A Note on the Validity of Statistical Bootstrapping for Estimating the Uncertainty of Tensor Parameters in Diffusion Tensor Images

Diffusion tensors are estimated from magnetic resonance images (MRIs) that are diffusion-weighted, and those images inherently contain noise. Therefore, noise in the diffusion-weighted images produces uncertainty in estimation of the tensors and their derived parameters, which include eigenvalues, eigenvectors, and the trajectories of fiber pathways that are reconstructed from those eigenvalues and eigenvectors. Although repetition and wild bootstrap methods have been widely used to quantify the uncertainty of diffusion tensors and their derived parameters, we currently lack theoretical derivations that would validate the use of these two bootstrap methods for the estimation of statistical parameters of tensors in the presence of noise. The aim of this paper is to examine theoretically and numerically the repetition and wild bootstrap methods for approximating uncertainty in estimation of diffusion tensor parameters under two different schemes for acquiring diffusion weighted images. Whether these bootstrap methods can be used to quantify uncertainty in some diffusion tensor parameters, such as fractional anisotropy (FA), depends critically on the morphology of the diffusion tensor that is being estimated. The wild and repetition bootstrap methods in particular cannot quantify uncertainty in the principal direction (PD) of isotropic (or oblate) tensor. We also examine the use of bootstrap methods in estimating tensors in a voxel containing multiple tensors, demonstrating their limitations when quantifying the uncertainty of tensor parameters in those locations. Simulation studies are also used to understand more thoroughly our theoretical results. Our findings raise serious concerns about the use of bootstrap methods to quantify the uncertainty of fiber pathways when those pathways pass through voxels that contain either isotropic tensors, oblate tensors, or multiple tensors

Bayesian uncertainty quantification in linear models for diffusion MRI

Diffusion MRI (dMRI) is a valuable tool in the assessment of tissue microstructure. By fitting a model to the dMRI signal it is possible to derive various quantitative features. Several of the most popular dMRI signal models are expansions in an appropriately chosen basis, where the coefficients are determined using some variation of least-squares. However, such approaches lack any notion of uncertainty, which could be valuable in e.g. group analyses. In this work, we use a probabilistic interpretation of linear least-squares methods to recast popular dMRI models as Bayesian ones. This makes it possible to quantify the uncertainty of any derived quantity. In particular, for quantities that are affine functions of the coefficients, the posterior distribution can be expressed in closed-form. We simulated measurements from single- and double-tensor models where the correct values of several quantities are known, to validate that the theoretically derived quantiles agree with those observed empirically. We included results from residual bootstrap for comparison and found good agreement. The validation employed several different models: Diffusion Tensor Imaging (DTI), Mean Apparent Propagator MRI (MAP-MRI) and Constrained Spherical Deconvolution (CSD). We also used in vivo data to visualize maps of quantitative features and corresponding uncertainties, and to show how our approach can be used in a group analysis to downweight subjects with high uncertainty. In summary, we convert successful linear models for dMRI signal estimation to probabilistic models, capable of accurate uncertainty quantification.Comment: Added results from a group analysis and a comparison with residual bootstra

Evaluating the accuracy of diffusion MRI models in white matter

Models of diffusion MRI within a voxel are useful for making inferences about the properties of the tissue and inferring fiber orientation distribution used by tractography algorithms. A useful model must fit the data accurately. However, evaluations of model-accuracy of some of the models that are commonly used in analyzing human white matter have not been published before. Here, we evaluate model-accuracy of the two main classes of diffusion MRI models. The diffusion tensor model (DTM) summarizes diffusion as a 3-dimensional Gaussian distribution. Sparse fascicle models (SFM) summarize the signal as a linear sum of signals originating from a collection of fascicles oriented in different directions. We use cross-validation to assess model-accuracy at different gradient amplitudes (b-values) throughout the white matter. Specifically, we fit each model to all the white matter voxels in one data set and then use the model to predict a second, independent data set. This is the first evaluation of model-accuracy of these models. In most of the white matter the DTM predicts the data more accurately than test-retest reliability; SFM model-accuracy is higher than test-retest reliability and also higher than the DTM, particularly for measurements with (a) a b-value above 1000 in locations containing fiber crossings, and (b) in the regions of the brain surrounding the optic radiations. The SFM also has better parameter-validity: it more accurately estimates the fiber orientation distribution function (fODF) in each voxel, which is useful for fiber tracking

