In the US, breast cancer treatment is the leading cause of lymphedema, negatively impacting quality of life. 1 Surgical approaches, including lymphaticovenous anastomosis (LVA), are increasingly used to treat lymphedema. In order to determine whether and where a successful anastomosis is possible, LVA requires accurate visualization and mapping of individual lymphatic channels, as well as veins. Lymphoscintigraphy is the imaging gold standard; however magnetic resonance lymphangiography (MRL) affords many benefits, including increased spatial resolution, higher signal-to-noise and higher temporal resolution. 2 For MRL, a gadolinium-based contrast agent is injected intracutaneously into the webspaces of the hands or feet where it is taken up by lymphatics. Unfortunately, there is all too often simultaneous venous gadolinium (Gd) uptake, making it difficult to distinguish between veins and lymphatics.

DARC-MRL was created to address venous contamination. 3 This is achieved through intravenous injection of ferumoxytol (AMAG Pharmaceuticals, MA, USA), an ultra-small superparamagnetic iron oxide (USPIO). Ferumoxytol has exceptionally high R2* relaxivity, markedly shortening blood T2* at equilibrium concentration (achieving a blood T2* < ~2.0 ms), which can be nulled using mildly lengthened echo times, effectively masking any gadolinium in the veins. This study seeks to determine the incidence of venous contamination with conventional MRL, and evaluate the effectiveness of DARC for suppressing these veins.

Patient Cohort: This IRB approved retrospective study identified 43 patients who underwent DARC-MRL (38 F, 5 M; age 50.6 ± 14.6; 28 upper extremity, 15 lower extremity) and 43 matched controls who underwent conventional MRL (37 F, 6 M; age 55.6 ± 13.5; 28 upper extremity, 15 lower extremity) during the 15 months prior to the clinical introduction of the DARC MRL protocol.

MRL Protocol: All patients were imaged at 3T (Ingenia, Philips, the Netherlands). For DARC-MRL, ferumoxytol 5 mg/kg was administered intravenously prior to intracutaneous gadolinium to allow for nulling of any venous contamination (Figure 1). In each case, the shortest TE pair (TE1, TE2) required for blood pool suppression was determined, starting at TE1 = 3.5 ms, with TE2 = TE1 + 1.1 ms, and ranging to TE1 = 8.0 ms. Lymphatic visualization was achieved for both conventional and DARC-MRL by intracutaneous administration of 1 ml GBCA (gadobenate dimeglumine, Bracco, Princeton, NJ) into each webspace (hand or foot). 3D two-point mDixon (Philips) datasets (approximate resolution 1.3 x 1.3 x 1.6 mm3 upper extremities, 1.5 x 1.5 x 2.0 mm3 lower extremities, reconstructed as water datasets) were acquired for 30-90 min to allow the transit of GBCA through the lymphatics. At the conclusion of the study, a venogram was obtained; for conventional MRL, gadolinium was injected intravenously and delayed (venous phase) images were obtained. For DARC-MRL, short TE (1.4/2.5 ms) mDixon was performed to create a dual MRL/MRV and ensure no inadvertent lymphatic suppression.

Data Analysis: Studies were divided into three stations (proximal, mid or distal) and graded for degree of venous contamination (Figures 2-3) and to look for lymphatic signal loss with DARC. Echo times required for DARC venous suppression were recorded.

There were no adverse events with either technique. Venous contamination was present in 42 of 43 conventional MRL studies (98%), but only 5 of 43 DARC MRL studies (12%) (Table 1, Figure 3). Contamination was rated as problematic in distinguishing lymphatics from veins in 24 conventional studies (56%), but none of the DARC MRL studies. Venous contamination by station for both types of studies is also presented in Table 1, and as can be seen was most problematic in the distal stations.

DARC-MRL achieved adequate venous suppression in all cases, although there was significant variation in requisite TE’s to achieve suppression. While the majority (54%) achieved good venous suppression at TE1 = 5.8 ms, an additional 30% suppressed at TE1 = 4.6 ms, while 4%, 3%, and 1% of the cases suppressed at TE1 = 3.5, 6.9, and 8.0 ms respectively. No instances of significant lymphatic suppression were seen despite these longer echo times.

Venous contamination is a common challenge in conventional MRL, and distinguishing lymphatic channels from small veins can be problematic. This study demonstrated 98% venous enhancement distally for conventional MRL, >50% of which was felt to be problematic. DARC MRL, however, effectively suppressed veins in the majority of cases (89%, all stations), with the remaining 11% all minimally interfering, typically just a short central venous segment. Thus DARC-MRL allowed for an unconfounded view of the lymphatics. Such clean lymphatic-venous separation may aid presurgical planning by allowing surgeons to confidently stratify potential candidates and identify anastomosis targets, and more easily lends itself to advanced post-processing for visualization (Figure 4).