Quantification de la microstructure de la moelle épinière humaine par IRM et application chez des patients avec sclérose en plaques

Les pathologies degeneratives de la moelle epiniere sont encore aujourd'hui mal diagnostiquees et laissent les patients dans un etat de souffrance et de doute. L'imagerie par resonance magnetique (IRM) permet d'obtenir des informations quantitatives sur la microstructure de la matiere blanche. Nous avons demontre la faisabilité d'estimer la densite et le diametre des axones dans la moelle epiniere humaine en utilisant une IRM unique au monde installee a Boston, le "scanner Connectom", capable d'atteindre des gradients de champ magnetique de r@@mT/m. Cependant cette methode ne donne qu'une information partielle de la microstructure de la matiere blanche et ne tient pas compte de la gaine de myeline entourant les axones. Cette gaine de myeline permet d'assurer une bonne conductivite des axones et peut degenerer dans certaines pathologies comme la sclerose en plaques. Nos collaborateurs de l'université McGill ont proposé de combiner cette technique avec l'IRM quantitative de la myeline afin de mesurer son g-ratio, ou ratio du diametre interne sur externe de la myeline. Durant cette these, j’ai mis en place les techniques d’IRM de la microstructure, j’ai valide ces methodes en utilisant l’histologie a large champ de vue, puis je les ai appliquees chez des patients avec sclerose en plaques pour une application clinique.----------ABSTRACT Degenerative pathologies of the spinal cord are still difficult to diagnose today, leaving patients in a state of constant suffering and constant doubt about their future. Magnetic Resonance Imaging (MRI) can gather quantitative information about the white matter microstructure by playing on the phase and relaxation of the spins. Using a unique MRI system capable of magnetic gradients of r@@mT/m, the “Connectom scanner”, we showed that neuronal fibers (axons) density and diameter can be measured in the human spinal cord in vivo using diffusion MRI. Although very informative, this method only provides a partial description of the tissue and no direct information about the myelin sheath that surrounds the axons is extracted. The myelin sheath improves the speed and frequency of action potentials that are transmitted through the axons, and an alteration of myelin integrity leads to paralysis in diseases such as multiple sclerosis. Our collaborators at McGill University proposed to combine the diffusion technique with quantitative myelin imaging technique in order to measure the thickness of the myelin sheath. In this thesis, I developed quantitative MRI techniques in the spinal cord, I validated these methods using large-scale histology, and I applied them on patients with multiple sclerosis

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

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

Continuum limit of amorphous elastic bodies: A finite-size study of low frequency harmonic vibrations

The approach of the elastic continuum limit in small amorphous bodies formed by weakly polydisperse Lennard-Jones beads is investigated in a systematic finite-size study. We show that classical continuum elasticity breaks down when the wavelength of the sollicitation is smaller than a characteristic length of approximately 30 molecular sizes. Due to this surprisingly large effect ensembles containing up to N=40,000 particles have been required in two dimensions to yield a convincing match with the classical continuum predictions for the eigenfrequency spectrum of disk-shaped aggregates and periodic bulk systems. The existence of an effective length scale \xi is confirmed by the analysis of the (non-gaussian) noisy part of the low frequency vibrational eigenmodes. Moreover, we relate it to the {\em non-affine} part of the displacement fields under imposed elongation and shear. Similar correlations (vortices) are indeed observed on distances up to \xi~30 particle sizes.Comment: 28 pages, 13 figures, 3 table

Learning the Parametric Transfer Function of Unitary Operations for Real-Time Evaluation of Manufacturing Processes Involving Operations Sequencing

For better designing manufacturing processes, surrogate models were widely considered in the past, where the effect of different material and process parameters was considered from the use of a parametric solution. The last contains the solution of the model describing the system under study, for any choice of the selected parameters. These surrogate models, also known as meta-models, virtual charts or computational vademecum, in the context of model order reduction, were successfully employed in a variety of industrial applications. However, they remain confronted to a major difficulty when the number of parameters grows exponentially. Thus, processes involving trajectories or sequencing entail a combinatorial exposition (curse of dimensionality) not only due to the number of possible combinations, but due to the number of parameters needed to describe the process. The present paper proposes a promising route for circumventing, or at least alleviating that difficulty. The proposed technique consists of a parametric transfer function that, as soon as it is learned, allows for, from a given state, inferring the new state after the application of a unitary operation, defined as a step in the sequenced process. Thus, any sequencing can be evaluated almost in real time by chaining that unitary transfer function, whose output becomes the input of the next operation. The benefits and potential of such a technique are illustrated on a problem of industrial relevance, the one concerning the induced deformation on a structural part when printing on it a series of stiffeners

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

A Temperature Phantom to Probe the Ensemble Average Propagator Asymmetry: an In-Silico Study

