Диагностика и визуализация лимфатической системы в клинической практике

Визуализация лимфатической системы в течение десятков лет ограничивалась лимфосцинтиграфией и чрессосудистой лимфангиографией под рентгеновским излучением. Данные методы не позволяют получить информацию о состоянии центральных крупных лимфатических коллекторах и сосудах.

Получение изображений центрального звена лимфатических путей при помощи рентгенологического исследования стало возможным благодаря введению контрастного вещества через лимфатический сосуд на стопе. Выраженная вариантная анатомия дистального лимфатического русла и технические сложности при выделении такого сосуда в хирургической ране затрудняют выполнение этих методов.

Применение техники интранодального введения контрастных веществ в лимфатическую систему вкупе с магнитно-резонансной томографией (МРТ) привело к разработке лимфангиографии с МРТ-динамическим контрастированием, которая обеспечивает исключительную возможность визуализации центральной лимфатической системы.

Ввиду физических свойств, в первую очередь вязкости контрастного вещества на масляной основе, визуализация центральной лимфатической системы может быть неадекватной без МРТ.

Также остаётся актуальным вопрос разработки надёжного способа доставки препарата в лимфатическое русло, что требует хирургического подхода к задаче. Роль лимфангиографии в качестве диагностического и лечебного метода до сих пор не определена. Большое число пациентов с хилотораксом и хилоперитонеумом (до 4% при торакальных вмешательствах) как ятрогенной, так и идиопатической этиологии (до 14%) делают лимфангиографию перспективным методом в лечении и диагностики с целью планирования доступа и объёма операции при неэффективности консервативного лечения.

1. Hsu MC, Itkin M. Lymphatic Anatomy. Tech Vasc Interv Radiol. 2016;19(4):247–254. PMID: 27993319 https://doi.org/10.1053/j.tvir.2016.10.003

2. Lee EW, Shin JH, Ko HK, Park J, Kim SH, Sung KB. Lymphangiography to treat postoperative lymphatic leakage: a technical review. Korean J Radiol. 2014;15(6):724–732. PMID: 25469083 https://doi.org/10.3348/kjr.2014.15.6.724

3. Kortes N, Radeleff B, Sommer CM, Bellemann N, Ott K, Richter GM, et al. Therapeutic lymphangiography and CT-guided sclerotherapy for the treatment of refractory lymphatic leakage. J Vasc Interv Radiol. 2014;25(1):127–132. PMID: 24262033 https://doi.org/10.1016/j.jvir.2013.10.011

4. Itkin M, Nadolski GJ. Modern Techniques of Lymphangiography and Interventions: Current Status and Future Development. Cardiovasc Intervent Radiol. 2018;41(3):366–376. PMID: 29256071 https://doi.org/10.1007/s00270-017-1863-2

5. Threefoot SA, Kent WT, Hatchett BF. Lymphaticovenous and lymphaticolymphatic communications demonstrated by plastic corrosion models of rats and by postmortem lymphangiography in man. J Lab Clin Med. 1963;61:9–22. PMID: 13981287

6. Momose M, Kawakami S, Koizumi T, Yoshida K, Kanda S, Kondo R, et al. Lymphoscintigraphy using technetium-99m HSA-DTPA with SPECT/CT in chylothorax after childbirth. Radiat Med. 2008;26(8):508–511. PMID: 18975054 https://doi.org/10.1007/s11604-008-0265-4

7. Wagayama H, Tanaka T, Shimomura M, Ogura K, Shiraki K. Pancreatic cancer with chylous ascites demonstrated by lymphoscintigraphy: successful treatment with peritoneovenous shunting. Dig Dis Sci. 2002;47(8):1836–1838. PMID: 12184538 https://doi.org/10.1023/a:1016461015632

8. Kinuya S, Taki J, Nakajima K, Kinuya K, Haji K, Michigishi T, et al. Inguinoscrotal lymphatic reflux detected by lymphoscintigraphy. Ann Nucl Med. 1996;10(3):351–352. PMID: 8883714 https://doi.org/10.1007/BF03164745

9. Seo Y, Shuke N, Yamamoto W, Usui K, Aburano T. Ruptured lymphocele as a cause of chylous ascites: demonstration by lymphoscintigraphy. Clin Nucl Med. 1999;24(1):60–61. PMID: 9890497 https://doi.org/10.1097/00003072-199901000-00014

10. Bluemel C, Herrmann K, Giammarile F, Nieweg OE, Dubreuil J, Testori A, et al. EANM practice guidelines for lymphoscintigraphy and sentinel lymph node biopsy in melanoma. Eur J Nucl Med Mol Imaging. 2015;42(11):1750–1766. PMID: 26205952 https://doi.org/10.1007/s00259-015-3135-1

