Two Non-gadolinium-based, Innovative Approaches to Preoperative Lymphangiography

Abstract

Most magnetic resonance lymphangiography techniques employ intravenous gadolinium-based contrast agents, which carry a US Food and Drug Administration warning about gadolinium retention in the body when used intravenously. Because of this, there may be reluctance to perform intradermal injections of gadolinium-based contrast agents in patients with obstructed lymphatic drainage due to concerns about gadolinium retention in the skin and soft tissues and potential-related toxicity. The aim of this study was to show proof of concept of 2 preoperative lymphangiographic techniques that do not use gadolinium-based contrast agents. One technique used contrast-enhanced ultrasound with intradermal injections of microbubbles (Lumason) in a patient with stage 3, nonpitting left upper extremity edema. Another technique used magnetic resonance imaging with intradermal injections of 0.03 mg/mL or 0.003% ferumoxytol (Feraheme) in a patient with stage 3, nonpitting right lower extremity edema. Both contrast-enhanced ultrasound with microbubbles and magnetic resonance lymphangiogram with ferumoxytol were able to identify candidates for lymphovenous bypass surgery. These candidates were not identified by conventional indocyanine green injections. The authors conclude that (1) low-dose ferumoxytol is a potentially effective non-gadolinium-based contrast alternative to gadolinium-based contrast agent in magnetic resonance lymphangiography and (2) contrast-enhanced ultrasound can identify candidate lymphatic vessels for anastomosis.

Fig. 1.

Sites and volume of ferumoxytol intradermal injections. Eight different sites were targeted for intradermal injection along the ventral surface of the right lower extremity (n,v) = (injection #, mL of 0.003% ferumoxytol).

Fig. 2.

MRI of the distal right calf (injection #5 and #6 in Fig. 1) about 25 minutes after intradermal ferumoxytol injection. Coronal reformatted image shows ferumoxytol contrast within suspected lymphatic vessels (arrows). The highest signaling areas correspond to the areas of injection laterally (*, injection #6) and medially (**, injection #5).

Fig. 3.

CEUS examination of the left upper extremity. Microbubble contrast is identified in what is believed to be lymphatic vessels (arrows) in the contrast-specific images. The contrast-specific image is a summation of 7 cine frames near the medial distal arm at the level of the elbow.

Fig. 4.

Intraoperative photograph. In the leg, end vein (triangles) to lymphatic (thin arrows) anastomosis was performed by telescopic technique with 11-0 Nylon sutures at the anastomosis (thick arrows). Thin arrows show the string-like lymphatics. Despite no lumen, copious clear lymph leak exuded from its stump. Image was taken under Mitaka MM51 Series ×30 magnification.