Metabolic counterparts of sodium accumulation in multiple sclerosis: A whole brain 23Na-MRI and fast 1H-MRSI study

Increase of brain total sodium concentrations (TSC) is present in multiple sclerosis (MS), but its pathological involvement has not been assessed yet. To determine in vivo the metabolic counterpart of brain sodium accumulation. Whole brain Na-MR imaging and 3D- H-EPSI data were collected in 21 relapsing-remitting multiple sclerosis (RRMS) patients and 20 volunteers. Metabolites and sodium levels were extracted from several regions of grey matter (GM), normal-appearing white matter (NAWM) and white matter (WM) T lesions. Metabolic and ionic levels expressed as Z-scores have been averaged over the different compartments and used to explain sodium accumulations through stepwise regression models. MS patients showed significant Na accumulations with lower choline and glutamate-glutamine (Glx) levels in GM; Na accumulations with lower N-acetyl aspartate (NAA), Glx levels and higher Myo-Inositol (m-Ins) in NAWM; and higher Na, m-Ins levels with lower NAA in WM T lesions. Regression models showed associations of TSC increase with reduced NAA in GM, NAWM and T lesions, as well as higher total-creatine, and smaller decrease of m-Ins in T lesions. GM Glx levels were associated with clinical scores. Increase of TSC in RRMS is mainly related to neuronal mitochondrial dysfunction while dysfunction of neuro-glial interactions within GM is linked to clinical scores

MR spectroscopy imaging at high (3 Tesla) and ultra high (7 Tesla) field : methodological development and clinical application on multiple sclerosis

La spectroscopie par résonance magnétique permet de manière non invasive, de caractériser et suivre l'évolution du métabolisme cérébral in vivo chez l’Homme. Néanmoins, de nombreux biais empêchent l’obtention d’une caractérisation métabolique cérébrale complète, un prérequis essentiel pour mieux comprendre une pathologie diffuse comme la Sclérose en Plaques (SEP).Mon premier projet a donc consisté à transposer une technique de spectroscopie rapide en 3 dimensions, acquise dans deux orientations spatiales. Cette comparaison a mis en évidence des diminutions de métabolites reliés à la viabilité et à l’activité neuronale, dans des régions fonctionnelles motrices et cognitives, mais également une activité gliale accrue dans les lésions de substance blanche mais aussi en dehors. La deuxième étude a visée à caractériser d'un point de vue métabolique, les accumulations cérébrales de sodium observées chez les patients atteints de SEP par IRM du 23Na. Nous avons pu mettre en évidence des corrélations significatives entre les accumulations de sodium et les diminutions de NAA mettant en lumière un lien fort entre ces accumulations et les phénomènes de souffrance neuronale.Enfin, le dernier projet a eu pour but d'améliorer la résolution spatiale de l'imagerie spectroscopique du proton en tirant partie des avantages d'un imageur clinique 7 Tesla. Après avoir corrigé différents problèmes comme les inhomogénéités B0 et B1 ainsi que l’artefact de déplacement chimique, nous avons obtenu le profil du NAA, de la Choline et de la Créatine pour 4 gros noyaux thalamiques. De plus, l’analyse statistique a mis en évidence des différences métabolique entre les noyaux Thalamiques.Magnetic Resonance Spectroscopy (MRS) allows to characterize, in vivo and non-invasively, the cerebral metabolism in Human. Nevertheless, use MRS in clinical routine is marginal and it is impossible to obtain whole brain metabolic topography, mandatory step in order to understand diffuse pathology like Multiple Sclerosis (MS).First of all, we aimed to transpose a fast 3D-MRSI sequence acquired in two different orientations. We observed significant decrease in metabolites linked with neuronal health and activity, in important motor and cognitive areas, and also increase in glial activation, inside white matter T2 lesions but also outside in normal appearing white and grey matter.Secondly, we aimed to characterize the metabolic counterpart of cerebral sodium accumulations observed, using 23Na MRI, in MS patients. We observed significant correlations between sodium accumulations and decrease in NAA highlighting a strong link between sodium accumulations and neuronal suffering.Finally, we attempted to improve spatial resolution of proton MR spectroscopy using 7 Tesla scanner. We also addressed ultra-high field artifacts like B0 and B1 inhomogeneities as well as chemical shift displacement error. We obtained metabolic profiles of NAA, Choline and Creatine for 4 big thalamic nuclei. Moreover, statistical analysis evidencing metabolic differences between nuclei in same hemisphere but also for some nuclei left/right differences

