Sodium (Na+), potassium (K+), and chloride (Cl-) ions play a vital role in many cellular processes such as the excitability of neurons and muscle cells. MRI of these nuclei – often denoted as X-nuclei MRI – is a promising approach to non-invasively examine cell viability.
Over the past decades, 23Na MRI has become a widely used technique to noninvasively determine the total tissue sodium concentration. It is a valuable tool in biomedical research despite its challenges that include low signal-to-noise-ratio (SNR) and fast signal decay [1,2]. Imaging of chloride  and potassium [4,5,6] is even more challenging due to the even lower signal intensity, which makes the use of ultra-high field strengths (B0 ≥ 7 T) indispensable.
Figure 1 shows exemplary sodium and potassium concentration maps of healthy lower leg muscle tissue acquired with a dual-tuned 23Na/39K calf coil at 7 T . Figure 2 shows sodium images of a healthy volunteer and a patient with Duchenne muscular dystrophy . Elevated muscular sodium signal intensities were regularly observed in patients with Duchenne muscular dystrophy (DMD) compared with controls, and were present even in absence of fatty degenerative changes and water T2 increases . This Na+ overload might contribute to the disease progression . Thus, 23Na MRI may be considered as a potential marker to characterize dystrophic muscle tissue at an early stage.
Figure 1. In vivo Na+ and K+ concentration maps of the lower leg of a healthy volunteer acquired with a dual-tuned 23Na/39K calf coil at 7 T.
A mean Na+ concentration of 18±2 mM and a mean K+ concentration of 72±8 mM within muscle tissue were calculated. Due to fast T2 relaxation and partial volume effects, the K+ concentration is underestimated.
Figure 2. Fat fraction (FF) maps, water T2 maps, Na+ concentration maps and Na+ inversion recovery images of the lower legs of a healthy control and a patient with Duchenne muscular dystrophy (DMD).
Four reference tubes were used for 23Na MRI (1, 40 mM NaCl; 2, 40 mM NaCl, and 5% agarose gel; 3, 20 mM NaCl; 4, 20 mM NaCl, and 5% agarose gel). Increased tissue sodium concentrations and intracellular-weighted sodium signals (ICwS) are already visible in dystrophic muscle tissue with normal T2 and FF values.
One approach to analyze the molecular environment is to examine the existence of multiple quantum coherences (MQC) as they are directly linked to the sodium ions’ molecular environment and the corresponding quadrupolar interactions . MQC describe superpositions between nuclear energy levels with a difference in nuclear quantum number of Δm > 1 that can be induced in a system of nuclei possessing a nuclear spin I ≥ 1. Spin-3/2 nuclei as 23Na and 39K exhibit four nuclear Zeeman levels, therefore double quantum coherences (Δm = 2) and triple quantum coherences (Δm = 3) can be generated. In contrast to single quantum coherences, MQC are not directly MR observable. Instead, so-called multiple quantum filters (MQF) have to be applied to detect them. Triple quantum filtered imaging (TQF) offers the possibility to detect signal of ions located within restricted motional regimes and has been shown to provide weighting towards intracellular space. Double quantum filtered MRI with magic angle excitation (DQF-MA) can be used to selectively detect ions located within anisotropic structures such as muscle fibers. However, all these techniques suffer from low SNR and are prone to magnetic field inhomogeneities [10,11].
In this project, imaging techniques based on multiple quantum filtration are developed and applied both to healthy subjects and patients with muscular pathologies. The aim of this project is to probe the molecular environments (e.g. intra vs. extracellular) of sodium and potassium ions by making use of their quadrupolar interactions.
In Figure 3, a spin density weighted (DW) 23Na image of human lower leg is compared to a triple quantum filtered (TQF) and a double quantum filtered with magic angle excitation (DQF-MA) 23Na image .
Figure 3. Spin density weighted (DW) (a), triple quantum filtered (TQF) (b), and double quantum filtered with magic angle excitation (DQF-MA) (c) 23Na images of a the lower leg of a healthy volunteer.
The TQF passes only signal from sodium nuclei that are located in a motional restricted environment. The DQF-MA selectively detects signal from sodium nuclei connected to ordered structures.
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