Effectiveness of regional diffusion MRI measures in distinguishing multiple sclerosis abnormalities within the cervical spinal cord.

INTRODUCTION: Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system. Although conventional magnetic resonance imaging (MRI) is widely used for MS diagnosis and clinical follow-up, quantitative MRI has the potential to provide valuable intrinsic values of tissue properties that can enhance accuracy. In this study, we investigate the efficacy of diffusion MRI in distinguishing MS lesions within the cervical spinal cord, using a combination of metrics extracted from diffusion tensor imaging and Ball-and-Stick models. METHODS: We analyzed spinal cord data acquired from multiple hospitals and extracted average diffusion MRI metrics per vertebral level using a collection of image processing methods and an atlas-based approach. We then performed a statistical analysis to evaluate the feasibility of these metrics for detecting lesions, exploring the usefulness of combining different metrics to improve accuracy. RESULTS: Our study demonstrates the sensitivity of each metric to underlying microstructure changes in MS patients. We show that selecting a specific subset of metrics, which provide complementary information, significantly improves the prediction score of lesion presence in the cervical spinal cord. Furthermore, the Ball-and-Stick model has the potential to provide novel information about the microstructure of damaged tissue. CONCLUSION: Our results suggest that diffusion measures, particularly combined measures, are sensitive in discriminating abnormal from healthy cervical vertebral levels in patients. This information could aid in improving MS diagnosis and clinical follow-up. Our study highlights the potential of the Ball-and-Stick model in providing additional insights into the microstructure of the damaged tissue.

Consensus-based guidance for conducting and reporting multi-analyst studies.

Any large dataset can be analyzed in a number of ways, and it is possible that the use of different analysis strategies will lead to different results and conclusions. One way to assess whether the results obtained depend on the analysis strategy chosen is to employ multiple analysts and leave each of them free to follow their own approach. Here, we present consensus-based guidance for conducting and reporting such multi-analyst studies, and we discuss how broader adoption of the multi-analyst approach has the potential to strengthen the robustness of results and conclusions obtained from analyses of datasets in basic and applied research.

The diffusion-simulated connectivity (DiSCo) dataset.

The methodological development in the mapping of the brain structural connectome from diffusion-weighted magnetic resonance imaging (DW-MRI) has raised many hopes in the neuroscientific community. Indeed, the knowledge of the connections between different brain regions is fundamental to study brain anatomy and function. The reliability of the structural connectome is therefore of paramount importance. In the search for accuracy, researchers have given particular attention to linking white matter tractography methods - used for estimating the connectome - with information about the microstructure of the nervous tissue. The creation and validation of methods in this context were hampered by a lack of practical numerical phantoms. To achieve this, we created a numerical phantom that mimics complex anatomical fibre pathway trajectories while also accounting for microstructural features such as axonal diameter distribution, myelin presence, and variable packing densities. The substrate has a micrometric resolution and an unprecedented size of 1 cubic millimetre to mimic an image acquisition matrix of 40 × 40 × 40 voxels. DW-MRI images were obtained from Monte Carlo simulations of spin dynamics to enable the validation of quantitative tractography. The phantom is composed of 12,196 synthetic tubular fibres with diameters ranging from 1.4 µm to 4.2 µm, interconnecting sixteen regions of interest. The simulated images capture the microscopic properties of the tissue (e.g. fibre diameter, water diffusing within and around fibres, free water compartment), while also having desirable macroscopic properties resembling the anatomy, such as the smoothness of the fibre trajectories. While previous phantoms were used to validate either tractography or microstructure, this phantom can enable a better assessment of the connectome estimation's reliability on the one side, and its adherence to the actual microstructure of the nervous tissue on the other.

Freewater estimatoR using iNtErpolated iniTialization (FERNET): Characterizing peritumoral edema using clinically feasible diffusion MRI data.

Characterization of healthy versus pathological tissue in the peritumoral area is confounded by the presence of edema, making free water estimation the key concern in modeling tissue microstructure. Most methods that model tissue microstructure are either based on advanced acquisition schemes not readily available in the clinic or are not designed to address the challenge of edema. This underscores the need for a robust free water elimination (FWE) method that estimates free water in pathological tissue but can be used with clinically prevalent single-shell diffusion tensor imaging data. FWE in single-shell data requires the fitting of a bi-compartment model, which is an ill-posed problem. Its solution requires optimization, which relies on an initialization step. We propose a novel initialization approach for FWE, FERNET, which improves the estimation of free water in edematous and infiltrated peritumoral regions, using single-shell diffusion MRI data. The method has been extensively investigated on simulated data and healthy dataset. Additionally, it has been applied to clinically acquired data from brain tumor patients to characterize the peritumoral region and improve tractography in it.

