Inflammatory Multiple-Sclerosis Plaques Generate Characteristic Metabolic Profiles in Cerebrospinal Fluid

International audienceBackgroundMultiple sclerosis (MS), an inflammatory disease of the central nervous system, manifests itself in numerous forms and stages. A number of brain metabolic alterations have been reported for MS patients vs. control subjects. However, metabolite profiles of cerebrospinal fluid (CSF) are not consistent among the published MS studies, most probably due to variations in the patient cohorts studied. We undertook the first investigation of highly homogeneous MS patient cohorts to determine characteristic effects of inflammatory MS plaques on the CSF metabolome, including only patients with clinically isolated syndrome (CIS) with or without inflammatory brain plaques, and controls.Methodology/Principal FindingsCSF obtained by lumbar puncture was analyzed by proton magnetic resonance spectroscopy. 27 metabolites were quantified. Differences between groups of control subjects (n = 10), CIS patients with (n = 21) and without (n = 12) inflammatory plaques were evaluated by univariate statistics and principal component analysis (PCA). Seven metabolites showed statistically significant inter-group differences (p<0.05). Interestingly, a significant increase in β-hydroxyisobutyrate (BHIB) was detected in CIS with vs. without active plaques, but not when comparing either CIS group with control subjects. Moreover, a significant correlation was found, for the first time, between CSF lactate concentration and the number of inflammatory MS brain plaques. In contrast, fructose concentrations were equally enhanced in CIS with or without active plaques. PCA based on all 27 metabolites yielded group-specific clusters.Conclusions/SignificanceCSF metabolic profiles suggest a close link between MS plaque activity in CIS patients on the one hand and organic-acid metabolism on the other. Our detection of increased BHIB levels points to a hitherto unsuspected role for this compound in MS with active plaques, and serves as a basis for further investigation. The metabolic effects described in our study are crucial elements in the explanation of biochemical mechanisms involved in specific MS manifestations

Etude multimodalitaire du rôle des canaux potassiques K2P TREK-1 et TRAAK dans la physiopathologie de l'ischémie cérébrale

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

MR spectroscopy of normal and impaired fetal brain

International audienceProton Magnetic Resonance Spectroscopy (MRS) is a non-invasive and quantitative method used to assess fetal brain metabolism during the 2nd and 3rd trimesters of gestation. Fetal brain MRS is performed in specialized centers using clinical MR systems operating at 1.5 or 3 T. Single voxel spectroscopy (SVS) with the Point RESolved Spectroscopy (PRESS) sequence (spin echo sequence) is currently the dominant method in this field. The major metabolic changes observed in the normal fetal brain are the increase of neuronal marker N-acetylaspartate and of creatine and phosphocreatine with advancing gestational age. Metabolic anomalies have been reported in cases of intrauterine restricted growth and cytomegalovirus infection

In vivo MRI assessment of the pharmacological opening of the blood brain barrier by intraperitoneal mannitol injection in mice.

International audienc

Nuclear magnetic resonance spectroscopy and imaging

International audienc

Clinical and preclinical imaging of hepatosplenic schistosomiasis.

International audienceSchistosomiasis, a neglected tropical disease, is a major cause of chronic morbidity and disability, and premature death. The hepatosplenic form of schistosomiasis is characterized by hepatosplenomegaly, liver fibrosis, portal hypertension and oesophageal varices, whose rupture may cause bleeding and death. We review currently available abdominal imaging modalities and describe their basic principles, strengths, weaknesses, and usefulness in the assessment of hepatosplenic schistosomiasis. Advanced imaging methods are presented that could be of interest for hepatosplenic schistosomiasis evaluation by yielding morphological, functional and molecular parameters of disease progression. We also provide a comprehensive view of preclinical imaging studies and current research objectives such as parasite visualisation in hosts, follow-up of host-immune response, and development of non-invasive quantitative methods for liver fibrosis assessment.

In vivo MRI assessment of the pharmacological opening of the blood brain barrier by intraperitoneal mannitol injection in mice.

International audienc

Spectroscopie de la maturation cérébrale et de ses anomalies

National audienceL'imagerie par résonance magnétique (IRM) est la technique de choix pour l'exploration de la maturation cérébrale et de ses anomalies. La spectroscopie par résonance magnétique (SRM) est une technique de résonance magnétique nucléaire non invasive et spatialement localisée qui permet d'accéder au métabolisme intracérébral. Elle prend une place importante en neuroradiologie clinique au cours d'un examen par IRM standard. Cependant, les indications restent limitées à un petit groupe de pathologies, principalement les tumeurs, la souffrance cérébrale diffuse en particulier en période néonatale, et les maladies innées du métabolisme cérébral. Dans cet article sont revus les principaux noyaux étudiés en SRM, les méthodes d'acquisition et de post-traitement des données, les principaux métabolites détectables en SRM du proton et leurs variations au cours de la maturation cérébrale, et les principales applications cliniques dans la population pédiatrique

In Vivo MRI Assessment of Hepatic and Splenic Disease in a Murine Model of Schistosomiasis

International audienceBACKGROUND: Schistosomiasis (or bilharzia), a major parasitic disease, affects more than 260 million people worldwide. In chronic cases of intestinal schistosomiasis caused by trematodes of the Schistosoma genus, hepatic fibrosis develops as a host immune response to the helminth eggs, followed by potentially lethal portal hypertension. In this study, we characterized hepatic and splenic features of a murine model of intestinal schistosomiasis using in vivo magnetic resonance imaging (MRI) and evaluated the transverse relaxation time T2 as a non-invasive imaging biomarker for monitoring hepatic fibrogenesis. METHODOLOGY/PRINCIPAL FINDINGS: CBA/J mice were imaged at 11.75 T two, six and ten weeks after percutaneous infection with Schistosoma mansoni. In vivo imaging studies were completed with histology at the last two time points. Anatomical MRI allowed detection of typical manifestations of the intestinal disease such as significant hepato- and splenomegaly, and dilation of the portal vein as early as six weeks, with further aggravation at 10 weeks after infection. Liver multifocal lesions observed by MRI in infected animals at 10 weeks post infection corresponded to granulomatous inflammation and intergranulomatous fibrosis with METAVIR scores up to A2F2. While most healthy hepatic tissue showed T2 values below 14 ms, these lesions were characterized by a T2 greater than 16 ms. The area fraction of increased T2 correlated (rS = 0.83) with the area fraction of Sirius Red stained collagen in histological sections. A continuous liver T2* decrease was also measured while brown pigments in macrophages were detected at histology. These findings suggest accumulation of hematin in infected livers. CONCLUSIONS/SIGNIFICANCE: Our multiparametric MRI approach confirms that this murine model replicates hepatic and splenic manifestations of human intestinal schistosomiasis. Quantitative T2 mapping proved sensitive to assess liver fibrogenesis non-invasively and may therefore constitute an objective imaging biomarker for treatment monitoring in diseases involving hepatic fibrosis