11. Fearn NR, Dylke ES, Bailey D, Kilbreath SL. Lymphoscintigraphy as an Outcome Measurement for Conservative Upper Limb Lymphedema Treatments: A Systematic Review. Lymphat Res Biol. 2022;20(3):248–259. PMID: 34748419 https://doi.org/10.1089/lrb.2021.0050

12. van Schaik CJ, Boer LL, Draaisma JMT, van der Vleuten CJM, Janssen JJ, Fütterer JJ, et al. The lymphatic system throughout history: From hieroglyphic translations to state of the art radiological techniques. Clin Anat. 2022;35(6):701–710. PMID: 35383381 https://doi.org/10.1002/ca.23867

13. Skanjeti A, Dhomps A, Paschetta C, Tordo J, Delgado Bolton RC, Giammarile F. Lymphoscintigraphy for Sentinel Node Mapping in Head and Neck Cancer. Semin Nucl Med. 2021;51(1):39–49. PMID: 33246538 https://doi.org/10.1053/j.semnuclmed.2020.07.004

14. Mahieu R, Krijger GC, Ververs FFT, de Roos R, de Bree R, de Keizer B. [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy: a novel technique for sentinel lymph node imaging. Eur J Nucl Med Mol Imaging. 2021;48(4):963–965. PMID: 33159222 https://doi.org/10.1007/s00259-020-05101-5

15. West NJ, Wadhwa S, Ayars C, Philips P, Martin RCG 2nd, Scoggins CR, et al. Interval Sentinel Lymph Nodes with the Use of Routine Lymphoscintigraphy in Extremity Melanoma. J Surg Res. 2024;293:613–617. PMID: 37837816 https://doi.org/10.1016/j.jss.2023.08.055

16. Kuemmel S, Holtschmidt J, Gerber B, Von der Assen A, Heil J, Thill M, et al. Prospective, Multicenter, Randomized Phase III Trial Evaluating the Impact of Lymphoscintigraphy as Part of Sentinel Node Biopsy in Early Breast Cancer: SenSzi (GBG80) Trial. J Clin Oncol. 2019;37(17):1490–1498. PMID: 31042410 https://doi.org/10.1200/JCO.18.02092

17. Hoogendam JP, Veldhuis WB, Hobbelink MG, Verheijen RH, van den Bosch MA, Zweemer RP. P. 99mTc SPECT/CT Versus Planar Lymphoscintigraphy for Preoperative Sentinel Lymph Node Detection in Cervical Cancer: A Systematic Review and Metaanalysis. J Nucl Med. 2015;56(5):675–680. PMID: 25858041 https://doi.org/10.2967/jnumed.114.152439

18. Dori Y. Novel Lymphatic Imaging Techniques. Tech Vasc Interv Radiol. 2016;19(4):255–261. PMID: 27993320 https://doi.org/10.1053/j.tvir.2016.10.002

19. Szuba A, Shin WS, Strauss HW, Rockson S. The third circulation: radionuclide lymphoscintigraphy in the evaluation of lymphedema. J Nucl Med. 2003;44(1):43–57. PMID: 12515876

20. Vaqueiro M, Gloviczki P, Fisher J, Hollier LH, Schirger A, Wahner HW. Lymphoscintigraphy in lymphedema: an aid to microsurgery. J Nucl Med. 1986;27(7):1125–1130. PMID: 3723188

21. Kariya S, Komemushi A, Nakatani M, Yoshida R, Kono Y, Tanigawa N. Intranodal lymphangiogram: technical aspects and findings. Cardiovasc Intervent Radiol. 2014;37(6):1606–1610. PMID: 24722896 https://doi.org/10.1007/s00270-014-0888-z

22. Bae JS, Yoo RE, Choi SH, Park SO, Chang H, Suh M, et al. Evaluation of lymphedema in upper extremities by MR lymphangiography: Comparison with lymphoscintigraphy. Magn Reson Imaging. 2018;49:63–70. PMID: 29306049 https://doi.org/10.1016/j.mri.2017.12.024

23. Pieper CC, Hur S, Sommer CM, Nadolski G, Maleux G, Kim J, et al. Back to the Future: Lipiodol in Lymphography-From Diagnostics to Theranostics. Invest Radiol. 2019;54(9):600–615. PMID: 31283538 https://doi.org/10.1097/RLI.0000000000000578

