Towards Clinically Useful Quantitative Lymphoscintigraphy: A Scoping Review

Juliana H. Kim; Sina Oh; Alex Heglin; Jaewon Yang; Orhan K. Öz; Robert C. Sibley

doi:10.3390/lymphatics4020020

journal article Open Access Apr 14, 2026

Towards Clinically Useful Quantitative Lymphoscintigraphy: A Scoping Review

Juliana H. Kim

Sina Oh

Alex Heglin Jaewon Yang

Orhan K. Öz

Robert C. Sibley

Lymphatics Vol. 4 No. 2 pp. 20 · MDPI AG

View at Publisher Save 10.3390/lymphatics4020020

Abstract

Lymphedema is a chronic condition marked by swelling in the body’s soft tissues due to impaired or damaged lymphatic function. Lymphedema is estimated to affect about 1 in 1000 in the United States and 1.4 per 1000 based on two European studies. Lymphedema diagnosis relies on clinical visual assessment by physicians, and the quantitative evaluation of lymphatic function is not widely employed due to the lack of standardized and validated metrics. Lymphoscintigraphy is considered the practical gold standard for evaluating lymphedema. With the emergence of advanced surgical therapies, there is a growing demand for quantitative evaluation metrics to objectively evaluate treatment response. To address this unmet need, we reviewed various methods of quantitative lymphoscintigraphy (qLSG) that were used for assessing lymphedema. We found that multiple qLSG approaches have been described. Moreover, the protocols vary widely in terms of tracer type, injection route, dosage, and exercise interventions. We compared the quantitative assessment strategies and highlighted the approaches that may help provide a more objective lymphedema diagnosis and follow-up.

Topics

No keywords indexed for this article. Browse by subject →

References

92

[1]

Greene, A.K. (2015). Epidemiology and Morbidity of Lymphedema. Lymphedema, Springer. 10.1007/978-3-319-14493-1

[2]

Rockson "Estimating the population burden of lymphedema" Ann. N. Y. Acad. Sci. (2008) 10.1196/annals.1413.014

[3]

Rockson "Comorbidity and Lymphatic Disease: The Lymphatic Continuum Re-Examined" Lymphat. Res. Biol. (2021) 10.1089/lrb.2021.0001

[4]

Schaverien "New and Emerging Treatments for Lymphedema" Semin. Plast. Surg. (2018) 10.1055/s-0038-1635116

[5]

Tian "Leukotriene B4 antagonism ameliorates experimental lymphedema" Sci. Transl. Med. (2017) 10.1126/scitranslmed.aal3920

[6]

Hassanein "Diagnostic Accuracy of Lymphoscintigraphy for Lymphedema and Analysis of False-Negative Tests" Plast. Reconstr. Surg. Glob. Open (2017) 10.1097/gox.0000000000001396

[7]

Donohoe "Appropriate Use Criteria for Lymphoscintigraphy in Sentinel Node Mapping and Lymphedema/Lipedema" J. Nucl. Med. (2023) 10.2967/jnumed.123.265560

[8]

Figueroa "Lymphoscintigraphy versus Indocyanine Green Lymphography—Which Should Be the Gold Standard for Lymphedema Imaging?" Lymphatics (2023) 10.3390/lymphatics1010004

[9]

Minimally invasive method for the point-of-care quantification of lymphatic vessel function

Anna K. Polomska, Steven T. Proulx, Davide Brambilla et al.

JCI Insight 2019 10.1172/jci.insight.126515

[10]

Pappalardo "Lymphoscintigraphy for the diagnosis of extremity lymphedema: Current controversies regarding protocol, interpretation, and clinical application" J. Surg. Oncol. (2020) 10.1002/jso.25526

[11]

Mihara, M., Hara, H., Araki, J., Kikuchi, K., Narushima, M., Yamamoto, T., Iida, T., Yoshimatsu, H., Murai, N., and Mitsui, K. (2012). Indocyanine green (ICG) lymphography is superior to lymphoscintigraphy for diagnostic imaging of early lymphedema of the upper limbs. PLoS ONE, 7. 10.1371/journal.pone.0038182

[12]

PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation

Andrea C. Tricco, Erin Lillie, Wasifa Zarin et al.

