The relaxometry hype cycle

ABSTRACT: Relaxometry is a field with a glorious and controversial history, and no review will ever do it justice. It is full of egos and inventions, patents and lawsuits, high expectations and deep disillusionments. Rather than a paragraph dedicated to each of these, we want to give it an impressionistic overview, painted over with a coat of personal opinions and ruminations about the future of the field. For those unfamiliar with the Gartner hype cycle, here’s a brief recap. The cycle starts with a technology trigger and goes through a phase of unrealistically inflated expectations. Eventually the hype dies down as implementations fail to deliver on their promise, and disillusionment sets in. Technologies that manage to live through the trough reach the slope of enlightenment, when there is a flurry of second and third generation products that make the initial promise feel feasible again. Finally, we reach the slope of productivity, where mainstream adoption takes off, and more incremental progress is made, eventually reaching steady state in terms of the technology’s visibility. The entire interactive timeline can be viewed at https://qmrlab.org/relaxometry/

Axon and myelin morphology in animal and human spinal cord

Characterizing precisely the microstructure of axons, their density, size and myelination is of interest for the neuroscientific community, for example to help maximize the outcome of studies on white matter (WM) pathologies of the spinal cord (SC). The existence of a comprehensive and structured database of axonal measurements in healthy and disease models could help the validation of results obtained by different researchers. The purpose of this article is to provide such a database of healthy SC WM, to discuss the potential sources of variability and to suggest avenues for robust and accurate quantification of axon morphometry based on novel acquisition and processing techniques. The article is organized in three sections. The first section reviews morphometric results across species according to range of densities and counts of myelinated axons, axon diameter and myelin thickness, and characteristics of unmyelinated axons in different regions. The second section discusses the sources of variability across studies, such as age, sex, spinal pathways, spinal levels, statistical power and terminology in regard to tracts and protocols. The third section presents new techniques and perspectives that could benefit histology studies. For example, coherent anti-stokes Raman spectroscopy (CARS) imaging can provide sub-micrometric resolution without the need for fixation and staining, while slide scanners and stitching algorithms can provide full cross-sectional area of SC. In combination with these acquisition techniques, automatic segmentation algorithms for delineating axons and myelin sheath can help provide large-scale statistics on axon morphometry

An interactive meta-analysis of MRI biomarkers of myelin

Several MRI measures have been proposed as in vivo biomarkers of myelin, each with applications ranging from plasticity to pathology. Despite the availability of these myelin-sensitive modalities, specificity and sensitivity have been a matter of discussion. Debate about which MRI measure is the most suitable for quantifying myelin is still ongoing. In this study, we performed a systematic review of published quantitative validation studies to clarify how different these measures are when compared to the underlying histology. We analysed the results from 43 studies applying meta-analysis tools, controlling for study sample size and using interactive visualization (https://neurolibre.github.io/myelin-meta-analysis). We report the overall estimates and the prediction intervals for the coefficient of determination and find that MT and relaxometry-based measures exhibit the highest correlations with myelin content. We also show which measures are, and which measures are not statistically different regarding their relationship with histology

AxonPacking: an open-source software to simulate arrangements of axons in white matter

Quantitative Magnetic Resonance Imaging (MRI) can provide parameters that describe white matter microstructure, such as the fiber volume fraction (FVF), the myelin volume fraction (MVF) or the axon volume fraction (AVF) via the fraction of restricted water (fr). While already being used for clinical application, the complex interplay between these parameters requires thorough validation via simulations. These simulations required a realistic, controlled and adaptable model of the white matter axons with the surrounding myelin sheath. While there already exist useful algorithms to perform this task, none of them combine optimisation of axon packing, presence of myelin sheath and availability as free and open source software. Here, we introduce a novel disk packing algorithm that addresses these issues. The performance of the algorithm is tested in term of reproducibility over 50 runs, resulting density, and stability over iterations. This tool was then used to derive multiple values of FVF and to study the impact of this parameter on fr and MVF in light of the known microstructure based on histology sample. The standard deviation of the axon density over runs was lower than 10(-3) and the expected hexagonal packing for monodisperse disks was obtained with a density close to the optimal density (obtained: 0.892, theoretical: 0.907). Using an FVF ranging within [0.58, 0.82] and a mean inter-axon gap ranging within [0.1, 1.1] mu m, MVF ranged within [0.32, 0.44] and fr ranged within [0.39, 0.71], which is consistent with the histology. The proposed algorithm is implemented in the open-source software AxonPacking (hups://github.comineuropoly/ axonpacking) and can be useful for validating diffusion models as well as for enabling researchers to study the interplay between microstructure parameters when evaluating qMRI methods

