Safety and utility of subcutaneous gadobutrol-enhanced MR lymphography for preoperative mapping in lymphovenous anastomosis: A phase II trial.

Abstract

Subcutaneous gadolinium-enhanced magnetic resonance lymphography (MRL) can reveal functionally impaired lymphatic vessels (LVs) in limb lymphedema. However, its safety and clinical value have not been prospectively evaluated. We assessed the safety and utility of subcutaneous gadobutrol-enhanced MRL as a preoperative imaging modality for lymphovenous anastomosis (LVA). This prospective, single-center phase II trial enrolled 30 patients with International Society of Lymphology stage 2 secondary limb lymphedema scheduled for LVA from June 2022 to May 2024. Participants underwent gadobutrol-enhanced MRL, followed by indocyanine green lymphography (ICG-L) and surgery. The primary endpoint was adverse events within 7 days. Secondary endpoints assessed MRL efficacy for LVA planning: maximal proximal extent of enhancement, depth, and diameter of anastomosed LVs. Twenty-nine participants (28 women, 1 man) and 33 limbs were analyzed. No severe adverse events occurred. Injection-site pain was absent in 21%, mild in 59%, and moderate in 21%, with no anaphylaxis or complications requiring treatment. MRL visualized LVs more proximally than did ICG-L (48.9 cm vs. 32.5 cm, p < .001). Among anastomosed LVs, 65% were identified exclusively by MRL and were deeper than LVs detectable on ICG-L (10 mm vs. 6 mm, p = .007). MRL-guided incisions yielded a 97% positive predictive value. MRL-assessed LV depth correlated with intraoperative depth (r = 0.68, p < .001). Subcutaneous gadobutrol-enhanced MRL demonstrated a favorable safety profile and improved preoperative mapping for LVA by identifying proximal and deep LVs beyond the detection capabilities of ICG-L. These results support its clinical utility in lymphatic surgery planning.