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Calderwood et al. Plast Aesthet Res 2021;8:40 https://dx.doi.org/10.20517/2347-9264.2021.14 Page 3 of 14

contrast administration to visualise the individual lymphatic channels (contrast-enhanced MRL). Finally, a
delayed sequence is performed with intravenous contrast injection to define the veins (venogram). Fast spin-
echo is used to obtain images in a shorter time to eliminate motion artefact [6,11,14,15,17-21] , and maximum
intensity projection is commonly used to present the reconstructed images [1-4,6-8,11,14-19,21-28] .

Contrast-enhanced MRL
Contrast-enhanced MRL sequences provide not only anatomical information of the lymphatic channels and
lymph nodes (to a higher resolution than non-contrast MRL and lymphoscintigraphy) but also information
on the drainage patterns of the lymphatic system [7,8,14,21,27] . A paramagnetic macromolecule contrast agent is
injected either subcutaneously or intradermally in the web spaces of the hand or foot, which is taken up into
the lymphatic vessels and allows them to be visualised with high resolution fat-suppressed T1-weighted
sequences [2,6,13,15,19,24,25,27,29] . Imaging acquisition is performed at either 5 min or 10 min intervals following
contrast administration [2,6,7,14-16,19,26] . The lymphatics can be seen approximately 7 to 15 min after contrast
injection [26,29] . However, they tend to show better enhancement in the later phase (35-55 min after
injection) [16,26] . The size of the paramagnetic macromolecules is key to their preferential uptake in the
[21]
lymphatic system and should be larger than 6-10 nm .

The most common agent used in the included articles was gadopentetate dimeglumine, although there are
[2]
currently 9 gadolinium-based contrast agents (GBCAs) commercially available . These gadolinium-based
agents are water-soluble, not subject to metabolism, and are excreted unchanged via the kidneys, therefore
causing minor tissue damage, and are widely used with very few adverse effects reported in patients with
normal renal function [2,3,14,16,18,23] . Gadopentetate dimeglumine was also reported to have benefits including its
[6]
thermal stability, high relaxivity, and potential for weak protein binding . However, it is noted that moving
forward from 2019, linear contrast agents, such as gadopentate dimeglumine, are no longer used due to
reports of gadolinium deposition in organs. Therefore, macrocyclic agents should be used from this point
onwards.

Local anaesthetic is commonly mixed with the contrast to reduce pain at the injection site [1-3,7,15,18,24,30] .
Although there is no consensus between the articles for which method of contrast administration is
preferred, the subcutaneous injection may result in more contrast uptake in blood vessels rather than
lymphatic vessels [7,14] . Massaging the injection site has been shown to enhance contrast uptake into the
lymphatic system. The scan typically takes 20-50 min to obtain adequate imaging for upper limb studies and
up to 1.5 h for the lower limb, during which the patient must remain still in the MRI machine [3,8,15,23]
[Figure 1].

Gadolinium-enhanced T1-weighted sequences have been shown to provide higher spatial resolution, higher
signal-to-noise ratio, and fewer artefacts than the non-contrast T2-weighted sequences. However, the range
of visualised lymphatic pathways may be limited by the location of the injection site . Contrast-enhanced
[14]
MRL appears to be optimal for evaluating distal lymphatic vessels, whereas non-contrast MRL may be
superior for evaluating proximal and deeper lymphatic trunks [19,31] . Lohrmann et al. reported that 92% of
[16]
lymphatic vessels in the lower leg were visualised after contrast injection, whereas only 54% of lymphatic
vessels in the upper leg in the same patients were seen. Several papers suggest that a combination of the two
scans should be performed to provide clinicians with a complete assessment [2,6,7,14,17,31] .

MR venogram
Venous contamination during contrast-enhanced MRL poses difficulty in interpreting images, as some of
the contrast administered subcutaneously will be absorbed into the venous system. Lohrmann et al. [16,26]
reported that 100% of patients studied had concomitant venous enhancement, and Notohamiprodjo et al.
[22]