Efficient estimation of propagator anisotropy and non‐Gaussianity in multishell diffusion MRI with micro‐structure adaptive convolution kernels and dual Fourier integral transforms

Producción CientíficaPurpose:We seek to reformulate the so-called Propagator Anisotropy (PA) andNon-Gaussianity (NG), originally conceived for the Mean Apparent Propagatordiffusion MRI (MAP-MRI), to the Micro-Structure adaptive convolution ker-nels and dual Fourier Integral Transforms (MiSFIT). These measures describerelevant normalized features of the Ensemble Average Propagator (EAP).Theory and Methods:First, the indices, which are defined as the EAP’sdissimilarity from an isotropic (PA) or a Gaussian (NG) one, are analyticallyreformulated within the MiSFIT framework. Then a comparison between theresulting maps is drawn by means of a visual analysis, a quantitative assess-ment via numerical simulations, a test-retest study across the MICRA dataset (6subjects scanned five times) and, finally, a computational time evaluation.Results:Findings illustrate the visual similarity between the indices computedwith either technique. Evaluation against synthetic ground truth data, however,demonstrates MiSFIT’s improved accuracy. In addition, the test–retest studyreveals MiSFIT’s higher degree of reliability in most of white matter regions.Finally, the computational time evaluation shows MiSFIT’s time reduction upto two orders of magnitude.Conclusions:Despite being a direct development on the MAP-MRI represen-tation, the PA and the NG can be reliably and efficiently computed withinMiSFIT’s framework. This, together with the previous findings in the originalMiSFIT’s article, could mean the difference that definitely qualifies diffusionMRI to be incorporated into regular clinical settings.Ministerio de Educación, Junta de Castilla y León y Fondo Social Europeo, (Grant/Award Number: OrdenEDU/1100/2017 12/12)Ministerio de Ciencia e Innovación, Grant/AwardNumbers: (RTI2018-094569-B-I00),(PID2021-124407NB-I00)Ministry of Science and Higher Education of Poland,(Grant/Award Number:692/STYP/13/2018)Narodowa Agencja Wymiany Akademickiej, (Grant/AwardNumber: PPN/BEK/2019/1/00421

Micro-structure diffusion scalar measures from reduced MRI acquisitions

In diffusion MRI, the Ensemble Average diffusion Propagator (EAP) provides relevant microstructural information and meaningful descriptive maps of the white matter previously obscured by traditional techniques like the Diffusion Tensor. The direct estimation of the EAP, however, requires a dense sampling of the Cartesian q-space. Due to the huge amount of samples needed for an accurate reconstruction, more efficient alternative techniques have been proposed in the last decade. Even so, all of them imply acquiring a large number of diffusion gradients with different b-values. In order to use the EAP in practical studies, scalar measures must be directly derived, being the most common the return-to-origin probability (RTOP) and the return-to-plane and return-to-axis probabilities (RTPP, RTAP). In this work, we propose the so-called “Apparent Measures Using Reduced Acquisitions” (AMURA) to drastically reduce the number of samples needed for the estimation of diffusion properties. AMURA avoids the calculation of the whole EAP by assuming the diffusion anisotropy is roughly independent from the radial direction. With such an assumption, and as opposed to common multi-shell procedures based on iterative optimization, we achieve closed-form expressions for the measures using information from one single shell. This way, the new methodology remains compatible with standard acquisition protocols commonly used for HARDI (based on just one b-value). We report extensive results showing the potential of AMURA to reveal microstructural properties of the tissues compared to state of the art EAP estimators, and is well above that of Diffusion Tensor techniques. At the same time, the closed forms provided for RTOP, RTPP, and RTAP-like magnitudes make AMURA both computationally efficient and robust

Moment-based representation of the diffusion inside the brain from reduced DMRI acquisitions: Generalized AMURA

