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Lymphatic · Lymphoedema

Lymphoedema & Lymphatic Imaging

Snapshot

Lymphoscintigraphy images lymph transport after a ⁹⁹ᵐTc-labelled colloid is injected into the web spaces of the hands or feet. It confirms that a swollen limb is lymphoedema (sensitivity 92%, specificity 100% against other causes of oedema in the Mayo series), shows the pattern (delayed transport, dermal backflow, collateral routes, reduced or absent nodes) and can be scored with a semi-quantitative transport index. The 2023 International Society of Lymphology (ISL) consensus notes that it has replaced oil-contrast lymphography wherever nuclear medicine is available.

Colloid particles of a few tens of nanometres, injected into the skin or subcutis, can leave only through lymphatics, so their movement measures lymph transport. When transport fails, lymph refluxes into dermal lymphatics (dermal backflow), reroutes through collaterals or the deep system, and nodes fill late, faintly or not at all.

TI ≥ 10Abnormal transport index
Dermal backflowHallmark of failed transport
Se 92% / Sp 100%Lymphoedema v other oedema
Reference values
  • Tracers: ⁹⁹ᵐTc-nanocolloid (human albumin, ≥ 95% of particles 20–80 nm) in Europe; filtered ⁹⁹ᵐTc-sulfur colloid in the US; ⁹⁹ᵐTc-human serum albumin. ⁹⁹ᵐTc-tilmanocept is licensed for lymphatic mapping in cancer.
  • Activity: 30–50 MBq per limb per compartment in 0.1–0.2 mL aliquots with a 25-G needle (Genoa protocol); protocols of about 9 MBq per injection in 0.05–0.1 mL are also used (Szuba 2003).
  • Imaging: dynamic for about 20 min, then static images at 30 min, 2 h and, if needed, 4 h, with standardised exercise in between (Genoa protocol).
  • Transport index (Kleinhans 1985) = K + D + 0.04T + N + V: kinetics, distribution, node appearance time (min), node and vessel visualisation, each of K, D, N, V scored 0, 3, 5 or 9. Range 0–45; normal < 10.
  • ISL severity by excess limb volume: minimal > 5 to < 20%, moderate 20–40%, severe > 40%.
Worked example

Scoring a transport index

Given. Left leg, 2 h after web-space injection: transport clearly slower than the right (marked delay); diffuse dermal backflow in the calf; faint inguinal nodes first seen at 60 min; lymph vessels barely visible.

  1. K (kinetics): marked delay = 5.
  2. D (distribution): diffuse dermal backflow = 5.
  3. T: 0.04 × 60 min = 2.4.
  4. N (nodes): barely visible = 5; V (vessels): barely visible = 5.
  5. TI = 5 + 5 + 2.4 + 5 + 5 = 22.4.

Answer. TI 22.4 (normal < 10): lymphatic insufficiency of the left leg. Repeat with the same tracer, injection and exercise protocol if the index is to be followed after treatment.

When to use

  • A swollen limb of uncertain cause: lymphoedema versus venous oedema, lipoedema or systemic oedema. In early lipoedema lymphoscintigraphy is generally normal (ISL 2023).
  • Primary lymphoedema in children and adults: the pattern supports the clinical and genetic classification (Connell 2013).
  • Secondary lymphoedema after node dissection, radiotherapy or infection, including latent (stage 0) disease in an at-risk limb.
  • Before and after lymphatic surgery: lymphaticovenous anastomosis (LVA), vascularised lymph node transfer (VLNT) or lymph vessel transplantation.

ISL 2023 staging

  • Stage 0: latent or subclinical; transport is impaired but there is no swelling yet.
  • Stage I: early accumulation of protein-rich fluid that subsides with elevation; pitting may occur.
  • Stage II: elevation alone rarely reduces the swelling and pitting is manifest; late in stage II the limb may not pit as fat and fibrosis develop.
  • Stage III: lymphostatic elephantiasis, with trophic skin changes (acanthosis, thickening, warty overgrowths) and often no pitting.
  • A limb may show more than one stage, and the stages describe only the physical state; there is no agreed imaging-based staging yet.

Protocol

  • Inject both limbs for comparison: first (and second) interdigital web spaces of the feet or hands. Colloids work best subcutaneously; intradermal injection of albumin gives faster transport.
  • Two-compartment protocols add subfascial injections (behind the lateral malleolus, in the plantar aponeurosis or under the ulnar styloid) to study the deep lymphatics.
  • Standardise exercise between early and delayed images (walking, an exercise bike, or squeezing a rubber ball): inactivity slows transport and mimics disease.
  • SPECT/CT gives 3-D localisation of nodes, collaterals and leaks in the pelvis, axilla or trunk.
  • Keep tracer, injection depth, timing and exercise identical for serial studies; each changes the transport index.