Comparison of different cardiovascular magnetic resonance sequences for native myocardial T1 mapping at 3T

Background: T1 mapping based on cardiovascular magnetic resonance (CMR) is a novel approach using the magnetic relaxation T1 time as a quantitative marker for myocardial tissue composition. Various T1 mapping sequences are being used, with different strengths and weaknesses. Data comparing different sequences head to head however are sparse.Methods: We compared three T1 mapping sequences, ShMOLLI, MOLLI and SASHA in phantoms and in a mid-ventricular slice of 40 healthy individuals (mean age 59 +/- 7 years, 45 % male) with low (68 %) or moderate cardiovascular risk. We calculated global and segmental T1 in vivo through exponential curve fitting and subsequent parametric mapping. We also analyzed image quality and inter-observer reproducibility.Results: There was no association of T1 with cardiovascular risk groups. T1 however differed significantly depending on the sequence, with SASHA providing consistently higher mean values than ShMOLLI and MOLLI (1487 +/- 36 ms vs. 1174 +/- 37 ms and 1199 +/- 28 ms, respectively; p < 0.001). This difference between sequences was much smaller in phantom measurements. In patients, segmental values were lower in the anterior wall for all sequences. Image quality, in general good for the steady-state-free-precession readouts in all sequences, was lower for SASHA parametric maps. On multivariate regression analysis, a longer T1 measured by MOLLI was correlated with lower ejection fraction and female gender. Inter-observer variability as assessed by intra-class correlation coefficients was excellent for all sequences (ShMOLLI: 0.995; MOLLI: 0.991; SASHA: 0.961; all p < 0.001).Conclusion: In a cross-sectional population with low to moderate cardiovascular risk, we observed a variation in T1 mapping results between inversion-recovery vs. saturation-recovery sequences in vivo, which were less evident in phantom images, despite a small interobserver variability. Thus, physiological factors, most likely related to B1 inhomogeneities, and tissue-specific properties, like magnetization transfer, that impact T1 values in vivo, render phantom validation insufficient, and have to be further investigated for a better understanding of the clinical utility of different T1 mapping approaches

AxonSeg: open source software for axon and myelin segmentation and morphometric analysis

Segmenting axon and myelin from microscopic images is relevant for studying the peripheral and central nervous system and for validating new MRI techniques that aim at quantifying tissue microstructure. While several software packages have been proposed, their interface is sometimes limited and/or they are designed to work with a specific modality (e.g., scanning electron microscopy (SEM) only). Here we introduce AxonSeg, which allows to perform automatic axon and myelin segmentation on histology images, and to extract relevant morphometric information, such as axon diameter distribution, axon density and the myelin g-ratio. AxonSeg includes a simple and intuitive MATLABbased graphical user interface (GUI) and can easily be adapted to a variety of imaging modalities. The main steps of AxonSeg consist of: (i) image pre-processing; (ii) pre-segmentation of axons over a cropped image and discriminant analysis (DA) to select the best parameters based on axon shape and intensity information; (iii) automatic axon and myelin segmentation over the full image; and (iv) atlas-based statistics to extract morphometric information. Segmentation results from standard optical microscopy (OM), SEM and coherent anti-Stokes Raman scattering (CARS) microscopy are presented, along with validation against manual segmentations. Being fully-automatic after a quick manual intervention on a cropped image, we believe AxonSeg will be useful to researchers interested in large throughput histology

Beyond advertising: New infrastructures for publishing integrated research objects