Evidencing different neurochemical profiles between thalamic nuclei using high resolution 2D-PRESS semi-LASER (1)H-MRSI at 7 T

International audienceOBJECTIVE: To demonstrate that high resolution (1)H semi-LASER MRSI acquired at 7 T permits discrimination of metabolic patterns of different thalamic nuclei. MATERIALS AND METHODS: Thirteen right-handed healthy volunteers were explored at 7 T using a high-resolution 2D-semi-LASER (1)H-MRSI sequence to determine the relative levels of N-Acetyl Aspartate (NAA), choline (Cho) and creatine-phosphocreatine (Cr) in eight VOIs (volume \textless0.3 ml) centered on four different thalamic nuclei located on the Oxford thalamic connectivity atlas. Post-processing was done using the CSIAPO software. Chemical shift displacement of metabolites was evaluated on a phantom and correction factors were applied to in vivo data. RESULTS: The global assessment (ANOVA p \textless 0.05) of the neurochemical profiles (NAA, Cho and Cr levels) with thalamic nuclei and hemispheres as factors showed a significant global effect (F = 11.98, p \textless 0.0001), with significant effect of nucleus type (p \textless 0.0001) and hemisphere (p \textless 0.0001). Post hoc analyses showed differences in neurochemical profiles between the left and the right hemisphere (p \textless 0.05), and differences in neurochemical profiles between nuclei within each hemisphere (p \textless 0.05). CONCLUSION: For the first time, using high resolution 2D-PRESS semi-LASER (1)H-MRSI acquired at 7 T, we demonstrated that the neurochemical profiles were different between thalamic nuclei, and that these profiles were dependent on the brain hemisphere

Supplementary Motor Area (SMA) is activated selectively by the accumulation of temporal rather than spatial information

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SMA Selectively Codes the Active Accumulation of Temporal, Not Spatial, Magnitude

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Whole-brain quantitative mapping of metabolites using short echo three-dimensional proton MRSI

International audienceBACKGROUND: To improve the extent over which whole brain quantitative three-dimensional (3D) magnetic resonance spectroscopic imaging (MRSI) maps can be obtained and be used to explore brain metabolism in a population of healthy volunteers. METHODS: Two short echo time (20 ms) acquisitions of 3D echo planar spectroscopic imaging at two orientations, one in the anterior commissure-posterior commissure (AC-PC) plane and the second tilted in the AC-PC +15° plane were obtained at 3 Tesla in a group of 10 healthy volunteers. B1 (+) , B1 (-) , and B0 correction procedures and normalization of metabolite signals with quantitative water proton density measurements were performed. A combination of the two spatially normalized 3D-MRSI, using a weighted mean based on the pixel wise standard deviation metabolic maps of each orientation obtained from the whole group, provided metabolite maps for each subject allowing regional metabolic profiles of all parcels of the automated anatomical labeling (AAL) atlas to be obtained. RESULTS: The combined metabolite maps derived from the two acquisitions reduced the regional intersubject variance. The numbers of AAL regions showing N-acetyl aspartate (NAA) SD/Mean ratios lower than 30% increased from 17 in the AC-PC orientation and 41 in the AC-PC+15° orientation, to a value of 76 regions of 116 for the combined NAA maps. Quantitatively, regional differences in absolute metabolite concentrations (mM) over the whole brain were depicted such as in the GM of frontal lobes (cNAA  = 10.03 + 1.71; cCho  = 1.78 ± 0.55; cCr  = 7.29 ± 1.69; cmIns  = 5.30 ± 2.67) and in cerebellum (cNAA  = 5.28 ± 1.77; cCho  = 1.60 ± 0.41; cCr  = 6.95 ± 2.15; cmIns  = 3.60 ± 0.74). CONCLUSION: A double-angulation acquisition enables improved metabolic characterization over a wide volume of the brain. J. Magn. Reson. Imaging 2015;42:280-289

Metabolic counterparts of sodium accumulation in Multiple Sclerosis: A whole brain 1H-MRSI and 23Na-MRI study

