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

Abstract

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.

Imaging the Transmembrane and Transendothelial Sodium Gradients in Gliomas

“…, in which all Na + is aqueous, whereas some Na + ions in tissue can be bound. These observations are in agreement with prior 23 Na-MRI results (Driver et al, 2020;Gilles et al, 2017;Huhn et al, 2019;Meyer et al, 2019;Ridley et al, 2018).…”

Sodium relaxometry using 23Na MR fingerprinting: A proof of concept

“…In the brain, 23 Na‐MRI has been exploited extensively for a variety of applications such as stroke, neurodegenerative diseases, and cancer 2,3 . For example, in multiple sclerosis (MS) patients, an increase in the tissue sodium concentration (TSC) was found 4‐6 . Furthermore, the TSC has been quantified in malignant tumors, where significant differences between tumors and contralateral brain tissue have been observed 7 .…”

“…2,3 For example, in multiple sclerosis (MS) patients, an increase in the tissue sodium concentration (TSC) was found. [4][5][6] Furthermore, the TSC has been quantified in malignant tumors, where significant differences between tumors and contralateral brain tissue have been observed. 7 Additionally, it has been shown that sodium MRI can predict tumor chemo-resistance before therapy and can, therefore, be a key component of individualizing cancer treatment strategies.…”

Frontiers of Sodium MRI Revisited: From Cartilage to Brain Imaging

“…Further studies confirmed these findings. [115][116][117][118] In order to obtain more specific information, Petracca et al used a method that combined SQ and TQF MRI, to quantify TSC and the intracellular sodium molar fraction (ISMF) and then derived ISC and ISVF, an indirect measure of ESC. The results generated from 19 relapsing-remitting MS patients and 17 heathy controls showed that global TSC and ISC evaluated in GM were higher, while GM and WM ISVF (indirect measure of extracellular sodium concentration) were lower in patients compared with healthy controls.…”