Magnetic resonance imaging of experimental autoimmune encephalomyelitis in the common marmoset.

Magnetic resonance imaging (MRI) is an invaluable tool for the diagnosis and monitoring of patients with multiple sclerosis (MS) as well as for the study of the disease pathophysiology. Because of its strong clinical, radiological and histopathological similarities with the human disease, experimental autoimmune encephalomyelitis (EAE) in the common marmoset has been studied more intensively over the past several years. Here, we review the current knowledge on MRI in the marmoset EAE, and we outline the physiopathological significance and translational values of these studies with respect to MS. Accumulating evidences suggest that the application of conventional, as well as non-conventional, MRI techniques in the marmoset EAE is a promising approach to elucidate the pathological processes underlying the development of inflammatory demyelinated lesions in the central nervous system, potentially improving the identification and development of new therapeutics

Propriétés magnétiques et de résonance du Zn1-xCoxO : un matériau candidat pour l électronique de spin

Pour permettre de nouveaux développements de la Spintronique, il est nécessaire aujourd hui d'élaborer un semiconducteur ferromagnétique à la température ambiante. L'oxyde de Zinc dopé par le Cobalt est à l'heure actuelle un candidat très prometteur, mais ses propriétés magnétiques restent toujours très discutées. Dans ce mémoire de thèse, nous présentons une étude de films minces de ZnO:Co (épitaxiés par jets moléculaires) se basant sur la Résonance Paramagnétique Electronique et la magnétométrie à SQUID. Cette étude, réalisée au sein du laboratoire L2MP et en collaboration avec le laboratoire CRHEA, a permis d'apporter de nouvelles informations sur les propriétés magnétiques et de résonance intrinsèques du ZnO:Co. Une anisotropie magnétique de type plan facile et des interactions d'échange antiferromagnétiques entre les ions Co2+ premiers voisins dans ZnO ont notamment été identifiées. De plus, le mécanisme à l origine de l élargissement des raies RPE du ZnO :Co a pu être déterminé.AIX-MARSEILLE3-BU Sc.St Jérô (130552102) / SudocSudocFranceF

Magnetic resonance imaging in multiple sclerosis animal models: A systematic review, meta-analysis, and white paper

Magnetic resonance imaging (MRI) is the most important paraclinical tool for assessing drug response in multiple sclerosis (MS) clinical trials. As such, MRI has also been widely used in preclinical research to investigate drug efficacy and pathogenic aspects in MS animal models. Keeping track of all published preclinical imaging studies, and possible new therapeutic approaches, has become difficult considering the abundance of studies. Moreover, comparisons between studies are hampered by methodological differences, especially since small differences in an MRI protocol can lead to large differences in tissue contrast. We therefore provide a comprehensive qualitative overview of preclinical MRI studies in the field of neuroinflammatory and demyelinating diseases, aiming to summarize experimental setup, MRI methodology, and risk of bias. We also provide estimates of the effects of tested therapeutic interventions by a meta-analysis. Finally, to improve the standardization of preclinical experiments, we propose guidelines on technical aspects of MRI and reporting that can serve as a framework for future preclinical studies using MRI in MS animal models. By implementing these guidelines, clinical translation of findings will be facilitated, and could possibly reduce experimental animal numbers

Statistical estimation of white matter microstructure from conventional MRI

Diffusion tensor imaging (DTI) has become the predominant modality for studying white matter integrity in multiple sclerosis (MS) and other neurological disorders. Unfortunately, the use of DTI-based biomarkers in large multi-center studies is hindered by systematic biases that confound the study of disease-related changes. Furthermore, the site-to-site variability in multi-center studies is significantly higher for DTI than that for conventional MRI-based markers. In our study, we apply the Quantitative MR Estimation Employing Normalization (QuEEN) model to estimate the four DTI measures: MD, FA, RD, and AD. QuEEN uses a voxel-wise generalized additive regression model to relate the normalized intensities of one or more conventional MRI modalities to a quantitative modality, such as DTI. We assess the accuracy of the models by comparing the prediction error of estimated DTI images to the scan-rescan error in subjects with two sets of scans. Across the four DTI measures, the performance of the models is not consistent: Both MD and RD estimations appear to be quite accurate, while AD estimation is less accurate than MD and RD; the accuracy of FA estimation is poor. Thus, in some cases when assessing white matter integrity, it may be sufficient to acquire conventional MRI sequences alone

Longitudinal MR spectroscopy of neurodegeneration in multiple sclerosis with diffusion of the intra-axonal constituent N-acetylaspartate

Multiple sclerosis (MS) is a pathologically complex CNS disease: inflammation, demyelination, and neuroaxonal degeneration occur concurrently and may depend on one another. Current therapies are aimed at the immune-mediated, inflammatory destruction of myelin, whereas axonal degeneration is ongoing and not specifically targeted. Diffusion-weighted magnetic resonance spectroscopy can measure the diffusivity of metabolites in vivo, such as the axonal/neuronal constituent N-acetylaspartate, allowing compartment-specific assessment of disease-related changes. Previously, we found significantly lower N-acetylaspartate diffusivity in people with MS compared to healthy controls (Wood et al., 2012) suggesting that this technique can measure axonal degeneration and could be useful in developing neuroprotective agents. In this longitudinal study, we found that N-acetylaspartate diffusivity decreased by 8.3% (p<0.05) over 6months in participants who were experiencing clinical or MRI evidence of inflammatory activity (n=13), whereas there was no significant change in N-acetylaspartate diffusivity in the context of clinical and radiological stability (n=6). As N-acetylaspartate diffusivity measurements are thought to more specifically reflect the intra-axonal space, these data suggest that N-acetylaspartate diffusivity can report on axonal health on the background of multiple pathological processes in MS, both cross-sectionally and longitudinally. Keywords: Multiple sclerosis, Diffusion-weighted magnetic resonance spectroscopy, Axonopathy, White matte

Detection of demyelination in multiple sclerosis by analysis of T2* relaxation at 7 T

Multiple sclerosis (MS) is a relatively common cause of inflammatory demyelinating lesions of the central nervous system. In an attempt to detect and characterize ongoing demyelination in MS patient brains, we used a novel magnetic resonance imaging (MRI) technique, involving the fitting of a three-component model to the T2* relaxation behavior at high-field (7 T). This model allowed estimation of the amount of myelin water (and thus indirectly myelin content), axonal water, and interstitial water. In this study, 25 relapsing–remitting MS patients underwent a 7 T MRI from which 12 gadolinium-enhancing lesions, 61 non-enhancing lesions, and their corresponding contralateral normal appearing white matter (NAWM) regions were analyzed. In both enhancing and non-enhancing lesions, the amplitude of myelin water was significantly decreased, and interstitial and axonal water were increased relative to the contralateral NAWM. Longer relaxation time T2* of interstitial and axonal water, and lower frequency shift of axonal water, were also observed in both enhancing and non-enhancing lesions when compared to the contralateral NAWM. No significant difference was found between enhancing lesions and non-enhancing lesions. These findings suggest that the fitting of a three-component model to the T2* decay curve in MS lesions may help to quantify myelin loss