•Multi-compartment relaxometry for myelin water imaging (MCR-MWI) can be performed with data comprising as few as 3 flip angles without introducing substantial bias or instability in the fitting ...procedure.•MCR-MWI is a reproducible measure of myelin water fraction (MWF) and incorporating DWI can further improve the measurement reproducibility.•MCR-MWI allows the acquisition of whole-brain 1.5 mm isotropic MWF maps in 9 min, even without the use of advanced model-based reconstructions.•Small MWF bias can present in cross-protocol comparison if the MT effect is not constant across GRE protocols (e.g., different TRs or flip angle combinations).•Compartmental relaxation parameters derived from MCR-MWI possess complimentary information beyond myelin water concentration.
In this study, we optimized the variable flip angle (VFA) acquisition scheme using numerical simulations to shorten the acquisition time of multicompartment relaxometry for myelin water imaging (MCR-MWI) to a clinically practical range in the absence of advanced image reconstruction methods. As the primary objective of this study, the test-retest repeatability of myelin water fraction (MWF) measurements of MCR-MWI is evaluated on three gradient echo (GRE) sequence settings using the optimized VFA schemes with different echo times and repetition times, emulating various scanner setups. The cross-protocol reproducibility of MCR-MWI and MCR with diffusion-informed myelin water imaging (MCR-DIMWI) is also examined. As a secondary objective, we explore the bundle-specific profiles of various microstructural parameters from MCR-(DI)MWI and their cross-correlations to determine if these parameters possess supplementary microstructure information beyond myelin concentration.
Numerical simulations indicate that MCR-MWI can be performed with a minimum of three flip angles covering a wide range of T1 weightings without adding significant bias. This is supported by the results of an in vivo experiment, allowing whole-brain 1.5 mm isotropic MWF maps to be acquired in 9 min, reducing the total scan time to 40% of the original implementation without significant quality degradation. Good test-retest repeatability is observed for MCR-MWI for all three GRE protocols. While good correlations can also be found in MWF across protocols, systematic differences are observed. Bundle-specific MWF analysis reveals that certain white matter bundles are similar in all participants. We also found that microstructure relaxation parameters have low linear correlations with MWF. MCR-MWI is a reproducible measure of myelin. However, attention should be paid to the protocol related MWF differences when comparing different studies, as the MWF bias up to 0.5% can be observed across the protocols examined in this work.
The role of white matter in reading has been established by diffusion tensor imaging (DTI), but DTI cannot identify specific microstructural features driving these relationships. Neurite orientation ...dispersion and density imaging (NODDI), inhomogeneous magnetization transfer (ihMT) and multicomponent driven equilibrium single-pulse observation of T1/T2 (mcDESPOT) can be used to link more specific aspects of white matter microstructure and reading due to their sensitivity to axonal packing and fiber coherence (NODDI) and myelin (ihMT and mcDESPOT). We applied principal component analysis (PCA) to combine DTI, NODDI, ihMT and mcDESPOT measures (10 in total), identify major features of white matter structure, and link these features to both reading and age. Analysis was performed for nine reading-related tracts in 46 neurotypical 6-16 year olds. We identified three principal components (PCs) which explained 79.5% of variance in our dataset. PC1 probed tissue complexity, PC2 described myelin and axonal packing, while PC3 was related to axonal diameter. Mixed effects regression models did not identify any significant relationships between principal components and reading skill. Bayes factor analysis revealed that the absence of relationships was not due to low power. Increasing PC1 in the left arcuate fasciculus with age suggest increases in tissue complexity, while increases of PC2 in the bilateral arcuate, inferior longitudinal, inferior fronto-occipital fasciculi, and splenium suggest increases in myelin and axonal packing with age. Multimodal white matter imaging and PCA provide microstructurally informative, powerful principal components which can be used by future studies of development and cognition. Our findings suggest major features of white matter undergo development during childhood and adolescence, but changes are not linked to reading during this period in our typically-developing sample.
Investigative studies of white matter (WM) brain structures using diffusion MRI (dMRI) tractography frequently require manual WM bundle segmentation, often called “virtual dissection.” Human errors ...and personal decisions make these manual segmentations hard to reproduce, which have not yet been quantified by the dMRI community. It is our opinion that if the field of dMRI tractography wants to be taken seriously as a widespread clinical tool, it is imperative to harmonize WM bundle segmentations and develop protocols aimed to be used in clinical settings. The EADC‐ADNI Harmonized Hippocampal Protocol achieved such standardization through a series of steps that must be reproduced for every WM bundle. This article is an observation of the problematic. A specific bundle segmentation protocol was used in order to provide a real‐life example, but the contribution of this article is to discuss the need for reproducibility and standardized protocol, as for any measurement tool. This study required the participation of 11 experts and 13 nonexperts in neuroanatomy and “virtual dissection” across various laboratories and hospitals. Intra‐rater agreement (Dice score) was approximately 0.77, while inter‐rater was approximately 0.65. The protocol provided to participants was not necessarily optimal, but its design mimics, in essence, what will be required in future protocols. Reporting tractometry results such as average fractional anisotropy, volume or streamline count of a particular bundle without a sufficient reproducibility score could make the analysis and interpretations more difficult. Coordinated efforts by the diffusion MRI tractography community are needed to quantify and account for reproducibility of WM bundle extraction protocols in this era of open and collaborative science.