24. Yoshimatsu R, Yamagami T, Miura H, Matsumoto T. Prediction of therapeutic effectiveness according to CT findings after therapeutic lymphangiography for lymphatic leakage. Jpn J Radiol. 2013;31(12):797–802. PMID: 24158649 https://doi.org/10.1007/s11604-013-0252-2

25. Tabchouri N, Frampas E, Marques F, Blanchard C, Jirka A, Regenet N. Chylous Ascites Management After Pancreatic Surgery. World J Surg. 2017;41(4):1054–1060. PMID: 27778074 https://doi.org/10.1007/s00268-016-3772-y

26. Boffa DJ, Sands MJ, Rice TW, Murthy SC, Mason DP, Geisinger MA, et al. A critical evaluation of a percutaneous diagnostic and treatment strategy for chylothorax after thoracic surgery. Eur J Cardiothorac Surg. 2008;33(3):435–439. PMID: 18207415 https://doi.org/10.1016/j.ejcts.2007.11.028

27. Kawasaki R, Sugimoto K, Fujii M, Miyamoto N, Okada T, Yamaguchi M, et al. Therapeutic effectiveness of diagnostic lymphangiography for refractory postoperative chylothorax and chylous ascites: correlation with radiologic findings and preceding medical treatment. AJR Am J Roentgenol. 2013;201(3):659–666. PMID: 23971461 https://doi.org/10.2214/AJR.12.10008

28. Juszczyk K, Waugh R, Sandroussi C. Lymphangiography as therapeutic management of chylothorax. J Med Imaging Radiat Oncol. 2013;57(4):460–461. PMID: 23870343 https://doi.org/10.1111/j.1754-9485.2012.02452.x

29. Cope C, Salem R, Kaiser LR. Management of chylothorax by percutaneous catheterization and embolization of the thoracic duct: prospective trial. J Vasc Interv Radiol. 1999;10(9):1248–1254. PMID: 10527204 https://doi.org/10.1016/s1051-0443 (99)70227-7

30. Alejandre-Lafont E, Krompiec C, Rau WS, Krombach GA. Effectiveness of therapeutic lymphography on lymphatic leakage. Acta Radiol. 2011;52(3):305–311. PMID: 21498367 https://doi.org/10.1258/ar.2010.090356

31. Gruber-Rouh T, Naguib NNN, Lehnert T, Harth M, Thalhammer A, Beeres M, et al. Direct lymphangiography as treatment option of lymphatic leakage: indications, outcomes and role in patient’s management. Eur J Radiol. 2014;83(12):2167–2171. PMID: 25445897 https://doi.org/10.1016/j.ejrad.2014.09.013

32. Nadolski GJ, Ponce-Dorrego MD, Darge K, Biko DM, Itkin M. Validation of the Position of Injection Needles with Contrast-Enhanced Ultrasound for Dynamic Contract-Enhanced MR Lymphangiography. J Vasc Interv Radiol. 2018;29(7):1028–1030. PMID: 29880296 https://doi.org/10.1016/j.jvir.2018.02.034

33. Wagenpfeil J, Kupczyk PA, Henkel A, Geiger S, Köster T, Luetkens JA, et al. Ultrasound-guided needle positioning for nodal dynamic contrast-enhanced MR lymphangiography. Sci Rep. 2022;12(1):3621. PMID: 35256625 https://doi.org/10.1038/s41598-022-07359-1

34. Nadolski GJ, Itkin M. Feasibility of ultrasound-guided intranodal lymphangiogram for thoracic duct embolization. J Vasc Interv Radiol. 2012;23(5):613–616. PMID: 22440590 https://doi.org/10.1016/j.jvir.2012.01.078

35. Jenner ZB, Li P, Kang L, Goldner BW, Brown CN, Raff GW, et al. Pediatric Intranodal CT Lymphangiography with Water-Soluble Contrast Medium. J Vasc Interv Radiol. 2022;33(11):1440–1443. PMID: 35970504 https://doi.org/10.1016/j.jvir.2022.08.012

36. Kim SW, Hur S, Kim SY, Cho JY, Kwak C, Kim HS, et al. The Efficacy of Lymph Node Embolization Using N-Butyl Cyanoacrylate Compared to Ethanol Sclerotherapy in the Management of Symptomatic Lymphorrhea after Pelvic Surgery. J Vasc Interv Radiol. 2019;30(2):195–202.e1. PMID: 30717950 https://doi.org/10.1016/j.jvir.2018.09.038

37. Kuetting D, Schild HH, Pieper CC. In Vitro Evaluation of the Polymerization Properties of N-Butyl Cyanoacrylate/Iodized Oil Mixtures for Lymphatic Interventions. J Vasc Interv Radiol. 2019;30(1):110–117. PMID: 30527658 3https://doi.org/10.1016/j.jvir.2018.07.028

