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Liang et al. Plast Aesthet Res 2019;6:23 I http://dx.doi.org/10.20517/2347-9264.2019.33 Page 5 of 9

injected into the lymphatic vessel dyed by methylene blue. It has been abandoned due to its traumatic
nature, technical complexity, poor repeatability and unacceptable contrast complications. Based on the
uptake of water-soluble non-ionic contrast agents by lymphatics, indirect lymphangiography avoids direct
administration of peripheral lymphatic vessels and has less complications, which is considered to be the
best way to differentiate between lipedema and lymphedema.

Magnetic resonance lymphangiography (MRL) involves the subcutaneous/intradermal injection of
gadolinium-based MR contrast agents, such as gadobenate dimeglumine, gadoterate meglumine etc. into
the 4 interdigital web spaces of the hand or foot, with 1% lidocaine as anesthetic. Recommended contrast
volume is 1 ml for each site. A 3D heavily T2-weighted sequence or a 3D steady-state free precession
[22]
balanced sequence is performed to assess the distribution and extent of edema before injection. Then a
fat-suppressed T1-weighted 3D spoiled gradient-echo (SPGR) is used for the lymphatic visualization before
and after injection. The number of phase acquisitions and interval varies [22-24] . A 3D workstation with
multiplanar reformations, maximum intensity projection reconstructions and the 3D cursor facilitates image
analysis. MRL depicts lymphatic channels, lymph nodes and drainage pattern with supplemental information
[25]
[24]
including fat deposition, muscle compartments and limb volume. Bae et al. and Neligan et al. suggested
excellent correlation of MRL with lymphoscintigraphy and ICG lymphography respectively. MRL allows for
early recognition, full assessment of lymphedema status and surgical planning especially LVA. Compared to
lymphoscintigraphy and ICG lymphography, it is free of radiation and depicts deeper lymphatic channels
with higher resolution. Though an extra MR venogram or intravenous administration of Ferumoxytol can
help differentiate lymphatic vessels from veins, venous contamination could be a major obstacle in image
interpretation. Furthermore, MRL is costly and potentially patient-unfriendly, because it requires patients
to stay in the prone or supine position for up to 2 h (the examination duration).

Tissue dielectric constant measurements
Tissue dielectric constant (TDC) is proven to be proportional to local skin-to-fat water content. The
Moisture Meter D or its compact version transmits an 300 MHz electromagnetic wave into the tissue and
displays absolute TDC values or a percentage of local tissue water, after automatically processing reflected
signal. It takes no more than 10 s for each measurement point. TDC ratio (TDC affected/TDC unaffected)
[26]
> 1.26 is considered suggestive of lymphedema by some . It can be applied in virtually any areas, midline
body regions included, for post-treatment monitoring and early detection. However, TDC is influenced by
[27]
skin thickness, gender, age, body mass index or race , thus comparison between groups should be dealt
[28]
with caution and diagnostic threshold is still debatable. In a study by Bakar et al. specificity was 94% with
[28]
only 65% sensitivity .
Bioelectrical impedance spectroscopy
Bioelectrical impedance spectroscopy (BIS) utilizes a low frequency current to measure electrical resistance
(R ) of local tissue, which inversely proportional to the volume of extracellular fluid volume. For unilateral
0
lymphoedema, the index R unaffected/ R affected is commonly used, the larger the ratio the greater the
0
0
differences in excess extracellular fluid between limbs. Diagnostic cut-off values varies for non/dominant
limbs due to natural asymmetry. The R/R ratio is the widely accepted BIS index for bilateral lymphoedema,
0
i
which R means the resistance of the unaffected body region with similar tissue compositon as the region
i
of interest. BIS examination only takes a few seconds and rarely causes adverse effects. It is uninfluenced
by BMI and reliable in predicting onset up to 10 months prior to clinical manifestation [29,30] . Sensitivity and
[31]
specificity for BIS were 64% and 100%,respectively . However BIS’s less sensitive in diagnosing fibrotic
lymphedema and breast or trunk measurement is limited. Extra caution should be taken when it comes to
patients with pregnancy, cardiac pacemaker or other implanted medical devices.