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Page 4 of 9 Liang et al. Plast Aesthet Res 2019;6:23 I http://dx.doi.org/10.20517/2347-9264.2019.33

tracer used in lymphoscintigraphy rarely causes the allergy and pulmonary embolism, so it’s safe and
relatively minimally invasive.

Despite its distinct advantages, the protocol of lymphoscintigraphy is poorly standardized, such as the
amount of the labeled particles and the injection volume, which substantially affect the quantitative
parameters and hinders comparisons between studies. Injection site is also one of the major debates.
[11]
Tartaglione et al. suggested intermetatarsal or intermetacarpal spaces injection, as compared with
traditional interdigital area, results in rapid uptake of tracers, improved imaging quality and reduced
[11]
examination time (average time 4 h reduced to < 1 h) . Though combined with computed tomography
(CT) or SPECT, spatial resolution of lymphoscintigraphy images improves, it is still far from enough and
[14]
limited for detection of the small lymphatic vessel leaks . Owing to discontinuous image acquisition,
diagnostic events could happen between acquisition points and be missed. Irradiation is the frequent
concern raised in many studies. Though, no cutaneous radio-necrosis has been reported, extra precautions
still needs to be taken concerning pregnant and breastfeeding women.

Lympho-fluoroscopies
Lympho-fluoroscopies applies fluorescent molecules such as indocyanine green (ICG), methylene blue
etc. as the imaging agent. ICG lymphography encompasses the subcutaneous injection of ICG, the usual
amount being 0.2 mL. Common injection sites include webspaces of the hand or foot, the medial and/or
lateral border of the Achilles tendon, the ulnar side of the palmaris longus tendon at the wrist level [15,16] .
Different near-infrared camera devices are used 12-24 h after injection to record the light emitted by ICG
thus visualizing the collecting lymphatic vessels. Linear pattern represents normal or mildly impeded
lymphatic collector function, while dermal backflow pattern including splash, stardust of diffuse pattern
indicates lymphedema. ICG lymphography is deemed to be the most valuable tool for superficial lymphatics
imaging. Compared to lymphoscintigraphy, ICG lymphography is not irradiating with similar sensitivity
[18]
[17]
and specificity (97% and 92% ) but superior resolution and at lower cost. Yamamoto et al. suggested
in their study when utilizing ICG lymphography to select optimal sites for LVA, the overall lymphatic
[18]
vessel detection rate, confirmed by intraoperative findings, is 96.1% . ICG lymphography can be used for
[19]
early recognition of lymphedema, as some patients without symptoms can still show abnormal images .
However, ICG lymphography is time consuming and operator dependent. It’s unable to observe lymphatics
where the tissue is thicker than 2 cm, limiting its possible application in the trunk area and obese patients.
Quantification might be more difficult compared to lymphoscintigraphy due to the injection of free ICG
(the amount, the concentration etc.). Potential toxicity in the lymphatic vessels and its persistence after
subcutaneous injection raise some concern because of the lack of studies about its side effects.

The fluorescein used in fluorescence microlymphography (FML) is fluorescein isothiocyanate (FITC)-
labeled dextran. 0.1 mL of 25% FITC-labeled dextran solution dissolved by 0.9% sodium or potassium
chloride solution is injected into the intradermal layer of the forearm, toes or even the face with a
[20]
tuberculin syringe and a 25-gauge needle . Under A fluorescent light microscope, a network of lymphatic
becomes visible as the dye spreads through the lymphatics. 10 min after injection, the distance between the
border of the injection site and the furthest visible lymphatics is measured in four directions. The maximum
extension distance in healthy limbs should not exceed 14 mm. Sensitivity and specificity for the 14 mm cut
[21]
[20]
off level is 91.4% and 85.7% . Sensitivity was higher in the secondary vs. primary lymphedema . FML
could be used near venous ulcers or indurated skin and rarely cause allergy or other major side effects.
However, deeper lymphatic vessels cannot be visualized by FML.

Lymphangiography
Lymphangiography applies various contrast medium and imaging systems to depict lymphatic structures.
In direct contrast x-ray lymphangiography, liposoluble contrast medium, such as iodine is directly