Analyzing Heterogeneity In Neuroimaging With Probabilistic Multivariate Clustering Approaches

Automated quantitative neuroimaging analysis methods have been crucial in elucidating normal and pathological brain structure and function, and in building in vivo markers of disease and its progression. Commonly used methods can identify and precisely quantify subtle and spatially complex imaging patterns of brain change associated with brain diseases. However, the overarching premise of these methods is that the disease group is a homogeneous entity resulting from a single, unifying pathophysiological process that has a single imaging signature. This assumption ignores ample evidence for the heterogeneous nature of neurodegenerative diseases and neuropsychiatric disorders, resulting in incomplete or misleading descriptions. Accurate characterization of heterogeneity is important for deepening our understanding of neurobiological processes, thus leading to improved disease diagnosis and prognosis. In this thesis, we leveraged machine learning techniques to develop novel tools that can analyze the heterogeneity in both cross-sectional and longitudinal neuroimaging studies. Specifically, we developed a semi-supervised clustering method for characterizing heterogeneity in cross-sectional group comparison studies, where normal and patient populations are modeled as high-dimensional point distributions, and heterogeneous disease effects are captured by estimating multiple transformations that align the two distributions, while accounting for the effect of nuisance covariates. Moreover, toward dissecting the heterogeneity in longitudinal cohorts, we proposed a method which simultaneously fits multiple population longitudinal multivariate trajectories and clusters subjects into subgroups. Longitudinal trajectories are modeled using spatiotemporally regularized cubic splines, while clustering is performed by assigning subjects to the subgroup whose population trajectory best fits their data. The proposed tools were extensively validated using synthetic data. Importantly, they were applied to study the heterogeneity in large clinical neuroimaging cohorts. We identified four disease subtypes with distinct imaging signatures using data from Alzheimer’s Disease Neuroimaging Initiative, and revealed two subgroups with different longitudinal patterns using data from Baltimore Longitudinal Study on Aging. Critically, we were able to further characterize the subgroups in each of the studies by performing statistical analyses evaluating subgroup differences with additional information such as neurocognitive data. Our results demonstrate the strength of the developed methods, and may pave the road for a broader understanding of the complexity of brain aging and Alzheimer’s disease

Laser Ultrasound Inspection Based on Wavelet Transform and Data Clustering for Defect Estimation in Metallic Samples

Laser-generated ultrasound is a modern non-destructive testing technique. It has been investigated over recent years as an alternative to classical ultrasonic methods, mainly in industrial maintenance and quality control procedures. In this study, the detection and reconstruction of internal defects in a metallic sample is performed by means of a time-frequency analysis of ultrasonic waves generated by a laser-induced thermal mechanism. In the proposed methodology, we used wavelet transform due to its multi-resolution time frequency characteristics. In order to isolate and estimate the corresponding time of flight of eventual ultrasonic echoes related to internal defects, a density-based spatial clustering was applied to the resulting time frequency maps. Using the laser scan beam’s position, the ultrasonic transducer’s location and the echoes’ arrival times were determined, the estimation of the defect’s position was carried out afterwards. Finally, clustering algorithms were applied to the resulting geometric solutions from the set of the laser scan points which was proposed to obtain a two-dimensional projection of the defect outline over the scan plane. The study demonstrates that the proposed method of wavelet transform ultrasonic imaging can be effectively applied to detect and size internal defects without any reference information, which represents a valuable outcome for various applications in the industry. View Full-TextPeer ReviewedPostprint (published version

KL Estimation of the Power Spectrum Parameters from the Angular Distribution of Galaxies in Early SDSS Data

We present measurements of parameters of the 3-dimensional power spectrum of galaxy clustering from 222 square degrees of early imaging data in the Sloan Digital Sky Survey. The projected galaxy distribution on the sky is expanded over a set of Karhunen-Loeve eigenfunctions, which optimize the signal-to-noise ratio in our analysis. A maximum likelihood analysis is used to estimate parameters that set the shape and amplitude of the 3-dimensional power spectrum. Our best estimates are Gamma=0.188 +/- 0.04 and sigma_8L = 0.915 +/- 0.06 (statistical errors only), for a flat Universe with a cosmological constant. We demonstrate that our measurements contain signal from scales at or beyond the peak of the 3D power spectrum. We discuss how the results scale with systematic uncertainties, like the radial selection function. We find that the central values satisfy the analytically estimated scaling relation. We have also explored the effects of evolutionary corrections, various truncations of the KL basis, seeing, sample size and limiting magnitude. We find that the impact of most of these uncertainties stay within the 2-sigma uncertainties of our fiducial result.Comment: Fig 1 postscript problem correcte

Mapping Topographic Structure in White Matter Pathways with Level Set Trees

Fiber tractography on diffusion imaging data offers rich potential for describing white matter pathways in the human brain, but characterizing the spatial organization in these large and complex data sets remains a challenge. We show that level set trees---which provide a concise representation of the hierarchical mode structure of probability density functions---offer a statistically-principled framework for visualizing and analyzing topography in fiber streamlines. Using diffusion spectrum imaging data collected on neurologically healthy controls (N=30), we mapped white matter pathways from the cortex into the striatum using a deterministic tractography algorithm that estimates fiber bundles as dimensionless streamlines. Level set trees were used for interactive exploration of patterns in the endpoint distributions of the mapped fiber tracks and an efficient segmentation of the tracks that has empirical accuracy comparable to standard nonparametric clustering methods. We show that level set trees can also be generalized to model pseudo-density functions in order to analyze a broader array of data types, including entire fiber streamlines. Finally, resampling methods show the reliability of the level set tree as a descriptive measure of topographic structure, illustrating its potential as a statistical descriptor in brain imaging analysis. These results highlight the broad applicability of level set trees for visualizing and analyzing high-dimensional data like fiber tractography output

Role of thermal friction in relaxation of turbulent Bose-Einstein condensates

In recent experiments, the relaxation dynamics of highly oblate, turbulent Bose-Einstein condensates (BECs) was investigated by measuring the vortex decay rates in various sample conditions [Phys. Rev. A $\bf 90$, 063627 (2014)] and, separately, the thermal friction coefficient $\alpha$ for vortex motion was measured from the long-time evolution of a corotating vortex pair in a BEC [Phys. Rev. A $\bf 92$, 051601(R) (2015)]. We present a comparative analysis of the experimental results, and find that the vortex decay rate $\Gamma$ is almost linearly proportional to $\alpha$. We perform numerical simulations of the time evolution of a turbulent BEC using a point-vortex model equipped with longitudinal friction and vortex-antivortex pair annihilation, and observe that the linear dependence of $\Gamma$ on $\alpha$ is quantitatively accounted for in the dissipative point-vortex model. The numerical simulations reveal that thermal friction in the experiment was too strong to allow for the emergence of a vortex-clustered state out of decaying turbulence.Comment: 7 pages, 5 figure