Détection et analyse des microsaignements cérébraux : application à des séquences d'imageries cliniques et à de grandes populations de sujets

CMBs, small hypo-intense foci with a maximum diameter of 10 millimeters, were first thought clinically silent. They are now considered as an imaging marker of cerebral small vessel diseases and their clinical involvement is increasingly recognized; they may be associated with an increased risk of hemorrhagic stroke, ischemia and dementia such as Alzheimer's disease. However, their relation with pathology and its causality remains largely to be understood, partly because of their tricky characterization in-vivo. Large scale studies or meta-analyses are made difficult because their identification varies with MRI sequence parameters and suffers from reproducibility issues and is time-consuming. Automatic identification methods have been proposed to address these issues but they all require manual post processing selection steps, because of a very high number of false positives. This suggests that a better characterization of CMBs may be the key to improve their detection, as it would allow better identifying them from misleading structures and lesions.This PhD focused on achieving a better characterization of CMBs to better detect them with an automatic method. It covers multiple aspects to improve CMBs identification. First, MR phase image was taken into account in addition to the standard MR magnitude image, because of its sensitivity to CMBs. A new MR phase image processing technique was thus developed to obtain the magnetic field of interest free of contamination from background sources in datasets equivalent to clinical routine. A comparison study was carried-out to evaluate the outcome of this tool for CMBs detection in a standardized dataset in a clinical environment. A proof-of-concept is given to illustrate the advantages of new features for automatically identifying CMBs.Les micro-saignements cérébraux (MSC) sont des dépôts d’hémosidérine particulièrement visibles sur des séquences IRM sensibles à la susceptibilité magnétique, comme par exemple la séquence en écho de gradient pondérée (GRE) en T2*. Néanmoins, leur détection in-vivo à partir de l’image d'amplitude GRE T2* obtenue en routine clinique est peu exacte et très sensible aux paramètres d’acquisition. Une détection automatique des MSC permettrait d’augmenter la portée et la pertinence de cette séquence, mais il est avant tout nécessaire de mieux caractériser les MSC pour augmenter la spécificité de détection. Cette thèse présente une nouvelle méthode pour extraire l’information d’intérêt (la carte champ interne) à partir d’images de phase obtenues avec les mêmes acquisitions cliniques GRE T2*. En effet, l’image de phase T2* contient directement une information sur la susceptibilité et pourrait donc améliorer la détection des MSC. Cette méthode a été évaluée avec succès sur des données multicentriques de qualité compatible avec la routine clinique pour des sujets avec un nombre très variable de MSC et a permis de différencier les MSC des micro-calcifications. Une étude de validation a également été menée pour évaluer l’utilité clinique de la carte de champ interne pour la détection par un expert, par rapport à d’autres types d’images et reconstructions utilisées en clinique. Elle a montré une amélioration de la spécificité. La thèse comprend également une preuve de concept d’une méthode d’identification automatique utilisant l’information provenant de plusieurs types d’image et de reconstruction afin d’augmenter la spécificité de l’identification. L’évaluation est menée sur les sujets précédemment décrits. Cette preuve de concept est basée sur un algorithme d’apprentissage supervisé ; cela consiste à combiner les informations issues des différents types d’image à partir desquels des descripteurs d’intensités et de forme ont été extraits pour créer un modèle de prédiction permettant discriminer les MSC

Discriminating brain microbleeds using phase contrast MRI in a multicentre clinical setting

International audienc

2D harmonic filtering of MR phase images in multicenter clinical setting: Toward a magnetic signature of cerebral microbleeds

International audienceCerebral microbleeds (CMBs) have emerged as a new imaging marker of small vessel disease. Composed of hemosiderin, CMBs are paramagnetic and can be detected with MRI sequences sensitive to magnetic susceptibility (typically, gradient recalled echo T2* weighted images). Nevertheless, their identification remains challenging on T2* magnitude images because of confounding structures and lesions. In this context, T2* phase image may play a key role in better characterizing CMBs because of its direct relationship with local magnetic field variations due to magnetic susceptibility difference. To address this issue, susceptibility-based imaging techniques were proposed, such as Susceptibility Weighted Imaging (SWI) and Quantitative Susceptibility Mapping (QSM). But these techniques have not yet been validated for 2D clinical data in multicenter settings. Here, we introduce 2DHF, a fast 2D phase processing technique embedding both unwrapping and harmonic filtering designed for data acquired in 2D, even with slice-to-slice inconsistencies. This method results in internal field maps which reveal local field details due to magnetic inhomogeneity within the region of interest only. This technique is based on the physical properties of the induced magnetic field and should yield consistent results. A synthetic phantom was created for numerical simulations. It simulates paramagnetic and diamagnetic lesions within a 'brain-like' tissue, within a background. The method was evaluated on both this synthetic phantom and multicenter 2D datasets acquired in standardized clinical setting, and compared with two state-of-the-art methods. It proved to yield consistent results on synthetic images and to be applicable and robust on patient data. As a proof-of-concept, we finally illustrate that it is possible to find a magnetic signature of CMBs and CMCs on internal field maps generated with 2DHF on 2D clinical datasets that give consistent results with CT-scans in a subsample of 10 subjects acquired with both modalities

