Reproducibility and consistency of evaluation techniques for HARDI data

Diffusion weighted (DW) MRI facilitates non-invasive quantification of tissue microstructure and, in combination with appropriate signal processing, three-dimensional estimates of fibrous orientation. In recent years, attention has shifted from the diffusion tensor model, which assumes a unimodal Gaussian diffusion displacement profile to recover fibre orientation (with various well-documented limitations), towards more complex high angular resolution diffusion imaging (HARDI) analysis techniques.Spherical deconvolution (SD) approaches assume that the fibre orientation density function (fODF) within a voxel can be obtained by deconvolving a ‘common’ single fibre response function from the observed set of DW signals. In practice, this common response function is not known a priori and thus an estimated fibre response must be used. Here the establishment of this single-fibre response function is referred to as ‘calibration’. This work examines the vulnerability of two different SD approaches to inappropriate response function calibration: (1) constrained spherical harmonic deconvolution (CSHD)—a technique that exploits spherical harmonic basis sets and (2) damped Richardson–Lucy (dRL) deconvolution—a technique based on the standard Richardson–Lucy deconvolution.Through simulations, the impact of a discrepancy between the calibrated diffusion profiles and the observed (‘Target’) DW-signals in both single and crossing-fibre configurations was investigated. The results show that CSHD produces spurious fODF peaks (consistent with well known ringing artefacts) as the discrepancy between calibration and target response increases, while dRL demonstrates a lower over-all sensitivity to miscalibration (with a calibration response function for a highly anisotropic fibre being optimal). However, dRL demonstrates a reduced ability to resolve low anisotropy crossing-fibres compared to CSHD. It is concluded that the range and spatial-distribution of expected single-fibre anisotropies within an image must be carefully considered to ensure selection of the appropriate algorithm, parameters and calibration. Failure to choose the calibration response function carefully may severely impact the quality of any resultant tractography.

Abstract. Due to the well-known limitations of diffusion tensor imaging, high angular resolution diffusion imaging (HARDI) is used to characterize non-Gaussian diffusion processes. One approach to ana-lyzing HARDI data is to model the apparent diffusion coefficient (ADC) with higher order diffusion tensors. The diffusivity function is positive semidefinite. In the literature, some methods have been proposed to preserve positive semidefiniteness of second order and fourth order diffusion tensors. None of them can work for arbitrarily high order diffusion tensors. In this paper, we propose a comprehensive model to approximate the ADC profile by a positive semidefinite diffusion tensor of either second or higher order. We call this the positive semidefinite diffusion tensor (PSDT) model. PSDT is a convex optimization problem with a convex quadratic objective function constrained by the nonnegativity requirement on the smallest Z-eigenvalue of the diffusivity function. The smallest Z-eigenvalue is a computable measure of the extent of positive definiteness of the diffusivity function. We also propose some other invariants for the ADC profile analysis. Experiment results show that higher order tensors could improve the estimation of anisotropic diffusion and that the PSDT model can depict the characterization of diffusion anisotropy which is consistent with known neuroanatomy.

HARDI (High Angular Resolution Diffusion Imaging) is a recent magnetic resonance imaging (MRI) technique for imaging water diffusion processes in fibrous tissues such as brain white matter and muscles. In this article we study left-invariant diffusion on the group of 3D rigid body movements (i.e. 3D Euclidean motion group) SE(3) and its application to crossing-preserving smoothing of HARDI images. The linear left-invariant (convection-)diffusions are forward Kolmogorov equations of Brownian motions on the space of positions and orientations in 3D embedded in SE(3) and can be solved by ℝ3 ⋊ S 2-convolution with the corresponding Green’s functions. We provide analytic approximation formulas and explicit sharp Gaussian estimates for these Green’s functions. In our design and analysis for appropriate (nonlinear) convection-diffusions on HARDI data we explain the underlying differential geometry on SE(3). We write our left-invariant diffusions in covariant derivatives on SE(3) using the Cartan connection. This Cartan connection has constant curvature and constant torsion, and so have the exponential curves which are the auto-parallels along which our left-invariant diffusion takes place. We provide experiments of our crossing-preserving Euclidean-invariant diffusions on artificial HARDI data containing crossing-fibers.

We develop a nonparametric technique for the estimation of curve trajectories using HARDI data. For various regions of the brain, we consider the imaging signal process and apply multivariate kernel smoothing techniques to a general function f describing the signal process obtained from the MRI image. At each location in the brain we search for the direction of maximum diffusion on the unit sphere, and then trace the integral curve driven by the vector field to obtain the estimates of curve trajectories. We establish the convergence of the properly normalized curve estimators to a Gaussian process. This method is computationally efficient as with each step of the curve tracing we construct a pointwise confidence ellipsoid region as opposed to exhaustive iterative sampling methods. These curve trajectories are models of axonal fibers whose location and geometry are important in neuroscience.