MAPL: Tissue microstructure estimation using Laplacian-regularized MAP-MRI and its application to HCP data.

The recovery of microstructure-related features of the brain's white matter is a current challenge in diffusion MRI. To robustly estimate these important features from multi-shell diffusion MRI data, we propose to analytically regularize the coefficient estimation of the Mean Apparent Propagator (MAP)-MRI method using the norm of the Laplacian of the reconstructed signal. We first compare our approach, which we call MAPL, with competing, state-of-the-art functional basis approaches. We show that it outperforms the original MAP-MRI implementation and the recently proposed modified Spherical Polar Fourier (mSPF) basis with respect to signal fitting and reconstruction of the Ensemble Average Propagator (EAP) and Orientation Distribution Function (ODF) in noisy, sparsely sampled data of a physical phantom with reference gold standard data. Then, to reduce the variance of parameter estimation using multi-compartment tissue models, we propose to use MAPL's signal fitting and extrapolation as a preprocessing step. We study the effect of MAPL on the estimation of axon diameter using a simplified Axcaliber model and axonal dispersion using the Neurite Orientation Dispersion and Density Imaging (NODDI) model. We show the positive effect of using it as a preprocessing step in estimating and reducing the variances of these parameters in the Corpus Callosum of six different subjects of the MGH Human Connectome Project. Finally, we correlate the estimated axon diameter, dispersion and restricted volume fractions with Fractional Anisotropy (FA) and clearly show that changes in FA significantly correlate with changes in all estimated parameters. Overall, we illustrate the potential of using a well-regularized functional basis together with multi-compartment approaches to recover important microstructure tissue parameters with much less variability, thus contributing to the challenge of better understanding microstructure-related features of the brain's white matter.

Spherical Deconvolution of Multichannel Diffusion MRI Data with Non-Gaussian Noise Models and Spatial Regularization.

Spherical deconvolution (SD) methods are widely used to estimate the intra-voxel white-matter fiber orientations from diffusion MRI data. However, while some of these methods assume a zero-mean Gaussian distribution for the underlying noise, its real distribution is known to be non-Gaussian and to depend on many factors such as the number of coils and the methodology used to combine multichannel MRI signals. Indeed, the two prevailing methods for multichannel signal combination lead to noise patterns better described by Rician and noncentral Chi distributions. Here we develop a Robust and Unbiased Model-BAsed Spherical Deconvolution (RUMBA-SD) technique, intended to deal with realistic MRI noise, based on a Richardson-Lucy (RL) algorithm adapted to Rician and noncentral Chi likelihood models. To quantify the benefits of using proper noise models, RUMBA-SD was compared with dRL-SD, a well-established method based on the RL algorithm for Gaussian noise. Another aim of the study was to quantify the impact of including a total variation (TV) spatial regularization term in the estimation framework. To do this, we developed TV spatially-regularized versions of both RUMBA-SD and dRL-SD algorithms. The evaluation was performed by comparing various quality metrics on 132 three-dimensional synthetic phantoms involving different inter-fiber angles and volume fractions, which were contaminated with noise mimicking patterns generated by data processing in multichannel scanners. The results demonstrate that the inclusion of proper likelihood models leads to an increased ability to resolve fiber crossings with smaller inter-fiber angles and to better detect non-dominant fibers. The inclusion of TV regularization dramatically improved the resolution power of both techniques. The above findings were also verified in human brain data.

On facilitating the use of HARDI in population studies by creating rotation-invariant markers.

