvolution. It can be seen as a generalization of multi-fiber signal models to a continuous distribution of fiber directions. To this approach we introduce a novel mathematical constraint. We show, that state-of-the-art methods for estimating the fiber distribution become more robust and gain accuracy when enforcing our constraint. Additionally, in the context of our own deconvolution scheme, it is algebraically equivalent to enforcing that the signal can be decomposed into fibers. This means, tractography and other methods that depend on identifying a discrete set of fiber directions greatly benefit from our constraint. Our third major contribution to DW-MRI deals with macroscopic structures of fiber bundle geometry. In recent years the question emerged, whether or not, crossing bundles form two-dimensional surfaces inside the brain. Although not completely obvious, there is a mathematical obstacle coming from differential topology, that prevents general tangential planes spanned by fiber directions at each point to be connected into consistent surfaces. Research into how well this constraint is fulfilled in our brain is hindered by the high precision and complexity needed by previous evaluation methods. This is why we present a drastically simpler method that negates the need for precisely finding fiber directions and instead only depends on the simple diffusion tensor method (DTI). We then use our new method to explore and improve streamsurface visualization.<br /

Detecting and visualizing differences in brain structures with SPHARM and functional data analysis

A new procedure for classifying brain structures described by SPHARM is presented. We combine a dimension reduction technique (functional principal component analysis or functional independent component analysis) with stepwise variable selection for linear discriminant classification. This procedure is compared with many well-known methods in a novel classification problem in neuroeducation, where the reversal error (a common error in mathematical problem solving) is analyzed by using the left and right putamens of 33 participants. The comparison shows that our proposal not only provides outstanding performance in terms of predictive power, but it is also valuable in terms of interpretation, since it yields a linear discriminant function for 3D structures

Shape analysis of the human brain.

Autism is a complex developmental disability that has dramatically increased in prevalence, having a decisive impact on the health and behavior of children. Methods used to detect and recommend therapies have been much debated in the medical community because of the subjective nature of diagnosing autism. In order to provide an alternative method for understanding autism, the current work has developed a 3-dimensional state-of-the-art shape based analysis of the human brain to aid in creating more accurate diagnostic assessments and guided risk analyses for individuals with neurological conditions, such as autism. Methods: The aim of this work was to assess whether the shape of the human brain can be used as a reliable source of information for determining whether an individual will be diagnosed with autism. The study was conducted using multi-center databases of magnetic resonance images of the human brain. The subjects in the databases were analyzed using a series of algorithms consisting of bias correction, skull stripping, multi-label brain segmentation, 3-dimensional mesh construction, spherical harmonic decomposition, registration, and classification. The software algorithms were developed as an original contribution of this dissertation in collaboration with the BioImaging Laboratory at the University of Louisville Speed School of Engineering. The classification of each subject was used to construct diagnoses and therapeutic risk assessments for each patient. Results: A reliable metric for making neurological diagnoses and constructing therapeutic risk assessment for individuals has been identified. The metric was explored in populations of individuals having autism spectrum disorders, dyslexia, Alzheimers disease, and lung cancer. Conclusion: Currently, the clinical applicability and benefits of the proposed software approach are being discussed by the broader community of doctors, therapists, and parents for use in improving current methods by which autism spectrum disorders are diagnosed and understood

Development of High Angular Resolution Diffusion Imaging Analysis Paradigms for the Investigation of Neuropathology

Diffusion weighted magnetic resonance imaging (DW-MRI), provides unique insight into the microstructure of neural white matter tissue, allowing researchers to more fully investigate white matter disorders. The abundance of clinical research projects incorporating DW-MRI into their acquisition protocols speaks to the value this information lends to the study of neurological disease. However, the most widespread DW-MRI technique, diffusion tensor imaging (DTI), possesses serious limitations which restrict its utility in regions of complex white matter. Fueled by advances in DW-MRI acquisition protocols and technologies, a group of exciting new DW-MRI models, developed to address these concerns, are now becoming available to clinical researchers. The emergence of these new imaging techniques, categorized as high angular resolution diffusion imaging (HARDI), has generated the need for sophisticated computational neuroanatomic techniques able to account for the high dimensionality and structure of HARDI data. The goal of this thesis is the development of such techniques utilizing prominent HARDI data models. Specifically, methodologies for spatial normalization, population atlas building and structural connectivity have been developed and validated. These methods form the core of a comprehensive analysis paradigm allowing the investigation of local white matter microarcitecture, as well as, systemic properties of neuronal connectivity. The application of this framework to the study of schizophrenia and the autism spectrum disorders demonstrate its sensitivity sublte differences in white matter organization, as well as, its applicability to large population DW-MRI studies