On the Reliability of Diffusion Neuroimaging

Over the last years, diffusion imaging techniques like DTI, DSI or Q-Ball received increasin

Varying coefficient model for modeling diffusion tensors along white matter tracts

Diffusion tensor imaging provides important information on tissue structure and orientation of fiber tracts in brain white matter in vivo. It results in diffusion tensors, which are $3\times3$ symmetric positive definite (SPD) matrices, along fiber bundles. This paper develops a functional data analysis framework to model diffusion tensors along fiber tracts as functional data in a Riemannian manifold with a set of covariates of interest, such as age and gender. We propose a statistical model with varying coefficient functions to characterize the dynamic association between functional SPD matrix-valued responses and covariates. We calculate weighted least squares estimators of the varying coefficient functions for the log-Euclidean metric in the space of SPD matrices. We also develop a global test statistic to test specific hypotheses about these coefficient functions and construct their simultaneous confidence bands. Simulated data are further used to examine the finite sample performance of the estimated varying coefficient functions. We apply our model to study potential gender differences and find a statistically significant aspect of the development of diffusion tensors along the right internal capsule tract in a clinical study of neurodevelopment.Comment: Published in at http://dx.doi.org/10.1214/12-AOAS574 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Anisotropy Across Fields and Scales

This open access book focuses on processing, modeling, and visualization of anisotropy information, which are often addressed by employing sophisticated mathematical constructs such as tensors and other higher-order descriptors. It also discusses adaptations of such constructs to problems encountered in seemingly dissimilar areas of medical imaging, physical sciences, and engineering. Featuring original research contributions as well as insightful reviews for scientists interested in handling anisotropy information, it covers topics such as pertinent geometric and algebraic properties of tensors and tensor fields, challenges faced in processing and visualizing different types of data, statistical techniques for data processing, and specific applications like mapping white-matter fiber tracts in the brain. The book helps readers grasp the current challenges in the field and provides information on the techniques devised to address them. Further, it facilitates the transfer of knowledge between different disciplines in order to advance the research frontiers in these areas. This multidisciplinary book presents, in part, the outcomes of the seventh in a series of Dagstuhl seminars devoted to visualization and processing of tensor fields and higher-order descriptors, which was held in Dagstuhl, Germany, on October 28–November 2, 2018

Imaging diffusional variance by MRI [public] : The role of tensor-valued diffusion encoding and tissue heterogeneity

Diffusion MRI provides a non-invasive probe of tissue microstructure. We recently proposed a novel method for diffusion-weighted imaging, so-called q-space trajectory encoding, that facilitates tensor-valued diffusion encoding. This method grants access to b-tensors with multiple shapes and enables us to probe previously unexplored aspects of the tissue microstructure. Specifically, we can disentangle diffusional heterogeneity that originates from isotropic and anisotropic tissue structures; we call this diffusional variance decomposition (DIVIDE).In Paper I, we investigated the statistical uncertainty of the total diffusional variance in the healthy brain. We found that the statistical power was heterogeneous between brain regions which needs to be taken into account when interpreting results.In Paper II, we showed how spherical tensor encoding can be used to separate the total diffusional variance into its isotropic and anisotropic components. We also performed initial validation of the parameters in phantoms, and demonstrated that the imaging sequence could be implemented on a high-performance clinical MRI system. In Paper III and V, we explored DIVIDE parameters in healthy brain tissue and tumor tissue. In healthy tissue, we found that diffusion anisotropy can be probed on the microscopic scale, and that metrics of anisotropy on the voxel scale are confounded by the orientation coherence of the microscopic structures. In meningioma and glioma tumors, we found a strong association between anisotropic variance and cell eccentricity, and between isotropic variance and variable cell density. In Paper IV, we developed a method to optimize waveforms for tensor-valued diffusion encoding, and in Paper VI we demonstrated that whole-brain DIVIDE is technically feasible at most MRI systems in clinically feasible scan times

