²³Na-MRI Measures Tissue Sodium in Human Leg Lymphedema

There are few objective tools to quantify lymphatic disease changes in anatomy and physiology of affected tissues. Tissue sodium could be a relevant physiological indicator of lymphatic disease. However, the importance of sodium to lymphatic physiology in humans has not been well-characterized nor exploited for clinical applications due to a lack of imaging methods to observe sodium and lymphatics together in vivo. The purpose of this study was to apply ²³Na-MRI to measure tissue sodium content (TSC) in human subjects with or without lower extremity lymphedema (LEL) and investigate the relationship between lymphatic dysfunction and tissue sodium.

A prospective, cross-sectional observational clinical trial enrolled participants with LEL and controls without lymphedema. ²³Na-MRI measured standardized TSC in the mid-calf. For each leg with lymphedema, clinical stage was determined by a licensed clinician, and lymphedema severity was determined by radiology assessment of noncontrast hydrogen (¹H)-magnetic resonance lymphangiography (MRL). Linear mixed-effects models determined differences in TSC between cases and controls and measured the association of TSC with clinical stage and lymphedema severity. Image subregions were analyzed to observe spatial patterns of TSC involvement. Results found that TSC was nearly 50% higher in lymphedema (n = 52 legs) in the skin (1.51-fold) and adipose tissue (1.47-fold) compared with controls (n = 31 legs; p < 0.001) and was directly related to both clinical stage and lymphedema severity by ¹H-MRL in the skin (p < 0.001) and adipose tissue (p < 0.001). TSC accumulated in patterns in the anterior subcutaneous adipose tissue, increasing with disease severity.

²³Na-MRI demonstrates that standardized TSC is distinctly elevated in lymphedema, sensitive to lymphedema disease severity, and a potential objective imaging tool for evaluating lymphedema in future clinical trials.