Characterization of myocardial microstructure for healthy female and male cohorts using cardiac diffusion tensor imaging with an ultra-high-performance gradient magnetic resonance imaging scanner

High angular resolution diffusion imaging (HARDI) methods have enabled the reconstruction of complex spin diffusion profiles in central nervous system white matter through diffusion-weighted MRI. For recovery of the underlying fiber orientations, conventional spherical deconvolution techniques based on spherical harmonics typically have difficulty producing fiber orientation distributions (FODs) that simultaneously satisfy the physical constraints of being real, symmetric, and non-negative. In this work, we propose a novel approach for HARDI reconstruction that is guaranteed to generate FODs satisfying these constraints. By using a meshed representation of the unit sphere, we formulate the spherical deconvolution as a convex optimization problem and compute the solution using a projected gradient descent algorithm. Flexible regularization is also included in our method to allow for tuning the sharpness of the reconstructed FOD. In our experiments, we present simulated results to examine the effects of varying the regularization parameters, and we illustrate the robustness of our method by applying it to several biological data sets to reconstruct known white matter fiber geometry.

We consider the problem of tracking white matter fibers in high angular resolution diffusion imaging (HARDI) data while simultaneously estimating the local fiber orientation profile. Prior work showed that an unscented Kalman filter (UKF) can be used for this problem, yet existing algorithms employ parametric mixture models to represent water diffusion and to define the state space. To address this restrictive model dependency, we propose to extend the UKF to HARDI data modeled by orientation distribution functions (ODFs), a more generic diffusion model. We consider the spherical harmonic representation of the HARDI signal as the state, enforce nonnegativity of the ODFs, and perform tractography using the directions at which the ODFs attain their peaks. In simulations, our method outperforms filtered two-tensor tractography at different levels of noise by achieving a reduction in mean Chamfer error of 0.05 to 0.27 voxels; it also produced in vivo fiber tracking that is consistent with the neuroanatomy.

Diffusion MRI provides important information about the brain white matter structures and has opened new avenues for neuroscience and translational research. However, acquisition time needed for advanced applications can still be a challenge in clinical settings. There is consequently a need to accelerate diffusion MRI acquisitions. A multi-task Bayesian compressive sensing (MT-BCS) framework is proposed to directly estimate the constant solid angle orientation distribution function (CSA-ODF) from under-sampled (i.e., accelerated image acquisition) multi-shell high angular resolution diffusion imaging (HARDI) datasets, and accurately recover HARDI data at higher resolution in q-space. The proposed MT-BCS approach exploits the spatial redundancy of the data by modeling the statistical relationships within groups (clusters) of diffusion signal. This framework also provides uncertainty estimates of the computed CSA-ODF and diffusion signal, directly computed from the compressive measurements. Experiments validating the proposed framework are performed using realistic multi-shell synthetic images and in vivo multi-shell high angular resolution HARDI datasets. Results indicate a practical reduction in the number of required diffusion volumes (q-space samples) by at least a factor of four to estimate the CSA-ODF from multi-shell data. This work presents, for the first time, a multi-task Bayesian compressive sensing approach to simultaneously estimate the full posterior of the CSA-ODF and diffusion-weighted volumes from multi-shell HARDI acquisitions. It demonstrates improvement of the quality of acquired datasets by means of CS de-noising, and accurate estimation of the CSA-ODF, as well as enables a reduction in the acquisition time by a factor of two to four, especially when "staggered" q-space sampling schemes are used. The proposed MT-BCS framework can naturally be combined with parallel MR imaging to further accelerate HARDI acquisitions.

High angular resolution diffusion imaging (HARDI) improves upon more traditional diffusion tensor imaging (DTI) in its ability to resolve the orientations of crossing and branching neural fibre tracts. The HARDI signals are measured over a spherical shell in q-space, and are usually used as an input to q-ball imaging (QBI) which allows estimation of the diffusion orientation distribution functions (ODFs) associated with a given region-of interest. Unfortunately, the partial nature of single-shell sampling imposes limits on the estimation accuracy. As a result, the recovered ODFs may not possess sufficient resolution to reveal the orientations of fibre tracts which cross each other at acute angles. A possible solution to the problem of limited resolution of QBI is provided by means of spherical deconvolution, a particular instance of which is sparse deconvolution. However, while capable of yielding high-resolution reconstructions over spacial locations corresponding to white matter, such methods tend to become unstable when applied to anatomical regions with a substantial content of isotropic diffusion. To resolve this problem, a new deconvolution approach is proposed in this paper. Apart from being uniformly stable across the whole brain, the proposed method allows one to quantify the isotropic component of cerebral diffusion, which is known to be a useful diagnostic measure by itself.