Anisotropy Across Fields and Scales

This open access book focuses on processing, modeling, and visualization of anisotropy information, which are often addressed by employing sophisticated mathematical constructs such as tensors and other higher-order descriptors. It also discusses adaptations of such constructs to problems encountered in seemingly dissimilar areas of medical imaging, physical sciences, and engineering. Featuring original research contributions as well as insightful reviews for scientists interested in handling anisotropy information, it covers topics such as pertinent geometric and algebraic properties of tensors and tensor fields, challenges faced in processing and visualizing different types of data, statistical techniques for data processing, and specific applications like mapping white-matter fiber tracts in the brain. The book helps readers grasp the current challenges in the field and provides information on the techniques devised to address them. Further, it facilitates the transfer of knowledge between different disciplines in order to advance the research frontiers in these areas. This multidisciplinary book presents, in part, the outcomes of the seventh in a series of Dagstuhl seminars devoted to visualization and processing of tensor fields and higher-order descriptors, which was held in Dagstuhl, Germany, on October 28–November 2, 2018

On noise, uncertainty and inference for computational diffusion MRI

Diffusion Magnetic Resonance Imaging (dMRI) has revolutionised the way brain microstructure and connectivity can be studied. Despite its unique potential in mapping the whole brain, biophysical properties are inferred from measurements rather than being directly observed. This indirect mapping from noisy data creates challenges and introduces uncertainty in the estimated properties. Hence, dMRI frameworks capable to deal with noise and uncertainty quantification are of great importance and are the topic of this thesis. First, we look into approaches for reducing uncertainty, by de-noising the dMRI signal. Thermal noise can have detrimental effects for modalities where the information resides in the signal attenuation, such as dMRI, that has inherently low-SNR data. We highlight the dual effect of noise, both in increasing variance, but also introducing bias. We then design a framework for evaluating denoising approaches in a principled manner. By setting objective criteria based on what a well-behaved denoising algorithm should offer, we provide a bespoke dataset and a set of evaluations. We demonstrate that common magnitude-based denoising approaches usually reduce noise-related variance from the signal, but do not address the bias effects introduced by the noise floor. Our framework also allows to better characterise scenarios where denoising can be beneficial (e.g. when done in complex domain) and can open new opportunities, such as pushing spatio-temporal resolution boundaries. Subsequently, we look into approaches for mapping uncertainty and design two inference frameworks for dMRI models, one using classical Bayesian methods and another using more recent data-driven algorithms. In the first approach, we build upon the univariate random-walk Metropolis-Hastings MCMC, an extensively used sampling method to sample from the posterior distribution of model parameters given the data. We devise an efficient adaptive multivariate MCMC scheme, relying upon the assumption that groups of model parameters can be jointly estimated if a proper covariance matrix is defined. In doing so, our algorithm increases the sampling efficiency, while preserving accuracy and precision of estimates. We show results using both synthetic and in-vivo dMRI data. In the second approach, we resort to Simulation-Based Inference (SBI), a data-driven approach that avoids the need for iterative model inversions. This is achieved by using neural density estimators to learn the inverse mapping from the forward generative process (simulations) to the parameters of interest that have generated those simulations. By addressing the problem via learning approaches offers the opportunity to achieve inference amortisation, boosting efficiency by avoiding the necessity of repeating the inference process for each new unseen dataset. It also allows inversion of forward processes (i.e. a series of processing steps) rather than only models. We explore different neural network architectures to perform conditional density estimation of the posterior distribution of parameters. Results and comparisons obtained against MCMC suggest speed-ups of 2-3 orders of magnitude in the inference process while keeping the accuracy in the estimates