ABSTRACT: Moving beyond static text and illustrations is a central challenge for scientific publishing in the 21st century. As early as 1995, Donoho and Buckheit paraphrased John Claerbout that “an article about [a] computational result is advertising, not scholarship. The actual scholarship is the full software environment, code and data, that produced the result” [1]. Awareness of this problem has only grown over the last 25 years; nonetheless, scientific publishing infrastructures remain remarkably resistant to change [2]. Even as these infrastructures have largely stagnated, the internet has ushered in a transition “from the wet lab to the web lab” [3]. New expectations have emerged in this shift, but these expectations must play against the reality of currently available infrastructures and associated sociological pressures. Here, we compare current scientific publishing norms against those associated with online content more broadly, and we argue that meeting the “Claerbout challenge” of providing the full software environment, code, and data supporting a scientific result will require open infrastructure development to create environments for authoring, reviewing, and accessing interactive research objects

qMRI-BIDS: An extension to the brain imaging data structure for quantitative magnetic resonance imaging data

The Brain Imaging Data Structure (BIDS) established community consensus on the organization of data and metadata for several neuroimaging modalities. Traditionally, BIDS had a strong focus on functional magnetic resonance imaging (MRI) datasets and lacked guidance on how to store multimodal structural MRI datasets. Here, we present and describe the BIDS Extension Proposal 001 (BEP001), which adds a range of quantitative MRI (qMRI) applications to the BIDS. In general, the aim of qMRI is to characterize brain microstructure by quantifying the physical MR parameters of the tissue via computational, biophysical models. By proposing this new standard, we envision standardization of qMRI through multicenter dissemination of interoperable datasets. This way, BIDS can act as a catalyst of convergence between qMRI methods development and application-driven neuroimaging studies that can help develop quantitative biomarkers for neural tissue characterization. In conclusion, this BIDS extension offers a common ground for developers to exchange novel imaging data and tools, reducing the entrance barrier for qMRI in the field of neuroimaging

The myelin-weighted connectome in Parkinson’s disease

Background Even though Parkinson's disease (PD) is typically viewed as largely affecting gray matter, there is growing evidence that there are also structural changes in the white matter. Traditional connectomics methods that study PD may not be specific to underlying microstructural changes, such as myelin loss. Objective The primary objective of this study is to investigate the PD-induced changes in myelin content in the connections emerging from the basal ganglia and the brainstem. For the weighting of the connectome, we used the longitudinal relaxation rate as a biologically grounded myelin-sensitive metric. Methods We computed the myelin-weighted connectome in 35 healthy control subjects and 81 patients with PD. We used partial least squares to highlight the differences between patients with PD and healthy control subjects. Then, a ring analysis was performed on selected brainstem and subcortical regions to evaluate each node's potential role as an epicenter for disease propagation. Then, we used behavioral partial least squares to relate the myelin alterations with clinical scores. Results Most connections (~80%) emerging from the basal ganglia showed a reduced myelin content. The connections emerging from potential epicentral nodes (substantia nigra, nucleus basalis of Meynert, amygdala, hippocampus, and midbrain) showed significant decrease in the longitudinal relaxation rate (P < 0.05). This effect was not seen for the medulla and the pons. Conclusions The myelin-weighted connectome was able to identify alteration of the myelin content in PD in basal ganglia connections. This could provide a different view on the importance of myelination in neurodegeneration and disease progression. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Societ

qMRLab: Quantitative MRI analysis, under one umbrella

ABSTRACT: Magnetic resonance imaging (MRI) has revolutionized the way we look at the human body. However, conventional MR scanners are not measurement devices. They produce digital images represented by “shades of grey”, and the intensity of the shades depends on the way the images are acquired. This is why it is difficult to compare images acquired at different clinical sites, limiting the diagnostic, prognostic, and scientific potential of the technology. Quantitative MRI (qMRI) aims to overcome this problem by assigning units to MR images, ensuring that the values represent a measurable quantity that can be reproduced within and across sites. While the vision for quantitative MRI is to overcome site-dependent variations, this is still a challenge due to variability in the hardware and software used by MR vendors to produce quantitative MRI maps. Although qMRI has yet to enter mainstream clinical use, imaging scientists see great promise in the technique’s potential to characterize tissue microstructure. However, most qMRI tools for fundamental research are developed in-house and are difficult to port across sites, which in turn hampers their standardization, reproducibility, and widespread adoption. To tackle this problem, we developed qMRLab, an open-source software package that provides a wide selection of qMRI methods for data fitting, simulation and protocol optimization Figure 1. It not only brings qMRI under one umbrella, but also facilitates its use through documentation that features online executable notebooks, a user friendly graphical user interface (GUI), interactive tutorials and blog posts