How to read it

  • Normal: discrete linear channels, symmetrical and timely inguinal or axillary nodes, little dermal activity.
  • Lymphoedema: slow clearance from the injection site; delayed, faint or absent nodes; dermal backflow; collateral channels; 'in-transit' nodes; popliteal nodes after web-space injection in the foot (rerouting to the deep system).
  • Primary patterns: aplasia or hypoplasia (little tracer leaves the injection site, few vessels) versus hyperplasia with reflux (many dilated channels). In Milroy disease (FLT4/VEGFR3) little or no tracer is transported.
  • Lymphoscintigraphy does not reliably separate primary from secondary disease, and recent cellulitis delays transport (Gloviczki 1989); interpret with the history.
  • Record the transport index or a structured description for both limbs.

Before lymphatic surgery

  • LVA needs functioning collecting lymphatics distal to the obstruction: scintigraphy confirms residual transport, and ICG (near-infrared) lymphography maps superficial channels for the incisions.
  • VLNT can cause donor-site lymphoedema; reverse lymphatic mapping, which identifies the nodes that drain the donor limb so they can be spared, reduces the risk (ISL 2023).
  • Follow-up: after autologous lymph vessel transplantation the mean index fell from 31.1 to 25.2 and limb volume from 3423 to 2580 mL (Kleinhans 1985). Scintigraphy supports selection and follow-up but does not prove that an anastomosis is patent.
In depth
  • Kleinhans 1985: five visually scored criteria gave a transport index with 97.4% sensitivity and 90.3% specificity in 122 studies, and interobserver correlation r = 0.96 in 179.
  • Gloviczki 1989 (Mayo, 190 limbs in 115 patients, ⁹⁹ᵐTc-antimony trisulfide colloid): sensitivity 92% and specificity 100% for lymphoedema against other oedema, but no consistent distinction between primary and secondary.
  • The ISL notes that lymphoscintigraphy is still not standardised (tracers, activities, volumes, injection depth, exercise, timing), so compare only like with like.
  • Particle size matters: albumin and very small particles clear quickly from the injection site, larger colloids slowly, so the tracer must be fixed for a department and never mixed within serial studies.
  • ICG (near-infrared fluorescence) lymphography shows only the superficial lymphatics and is used mainly to plan and guide surgery; MR lymphography shows deep anatomy, including the thoracic duct; lymphoscintigraphy remains the functional whole-limb test.
  • The multisociety appropriate use criteria for lymphoscintigraphy (2022; 11 societies) include clinical scenarios for lymphoedema and lipoedema, with paediatric considerations.

Sources: Kleinhans 1985 (PMID 4006977) · Gloviczki 1989 (PMID 2724456) · ISL consensus 2023 (PMID 39207406) · Genoa protocol, Villa 2019 (PMID 30828401) · AUC summary, Donohoe 2023 (PMID 36958856)

Sources

  1. Executive Committee of the International Society of Lymphology. The diagnosis and treatment of peripheral lymphedema: 2023 consensus document of the International Society of Lymphology. Lymphology. 2023;56:133–51.
  2. Kleinhans E, Baumeister RG, Hahn D, et al. Evaluation of transport kinetics in lymphoscintigraphy: follow-up study in patients with transplanted lymphatic vessels. Eur J Nucl Med. 1985;10:349–52.
  3. Szuba A, Shin WS, Strauss HW, Rockson S. The third circulation: radionuclide lymphoscintigraphy in the evaluation of lymphedema. J Nucl Med. 2003;44:43–57.
  4. Villa G, Campisi CC, Ryan M, et al. Procedural recommendations for lymphoscintigraphy in the diagnosis of peripheral lymphedema: the Genoa protocol. Nucl Med Mol Imaging. 2019;53:47–56.
  5. Gloviczki P, Calcagno D, Schirger A, et al. Noninvasive evaluation of the swollen extremity: experiences with 190 lymphoscintigraphic examinations. J Vasc Surg. 1989;9:683–9.
  6. Donohoe KJ, Carroll BJ, Chung DKV, et al. Summary: appropriate use criteria for lymphoscintigraphy in sentinel node mapping and lymphedema/lipedema. J Nucl Med. 2023;64:525–8.
  7. Connell FC, Gordon K, Brice G, et al. The classification and diagnostic algorithm for primary lymphatic dysplasia: an update from 2010 to include molecular findings. Clin Genet. 2013;84:303–14.
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