The anisotropy of brain white matter microstructure manifests itself in orientational-dependence of various MRI contrasts, and can result in significant quantification biases if ignored. ...Understanding the origins of this orientation-dependence could enhance the interpretation of MRI signal changes in development, ageing and disease and ultimately improve clinical diagnosis. Using a novel experimental setup, this work studies the contributions of the intra- and extra-axonal water to the orientation-dependence of one of the most clinically-studied parameters, apparent transverse relaxation T2. Specifically, a tiltable receive coil is interfaced with an ultra-strong gradient MRI scanner to acquire multidimensional MRI data with an unprecedented range of acquisition parameters. Using this setup, compartmental T2 can be disentangled based on differences in diffusional-anisotropy, and its orientation-dependence further elucidated by re-orienting the head with respect to the main magnetic field B→0. A dependence of (compartmental) T2 on the fibre orientation w.r.t. B→0 was observed, and further quantified using characteristic representations for susceptibility- and magic angle effects. Across white matter, anisotropy effects were dominated by the extra-axonal water signal, while the intra-axonal water signal decay varied less with fibre-orientation. Moreover, the results suggest that the stronger extra-axonal T2 orientation-dependence is dominated by magnetic susceptibility effects (presumably from the myelin sheath) while the weaker intra-axonal T2 orientation-dependence may be driven by a combination of microstructural effects. Even though the current design of the tiltable coil only offers a modest range of angles, the results demonstrate an overall effect of tilt and serve as a proof-of-concept motivating further hardware development to facilitate experiments that explore orientational anisotropy. These observations have the potential to lead to white matter microstructural models with increased compartmental sensitivity to disease, and can have direct consequences for longitudinal and group-wise T2- and diffusion-MRI data analysis, where the effect of head-orientation in the scanner is commonly ignored.
It is estimated that in the human brain, short association fibres (SAF) represent more than half of the total white matter volume and their involvement has been implicated in a range of neurological ...and psychiatric conditions. This population of fibres, however, remains relatively understudied in the neuroimaging literature. Some of the challenges pertinent to the mapping of SAF include their variable anatomical course and proximity to the cortical mantle, leading to partial volume effects and potentially affecting streamline trajectory estimation. This work considers the impact of seeding and filtering strategies and choice of scanner, acquisition, data resampling to propose a whole-brain, surface-based short (≤30–40 mm) SAF tractography approach. The framework is shown to produce longer streamlines with a predilection for connecting gyri as well as high cortical coverage. We further demonstrate that certain areas of subcortical white matter become disproportionally underrepresented in diffusion-weighted MRI data with lower angular and spatial resolution and weaker diffusion weighting; however, collecting data with stronger gradients than are usually available clinically has minimal impact, making our framework translatable to data collected on commonly available hardware. Finally, the tractograms are examined using voxel- and surface-based measures of consistency, demonstrating moderate reliability, low repeatability and high between-subject variability, urging caution when streamline count-based analyses of SAF are performed.
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At the typical spatial resolution of MRI in the human brain, approximately 60–90% of voxels contain multiple fiber populations. Quantifying microstructural properties of distinct fiber populations ...within a voxel is therefore challenging but necessary. While progress has been made for diffusion and T1-relaxation properties, how to resolve intra-voxel T2 heterogeneity remains an open question. Here a novel framework, named COMMIT-T2, is proposed that uses tractography-based spatial regularization with diffusion-relaxometry data to estimate multiple intra-axonal T2 values within a voxel. Unlike previously-proposed voxel-based T2 estimation methods, which (when applied in white matter) implicitly assume just one fiber bundle in the voxel or the same T2 for all bundles in the voxel, COMMIT-T2 can recover specific T2 values for each unique fiber population passing through the voxel. In this approach, the number of recovered unique T2 values is not determined by a number of model parameters set a priori, but rather by the number of tractography-reconstructed streamlines passing through the voxel. Proof-of-concept is provided in silico and in vivo, including a demonstration that distinct tract-specific T2 profiles can be recovered even in the three-way crossing of the corpus callosum, arcuate fasciculus, and corticospinal tract. We demonstrate the favourable performance of COMMIT-T2 compared to that of voxelwise approaches for mapping intra-axonal T2 exploiting diffusion, including a direction-averaged method and AMICO-T2, a new extension to the previously-proposed Accelerated Microstructure Imaging via Convex Optimization (AMICO) framework.