Producción CientíficaAMURA (Apparent Measures Using Reduced Acquisitions) was originally proposed as a method to infer micro-structural information from single-shell acquisitions in diffusion MRI. It reduces the number of samples needed and the computational complexity of the estimation of diffusion properties of tissues by assuming the diffusion anisotropy is roughly independent on the b-value. This simplification allows the computation of simplified expressions and makes it compatible with standard acquisition protocols commonly used even in clinical practice. The present work proposes an extension of AMURA that allows the calculation of general moments of the diffusion signals that can be applied to describe the diffusion process with higher accuracy. We provide simplified expressions to analytically compute a set of scalar indices as moments of arbitrary orders over either the whole 3-D space, particular directions, or particular planes. The existing metrics previously proposed for AMURA (RTOP, RTPP and RTAP) are now special cases of this generalization. An extensive set of experiments is performed on public data and a clinical clase acquired with a standard type acquisition. The new metrics provide additional information about the diffusion processes inside the brain.Ministerio de Ciencia, Innovación y Universidades (grant RTI2018-094569-B-I00)Polish National Agency for Academic Exchange (grant PN/BEK/2019/1/00421)Ministry of Science and Higher Education of Poland (scholarship 692/STYP/13/2018)Junta de Castilla y León - Fondo Social Europeo (ID: 376062

Cumulant expansion with localization: a new representation of the diffusion MRI signal

Diffusion MR is sensitive to the microstructural features of a sample. Fine-scale characteristics can be probed by employing strong diffusion gradients while the low b-value regime is determined by the cumulants of the distribution of particle displacements. A signal representation based on the cumulants, however, suffers from a finite convergence radius and cannot represent the ‘localization regime' characterized by a stretched exponential decay that emerges at large gradient strengths. Here, we propose a new representation for the diffusion MR signal. Our method provides not only a robust estimate of the first three cumulants but also a meaningful extrapolation of the entire signal decay

Cumulant expansion with localization: a new representation of the diffusion MRI signal

Diffusion MR is sensitive to the microstructural features of a sample. Fine-scale characteristics can be probed by employing strong diffusion gradients while the low b-value regime is determined by the cumulants of the distribution of particle displacements. A signal representation based on the cumulants, however, suffers from a finite convergence radius and cannot represent the ‘localization regime' characterized by a stretched exponential decay that emerges at large gradient strengths. Here, we propose a new representation for the diffusion MR signal. Our method provides not only a robust estimate of the first three cumulants but also a meaningful extrapolation of the entire signal decay

Robust Estimation of the Apparent Diffusion Coefficient Invariant to Acquisition Noise and Physiological Motion

Purpose: In this work we have proposed a methodology for the estimation of the apparent diffusion coeffcient in the body from multiple breath hold diffusion weighted images, which is robust to two preeminent confounding factors: noise and motion during acquisition. Methods: We have extended a method for the joint groupwise multimodal registration and apparent diffusion coefficient estimation, previously proposed by the authors, in order to correct the bias that arises from the non-Gaussianity of the data and the registration procedure. Results: Results show that the proposed methodology provides a statistically signi ficant improvement both in robustness for displacement elds calculation and in terms of accuracy for the apparent diffusion coefficient estimation as compared with traditional sequential approaches. Reproducibility has also been measured on real data in terms of the distribution of apparent diffusion coefficient differences obtained from different b-values subsets. Conclusions: Our proposal has shown to be able to effectively correct the estimation bias by introducing additional computationally light procedures to the original method, thus providing robust apparent diffusion coefficient maps in the liver and allowing an accurate and reproducible analysis of the tissue

Spherical means-based free-water volume fraction from diffusion MRI increases non-linearly with age in the white matter of the healthy human brain

Producción CientíficaThe term free-water volume fraction (FWVF) refers to the signal fraction that could be found as the cerebrospinal fluid of the brain, which has been demonstrated as a sensitive measure that correlates with cognitive performance and various neuropathological processes. It can be quantified by properly fitting the isotropic component of the magnetic resonance (MR) signal in diffusion-sensitized sequences. Using healthy subjects (178F/109M) aged 25-94, this study examines in detail the evolution of the FWVF obtained with the spherical means technique from multi-shell acquisitions in the human brain white matter across the adult lifespan, which has been previously reported to exhibit a positive trend when estimated from single-shell data using the bi-tensor signal representation. We found evidence of a noticeably non-linear gain after the sixth decade of life, with a region-specific variate and varying change rate of the spherical means-based multi-shell FWVF parameter with age, at the same time, a heteroskedastic pattern across the adult lifespan is suggested. On the other hand, the FW corrected diffusion tensor imaging (DTI) leads to a region-dependent flattened age-related evolution of the mean diffusivity (MD) and fractional anisotropy (FA), along with a considerable reduction in their variability, as compared to the studies conducted over the standard (single-component) DTI. This way, our study provides a new perspective on the trajectory-based assessment of the brain and explains the conceivable reason for the variations observed in FA and MD parameters across the lifespan with previous studies under the standard diffusion tensor imaging.Ministerio de Ciencia e Innovación (MCIN-AEI) y FEDER-UE (grant PID2021-124407NB-I00)Ministerio de Ciencia e Innovación (MCIN-AEI) - Unión Europea “NextGenerationEU/PRTR” (grant TED2021-130758B-I00)Ministry of Science and Higher Education (Poland) - Bekker programme (grant PPN/BEK/2019/1/00421)Norwegian ExtraFoundation for Health and Rehabilitation (2015/FO5146)European Union's Horizon 2020 research and Innovation program (ERC 802998