Annals of Internal Medicine 2018 10.7326/m18-0850

[13]

The Measurement of Observer Agreement for Categorical Data

J. Richard Landis, Gary G. Koch

Biometrics 1977 10.2307/2529310

[14]

Stewart "Isotope lymphography: A new method of investigating the role of the lymphatics in chronic limb oedema" Br. J. Surg. (1985) 10.1002/bjs.1800721120

[15]

Vaqueiro "Lymphoscintigraphy in lymphedema: An aid to microsurgery" J. Nucl. Med. (1986)

[16]

Carena "Quantitative lymphoscintigraphy" Eur. J. Nucl. Med. (1988) 10.1007/bf00253447

[17]

Weissleder "Lymphedema—Evaluation of Qualitative and Quantitative Lymphoscintigraphy in 238 Patients" Radiology (1988) 10.1148/radiology.167.3.3363131

[18]

Baulieu "Factorial analysis of dynamic lymphoscintigraphy in lower limb lymphoedema" Nucl. Med. Commun. (1989) 10.1097/00006231-198902000-00005

[19]

Baulieu "Factorial analysis in radionuclide lymphography: Assessment of the effects of sequential pneumatic compression" Lymphology (1989)

[20]

Rijke "Lymphoscintigraphy and Lymphedema of the Lower-Extremities" J. Nucl. Med. (1990)

[21]

Brautigam "The importance of the subfascial lymphatics in the diagnosis of lower limb edema: Investigations with semiquantitative lymphoscintigraphy" Angiology (1993) 10.1177/000331979304400606

[22]

Bull "Abnormal lymph drainage in patients with chronic venous leg ulcers" J. Am. Acad. Dermatol. (1993) 10.1016/0190-9622(93)70078-8

[23]

Liu "The influence of local hyperthermia on lymphedema and lymphedematous skin of the human leg" Lymphology (1993)

[24]

Freedman "Abnormal lymphatic function in presymptomatic bancroftian filariasis" J. Infect. Dis. (1995) 10.1093/infdis/171.4.997

[25]

Bull "Lymphatic function in the yellow nail syndrome" Br. J. Dermatol. (1996) 10.1111/j.1365-2133.1996.tb07619.x

[26]

Harwood "Lymphatic and venous function in lipoedema" Br. J. Dermatol. (1996) 10.1046/j.1365-2133.1996.d01-741.x

[27]

Pecking "Efficacy of Daflon 500 mg in the treatment of lymphedema (secondary to conventional therapy of breast cancer)" Angiology (1997) 10.1177/000331979704800115

[28]

Brautigam "Analysis of lymphatic drainage in various forms of leg edema using two compartment lymphoscintigraphy" Lymphology (1998)

[29]

Svensson "Measurement of lymphatic function with technetium-99m-labelled polyclonal immunoglobulin" Eur. J. Nucl. Med. (1999) 10.1007/s002590050418

[30]

Stanton "Differences in lymph drainage between swollen and non-swollen regions in arms with breast-cancer-related lymphoedema" Clin. Sci. (2001) 10.1042/cs1010131

[31]

Suga "Assessment of leg oedema by dynamic lymphoscintigraphy with intradermal injection of technetium-99m human serum albumin and load produced by standing" Eur. J. Nucl. Med. (2001) 10.1007/s002590000418

[32]

Pain "Quantification of lymphatic function for investigation of lymphedema: Depot clearance and rate of appearance of soluble macromolecules in blood" J. Nucl. Med. (2002)

[33]

Szuba "Quantitative radionuclide lymphoscintigraphy predicts outcome of manual lymphatic therapy in breast cancer-related lymphedema of the upper extremity" Nucl. Med. Commun. (2002) 10.1097/00006231-200212000-00004

