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

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

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

Brain sodium concentrations in healthy subjects are constant over time: a 3-year longitudinal 23Na MRI study at 3T

International audienceLongitudinal evaluation of brain sodium concentration in physiological condition

Brain sodium concentrations in healthy subjects are constant over time: a 3-year longitudinal 23Na MRI study at 3T

International audienceLongitudinal evaluation of brain sodium concentration in physiological condition

Distribution of brain sodium long and short relaxation times and concentrations: a multi-echo ultra-high field 23Na MRI study

International audienceSodium (23 Na) MRI proffers the possibility of novel information for neurological research but also particular challenges. Uncertainty can arise in in vivo 23 Na estimates from signal losses given the rapidity of T2* decay due to biexponential relaxation with both short (T 2 * short) and long (T 2 * long) components. We build on previous work by characterising the decay curve directly via multi-echo imaging at 7 T in 13 controls with the requisite number, distribution and range to assess the distribution of both in vivo T 2 * short and T 2 * long and in variation between grey and white matter, and subregions. By modelling the relationship between signal and reference concentration and applying it to in vivo 23 Na-MRI signal, 23 Na concentrations and apparent transverse relaxation times of different brain regions were measured for the first time. Relaxation components and concentrations differed substantially between regions of differing tissue composition, suggesting sensitivity of multi-echo 23 Na-MRI toward features of tissue composition. As such, these results raise the prospect of multi-echo 23 Na-MRI as an adjunct source of information on biochemical mechanisms in both physiological and pathophysiological states. In the physiological state, the maintenance of the transmembrane sodium (23 Na) concentration gradient (10-15 mM intracellular sodium concentration and ~140 mM extracellular sodium concentration) is a precondition for several critical cellular functions. These include the transport of ions, neurotransmitters and nutrients; regulation of osmotic and electrostatic forces on cells and macromolecules; as well as the transmission of action potentials 1-3. In the diseased state, multiple pathological pathways can lead to aberrations of these functions. Such alterations can lead to changes in intra-and extracellular concentrations due to a reduced ability to maintain resting conditions and due to conformational changes in cells themselves as well as the cellular environment in which they are embedded. Thus, 23 Na-MRI is a potential source of more direct and quantitative biochemical information than is generally possible with conventional proton (1 H) MRI 4. As such, there is substantial interest in 23 Na-MRI regarding a range of neurological conditions despite the additional complications of acquiring 23 Na-MRI signal, including stroke 5 , epilepsy 6 , tumors 7 and neurodegenerative diseases 8-12. The quadrupolar 23 Na nucleus (spin = 3/2) is subject to the influence of fluctuations in neighbouring electric fields due to net positive and non-uniform distribution of charge 3,13-15. In the presence of a magnetic field, 23 Na nuclei exhibit four discrete energy states, with three possible (single quantum, SQ) transitions (−1/2, +1/2 "cen-tral transition"; −3/2, −1/2 and 1/2, 3/2 "satellite transitions"). In highly motile environments such as plasma or cerebrospinal fluid (CSF), the correlation time (τ C) is much shorter than the Larmor period (ω 0 −1) (ω 0 • τ C ≪ 1), leading to monoexponential longitudinal (T 1) and transverse (T 2) relaxation. This is in contrast to tissue environments such as within cells and the interstitial spaces between cells where diffusion is restricted by interactions of the 23 Na cation with macromolecular anions. Such interactions modulate decay behaviour in a measurable way: the satellite transitions are subject to additional fast relaxation processes so that both T 1 and T 2 reflec

Increased total sodium concentration in gray matter better explains cognition than atrophy in MS

International audienceOBJECTIVE: To investigate whether brain total sodium accumulation assessed by (23)Na MRI is associated with cognitive deficit in relapsing-remitting multiple sclerosis (RRMS). METHODS: Eighty-nine participants were enrolled in the study (58 patients with RRMS with a disease duration ≤10 years and 31 matched healthy controls). Patients were classified as cognitively impaired if they failed at least 2 tasks on the Brief Repeatable Battery. MRI was performed at 3T using (23)Na MRI to obtain total sodium concentration (TSC) in the different brain compartments (lesions, normal-appearing white matter [NAWM], gray matter [GM]) and (1)H- magnetization-prepared rapid gradient echo to assess GM atrophy (GM fraction). RESULTS: The mean disease duration was 3.1 years and the median Expanded Disability Status Scale score was 1 (range 0-4.5). Thirty-seven patients were classified as cognitively preserved and 21 as cognitively impaired. TSC was increased in GM and NAWM in cognitively impaired patients compared to cognitively preserved patients and healthy controls. Voxel-wise analysis demonstrated that sodium accumulation was mainly located in the neocortex in cognitively impaired patients. Regression analysis evidenced than the 2 best independent predictors of cognitive impairment were GM TSC and age. Receiver operating characteristic analyses demonstrated that sensitivity and specificity of the GM TSC to classify patients according to their cognitive status were 76% and 71%, respectively. CONCLUSIONS: This study provides 2 main findings. (1) In RRMS, total sodium accumulation in the GM is better associated with cognitive impairment than GM atrophy; and (2) total sodium accumulation in patients with cognitive impairment is mainly located in the neocortex

Grey-matter sodium concentration as an individual marker of multiple sclerosis severity

