Rotationally-invariant mapping of scalar and orientational metrics of neuronal microstructure with diffusion MRI

We develop a general analytical and numerical framework for estimating intra- and extra-neurite water fractions and diffusion coefficients, as well as neurite orientational dispersion, in each imaging voxel. By employing a set of rotational invariants and their expansion in the powers of diffusion weighting, we analytically uncover the nontrivial topology of the parameter estimation landscape, showing that multiple branches of parameters describe the measurement almost equally well, with only one of them corresponding to the biophysical reality. A comprehensive acquisition shows that the branch choice varies across the brain. Our framework reveals hidden degeneracies in MRI parameter estimation for neuronal tissue, provides microstructural and orientational maps in the whole brain without constraints or priors, and connects modern biophysical modeling with clinical MRI.Comment: 25 pages, 12 figures, elsarticle two-colum

Noninvasive quantification of axon radii using diffusion MRI

Axon caliber plays a crucial role in determining conduction velocity and, consequently, in the timing and synchronization of neural activation. Noninvasive measurement of axon radii could have significant impact on the understanding of healthy and diseased neural processes. Until now, accurate axon radius mapping has eluded in vivo neuroimaging, mainly due to a lack of sensitivity of the MRI signal to micron-sized axons. Here, we show how – when confounding factors such as extra-axonal water and axonal orientation dispersion are eliminated – heavily diffusion-weighted MRI signals become sensitive to axon radii. However, diffusion MRI is only capable of estimating a single metric, the effective radius, representing the entire axon radius distribution within a voxel that emphasizes the larger axons. Our findings, both in rodents and humans, enable noninvasive mapping of critical information on axon radii, as well as resolve the long-standing debate on whether axon radii can be quantified

What's new and what's next in diffusion MRI preprocessing

Diffusion MRI (dMRI) provides invaluable information for the study of tissue microstructure and brain connectivity, but suffers from a range of imaging artifacts that greatly challenge the analysis of results and their interpretability if not appropriately accounted for. This review will cover dMRI artifacts and preprocessing steps, some of which have not typically been considered in existing pipelines or reviews, or have only gained attention in recent years: brain/skull extraction, B-matrix incompatibilities w.r.t the imaging data, signal drift, Gibbs ringing, noise distribution bias, denoising, between- and within-volumes motion, eddy currents, outliers, susceptibility distortions, EPI Nyquist ghosts, gradient deviations, bias fields, and spatial normalization. The focus will be on “what’s new” since the notable advances prior to and brought by the Human Connectome Project (HCP), as presented in the predecessing issue on “Mapping the Connectome” in 2013. In addition to the development of novel strategies for dMRI preprocessing, exciting progress has been made in the availability of open source tools and reproducible pipelines, databases and simulation tools for the evaluation of preprocessing steps, and automated quality control frameworks, amongst others. Finally, this review will consider practical considerations and our view on “what’s next” in dMRI preprocessing

"Silver" mode for the heavy Higgs search in the presence of a fourth SM family

We investigate the possible enhancement to the discovery of the heavy Higgs boson through the possible fourth SM family heavy neutrino. Using the channel h-> v4 v4->mu W mu W, it is found that for certain ranges of Higgs boson and v4 masses LHC could discover both of them simultaneously with 1 fb^-1 integrated luminosity

Characterization of Prostate Microstructure Using Water Diffusion and NMR Relaxation

For many pathologies, early structural tissue changes occur at the cellular level, on the scale of micrometers or tens of micrometers. Magnetic resonance imaging (MRI) is a powerful non-invasive imaging tool used for medical diagnosis, but its clinical hardware is incapable of reaching the cellular length scale directly. In spite of this limitation, microscopic tissue changes in pathology can potentially be captured indirectly, from macroscopic imaging characteristics, by studying water diffusion. Here we focus on water diffusion and NMR relaxation in the human prostate, a highly heterogeneous organ at the cellular level. We present a physical picture of water diffusion and NMR relaxation in the prostate tissue, that is comprised of a densely-packed cellular compartment (composed of stroma and epithelium), and a luminal compartment with almost unrestricted water diffusion. Transverse NMR relaxation is used to identify fast and slow T2 components, corresponding to these tissue compartments, and to disentangle the luminal and cellular compartment contributions to the temporal evolution of the overall water diffusion coefficient. Diffusion in the luminal compartment falls into the short-time surface-to-volume (S/V) limit, indicating that only a small fraction of water molecules has time to encounter the luminal walls of healthy tissue; from the S/V ratio, the average lumen diameter averaged over three young healthy subjects is measured to be 217.7 ± 188.7 μm. Conversely, the diffusion in the cellular compartment is highly restricted and anisotropic, consistent with the fibrous character of the stromal tissue. Diffusion transverse to these fibers is well described by the random permeable barrier model (RPBM), as confirmed by the dynamical exponent ϑ = 1/2 for approaching the long-time limit of diffusion, and the corresponding structural exponent p = −1 in histology. The RPBM-derived fiber diameter and membrane permeability were 19.8 ± 8.1 μm and 0.044 ± 0.045 μm/ms, respectively, in agreement with known values from tissue histology and membrane biophysics. Lastly, we revisited 38 prostate cancer cases from a recently published study, and found the same dynamical exponent ϑ = 1/2 of diffusion in tumors and benign regions. Our results suggest that a multi-parametric MRI acquisition combined with biophysical modeling may be a powerful non-invasive complement to prostate cancer grading, reducing the need for biopsies