38. Chovanec V, Drugda J, Lojík M, Vodárek P, Žák P, Hanke I, et al. Chylothorax treatment with thoracic duct embolization. Rozhl Chir. 2022;101(12):607–611. PMID: 36759208 https://doi.org/10.33699/PIS.2022.101.12.607-611

39. Majdalany BS, Saad WA, Chick JFB, Khaja MS, Cooper KJ, Srinivasa RN. Pediatric lymphangiography, thoracic duct embolization and thoracic duct disruption: a single-institution experience in 11 children with chylothorax. Pediatr Radiol. 2018;48(2):235–240. PMID: 28956103 https://doi.org/10.1007/s00247-017-3988-5

40. Stecker MS, Fan CM. Lymphangiography for Thoracic Duct Interventions. Tech Vasc Interv Radiol. 2016;19(4):277–285. PMID: 27993323 https://doi.org/10.1053/j.tvir.2016.10.010

41. Biko DM, Dori Y, Savoca M, Krishnamurthy G, Smith CL, Laje P, et al. Pediatric pulmonary lymphatic flow Disorders: Diagnosis and management. Paediatr Respir Rev. 2020;36:2–7. PMID: 31884062 https://doi.org/10.1016/j.prrv.2019.11.002

42. Liu NF, Yan ZX, Wu XF. Classification of lymphatic-system malformations in primary lymphoedema based on MR lymphangiography. Eur J Vasc Endovasc Surg. 2012;44(3):345–349. PMID: 22831870 https://doi.org/10.1016/j.ejvs.2012.06.019

43. Turkbey B, Kobayashi H, Hoyt RF Jr, Choyke PL, Nakajima T, Griffiths GL, et al. Magnetic resonance lymphography of the thoracic duct after interstitial injection of gadofosveset trisodium: a pilot dosing study in a porcine model. Lymphat Res Biol. 2014;12(1):32–36. PMID: 24502282 https://doi.org/10.1089/lrb.2013.0029

44. Mitsumori LM, McDonald ES, Wilson GJ, Neligan PC, Minoshima S, Maki JH. MR lymphangiography: How i do it. J Magn Reson Imaging. 2015;42(6):1465–1477. PMID: 25906741 https://doi.org/10.1002/jmri.24887

45. Dori Y, Zviman MM, Itkin M. Dynamic contrast-enhanced MR lymphangiography: feasibility study in swine. Radiology. 2014;273(2):410–416. PMID: 24988434 https://doi.org/10.1148/radiol.14132616

46. Brownell JN, Biko DM, Mamula P, Krishnamurthy G, Escobar F, Srinivasan A, et al. Dynamic Contrast Magnetic Resonance Lymphangiography Localizes Lymphatic Leak to the Duodenum in Protein-Losing Enteropathy. J Pediatr Gastroenterol Nutr. 2022;74(1):38–45. PMID: 34406998 https://doi.org/10.1097/MPG.0000000000003287

47. Birkhäuser FD, Studer UE, Froehlich JM, Triantafyllou M, Bains LJ, Petralia G, et al. Combined ultrasmall superparamagnetic particles of iron oxide-enhanced and diffusion-weighted magnetic resonance imaging facilitates detection of metastases in normal-sized pelvic lymph nodes of patients with bladder and prostate cancer. Eur Urol. 2013;64(6):953–960. PMID: 23916692 https://doi.org/10.1016/j.eururo.2013.07.032

48. Heesakkers RA, Jager GJ, Hövels AM, de Hoop B, van den Bosch HC, Raat F, et al. Prostate cancer: detection of lymph node metastases outside the routine surgical area with ferumoxtran-10-enhanced MR imaging. Radiology. 2009;251(2):408–414. PMID: 19401573 https://doi.org/10.1148/radiol.2512071018

49. Heesakkers RA, Hövels AM, Jager GJ, van den Bosch HC, Witjes JA, Raat HP, et al. MRI with a lymph-node-specific contrast agent as an alternative to CT scan and lymph-node dissection in patients with prostate cancer: a prospective multicohort study. Lancet Oncol. 2008;9(9):850–856. PMID: 18708295 https://doi.org/10.1016/S1470-2045(08)70203-1

50. Turkbey B, Czarniecki M, Shih JH, Harmon SA, Agarwal PK, Apolo AB, et al. Ferumoxytol-Enhanced MR Lymphography for Detection of Metastatic Lymph Nodes in Genitourinary Malignancies: A Prospective Study. AJR Am J Roentgenol. 2020;214(1):105–113. PMID: 31613660 https://doi.org/10.2214/AJR.19.21264

