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

Donadieu, Maxime; Fur, Yann Le; Maarouf, Adil; Gherib, Soraya; Ridley, Ben; Pini, Lauriane; Rapacchi, Stanislas; Confort‐Gouny, Sylviane; Guye, Maxime; Schad, Lothar R.; Maudsley, Andrew A.; Pelletier, Jean; Audoin, Bertrand; Zaaraoui, Wafaa; Ranjeva, Jean Philippe

doi:10.1177/1352458517736146

Cited by 15 publications

(23 citation statements)

References 35 publications

(82 reference statements)

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“…To gain complementary information on microstructural pathologies, a recent analysis of 21 RRMS patients and 20 controls applied a DA-3DPR sodium MRI sequence at 3 T in combination with a proton based MR spectroscopy (proton echo planar spectroscopic imaging, 3D 1 H-EPSI). Spectroscopy studies included N-acetyl aspartate (NAA; marker for mitochondrial activity), glutamate/glutamine (Glx; marker for neuro-astrocytic metabolism), total creatine (tCr; marker for cellularity), choline (Cho; marker for inflammatory demyelination) and myo-inositol (m-Ins; marker for glial activation) (107). TSC was elevated in all types of brain tissue in MS patients.…”

Section: Sodium Mri In Multiple Sclerosis (Ms)mentioning

confidence: 99%

Potential of Sodium MRI as a Biomarker for Neurodegeneration and Neuroinflammation in Multiple Sclerosis

et al. 2019

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In multiple sclerosis (MS), experimental and ex vivo studies indicate that pathologic intra- and extracellular sodium accumulation may play a pivotal role in inflammatory as well as neurodegenerative processes. Yet, in vivo assessment of sodium in the microenvironment is hard to achieve. Here, sodium magnetic resonance imaging (23NaMRI) with its non-invasive properties offers a unique opportunity to further elucidate the effects of sodium disequilibrium in MS pathology in vivo in addition to regular proton based MRI. However, unfavorable physical properties and low in vivo concentrations of sodium ions resulting in low signal-to-noise-ratio (SNR) as well as low spatial resolution resulting in partial volume effects limited the application of 23NaMRI. With the recent advent of high-field MRI scanners and more sophisticated sodium MRI acquisition techniques enabling better resolution and higher SNR, 23NaMRI revived. These studies revealed pathologic total sodium concentrations in MS brains now even allowing for the (partial) differentiation of intra- and extracellular sodium accumulation. Within this review we (1) demonstrate the physical basis and imaging techniques of 23NaMRI and (2) analyze the present and future clinical application of 23NaMRI focusing on the field of MS thus highlighting its potential as biomarker for neuroinflammation and -degeneration.

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Section: Sodium Mri In Multiple Sclerosis (Ms)mentioning

confidence: 99%

Potential of Sodium MRI as a Biomarker for Neurodegeneration and Neuroinflammation in Multiple Sclerosis

et al. 2019

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“…Sodium MRI (NaMRI) has been applied to the study of multiple sclerosis (MS) for a decade and nearly all studies have focused on sodium density-weighted (NaDW) methods and tissue sodium concentration (TSC) measurement (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). However, the underlying microstructural or metabolic sources of the reported range of 20-80% greater TSC in lesions and 5-39% greater TSC in Normal Appearing White Matter (NAWM) remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Sodium Intensity Changes Differ Between Relaxation- and Density-Weighted MRI in Multiple Sclerosis

