Validation of a Magnetic Resonance Lymphography protocol in upper extremity lymphedema and healthy subjects*

Patients who do not benefit from conservative therapy, may need surgical
intervention to relief symptoms, such as lymphaticovenous anastomosis (LVA). It
is important to map the lymphatic system for diagnostic purposes and to
evaluate which therapy has the greatest chance of succeeding. Imaging the
lymphatic system is also useful for planning microsurgical lymphatic
interventions. In contrary to the vascular system, the lymphatic system is
difficult to visualize due to the fact that lymphatic fluid is not driven by a
central pump. Therefore, lymphatic fluid has no continuous flow. Munn et al.
(2014) discussed several techniques for visualization of the lymphatic system,
including the MR Lymphangiography (MRL). They noted that the poor spatial
resolution and sensitivity are limitations of MRL, but that further
advancements of this technique may provide us with promising results for
imaging the lymphatic system via MRL. Other authors have stated that MRL is a
safe and feasible imaging technique for primary and secondary lymphedema.
In the Maastricht University Medical Center the lymphatic system is
pre-operatively visualized by a NIRF-camera for the more superficial lymphatic
vessels and by lymphoscintigraphy for the deeper lymphatic system. Both
lymphoscintigraphy and NIRF imaging have their limitations, such as poor
resolution and depiction of only the superficial lymphatic system,
respectively.

To determine the feasibility and applicability of the MRL protocol by comparing
the images in upper extremity in patients with secondary lymphedema and healthy
subjects, and to assess differences in the lymphatic system between the
lymphedema patients and healthy volunteers

Study design:
A validation study of an MRL protocol for the upper extremity with the Siemens
3Tesla Magnetom Prisma Fit at Scannexus, Maastricht.
All participants will undergo an MRL examination with the same protocol,
developed in a previous *proof of principle* study, in the Maastricht
University Medical Center+.

Duration of the study:
Inclusion will take 3 months. MRL scanning period will last for 3 months.
Thereafter, data analysis will start.

The burden for the participants is a visit of approximately 2,5 hours. The MRL
examination will take around 2 hours. With explanation and preparations of 0,5
hours de visit will take 2,5 hours.

There are only small potential risks.
Gadolinium-based contrast agents are indicated for intravenous use in
diagnostic MRI in adults and children (2 years of age and older) to detect and
visualize areas with disrupted blood brain barrier and/or abnormal vascularity
of the central nervous system. It is also used in MRL to visualize the
lymphatic system.
In rare cases, the contrast agent (gadobutrol) might result in side effects,
such as headache, nausea, injection site reaction, feeling hot, dizziness, and
vomiting. It also increases the risk for nephrogenic systemic fibrosis among
patients with severe kidney disease.
The recommended dose of gadobutrol is 0.1mL/kg body weight when injecting IV.
In this study, we inject a maximum of 2-2.8 mL, intracutaneously.
Patients at risk (e.g. allergy for contrast agents, contraindications for MRI,
such as renal insufficiency and claustrophobia) are excluded from the study to
minimalize the chance of adverse reactions.
In previous studies, no adverse effects were reported regarding the MRL
examination or contrast agent.