Synopsis

Ions such as sodium (Na⁺), chlorine (Cl^-) and potassium (K⁺) play an important role in many cellular physiological processes. In healthy tissue, the extracellular concentration of Na⁺ is approximately ten-fold higher than the intracellular concentration. A breakdown of this concentration gradient or an increase of the intracellular Na⁺ content can be used as an early marker in many disease processes. In this presentation, the focus will be on musculoskeletal and brain-related applications of Na⁺ MRI. In addition, the required hardware, as well as image acquisition and post-processing techniques that are suitable for Na⁺, K⁺, and Cl^- MRI will be discussed.

Target Audience

Introduction

Ions such as sodium (Na⁺), chlorine (Cl^-) and potassium (K⁺) play an important role in many cellular physiological processes. The high concentration gradients across the cell membranes for Na⁺, Cl^-, and K⁺ are the physiological basis for the respective process of excitation and inhibition of neurons, heart and muscle cells. In healthy tissue, the extracellular concentration of Na⁺ is approximately ten-fold higher than the intracellular concentration ([Na⁺] = 10 – 15 mmol/L, [Na⁺] = 145 mmol/L). For K⁺ the concentration gradient is reversed and even more pronounced. The enzyme Na⁺-K⁺-ATPase helps to maintain this gradient by pumping Na⁺ out and potassium (K⁺) into the cell with a ratio of 3:2. A breakdown of this concentration gradient or an increase of the intracellular sodium content can be used as an early marker in many disease processes.

Although, ²³Na exhibits the most favorable properties for in vivo MRI after ¹H, in vivo ²³Na MRI is challenging due to low MR sensitivity, low in vivo concentrations and short transverse relaxation times. ³⁹K or ³⁵Cl MRI are even more challenging due to further reduced MR sensitivity. However, in the past decade, the increasing availability of high-field (B₀ = 3 T) and ultra-high field (UHF) MRI systems (B₀ ≥ 7 T) largely extended the capabilities of sodium MRI, since the increased signal-to-noise ratio (SNR) enables increased spatial resolutions. High-performance radiofrequency coils (1), efficient ultra-short echo time (UTE) pulse sequences (2), iterative image reconstruction techniques (3-5), and new post-processing techniques (6) have further improved image quality and quantitative accuracy of sodium MRI. In addition, the advent of UHF systems enabled to proof the feasibility of ³⁵Cl and ³⁹K MRI of human brain and muscle (7-9).

There is a large variety of biomedical research applications where sodium MRI has been applied (e.g. (10-14)). In this presentation, the focus will be on musculoskeletal and brain-related applications. In addition, the required hardware, as well as image acquisition and post-processing techniques that are suitable for sodium MRI will be discussed.

Selected Clinical Research Applications of ²³Na MRI in the Brain and the Musculoskeletal System

In brain, sodium MRI has been used – among others – to study brain tumors (13,15-19), ischemic stroke (20,21), Alzheimer’s diseases (22), and multiple sclerosis (14). Sodium ion channels and sodium accumulation are expected to play a role in the pathogenesis of multiple sclerosis (23,24). Thus, several recent studies focused on sodium MRI in multiple sclerosis (14). In brain tumors, sodium concentrations are typically increased. This increase can be caused by edema (i.e. increased extracellular volume fraction) or by an increase of the intracellular concentration (e.g. due to cell depolarization). Sodium inversion recovery imaging might help to separate between these two underlying reasons (16). In ischemic stroke, sodium MRI might be used to identify regions with preservation of the ionic homeostasis (25). Tissue sodium concentrations above approximately 70 mmol/L indicate irreversible tissue damage (21).

There are also several ²³Na MRI studies that focus on muscle tissue. Elevated muscular tissue Na⁺ content that is either a consequence of the disease process or a major driver in the progression of the disease is observed in many pathologies such as myotonic dystrophy (26,27), Duchenne muscular dystrophy (28,29), hypertension (30), severe kidney disease (31), and muscular channelopathies (32,33).

Among all tissues of the human body, healthy cartilage tissue contains the highest Na⁺ content (≈ 300 mmol/L). Na⁺ content of cartilage is considered to be an important biomarker for cartilage degeneration, e.g. in osteoarthritis (12,34). However, ²³Na MRI or articular cartilage suffers from low spatial resolution and partial volume effects.

Conclusions

Acknowledgements

References

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