International audienceThe detection and quantification of asymmetry in the Ensemble Average Propagator (EAP) obtained from the Diffusion-Weighted (DW) signal has been shown only for theoretical models. EAP asymmetry appears for instance when diffusion occurs within fibers with particular geometries. However the quan-tification of EAP asymmetry corresponding to such geometries in controlled experimental conditions is limited by the difficulty of designing fiber geometries on a micrometer scale. To overcome this limitation we propose to adopt an alternative paradigm to induce asymmetry in the EAP. We apply a temperature gradient to a spinal cord tract to induce a corresponding diffusivity profile that alters locally the diffusion process to be asymmetric. We simulate the EAP and the corresponding complex DW signal in such a scenario. We quantify EAP asymmetry and investigate its relationship with the applied experimental conditions and with the acquisition parameters of a Pulsed Gradient Spin-Echo sequence. Results show that EAP asymmetry is sensible to the applied temperature-induced diffusivity gradient and that its quantification is influenced by the selected acquisition parameters

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

The Athena X-ray Integral Field Unit (X-IFU)

The X-ray Integral Field Unit (X-IFU) is the high resolution X-ray spectrometer of the ESA Athena X-ray observatory. Over a field of view of 5' equivalent diameter, it will deliver X-ray spectra from 0.2 to 12 keV with a spectral resolution of 2.5 eV up to 7 keV on similar to 5 '' pixels. The X-IFU is based on a large format array of super-conducting molybdenum-gold Transition Edge Sensors cooled at similar to 90 mK, each coupled with an absorber made of gold and bismuth with a pitch of 249 mu m. A cryogenic anti-coincidence detector located underneath the prime TES array enables the non X-ray background to be reduced. A bath temperature of similar to 50 mK is obtained by a series of mechanical coolers combining 15K Pulse Tubes, 4K and 2K Joule-Thomson coolers which pre-cool a sub Kelvin cooler made of a He-3 sorption cooler coupled with an Adiabatic Demagnetization Refrigerator. Frequency domain multiplexing enables to read out 40 pixels in one single channel. A photon interacting with an absorber leads to a current pulse, amplified by the readout electronics and whose shape is reconstructed on board to recover its energy with high accuracy. The defocusing capability offered by the Athena movable mirror assembly enables the X-IFU to observe the brightest X-ray sources of the sky (up to Crab-like intensities) by spreading the telescope point spread function over hundreds of pixels. Thus the X-IFU delivers low pile-up, high throughput (> 50%), and typically 10 eV spectral resolution at 1 Crab intensities, i.e. a factor of 10 or more better than Silicon based X-ray detectors. In this paper, the current X-IFU baseline is presented, together with an assessment of its anticipated performance in terms of spectral resolution, background, and count rate capability. The X-IFU baseline configuration will be subject to a preliminary requirement review that is scheduled at the end of 2018. The X-IFU will be provided by an international consortium led by France, the Netherlands and Italy, with further ESA member state contributions from Belgium, Czech Republic, Finland, Germany, Ireland, Poland, Spain, Switzerland and contributions from Japan and the United States.Peer reviewe

The Athena X-ray Integral Field Unit: a consolidated design for the system requirement review of the preliminary definition phase

The Athena X-ray Integral Unit (X-IFU) is the high resolution X-ray spectrometer, studied since 2015 for flying in the mid-30s on the Athena space X-ray Observatory, a versatile observatory designed to address the Hot and Energetic Universe science theme, selected in November 2013 by the Survey Science Committee. Based on a large format array of Transition Edge Sensors (TES), it aims to provide spatially resolved X-ray spectroscopy, with a spectral resolution of 2.5 eV (up to 7 keV) over an hexagonal field of view of 5 arc minutes (equivalent diameter). The X-IFU entered its System Requirement Review (SRR) in June 2022, at about the same time when ESA called for an overall X-IFU redesign (including the X-IFU cryostat and the cooling chain), due to an unanticipated cost overrun of Athena. In this paper, after illustrating the breakthrough capabilities of the X-IFU, we describe the instrument as presented at its SRR, browsing through all the subsystems and associated requirements. We then show the instrument budgets, with a particular emphasis on the anticipated budgets of some of its key performance parameters. Finally we briefly discuss on the ongoing key technology demonstration activities, the calibration and the activities foreseen in the X-IFU Instrument Science Center, and touch on communication and outreach activities, the consortium organisation, and finally on the life cycle assessment of X-IFU aiming at minimising the environmental footprint, associated with the development of the instrument. Thanks to the studies conducted so far on X-IFU, it is expected that along the design-to-cost exercise requested by ESA, the X-IFU will maintain flagship capabilities in spatially resolved high resolution X-ray spectroscopy, enabling most of the original X-IFU related scientific objectives of the Athena mission to be retained. (abridged).Comment: 48 pages, 29 figures, Accepted for publication in Experimental Astronomy with minor editin