We provide a rich multi-contrast microstructural MRI dataset acquired on an ultra-strong gradient 3T Connectom MRI scanner comprising 5 repeated sets of MRI microstructural contrasts in 6 healthy ...human participants. The availability of data sets that support comprehensive simultaneous assessment of test-retest reliability of multiple microstructural contrasts (i.e., those derived from advanced diffusion, multi-component relaxometry and quantitative magnetisation transfer MRI) in the same population is extremely limited. This unique dataset is offered to the imaging community as a test-bed resource for conducting specialised analyses that may assist and inform their current and future research. The Microstructural Image Compilation with Repeated Acquisitions (MICRA) dataset includes raw data and computed microstructure maps derived from multi-shell and multi-direction encoded diffusion, multi-component relaxometry and quantitative magnetisation transfer acquisition protocols. Our data demonstrate high reproducibility of several microstructural MRI measures across scan sessions as shown by intra-class correlation coefficients and coefficients of variation. To illustrate a potential use of the MICRA dataset, we computed sample sizes required to provide sufficient statistical power a priori across different white matter pathways and microstructure measures for different statistical comparisons. We also demonstrate whole brain white matter voxel-wise repeatability in several microstructural maps. The MICRA dataset will be of benefit to researchers wishing to conduct similar reliability tests, power estimations or to evaluate the robustness of their own analysis pipelines.
Surgical resection is an effective treatment for temporal lobe epilepsy but can result in visual field defects. This could be minimized if surgeons knew the exact location of the anterior part of the ...optic radiation (OR), the Meyer's loop. To this end, there is increasing prevalence of image-guided surgery using diffusion MRI tractography. Despite considerable effort in developing analysis methods, a wide discrepancy in Meyer's loop reconstructions is observed in the literature. Moreover, the impact of differences in image acquisition on Meyer's loop tractography remains unclear. Here, while employing the same state-of-the-art analysis protocol, we explored the extent to which variance in data acquisition leads to variance in OR reconstruction.
Diffusion MRI data were acquired for the same thirteen healthy subjects using standard and state-of-the-art protocols on three scanners with different maximum gradient amplitudes (MGA): Siemens Connectom (MGA = 300 mT/m); Siemens Prisma (MGA = 80 mT/m) and GE Excite-HD (MGA = 40 mT/m). Meyer's loop was reconstructed on all subjects and its distance to the temporal pole (ML-TP) was compared across protocols.
A significant effect of data acquisition on the ML-TP distance was observed between protocols (p < .01 to 0.0001). The biggest inter-acquisition discrepancy for the same subject across different protocols was 16.5 mm (mean: 9.4 mm, range: 3.7–16.5 mm).
We showed that variance in data acquisition leads to substantive variance in OR tractography. This has direct implications for neurosurgical planning, where part of the OR is at risk due to an under-estimation of its location using conventional acquisition protocols.
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•Diffusion MRI data from 13 subjects on 3 scanners with different maximum gradient amplitude.•Optic radiation tractography was performed using “standard” and “state-of-the-art” acquisitions.•Meyer's loop to Temporal Pole distance varies up to 16.5 mm for the same subject across protocols.•State-of-the-art protocols provide Meyer's loop measurements that are in line with ex-vivo studies.•Surgical planning for anterior temporal lobe resection depends on protocol and available hardware.
Fiber tractography plays an important role in exploring the architectural organization of fiber trajectories, both in fundamental neuroscience and in clinical applications. With the advent of ...diffusion MRI (dMRI) approaches that can also model "crossing fibers", the complexity of the fiber network as reconstructed with tractography has increased tremendously. Many pathways interdigitate and overlap, which hampers an unequivocal 3D visualization of the network and impedes an efficient study of its organization. We propose a novel fiber tractography visualization approach that interactively and selectively adapts the transparency rendering of fiber trajectories as a function of their orientation to enhance the visibility of the spatial context. More specifically, pathways that are oriented (locally or globally) along a user-specified opacity axis can be made more transparent or opaque. This substantially improves the 3D visualization of the fiber network and the exploration of tissue configurations that would otherwise be largely covered by other pathways. We present examples of fiber bundle extraction and neurosurgical planning cases where the added benefit of our new visualization scheme is demonstrated over conventional fiber visualization approaches.
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