[34]

Pain "Side-to-side symmetry of radioprotein transfer from tissue space to systemic vasculature following subcutaneous injection in normal subjects and patients with breast cancer" Eur. J. Nucl. Med. Mol. Imaging (2003) 10.1007/s00259-003-1135-z

[35]

Stanton "Impairment of lymph drainage in subfascial compartment of forearm in breast cancer-related lymphedema" Lymphat. Res. Biol. (2003) 10.1089/153968503321642615

[36]

Gothard "Non-randomised phase II trial of hyperbaric oxygen therapy in patients with chronic arm lymphoedema and tissue fibrosis after radiotherapy for early breast cancer" Radiother. Oncol. (2004) 10.1016/s0167-8140(03)00235-4

[37]

Rose "Finding an optimal method for imaging lymphatic vessels of the upper limb" Eur. J. Nucl. Med. Mol. Imaging (2004) 10.1007/s00259-003-1399-3

[38]

Pain "Tissue-to-blood transport of radiolabelled immunoglobulin injected into the web spaces of the hands of normal subjects and patients with breast cancer-related lymphoedema" J. Vasc. Res. (2004) 10.1159/000077289

[39]

Pain "Variation in lymphatic function may predispose to development of breast cancer-related lymphoedema" Eur. J. Surg. Oncol. (2004) 10.1016/j.ejso.2004.02.008

[40]

Pain "Local vascular access of radioprotein injected subcutaneously in healthy subjects and patients with breast cancer-related lymphedema" J. Nucl. Med. (2004)

[41]

Modi "Regional distribution of epifascial swelling and epifascial lymph drainage rate constants in breast cancer-related lymphedema" Lymphat. Res. Biol. (2005) 10.1089/lrb.2005.3.3

[42]

Perez "Lymphscintigraphic evaluation of manual lymphatic drainage for lower extremity lymphedema" Lymphology (2006)

[43]

Solanki "Imaging of lymphatic vessels in breast cancer-related lymphedema: Intradermal versus subcutaneous injection of 99mTc-immunoglobulin" AJR Am. J. Roentgenol. (2006) 10.2214/ajr.04.1341

[44]

Stanton "A quantitative lymphoscintigraphic evaluation of lymphatic function in the swollen hands of women with lymphoedema following breast cancer treatment" Clin. Sci. (2006) 10.1042/cs20050277

[45]

Szuba "Presence of functional axillary lymph nodes and lymph drainage within arms in women with and without breast cancer-related lymphedema" Lymphology (2007)

[46]

Celebioglu "Lymph drainage studied by lymphoscintigraphy in the arms after sentinel node biopsy compared with axillary lymph node dissection following conservative breast cancer surgery" Acta Radiol. (2007) 10.1080/02841850701305440

[47]

Lane "Upper extremity lymphatic function at rest and during exercise in breast cancer survivors with and without lymphedema compared with healthy controls" J. Appl. Physiol. (2007) 10.1152/japplphysiol.00077.2007

[48]

Modi "Human lymphatic pumping measured in healthy and lymphoedematous arms by lymphatic congestion lymphoscintigraphy" J. Physiol. (2007) 10.1113/jphysiol.2007.130401

[49]

Dabrowski "Optimized lymphoscintigraphy and diagnostics of lymphatic oedema of the lower extremities" Nucl. Med. Rev. (2008)

[50]

Damstra "Erysipelas as a sign of subclinical primary lymphoedema: A prospective quantitative scintigraphic study of 40 patients with unilateral erysipelas of the leg" Br. J. Dermatol. (2008) 10.1111/j.1365-2133.2008.08503.x

Showing 50 of 92 references

Metrics

0

Citations

92

References

Details

Published: Apr 14, 2026
Vol/Issue: 4(2)
Pages: 20
License: View

Authors

J

Juliana H. Kim