We design and evaluate a novel method to compute rotationally invariant features using High Angular Resolution Diffusion Imaging (HARDI) data. These measures quantify the complexity of the angular diffusion profile modeled using a higher order model, thereby giving more information than classical diffusion tensor-derived parameters. The method is based on the spherical harmonic (SH) representation of the angular diffusion information, and is generalizable to a range of HARDI reconstruction models. These scalars are obtained as homogeneous polynomials of the SH representation of a HARDI reconstruction model. We show that finding such polynomials is equivalent to solving a large linear system of equations, and present a numerical method based on sparse matrices to efficiently solve this system. Among the solutions, we only keep a subset of algebraically independent polynomials, using an algorithm based on a numerical implementation of the Jacobian criterion. We compute a set of 12 or 25 rotationally invariant measures representative of the underlying white matter for the rank-4 or rank-6 spherical harmonics (SHs) representation of the apparent diffusion coefficient (ADC) profile, respectively. Synthetic data was used to investigate and quantify the difference in contrast. Real data acquired with multiple repetitions showed that within subject variation in the invariants was less than the difference across subjects - facilitating their use to study population differences. These results demonstrate that our measures are able to characterize white matter, especially complex white matter found in regions of fiber crossings and hence can be used to derive new biomarkers for HARDI and can be used for HARDI-based population analysis.

Quantitative comparison of reconstruction methods for intra-voxel fiber recovery from diffusion MRI.

Validation is arguably the bottleneck in the diffusion magnetic resonance imaging (MRI) community. This paper evaluates and compares 20 algorithms for recovering the local intra-voxel fiber structure from diffusion MRI data and is based on the results of the "HARDI reconstruction challenge" organized in the context of the "ISBI 2012" conference. Evaluated methods encompass a mixture of classical techniques well known in the literature such as diffusion tensor, Q-Ball and diffusion spectrum imaging, algorithms inspired by the recent theory of compressed sensing and also brand new approaches proposed for the first time at this contest. To quantitatively compare the methods under controlled conditions, two datasets with known ground-truth were synthetically generated and two main criteria were used to evaluate the quality of the reconstructions in every voxel: correct assessment of the number of fiber populations and angular accuracy in their orientation. This comparative study investigates the behavior of every algorithm with varying experimental conditions and highlights strengths and weaknesses of each approach. This information can be useful not only for enhancing current algorithms and develop the next generation of reconstruction methods, but also to assist physicians in the choice of the most adequate technique for their studies.

lop-DWI: A Novel Scheme for Pre-Processing of Diffusion-Weighted Images in the Gradient Direction Domain.

We describe and evaluate a pre-processing method based on a periodic spiral sampling of diffusion-gradient directions for high angular resolution diffusion magnetic resonance imaging. Our pre-processing method incorporates prior knowledge about the acquired diffusion-weighted signal, facilitating noise reduction. Periodic spiral sampling of gradient direction encodings results in an acquired signal in each voxel that is pseudo-periodic with characteristics that allow separation of low-frequency signal from high frequency noise. Consequently, it enhances local reconstruction of the orientation distribution function used to define fiber tracks in the brain. Denoising with periodic spiral sampling was tested using synthetic data and in vivo human brain images. The level of improvement in signal-to-noise ratio and in the accuracy of local reconstruction of fiber tracks was significantly improved using our method.

A computational diffusion MRI and parametric dictionary learning framework for modeling the diffusion signal and its features.

In this work, we first propose an original and efficient computational framework to model continuous diffusion MRI (dMRI) signals and analytically recover important diffusion features such as the Ensemble Average Propagator (EAP) and the Orientation Distribution Function (ODF). Then, we develop an efficient parametric dictionary learning algorithm and exploit the sparse property of a well-designed dictionary to recover the diffusion signal and its features with a reduced number of measurements. The properties and potentials of the technique are demonstrated using various simulations on synthetic data and on human brain data acquired from 7T and 3T scanners. It is shown that the technique can clearly recover the dMRI signal and its features with a much better accuracy compared to state-of-the-art approaches, even with a small and reduced number of measurements. In particular, we can accurately recover the ODF in regions of multiple fiber crossing, which could open new perspectives for some dMRI applications such as fiber tractography.

Design of multishell sampling schemes with uniform coverage in diffusion MRI.

PURPOSE: In diffusion MRI, a technique known as diffusion spectrum imaging reconstructs the propagator with a discrete Fourier transform, from a Cartesian sampling of the diffusion signal. Alternatively, it is possible to directly reconstruct the orientation distribution function in q-ball imaging, providing so-called high angular resolution diffusion imaging. In between these two techniques, acquisitions on several spheres in q-space offer an interesting trade-off between the angular resolution and the radial information gathered in diffusion MRI. A careful design is central in the success of multishell acquisition and reconstruction techniques. METHODS: The design of acquisition in multishell is still an open and active field of research, however. In this work, we provide a general method to design multishell acquisition with uniform angular coverage. This method is based on a generalization of electrostatic repulsion to multishell. RESULTS: We evaluate the impact of our method using simulations, on the angular resolution in one and two bundles of fiber configurations. Compared to more commonly used radial sampling, we show that our method improves the angular resolution, as well as fiber crossing discrimination. DISCUSSION: We propose a novel method to design sampling schemes with optimal angular coverage and show the positive impact on angular resolution in diffusion MRI.

Motion Detection in Diffusion MRI via Online ODF Estimation.

The acquisition of high angular resolution diffusion MRI is particularly long and subject motion can become an issue. The orientation distribution function (ODF) can be reconstructed online incrementally from diffusion-weighted MRI with a Kalman filtering framework. This online reconstruction provides real-time feedback throughout the acquisition process. In this article, the Kalman filter is first adapted to the reconstruction of the ODF in constant solid angle. Then, a method called STAR (STatistical Analysis of Residuals) is presented and applied to the online detection of motion in high angular resolution diffusion images. Compared to existing techniques, this method is image based and is built on top of a Kalman filter. Therefore, it introduces no additional scan time and does not require additional hardware. The performance of STAR is tested on simulated and real data and compared to the classical generalized likelihood ratio test. Successful detection of small motion is reported (rotation under 2°) with no delay and robustness to noise.

Diffusion MRI signal reconstruction with continuity constraint and optimal regularization.

In diffusion MRI, the reconstruction of the full Ensemble Average Propagator (EAP) provides new insights in the diffusion process and the underlying microstructure. The reconstruction of the signal in the whole Q-space is still extremely challenging however. It requires very long acquisition protocols, and robust reconstruction to cope with the very low SNR at large b-values. Several reconstruction methods were proposed recently, among which the Spherical Polar Fourier (SPF) expansion, a promising basis for signal reconstruction. Yet the reconstruction in SPF is still subject to noise and discontinuity of the reconstruction. In this work, we present a method for the reconstruction of the diffusion attenuation in the whole Q-space, with a special focus on continuity and optimal regularization. We derive a modified Spherical Polar Fourier (mSPF) basis, orthonormal and compatible with SPF, for the reconstruction of a signal with continuity constraint. We also derive the expression of a Laplace regularization operator in the basis, together with a method based on generalized cross validation for the optimal choice of the parameter. Our method results in a noticeable dimension reduction as compared with SPF. Tested on synthetic and real data, the reconstruction with this method is more robust to noise and better preserves fiber directions and crossings.

Parametric dictionary learning for modeling EAP and ODF in diffusion MRI.

In this work, we propose an original and efficient approach to exploit the ability of Compressed Sensing (CS) to recover diffusion MRI (dMRI) signals from a limited number of samples while efficiently recovering important diffusion features such as the ensemble average propagator (EAP) and the orientation distribution function (ODF). Some attempts to sparsely represent the diffusion signal have already been performed. However and contrarly to what has been presented in CS dMRI, in this work we propose and advocate the use of a well adapted learned dictionary and show that it leads to a sparser signal estimation as well as to an efficient reconstruction of very important diffusion features. We first propose to learn and design a sparse and parametric dictionary from a set of training diffusion data. Then, we propose a framework to analytically estimate in closed form two important diffusion features: the EAP and the ODF. Various experiments on synthetic, phantom and human brain data have been carried out and promising results with reduced number of atoms have been obtained on diffusion signal reconstruction, thus illustrating the added value of our method over state-of-the-art SHORE and SPF based approaches.

Impact of radial and angular sampling on multiple shells acquisition in diffusion MRI.

We evaluate the impact of radial and angular sampling on multiple shells (MS) acquisition in diffusion MRI. The validation of our results is based on a new and efficient method to accurately reconstruct the Ensemble Average Propagator (EAP) in term of the Spherical Polar Fourier (SPF) basis from very few diffusion weighted magnetic resonance images (DW-MRI). This approach nicely exploits the duality between SPF and a closely related basis in which one can respectively represent the EAP and the diffusion signal using the same coefficients. We efficiently combine this relation to the recent acquisition and reconstruction technique called Compressed Sensing (CS). Based on results of multi-tensors models reconstruction, we show how to construct a robust acquisition scheme for both neural fibre orientation detection and attenuation signal/EAP reconstruction.