Magnetic Resonance Imaging of Physiologic Sodium (23Na) for Human Lymphatic Disease
No Thumbnail Available
Date
2025-06-11
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Despite the prevalence of lymphedema, few objective tools exist to quantify the severity of lymphatic disease in a way that is sensitive to the complex physiologic changes occurring in affected tissues. Current clinical tools are not sufficient to capture disease features, especially when adipose tissue remodeling is prominent. Tissue sodium could be a relevant physiologic indicator of lymphatic disease, based on preclinical models showing that lymphatics participate in sodium storage and clearance to maintain homeostasis. However, the importance of sodium to lymphatic physiology in humans is not well-characterized, nor exploited for clinical applications, largely due to a lack of methods to observe both sodium and lymphatics together in vivo. Sodium (23Na) magnetic resonance imaging (MRI) is a translational imaging modality capable of noninvasively measuring tissue sodium. We hypothesize that sodium content is elevated in tissues that exhibit lymphatic insufficiency and tissue remodeling in human lymphatic disease. In this dissertation, we implemented sodium (23Na)-MRI together with hydrogen (1H)-MR lymphangiography and anatomical imaging in patients with localized leg lymphedema to study disease characteristics and the relationship between lymphatic function and tissue sodium. Results found that tissue sodium content, measured with 23Na-MRI, increases with lymphedema disease severity and decreases following lymph-mobilization therapy. Sodium accumulation was observed in distinct locations in the adipose tissue, suggesting a link between sodium storage, lymphatic anatomy, and tissue remodeling. We also evaluated the relationship between local tissue sodium measurements and systemic sodium excretion to offer study design guidance for future 23Na-MRI studies in lymphatic disease, further promoting the clinical translation of this technique. Altogether, this work implemented objective, physiologic imaging methods to demonstrate an anatomical and functional relationship between lymphatics and tissue sodium in human lymphedema. This research addresses a clinical unmet need of patients with lymphedema by introducing a non-invasive tool sensitive to underlying disease mechanisms and laying foundations for clinically translatable ²³Na-MRI in lymphatic disease. More broadly, this work supports the emerging role of lymphatic circulation in human diseases involving sodium storage, and it demonstrates translational imaging approaches necessary to explore lymphatic health and disease.
Description
Keywords
magnetic resonance imaging, lymphedema, sodium, adipose tissue