Nanostructure-specific X-ray tomography reveals myelin levels, integrity and axon orientations in mouse and human nervous tissue

Myelin insulates neuronal axons and enables fast signal transmission, constituting a key component of brain development, aging and disease. Yet, myelin-specific imaging of macroscopic samples remains a challenge. Here, we exploit myelin’s nanostructural periodicity, and use small-angle X-ray scattering tensor tomography (SAXS-TT) to simultaneously quantify myelin levels, nanostructural integrity and axon orientations in nervous tissue. Proof-of-principle is demonstrated in whole mouse brain, mouse spinal cord and human white and gray matter samples. Outcomes are validated by 2D/3D histology and compared to MRI measurements sensitive to myelin and axon orientations. Specificity to nanostructure is exemplified by concomitantly imaging different myelin types with distinct periodicities. Finally, we illustrate the method’s sensitivity towards myelin-related diseases by quantifying myelin alterations in dysmyelinated mouse brain. This non-destructive, stain-free molecular imaging approach enables quantitative studies of myelination within and across samples during development, aging, disease and treatment, and is applicable to other ordered biomolecules or nanostructures

Cross-scanner and cross-protocol multi-shell diffusion MRI data harmonization: algorithms and result

Cross-scanner and cross-protocol variability of diffusion magnetic resonance imaging (dMRI) data are known to be major obstacles in multi-site clinical studies since they limit the ability to aggregate dMRI data and derived measures. Computational algorithms that harmonize the data and minimize such variability are critical to reliably combine datasets acquired from different scanners and/or protocols, thus improving the statistical power and sensitivity of multi-site studies. Different computational approaches have been proposed to harmonize diffusion MRI data or remove scanner-specific differences. To date, these methods have mostly been developed for or evaluated on single b-value diffusion MRI data. In this work, we present the evaluation results of 19 algorithms that are developed to harmonize the cross-scanner and cross-protocol variability of multi-shell diffusion MRI using a benchmark database. The proposed algorithms rely on various signal representation approaches and computational tools, such as rotational invariant spherical harmonics, deep neural networks and hybrid biophysical and statistical approaches. The benchmark database consists of data acquired from the same subjects on two scanners with different maximum gradient strength (80 and 300 ​mT/m) and with two protocols. We evaluated the performance of these algorithms for mapping multi-shell diffusion MRI data across scanners and across protocols using several state-of-the-art imaging measures. The results show that data harmonization algorithms can reduce the cross-scanner and cross-protocol variabilities to a similar level as scan-rescan variability using the same scanner and protocol. In particular, the LinearRISH algorithm based on adaptive linear mapping of rotational invariant spherical harmonics features yields the lowest variability for our data in predicting the fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK) and the rotationally invariant spherical harmonic (RISH) features. But other algorithms, such as DIAMOND, SHResNet, DIQT, CMResNet show further improvement in harmonizing the return-to-origin probability (RTOP). The performance of different approaches provides useful guidelines on data harmonization in future multi-site studies

brainlife.io: A decentralized and open source cloud platform to support neuroscience research

Neuroscience research has expanded dramatically over the past 30 years by advancing standardization and tool development to support rigor and transparency. Consequently, the complexity of the data pipeline has also increased, hindering access to FAIR data analysis to portions of the worldwide research community. brainlife.io was developed to reduce these burdens and democratize modern neuroscience research across institutions and career levels. Using community software and hardware infrastructure, the platform provides open-source data standardization, management, visualization, and processing and simplifies the data pipeline. brainlife.io automatically tracks the provenance history of thousands of data objects, supporting simplicity, efficiency, and transparency in neuroscience research. Here brainlife.io's technology and data services are described and evaluated for validity, reliability, reproducibility, replicability, and scientific utility. Using data from 4 modalities and 3,200 participants, we demonstrate that brainlife.io's services produce outputs that adhere to best practices in modern neuroscience research

Recommendations and guidelines from the ISMRM Diffusion Study Group for preclinical diffusion MRI: Part 1 -- In vivo small-animal imaging

The value of in vivo preclinical diffusion MRI (dMRI) is substantial. Small-animal dMRI has been used for methodological development and validation, characterizing the biological basis of diffusion phenomena, and comparative anatomy. Many of the influential works in this field were first performed in small animals or ex vivo samples. The steps from animal setup and monitoring, to acquisition, analysis, and interpretation are complex, with many decisions that may ultimately affect what questions can be answered using the data. This work aims to serve as a reference, presenting selected recommendations and guidelines from the diffusion community, on best practices for preclinical dMRI of in vivo animals. In each section, we also highlight areas for which no guidelines exist (and why), and where future work should focus. We first describe the value that small animal imaging adds to the field of dMRI, followed by general considerations and foundational knowledge that must be considered when designing experiments. We briefly describe differences in animal species and disease models and discuss how they are appropriate for different studies. We then give guidelines for in vivo acquisition protocols, including decisions on hardware, animal preparation, imaging sequences and data processing, including pre-processing, model-fitting, and tractography. Finally, we provide an online resource which lists publicly available preclinical dMRI datasets and software packages, to promote responsible and reproducible research. An overarching goal herein is to enhance the rigor and reproducibility of small animal dMRI acquisitions and analyses, and thereby advance biomedical knowledge.Comment: 69 pages, 6 figures, 1 tabl