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

Abstract

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.

Quantitative 7T sodium magnetic resonance imaging of the human brain using a 32‐channel phased‐array head coil: Application to patients with secondary progressive multiple sclerosis

“…As a result, sodium ions are more visible for MRI not optimized for minimal residual quadrupole signal loss (high nominal FAs with accordingly longer RF pulses). 13,23 Regarding these results, the measured aTSC increase is not expected to result from a higher amount of sodium, but from increased T 2 relaxation times related to myelin damage, which facilitate the detection by 23 Na MRI. Nevertheless, future studies on 23 Na MRI should further evaluate the origin of signal intensity changes between MS patients and healthy controls, in particular the influence of altered relaxation behavior and real increases in sodium concentration, for example, due to extended extracellular space.…”

“…36 Furthermore, a recent study gave hints for a more fluid-like lesion environment compared with healthy WM. 13 Therefore, the relaxation parameters of healthy WM were assumed as lower bound (model 1:…”

“…By contrast, in a study using very short RF pulses with lower nominal FAs, no significant elevation in NAWM TSC was detected. 13 This could be explained by the loss of myelin in MS patients and the resulting changes in the molecular environment of the sodium ions in NAWM. The degradation of WM results in a more homogeneous environment with a reduced residual quadrupole splitting and lengthened relaxation times.…”

“…It was shown that 23 Na MRI intensity changes between different types of MS and healthy controls also depend on the 23 Na MR imaging technique used and the resulting contrast. 13 Overall, there is increasing evidence that 23 Na MRI can provide potential biomarkers for neurodegeneration and neuroinflammation in MS. 4 However, despite the progress in 23 Na brain MRI during recent years, 14,15 many studies are still limited by the inherent physical properties of 23 Na MRI. Due to the intrinsically reduced NMR sensitivity and the low in vivo concentrations compared with proton ( 1 H) MRI, large voxel volumes and long acquisition times are necessary to achieve a sufficient signal-to-noise ratio (SNR).…”

“…As the TSC represents a volume‐weighted average of intracellular and extracellular sodium, it is sensitive to changes in both spaces and an increase can be related to a neuronal energy deficit, which results in intra‐axonal accumulation of sodium ions, 2,10–12 as well as to neuronal degeneration with extension of the extra‐axonal space and altered tissue microstructure. It was shown that 23 Na MRI intensity changes between different types of MS and healthy controls also depend on the 23 Na MR imaging technique used and the resulting contrast 13 . Overall, there is increasing evidence that 23 Na MRI can provide potential biomarkers for neurodegeneration and neuroinflammation in MS 4 …”