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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 propose d 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.
Dynamic Contrast-enhanced Magnetic Resonance Imaging (DCE-MRI) is an important tool for detecting subtle kinetic changes in cancerous tissue. Quantitative analysis of DCE-MRI typically involves the convolution of an arterial input function (AIF) with a nonlinear pharmacokinetic model of the contrast agent concentration. Parameters of the kinetic model are biologically meaningful, but the optimization of the non-linear model has significant computational issues. In practice, convergence of the optimization algorithm is not guaranteed and the accuracy of the model fitting may be compromised. To overcome this problems, this paper proposes a semi-parametric penalized spline smoothing approach, with which the AIF is convolved with a set of B-splines to produce a design matrix using locally adaptive smoothing parameters based on Bayesian penalized spline models (P-splines). It has been shown that kinetic parameter estimation can be obtained from the resulting deconvolved response function, which also includes the onset of contrast enhancement. Detailed validation of the method, both with simulated and in vivo data, is provided.
Imaging in clinical oncology trials provides a wealth of information that contributes to the drug development process, especially in early phase studies. This paper focuses on kinetic modeling in DCE-MRI, inspired by mixed-effects models that are fre quently used in the analysis of clinical trials. Instead of summarizing each scanning session as a single kinetic parameter -- such as median $ktrans$ across all voxels in the tumor ROI -- we propose to analyze all voxel time courses from all scans and across all subjects simultaneously in a single model. The kinetic parameters from the usual non-linear regression model are decomposed into unique components associated with factors from the longitudinal study; e.g., treatment, patient and voxel effects. A Bayesian hierarchical model provides the framework in order to construct a data model, a parameter model, as well as prior distributions. The posterior distribution of the kinetic parameters is estimated using Markov chain Monte Carlo (MCMC) methods. Hypothesis testing at the study level for an overall treatment effect is straightforward and the patient- and voxel-level parameters capture random effects that provide additional information at various levels of resolution to allow a thorough evaluation of the clinical trial. The proposed method is validated with a breast cancer study, where the subjects were imaged before and after two cycles of chemotherapy, demonstrating the clinical potential of this method to longitudinal oncology studies.
The fundamental equations that model turbulent flow do not provide much insight into the size and shape of observed turbulent structures. We investigate the efficient and accurate representation of structures in two-dimensional turbulence by applying statistical models directly to the simulated vorticity field. Rather than extract the coherent portion of the image from the background variation, as in the classical signal-plus-noise model, we present a model for individual vortices using the non-decimated discrete wavelet transform. A template image, supplied by the user, provides the features to be extracted from the vorticity field. By transforming the vortex template into the wavelet domain, specific characteristics present in the template, such as size and symmetry, are broken down into components associated with spatial frequencies. Multivariate multiple linear regression is used to fit the vortex template to the vorticity field in the wavelet domain. Since all levels of the template decomposition may be used to model each level in the field decomposition, the resulting model need not be identical to the template. Application to a vortex census algorithm that records quantities of interest (such as size, peak amplitude, circulation, etc.) as the vorticity field evolves is given. The multiresolution census algorithm extracts coherent structures of all shapes and sizes in simulated vorticity fields and is able to reproduce known physical scaling laws when processing a set of voriticity fields that evolve over time.
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