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

Prevalence of Grey Matter Pathology in Early Multiple Sclerosis Assessed by Magnetization Transfer Ratio Imaging

The aim of the study was to assess the prevalence, the distribution and the impact on disability of grey matter (GM) pathology in early multiple sclerosis. Eighty-eight patients with a clinically isolated syndrome with a high risk developing multiple sclerosis were included in the study. Forty-four healthy controls constituted the normative population. An optimized statistical mapping analysis was performed to compare each subject's GM Magnetization Transfer Ratio (MTR) imaging maps with those of the whole group of controls. The statistical threshold of significant GM MTR decrease was determined as the maximum p value (p<0.05 FDR) for which no significant cluster survived when comparing each control to the whole control population. Using this threshold, 51% of patients showed GM abnormalities compared to controls. Locally, 37% of patients presented abnormalities inside the limbic cortex, 34% in the temporal cortex, 32% in the deep grey matter, 30% in the cerebellum, 30% in the frontal cortex, 26% in the occipital cortex and 19% in the parietal cortex. Stepwise regression analysis evidenced significant association (p = 0.002) between EDSS and both GM pathology (p = 0.028) and T2 white matter lesions load (p = 0.019). In the present study, we evidenced that individual analysis of GM MTR map allowed demonstrating that GM pathology is highly heterogeneous across patients at the early stage of MS and partly underlies irreversible disability

Développements méthodologiques en imagerie et en spectrométrie RMN à haut champ magnétique (du cerveau de la souris à celui de l'homme)

Cette thèse a été réalisée afin de proposer certains développements méthodologiques en RMN applicables à l'étude in vivo des cerveaux de l'homme et de la souris. Dans une première étude, l'imagerie par transfert d'aimantation et la spectrométrie localisée par RMN ont été implantées à 9,4 T. Ces techniques ont été employées pour analyser un modèle animal de démyélinisation et de remyélinisation. Les résultats de RMN ont été vérifiés par des examens histologiques. Le taux de transfert d'aimantation (MTR) s'est avéré être un marqueur sensible des variations du contenu de la myéline. Aucun marqueur métabolique traduisant ces phénomènes n'a encore été identifié. La seconde étude consistait à déterminer les temps de relaxation transversale T2 des métabolites du cerveau humain à 3 T. Une méthode à deux points optimisée pour la moindre erreur d'estimation pour un temps fixé d'expérience a été proposée. Cette méthode a été combinée à une séquence de spectrométrie RMN tridimensionnelle afin d'examiner en une heure, 320 voxels d'1 cm3 de résolution spatiale. Les T2 du NAA, de la créatine et de la choline ont été évalués dans différentes structures cérébrales. A notre connaissance, ces valeurs ont été obtenues pour la première fois à 3 T, avec cette couverture spatiale, cette résolution spatiale et cette précision. Ces résultats sont essentiels pour les quantifications absolues des métabolites.This work was designed to implement several NMR methodological developments to study the human and the mouse brain in vivo. In the first study, magnetization transfer imaging and localized MR spectroscopy were set up at 9,4 T. These techniques were used to analyze an animal model of demyelinisation and remyelinisation. The MR results were verified by histological examinations. The magnetization transfer ratio (MTR) was found to be a relevant sensitive marker of myelin content changes. A surrogate metabolic marker of these phenomena was not yet identified. The second study was devised to determine the transverse relaxation time T2 of human brain metabolites at 3 T. An optimized two-point method for the least error per given experimental time was proposed. This method was combined to a three-dimensional MR spectroscopic sequence to examine, within 1 hour, 320 voxels at 1 cm3 spatial resolution. T2 of NAA, cretatine and choline were assessed for different brain structures. To our knowledge, these values were obtained for the first time at 3 T with this spatial resolution, coverage and precision. These results are essential for reliable absolute metabolic quantification.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Variability by region and method in human brain sodium concentrations estimated by 23Na magnetic resonance imaging: a meta-analysis