51. Crescenzi R, Donahue PMC, Hartley KG, Desai AA, Scott AO, Braxton V, et al. Lymphedema evaluation using noninvasive 3T MR lymphangiography. J Magn Reson Imaging. 2017;46(5):1349–1360. PMID: 28245075 https://doi.org/10.1002/jmri.25670

52. Arrivé L, Derhy S, El Mouhadi S, Monnier-Cholley L, Menu Y, Becker C. Noncontrast Magnetic Resonance Lymphography. J Reconstr Microsurg. 2016;32(1):80–86. PMID: 25826439 https://doi.org/10.1055/s-0035-1549133

53. Forte AJ, Boczar D, Huayllani MT, Avila FR, Guliyeva G, Lu X, et al. Use of magnetic resonance imaging lymphangiography for preoperative planning in lymphedema surgery: A systematic review. Microsurgery. 2021;41(4):384–390. PMID: 33710683 https://doi.org/10.1002/micr.30731

54. Lee E, Biko DM, Sherk W, Masch WR, Ladino-Torres M, Agarwal PP. Understanding Lymphatic Anatomy and Abnormalities at Imaging. Radiographics. 2022;42(2):487–505. PMID: 35179984 https://doi.org/10.1148/rg.210104

55. Salehi BP, Sibley RC, Friedman R, Kim G, Singhal D, Loening AM, et al. MRI of Lymphedema. J Magn Reson Imaging. 2023;57(4):977–991. PMID: 36271779 https://doi.org/10.1002/jmri.28496

56. Mihara M, Hara H, Araki J, Kikuchi K, Narushima M, Yamamoto T, et aql. Indocyanine green (ICG) lymphography is superior to lymphoscintigraphy for diagnostic imaging of early lymphedema of the upper limbs. PLoS One. 2012;7(6):e38182. PMID: 22675520 https://doi.org/10.1371/journal.pone.0038182

57. Jørgensen MG, Toyserkani NM, Hansen FCG, Thomsen JB, Sørensen JA. Prospective Validation of Indocyanine Green Lymphangiography Staging of Breast Cancer-Related Lymphedema. Cancers (Basel). 2021;13(7):1540. PMID: 33810570 https://doi.org/10.3390/cancers13071540

58. Pons G, Clavero JA, Alomar X, Rodríguez-Bauza E, Tom LK, Masia J. Preoperative planning of lymphaticovenous anastomosis: The use of magnetic resonance lymphangiography as a complement to indocyanine green lymphography. J Plast Reconstr Aesthet Surg. 2019;72(6):884–891. PMID: 30944074 https://doi.org/10.1016/j.bjps.2019.02.024

59. Guerrini S, Gentili F, Mazzei FG, Gennaro P, Volterrani L, Mazzei MA.Magnetic resonance lymphangiography: with or without contrast? Diagn Interv Radiol. 2020;26(6):587–595. PMID: 33032980 https://doi.org/10.5152/dir.2020.19482

60. Kajita H, Oh A, Urano M, Takemaru M, Imanishi N, Otaki M, et al. Photoacoustic lymphangiography. J Surg Oncol. 2020;121(1):48–50. PMID: 31165483 https://doi.org/10.1002/jso.25575

61. Suzuki Y, Kajita H, Oh A, Urano M, Watanabe S, Sakuma H, et al. Photoacoustic lymphangiography exhibits advantages over nearinfrared fluorescence lymphangiography as a diagnostic tool in patients with lymphedema. J Vasc Surg Venous Lymphat Disord. 2022;10(2):454–462.e1. PMID: 34352419 https://doi.org/10.1016/j.jvsv.2021.07.012

62. Watanabe S, Kajita H, Suzuki Y, Urano M, Otaki M, Sakuma H, et al. Photoacoustic lymphangiography is a possible alternative for lymphedema staging. J Vasc Surg Venous Lymphat Disord. 2022;10(6):1318–1324.e2. PMID: 35995329 https://doi.org/10.1016/j.jvsv.2022.07.012

63. Sukhbaatar A, Mori S, Sugiura T, Kodama T. Docetaxel administered through a novel lymphatic drug delivery system (LDDS) improved treatment outcomes for lymph node metastasis. Biomed Pharmacother. 2024;171:116085. PMID: 38171241 https://doi.org/10.1016/j.biopha.2023.116085

64. Sukhbaatar A, Mori S, Kodama T. Intranodal delivery of modified docetaxel: Innovative therapeutic method to inhibit tumor cell growth in lymph nodes. