Abstract

The purpose of this study is to assess the repeatability of the quantification of pseudo-intracellular sodium concentration (C1) and pseudo-extracellular volume fraction (α) estimated in brain in vivo using sodium magnetic resonance (MRI) at 3 T. Eleven healthy subjects were scanned twice, with two sodium MRI acquisitions (with and without fluid suppression by inversion recovery), and two double inversion recovery (DIR) proton MRI. DIR MRIs were used to create masks of gray and white matter (GM, WM), that were subsequently applied to the C1 and α maps calculated from sodium MRI and a tissue three-compartment model, in order to measure the distributions of these two parameters in GM, WM or full brain (GM+WM) separately. The mean, median, mode, standard deviation (std), skewness and kurtosis of the C1 and α distributions in whole GM, WM and full brain were calculated for each subject, averaged over all data, and used as parameters for the repeatability assessment. The coefficient of variation (CV) was calculated as a measure of reliability for the detection of intra-subject changes in C1 and αfor each parameter, while intraclass correlation (ICC) was used as a measure of repeatability. It was found that the CV of most of the parameters was around 10–20% (except for C1 kurtosis which is about 40%) for C1 and α measurements, and that ICC was moderate to very good (0.4 to 0.9) for C1 parameters and for some of the α parameters (mainly skewness and kurtosis). In conclusion, the proposed method could allow to reliably detect changes of 50% and above of the different measurement parameters of C1 and αin neuropathologies (multiple sclerosis, tumor, stroke, Alzheimer’s disease) compared to healthy subjects, and that skewness and kurtosis of the distributions of C1 and αseem to be the more sensitive parameters to these changes.

Highlights

  • Sodium ions (23Na+) are vital components in the human brain, and their homeostasis is a major process in cells through coupled exchange with potassium ions K+ between the intraand extracellular compartments through the Na+/K+-ATPase [1]

  • Measuring variations in α could give more information on effusion or disruption of cell packing [8], dehydration [9], changes in vascularization and tumor edema angiogenesis [10, 11] or metabolite clearance in the brain [12]. Measuring both C1 and α in vivo could be of great importance for assessing early signs of neuropathologies characterized by a loss of cell integrity or homeostasis, such as brain tumors [13,14,15], multiple sclerosis [16], stroke [17, 18], or Alzheimer’s disease [19]

  • We recently developed a simple method based on sodium magnetic resonance imaging (MRI) along with double inversion recovery (DIR) proton MRI, for estimating these two parameters in the gray matter (GM), white matter (WM) and full brain separately [23]

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Summary

Introduction

Sodium ions (23Na+) are vital components in the human brain, and their homeostasis is a major process in cells through coupled exchange with potassium ions K+ between the intraand extracellular compartments through the Na+/K+-ATPase (sodium-potassium pump) [1]. Measuring variations in α could give more information on effusion or disruption of cell packing [8], dehydration [9], changes in vascularization and tumor edema angiogenesis [10, 11] or metabolite clearance in the brain [12] Measuring both C1 and α in vivo could be of great importance for assessing early signs of neuropathologies characterized by a loss of cell integrity or homeostasis, such as brain tumors [13,14,15], multiple sclerosis [16], stroke [17, 18], or Alzheimer’s disease [19]

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