International audienceTo determine the metabolic counterparts of cerebral total sodium accumulations in patients with Multiple Sclerosis, we acquired fast 3D-^\textrm1H-EPSI and Density-adapted 3D-UTE ^\textrm23Na MRI at 3 Tesla covering the whole brain in 21 patients and 20 volunteers. Patients showed increased ^\textrm23Na and decreased NAA, Glx and Cho levels. Stepwise analyses highlights association of ^\textrm23Na accumulations with i) decreased NAA and Glx levels and increased Cho levels within GM, ii) with decreased NAA and increased Cho levels within NAWM and T_\textrm2 lesion compartments. Clinical status of patients assessed by MSFC was correlated to GM and NAWM ^\textrm23Na, NAA and Glx levels

Metabolic voxel-based analysis of the complete human brain using fast 3D-MRSI: Proof of concept in multiple sclerosis

International audiencePURPOSE: To detect local metabolic abnormalities over the complete human brain in multiple sclerosis (MS) patients, we used optimized fast volumic echo planar spectroscopic imaging (3D-EPSI). MATERIALS AND METHODS: Weighted mean combination of two 3D-EPSI covering the whole brain acquired at 3T in AC-PC and AC-PC+15° axial planes was performed to obtain high-quality metabolite maps for five metabolites: N-acetyl aspartate (NAA), glutamate+glutamine (Glx), choline (Cho), myo-inositol (m-Ins), and creatine+phosphocreatine (tCr). After spatial normalization, maps from 19 patients suffering from relapsing-remitting MS were compared to 19 matched controls using statistical mapping analyses to determine the topography of metabolic abnormalities. Probabilistic white matter (WM) T2 lesion maps and gray matter (GM) atrophy maps were also generated. RESULTS: Two-group analysis of variance (ANOVA) (SPM8, P \textless 0.005, false discovery rate [FDR]-corrected P \textless 0.05 at the cluster level with age and sex as confounding covariates) comparing patients and controls matched for age and sex showed clusters of abnormal metabolite levels with 1) decreased NAA (around -15%) and Glx (around 20%) predominantly in GM within prefrontal cortices, motor cortices, bilateral thalami, and mesial temporal cortices in line with neuronal/neuro-astrocytic dysfunction; 2) increased m-Ins (around + 20%) inside WM T2 lesions and in the normal-appearing WM of temporal-occipital lobes, suggesting glial activation. CONCLUSION: We demonstrate the ability to noninvasively map over the complete brain-from vertex to cerebellum-with a validated sequence, the metabolic abnormalities associated with MS, for characterizing the topography of pathological processes affecting widespread areas of WM and GM and its functional impact. J. Magn. Reson. Imaging 2016;44:411-419

Metabolic counterparts of sodium accumulation in multiple sclerosis: A whole brain (23)Na-MRI and fast (1)H-MRSI study

International audienceBACKGROUND: Increase of brain total sodium concentrations (TSC) is present in multiple sclerosis (MS), but its pathological involvement has not been assessed yet. OBJECTIVE: To determine in vivo the metabolic counterpart of brain sodium accumulation. MATERIALS/METHODS: Whole brain (23)Na-MR imaging and 3D-(1)H-EPSI data were collected in 21 relapsing-remitting multiple sclerosis (RRMS) patients and 20 volunteers. Metabolites and sodium levels were extracted from several regions of grey matter (GM), normal-appearing white matter (NAWM) and white matter (WM) T2 lesions. Metabolic and ionic levels expressed as Z-scores have been averaged over the different compartments and used to explain sodium accumulations through stepwise regression models. RESULTS: MS patients showed significant (23)Na accumulations with lower choline and glutamate-glutamine (Glx) levels in GM; (23)Na accumulations with lower N-acetyl aspartate (NAA), Glx levels and higher Myo-Inositol (m-Ins) in NAWM; and higher (23)Na, m-Ins levels with lower NAA in WM T2 lesions. Regression models showed associations of TSC increase with reduced NAA in GM, NAWM and T2 lesions, as well as higher total-creatine, and smaller decrease of m-Ins in T2 lesions. GM Glx levels were associated with clinical scores. CONCLUSION: Increase of TSC in RRMS is mainly related to neuronal mitochondrial dysfunction while dysfunction of neuro-glial interactions within GM is linked to clinical scores