Improved cerebral microbleeds detection using their magnetic signature on T2*-phase-contrast: a comparison study in a clinical setting

International audiencentroduction/Purpose: In vivo detection of cerebral microbleeds (CMBs) from T2* gradient recalled echo (GRE) magnitude image suffers from low specificity, modest inter-rater reproducibility and is biased by its sensitivity to acquisition parameters. New methods were proposed for improving this identification, but they mostly rely on 3D acquisitions, not always feasible in clinical practice. A fast 2D phase processing technique for computing internal field maps (IFM) has been shown to make it possible to characterize CMBs through their magnetic signature in routine clinical setting, based on 2D multi-slice acquisitions. However, its clinical interest for CMBs identification with respect to more common images remained to be assessed. To do so, systematic experiments were undertaken to compare the ratings obtained by trained observers with several image types, T2* magnitude, Susceptibility Weighted Imaging reconstructions (SWI) and IFM built from the same T2*-weighted acquisition.Materials/Methods: 15 participants from the MEMENTO multi-center cohort were selected: six subjects with numerous CMBs (20+/-6 CMBs), five subjects with a few CMBs (2 +/-1 CMBs) and four subjects without CMB. 2D multi-slice T2* GRE sequences were acquired on Philips and Siemens 3T systems. After pilot experiments, T2* magnitude, Susceptibility Weighted Imaging (SWI) minimum intensity projection (mIP) on three slices and IFM were considered for the rating experiments. A graphical user interface (GUI) was designed in order to consistently display images in random order. Six raters of various background and expertise independently selected “definite” or “possible” CMBs. Rating results were compared with respect to a specific consensus reference, on both lesion and subject type points of view.Results: IFM yielded increased sensitivity and decreased false positives rate (FPR) for CMBs identification compared to T2* magnitude and SWI-mIP images. Inter-rater variability was decreased with IFM when identifying subjects with numerous lesions, with only a limited increase in rating time. IFM thus appears as an interesting candidate to improve CMBs identification in clinical setting

A standardised clinical multicentric whole brain T2* mapping protocol at 3T

International audienceThe purpose of this work is to report the implementation of a T2* map in multicenter neuroimaging studies. We focus on T2* because it is an endogenous biomarker for paramagnetic products like iron or melanin, which is very interesting to assess, among other diseases, Parkinson’s disease. We developed a MR sequence which meets several specific requirements. This sequence is accessible on 3 major manufacturer 3T MRI scanners and ensures good measurement accuracy at a standard millimeter isotropic resolution. This “universal” sequence allows to acquire, in a reliable and repeatable way, T2* maps of the whole brain

Cartographie T2* sur cerveau entier pour les études multicentriques de recherche clinique

National audienc

Cerebral microbleeds and CSF Alzheimer biomarkers in primary progressive aphasias

International audienceObjective : To reveal the prevalence and localization of cerebral microbleeds (CMBs) in the 3 main variants of primary progressive aphasia (PPA) (logopenic, semantic, and nonfluent/agrammatic), to identify the relationship with underlying Alzheimer pathology, and to explore whether CMBs contribute to language breakdown.Methods : We used a cross-sectional design in a multicenter cohort of 82 patients with PPA and 19 similarly aged healthy controls. MRI allowed for rating CMBs (2-dimensional gradient recalled echo T2*, susceptibility weighted imaging sequences) and white matter hyperintensities. CSF Alzheimer disease biomarker analyses available in 63 of the 82 patients provided the stratification of PPA into subgroups with patients who had or did not have probable underlying Alzheimer pathology.Results : The prevalence of CMBs was higher in patients with PPA (28%) than in controls (16%). They were more prevalent in logopenic PPA (50%) than in semantic PPA (18%) and nonfluent/agrammatic PPA (17%). The localization of CMBs was mainly lobar (81%) with no difference between the PPA variants. CMBs were more frequent in PPA patients with positive than with negative CSF Alzheimer disease biomarkers (67% vs 20%). Patients with and without lobar CMBs had similar volumes of white matter hyperintensities. Language and general cognitive impairment in PPA was unrelated to CMB rates.Conclusions: CMB prevalence in PPA is higher than in healthy controls. CMBs were most prevalent in the logopenic variant, were related to underlying Alzheimer pathology, and did not affect the language/cognitive impairment. Our findings also suggest that CMB detection with MRI contributes to PPA variant diagnosis, especially of logopenic PPA, and provides an estimator of the underlying neuropathology