The detection of white matter microstructural changes using diffusion magnetic resonance imaging (dMRI) often involves extracting a small set of scalar features, such as fractional anisotropy (FA) and mean diffusivity (MD) in diffusion tensor imaging (DTI). With the advent of more advanced dMRI techniques, such as high angular resolution diffusion imaging (HARDI), a number of mathematically inspired new scalar features have been proposed. However, it is unclear how to select the most biologically informative combinations of features for biomarker discovery. This paper proposes an automatic HARDI feature selection algorithm which is based on registering HARDI features to feature atlases for optimal clinical usability in population studies. We apply our framework to the characterization of beta-amyloid (Aβ) pathology for the early detection of Alzheimer’s disease (AD) to better understand the relationship between Aβ pathology and degenerative changes in neuroanatomy.

We introduce a geodesic based tractography method for High Angular Resolution Diffusion Imaging (HARDI). The concepts used are similar to the ones in geodesic based tractography for Diffusion Tensor Imaging (DTI). In DTI, the inverse of the second-order diffusion tensor is used to define the manifold where the geodesics are traced. HARDI models have been developed to resolve complex fiber populations within a voxel, and higher order tensors (HOT) are possible representations for HARDI data. In our framework, we apply Finsler geometry, which extends Riemannian geometry to a directionally dependent metric. A Finsler metric is defined in terms of HARDI higher order tensors. Furthermore, the Euler-Lagrange geodesic equations are derived based on the Finsler geometry. In contrast to other geodesic based tractography algorithms, the multi-valued numerical solution of the geodesic equations can be obtained. This gives the possibility to capture all geodesics arriving at a single voxel instead of only computing the shortest one. Results are analyzed to show the potential and characteristics of our algorithm.

Diffusion MRI (dMRI) is a unique imaging modality for in vivo delineation of the anatomical structure of white matter in the brain. In particular, high angular resolution diffusion imaging (HARDI) is a specific instance of dMRI which is known to excel in detection of multiple neural fibers within a single voxel. Unfortunately, the angular resolution of HARDI is known to be inversely proportional to SNR, which makes the problem of denoising of HARDI data be of particular practical importance. Since HARDI signals are effectively band-limited, denoising can be accomplished by means of linear filtering. However, the spatial dependency of diffusivity in brain tissue makes it impossible to find a single set of linear filter parameters which is optimal for all types of diffusion signals. Hence, adaptive filtering is required. In this paper, we propose a new type of non-local means (NLM) filtering which possesses the required adaptivity property. As opposed to similar methods in the field, however, the proposed NLM filtering is applied in the spherical domain of spatial orientations. Moreover, the filter uses an original definition of adaptive weights, which are designed to be invariant to both spatial rotations as well as to a particular sampling scheme in use. As well, we provide a detailed description of the proposed filtering procedure, its efficient implementation, as well as experimental results with synthetic data. We demonstrate that our filter has substantially better adaptivity as compared to a number of alternative methods.

Collaborative patch-based super-resolution for diffusion-weighted images

A new method for mapping diffusivity profiles in tissue is presented. The Bloch-Torrey equation is modified to include a diffusion term with an arbitrary rank Cartesian tensor. This equation is solved to give the expression for the generalized Stejskal-Tanner formula quantifying diffusive attenuation in complicated geometries. This makes it possible to calculate the components of higher-rank tensors without using the computationally-difficult spherical harmonic transform. General theoretical relations between the diffusion tensor (DT) components measured by traditional (rank-2) DT imaging (DTI) and 3D distribution of diffusivities, as measured by high angular resolution diffusion imaging (HARDI) methods, are derived. Also, the spherical tensor components from HARDI are related to the rank-2 DT. The relationships between higher- and lower-rank Cartesian DTs are also presented. The inadequacy of the traditional rank-2 tensor model is demonstrated with simulations, and the method is applied to excised rat brain data collected in a spin-echo HARDI experiment.

High angular resolution diffusion imaging (HARDI) allows in vivo analysis of the white matter structure and connectivity. Based on orientation distribution functions (ODFs) that represent the directionality of water diffusion at each point in the brain, tractography methods can recover major axonal pathways. This enables tract-based analysis of fiber integrity and connectivity. For multi-subject comparisons, fibers may be clustered into bundles that are consistently found across subjects. To do this, we scanned 20 young adults with HARDI at 4 T. From the reconstructed ODFs, we performed whole-brain tractography with a novel Hough transform method. We then used measures of agreement between the extracted 3D curves and a co-registered probabilistic DTI atlas to select key pathways. Using median filtering and a shortest path graph search, we derived the maximum density path to compactly represent each tract in the population. With this tract-based method, we performed tract-based analysis of fractional anisotropy, and assessed how the chosen tractography algorithm influenced the results. The resulting method may expedite population-based statistical analysis of HARDI and DTI.