HYDI-DSI revisited: Constrained non-parametric EAP imaging without q-space re-gridding

Producción CientíficaHybrid Diffusion Imaging (HYDI) was one of the first attempts to use multi-shell samplings of the q-space to infer diffusion properties beyond Diffusion Tensor Imaging (DTI) or High Angular Resolution Diffusion Imaging (HARDI). HYDI was intended as a flexible protocol embedding both DTI (for lower -values) and HARDI (for higher -values) processing, as well as Diffusion Spectrum Imaging (DSI) when the entire data set was exploited. In the latter case, the spherical sampling of the q-space is re-gridded by interpolation to a Cartesian lattice whose extent covers the range of acquired b-values, hence being acquisition-dependent. The Discrete Fourier Transform (DFT) is afterwards used to compute the corresponding Cartesian sampling of the Ensemble Average Propagator (EAP) in an entirely non-parametric way. From this lattice, diffusion markers such as the Return To Origin Probability (RTOP) or the Mean Squared Displacement (MSD) can be numerically estimated. We aim at re-formulating this scheme by means of a Fourier Transform encoding matrix that eliminates the need for q-space re-gridding at the same time it preserves the non-parametric nature of HYDI-DSI. The encoding matrix is adaptively designed at each voxel according to the underlying DTI approximation, so that an optimal sampling of the EAP can be pursued without being conditioned by the particular acquisition protocol. The estimation of the EAP is afterwards carried out as a regularized Quadratic Programming (QP) problem, which allows to impose positivity constraints that cannot be trivially embedded within the conventional HYDI-DSI. We demonstrate that the definition of the encoding matrix in the adaptive space allows to analytically (as opposed to numerically) compute several popular descriptors of diffusion with the unique source of error being the cropping of high frequency harmonics in the Fourier analysis of the attenuation signal. They include not only RTOP and MSD, but also Return to Axis/Plane Probabilities (RTAP/RTPP), which are defined in terms of specific spatial directions and are not available with the former HYDI-DSI. We report extensive experiments that suggest the benefits of our proposal in terms of accuracy, robustness and computational efficiency, especially when only standard, non-dedicated q-space samplings are available.Ministerio de Ciencia e Innovación (PID2021-124407NB-I00 and TED2021-130758B-I00)Ministry of Science and Higher Education (Poland) (PPN/BEK/ 2019/1/00421

The sensitivity of diffusion MRI to microstructural properties and experimental factors

Diffusion MRI is a non-invasive technique to study brain microstructure. Differences in the microstructural properties of tissue, including size and anisotropy, can be represented in the signal if the appropriate method of acquisition is used. However, to depict the underlying properties, special care must be taken when designing the acquisition protocol as any changes in the procedure might impact on quantitative measurements. This work reviews state-of-the-art methods for studying brain microstructure using diffusion MRI and their sensitivity to microstructural differences and various experimental factors. Microstructural properties of the tissue at a micrometer scale can be linked to the diffusion signal at a millimeter-scale using modeling. In this paper, we first give an introduction to diffusion MRI and different encoding schemes. Then, signal representation-based methods and multi-compartment models are explained briefly. The sensitivity of the diffusion MRI signal to the microstructural components and the effects of curvedness of axonal trajectories on the diffusion signal are reviewed. Factors that impact on the quality (accuracy and precision) of derived metrics are then reviewed, including the impact of random noise, and variations in the acquisition parameters (i.e., number of sampled signals, b-value and number of acquisition shells). Finally, yet importantly, typical approaches to deal with experimental factors are depicted, including unbiased measures and harmonization. We conclude the review with some future directions and recommendations on this topic