International audienceObjective: Quantification of brain injury in patients with variable disability despite similar disease duration may be relevant to identify the mechanisms underlying disability in MS. We aimed to compare grey-matter sodium abnormalities (GMSA), a parameter reflecting neuronal and astrocyte dysfunction, in MS patients with benign MS (BMS) and non-benign MS (NBMS). Methods: We identified never-treated BMS patients in our local MS database of 1352 patients. A group with NBMS was identified with same disease duration. All participants underwent 23 Na MRI. The existence of GMSA was detected by statistical analysis. Results: In total, 102 individuals were included (21 BMS, 25 NBMS and 56 controls). GMSA was detected in 10 BMS and 19 NBMS (11/16 RRMS and 8/9 SPMS) patients (p=0.05). On logistic regression including the presence or absence of GMSA, thalamic volume, cortical grey matter volume and T2-weighted lesion load, thalamic volume was independently associated with BMS status (OR=0.64 for each unit). Nonetheless, the absence of GMSA was independently associated when excluding patients with significant cognitive alteration (n=7) from the BMS group (OR=4.6). Conclusion: Detection of GMSA in individuals and thalamic volume are promising to differentiate BMS from NBMS as compared with cortical or whole grey-matter atrophy and T2-weighted lesions

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

Clinical brain QSM acquisition and automated processing at 3T and 7T for routine use

International audienceQuantitative susceptibility mapping (QSM) is a recent MRI technique that measures tissue magnetic susceptibility mostly influenced by iron, myelin and calcium content in the brain that may provide additional biomarkers [1-3]. QSM involves advanced numerical methods designed to solve the complex inverse problem from the measured magnetic field inhomogeneity (derived from phase) to the spatial distribution of susceptibility. The reconstruction algorithms now become sufficiently robust to be implemented in routine brain exams. We present here the installation of an online reconstruction solution and initial in vivo results at high 3 T and ultra-high 7 T clinical fields. Clinical brain QSM acquisition and automated processing at 3T and 7T for routine use MRI systems and sequences: Siemens Verio 3T and Magnetom 7T were used (VB17 revision) with 32 channel head coils. A 3D multi-echo gradient echo sequence was applied. At 3T, the R2* mapping protocol designed for multicenter studies [4] was used (1 mm resolution, Tacq=10min); at 7T, isotropic 600 µm resolution were targeted (Tacq=12.5min). A modified reconstruction software (ICE functor) was used to generate proper combined phase images for QSM in which the first-echo individual coil images are used as a reference to solve the known issue in coil combination [5]. QSM reconstruction: The amplitude and phase DICOM images were sent to a separate DICOM server based on dicom toolkit (dcmtk open source software). Additional scripts were automatically triggered on reception to start the QSM post-processing. QSM reconstruction involved a field inhomogeneity calculation and unwrapping step from the multiple echoes, followed by a brain extraction (BET) step, an estimation of the internal field and the final MEDI reconstruction [2]. The BET algorithm was modified at 7T for an enhanced brain coverage. Images were then sent automatically back to the MRI when completed. Methods Conclusion References: 1. de Rochefort et al., MRM 2010;63:194. 2. Liu et al., MRM 2011;66:777 3. Eskreis-Winkler et al., NMR Biomed 2016. 4. D. Gay et al., ISMRM 2016, 5. Bernstein MA et al., MRM 1994; 32: 330-33. QSM can be readily applied to ongoing protocols involving 3D or 2D-multislice multi-echo gradient echo data providing additional quantitative information as compared to previously available qualitative SWI and quantitative R2* mapping. QSM seems more sensitive than R2*, with the possibility to easily separate diamagnetic and paramagnetic structures and with less sensitivity to magnetic field strength. 7T QSM should provide a significant gain in terms of achievable spatial resolution and sensitivity in routine clinical studies at our site. Results Fig.1 and 2 present typical results obtained at 3T in ongoing Parkinson and Multiple Sclerosis (MS) protocols, respectively, and Fig. 3 display 7T volunteer data. QSM images appeared on scanners within 10min with consistent image quality. Two-to-four cases per week in research protocols are currently performed. Figure 1-1-mm isotropic images obtained on a patient with Parkinson disease at 3T. The MEDIC image (square root of the squared magnitude over echoes) displays a limited T2* weighting. On the R2* map, CSF has low R2* as expected, WM/GM R2* and close to 20 s-1 , vessels, deep grey nuclei, calcifications then have higher R2* values. The QSM map, while cropping some brain boundaries, clearly separates paramagnetic structures (vessels, deep grey nuclei) from diamagnetic calcifications, and displays some WM/GM susceptibility differences. Figure 2-MEDIC, R2* map and QSM acquired at 3T on a 56 y.o. male MS patient on which MS lesions are easily identifiable by their paramagnetic values (the view is centered on one of them). While some reduction in R2* values can also be seen at the same location, the contrast is higher on the QSM maps. Figure 3-600-µm isotropic images obtained on a volunteer at 7T. The MEDIC image displays a limited T2* weighting. On the R2* map, CSF has low R2* as expected, WM/GM R2* and close to 40 s-1 , vessels, deep grey nuclei, calcifications have higher R2* values. The window level has been multiplied by 2 as compared to 3T, indicating the trend for linear increase of R2* with B0. The QSM map clearly separates paramagnetic structures (vessels, deep grey nuclei) from diamagnetic calcifications, and displays some WM/GM susceptibility differences with finer details as compared to 3T