et al. 2021

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Introduction: The source of Tissue Sodium Concentration (TSC) increase in Multiple Sclerosis (MS) remains unclear, and could be attributed to altered intracellular sodium concentration or tissue microstructure. This paper investigates sodium in MS using three new MRI sequences.Methods: Three sodium scans were acquired at 4.7 T from 30 patients (11 relapsing-remitting, 10 secondary-progressive, 9 primary-progressive) and 9 healthy controls including: Density-Weighted (NaDW), with very short 30° excitation for more accurate TSC measurement; Projection Acquisition with Coherent MAgNetization (NaPACMAN), designed for enhanced relaxation-based contrast; and Soft Inversion Recovery FLuid Attenuation (NaSIRFLA), developed to reduce fluid space contribution. Signal was measured in both lesions (n = 397) and normal appearing white matter (NAWM) relative to controls in the splenium of corpus callosum and the anterior and posterior limbs of internal capsule. Correlations with clinical and cognitive evaluations were tested over all MS patients.Results: Sodium intensity in MS lesions was elevated over control WM by a greater amount for NaPACMAN (75%) than NaDW (35%), the latter representing TSC. In contrast, NaSIRFLA exhibited lower intensity, but only for region specific analysis in the SCC (−7%). Sodium intensity in average MS NAWM was not significantly different than control WM for either of the three scans. NaSIRFLA in the average NAWM and specifically the posterior limb of internal capsules positively correlated with the Paced Auditory Serial Addition Test (PASAT).Discussion: Lower NaSIRFLA signal in lesions and ~2× greater NaPACMAN signal elevation over control WM than NaDW can be explained with a demyelination model that also includes edema. A NAWM demyelination model that includes tissue atrophy suggests no signal change for NaSIRFLA, and only slightly greater NAWM signal than control WM for both NaDW and NaPACMAN, reflecting experimental results. Models were derived from previous total and myelin water fraction study in MS with T2-relaxometry, and for the first time include sodium within the myelin water space. Reduced auditory processing association with lower signal on NaSIRFLA cannot be explained by greater demyelination and its modeled impact on the three sodium MRI sequences. Alternative explanations include intra- or extracellular sodium concentration change. Relaxation-weighted sodium MRI in combination with sodium-density MRI may help elucidate microstructural and metabolic changes in MS.

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“…Higher values appear to be linked with progressive disease and greater disability [70]. In a combined 23 Na MRI and MRS analysis, sodium accumulation was directly associated with neuronal metabolic dysfunction, as reflected by decreased NAA levels, in focal lesions, grey matter and normal-appearing white matter of 21 individuals with relapsing-remitting MS. [72]…”

Section: Main Textmentioning

confidence: 99%

Detecting neurodegenerative pathology in multiple sclerosis before irreversible brain tissue loss sets in

Schependom

Guldolf

D’hooghe

et al. 2019

Transl Neurodegener

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BackgroundMultiple sclerosis (MS) is a complex chronic inflammatory and degenerative disorder of the central nervous system. Accelerated brain volume loss, or also termed atrophy, is currently emerging as a popular imaging marker of neurodegeneration in affected patients, but, unfortunately, can only be reliably interpreted at the time when irreversible tissue damage likely has already occurred. Timing of treatment decisions based on brain atrophy may therefore be viewed as suboptimal.Main bodyThis Narrative Review focuses on alternative techniques with the potential of detecting neurodegenerative events in the brain of subjects with MS prior to the atrophic stage. First, metabolic and molecular imaging provide the opportunity to identify early subcellular changes associated with energy dysfunction, which is an assumed core mechanism of axonal degeneration in MS. Second, cerebral hypoperfusion has been observed throughout the entire clinical spectrum of the disorder but it remains an open question whether this serves as an alternative marker of reduced metabolic activity, or exists as an independent contributing process, mediated by endothelin-1 hyperexpression. Third, both metabolic and perfusion alterations may lead to repercussions at the level of network performance and structural connectivity, respectively assessable by functional and diffusion tensor imaging. Fourth and finally, elevated body fluid levels of neurofilaments are gaining interest as a biochemical mirror of axonal damage in a wide range of neurological conditions, with early rises in patients with MS appearing to be predictive of future brain atrophy.ConclusionsRecent findings from the fields of advanced neuroradiology and neurochemistry provide the promising prospect of demonstrating degenerative brain pathology in patients with MS before atrophy has installed. Although the overall level of evidence on the presented topic is still preliminary, this Review may pave the way for further longitudinal and multimodal studies exploring the relationships between the abovementioned measures, possibly leading to novel insights in early disease mechanisms and therapeutic intervention strategies.

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

Abstract: 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.

Cited by 15 publications

References 35 publications

Potential of Sodium MRI as a Biomarker for Neurodegeneration and Neuroinflammation in Multiple Sclerosis

Potential of Sodium MRI as a Biomarker for Neurodegeneration and Neuroinflammation in Multiple Sclerosis

Sodium Intensity Changes Differ Between Relaxation- and Density-Weighted MRI in Multiple Sclerosis

Detecting neurodegenerative pathology in multiple sclerosis before irreversible brain tissue loss sets in

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

Abstract: 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.

Cited by 15 publications

References 35 publications

Potential of Sodium MRI as a Biomarker for Neurodegeneration and Neuroinflammation in Multiple Sclerosis

Potential of Sodium MRI as a Biomarker for Neurodegeneration and Neuroinflammation in Multiple Sclerosis

Sodium Intensity Changes Differ Between Relaxation- and Density-Weighted MRI in Multiple Sclerosis

Detecting neurodegenerative pathology in multiple sclerosis before irreversible brain tissue loss sets in

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