International audienceSodium imaging ( 23 Na-MRI) is of interest in neurological conditions given potential sensitivity to the physiological and metabolic status of tissues. Benchmarks have so far been restricted to parenchyma or grey/white matter (GM/WM). We investigate (1) the availability of evidence, (2) regional pooled estimates and (3) variability attributable to region/methodology. MEDLINE literature search for tissue sodium concentration (TSC) measured in specified ‘healthy’ brain regions returned 127 reports, plus 278 retrieved from bibliographies. 28 studies met inclusion criteria, including 400 individuals. Reporting variability led to nested data structure, so we used multilevel meta-analysis and a random effects model to pool effect sizes. The pooled mean from 141 TSC estimates was 40.51 mM (95% CI 37.59–43.44; p < 0.001, I 2 Total= 99.4%). Tissue as a moderator was significant (F 2 14 = 65.34, p-val < .01). Six sub-regional pooled means with requisite statistical power were derived. We were unable to consider most methodological and demographic factors sought because of non-reporting, but each factor included beyond tissue improved model fit. Significant residual heterogeneity remained. The current estimates provide an empirical point of departure for better understanding in 23 Na-MRI. Improving on current estimates supports: (1) larger, more representative data collection/sharing, including (2) regional data, and (3) agreement on full reporting standards

Validation and Initial Results from Dynamic 23Na fMRI

International audienceIn this abstract we develop and validate an MRI acquisition/reconstruction method to derive the temporal dynamics of 23Na within a 20 min scan

The use of SPIRIT to reject and replace motion-corrupted data

International audienceThe SPIRIT parallel imaging algorithm was evaluated for use in a data rejection and replacement scheme to reduce motion artefacts

MUTANT : a new image filtering paradigm for improved parameters determination. Application to myelin water fraction mapping and sodium concentrations imaging

International audienc

Sodium short and long T2* components in the normal human brain: a multi-TE 23Na MRI study at 7T

International audienceThe study aimed to provide values of the short and long T2* sodium components of the human brain at 7T using a multi-echoes 23Na MRI approach (n=24 TE). These results may help improving sodium quantification at 7T

Assessment of neuronal dysfunction in benign multiple sclerosis: a sodium MRI study

International audienceAssessment of neuro-degenerative process in multiple sclerosis using sodium MRI. A study in a population of 135 subjects at different disability and disease duratio

Association between brain and upper cervical spinal cord atrophy assessed by MRI and disease aggressiveness in amyotrophic lateral sclerosis

PurposeTo study the relative contributions of brain and upper cervical spinal cord compartmental atrophy to disease aggressiveness in amyotrophic lateral sclerosis (ALS).MethodsTwenty-nine ALS patients and 24 age- and gender-matched healthy controls (HC) were recruited. Disease duration and the Revised-ALS Functional Rating Scale (ALSFRS-R) at baseline, 3- and 6-months follow-up were assessed. Patients were clinically differentiated into fast (n=13) and slow (n=16) progressors according to their ALSFRS-R progression rate. Brain grey (GM) and white matter, brainstem sub-structures volumes and spinal cord cross-sectional area (SC-CSA) at C1-C2 vertebral levels were measured from a 3D-T1-weighted MRI.ResultsFast progressors showed significant GM, medulla oblongata and SC atrophy compared to HC (p<0.001, p=0.013 and p=0.008) and significant GM atrophy compared to slow progressors (p=0.008). GM volume correlated with the ALSFRS-R progression rate (Rho/p=-0.487/0.007), the ALSFRS-R at 3-months (Rho/p=0.622/0.002), and ALSFRS-R at 6-months (Rho/p=0.407/0.039). Medulla oblongata volume and SC-CSA correlated with the ALSFRS-R at 3-months (Rho/p=0.510/0.015 and Rho/p=0.479/0.024). MRI measures showed high performance to discriminate between fast and slow progressors.ConclusionOur study suggests an association between compartmental atrophy and disease aggressiveness. This result is consistent with the combination of upper and lower motor neuron degeneration as the main driver of disease worsening and severity in ALS. Our study highlights the potential of brain and spinal cord atrophy measured by MRI as biomarker of disease aggressiveness signature