Frontiers of Sodium MRI Revisited: From Cartilage to Brain Imaging

Abstract

Sodium magnetic resonance imaging (²³ Na-MRI) is a highly promising imaging modality that offers the possibility to noninvasively quantify sodium content in the tissue, one of the most relevant parameters for biochemical investigations. Despite its great potential, due to the intrinsically low signal-to-noise ratio (SNR) of sodium imaging generated by low in vivo sodium concentrations, low gyromagnetic ratio, and substantially shorter relaxation times than for proton (¹ H) imaging, ²³ Na-MRI is extremely challenging. In this article, we aim to provide a comprehensive overview of the literature that has been published in the last 10-15 years and which has demonstrated different technical designs for a range of ²³ Na-MRI methods applicable for disease diagnoses and treatment efficacy evaluations. Currently, a wider use of 3.0T and 7.0T systems provide imaging with the expected increase in SNR and, consequently, an increased image resolution and a reduced scanning time. A great interest in translational research has enlarged the field of sodium MRI applications to almost all parts of the body: articular cartilage tendons, spine, heart, breast, muscle, kidney, and brain, etc., and several pathological conditions, such as tumors, neurological and degenerative diseases, and others. The quantitative parameter, tissue sodium concentration, which reflects changes in intracellular sodium concentration, extracellular sodium concentration, and intra-/extracellular volume fractions is becoming acknowledged as a reliable biomarker. Although the great potential of this technique is evident, there must be steady technical development for ²³ Na-MRI to become a standard imaging tool. The future role of sodium imaging is not to be considered as an alternative to ¹ H MRI, but to provide early, diagnostically valuable information about altered metabolism or tissue function associated with disease genesis and progression. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1.

Keywords: MRI; clinical applications; sodium; technical developments.

FIGURE 1

A 39‐year‐old male patient who had a small cartilage defect less than 15% of the cartilage thickness (ICRS grade 2 lesion) in the proximal trochlear region of the lateral femoral condyle. (a) A fat‐suppressed proton density (FS‐PD) image in a sagittal orientation shows a lesion with intra‐chondral signal alterations. Sodium ²³Na‐MRI images generated (b) 3 days and (c) 4 weeks after the defect.

FIGURE 2

A 50‐year‐old male patient with a lesion in the patellar cartilage in the area crista patellae. (a) A proton density sequence with fat suppression (FS‐PD) demonstrates an early stage degeneration of articular cartilage with a minor chondral signal alteration and a minor reduction of cartilage thickness, and a surface that appears intact (ICRS grade 1 lesion). (b) Yellow arrow shows the corresponding area on the sodium image.

FIGURE 3

Illustration of (a) fat fraction maps, (b) water T₂ maps, (c) DW ²³Na images, and (d) IR ²³Na images in the leg of 7‐year‐old, 9‐year‐old, and 11‐year‐old DMD patients, as well as a 10‐year‐old control. For ²³Na MRI, four reference tubes were used (1, 40  mM NaCl; 2, 40 mM NaCl, and 5% agarose gel; 3, 20 mM NaCl; 4, 20 mM NaCl, and 5% agarose gel). The leg muscles of DMD patients showed generally elevated FF, water T₂, and sodium signals compared with age‐matched controls. While the 7‐year‐old DMD patient exhibited slightly elevated FF (mean FF 0.08 ± 0.04), the FF was much higher in the muscles of the 11‐year‐old DMD patient (mean FF 0.19 ± 0.1), who was not able to walk more than 10 m without human assistance. Increased total sodium and intracellular‐weighted sodium signals are also visible in the dystrophic muscle tissue with normal T₂ and FF values (figure reproduced from Ref. 73 with permission from Wiley).

FIGURE 4

An example of proton and sodium images with segmentation masks used for quantification and postprocessing. (a) ¹H MRI image (with navigator stripes) before registration. (b) ²³Na MRI with corresponding masks (red = blood mask, green = myocardial mask) based on the ¹H image. (c) Simulated ²³Na MRI of the heart based on ¹H masks. (d) ¹H MRI image after registration. (e) Registered ¹H image with cardiac ²³Na MRI as an overlay. (f) Cardiac ²³Na MRI (figure adapted from Ref. 96 and reproduced with permission from Wiley).

FIGURE 5

A 60‐year‐old female patient with invasive ductal carcinoma (IDC) and a grade 3 proliferation (G3) in the lateral part of the left breast. (a) DIXON water image shows a heterogeneous lesion with irregular margins typical of malignant tumors, and (b) a corresponding color‐coded bilateral ²³Na image corrected for coil sensitivity and obtained with a 3D radial projection sequence (DA‐3DPR).

FIGURE 6

Representative sodium (²³Na), diffusion‐weighted (DWI), T₂‐weighted, and fluid‐attenuated inversion recovery (FLAIR) images from patients 7 to 52 hours after ischemic stroke onset. Areas of sodium signal intensity increase correspond to the lesions identified on DWI. The sodium signal intensity in the areas of ischemia qualitatively increased with time (figure reproduced from Ref. 112 with permission from Wiley).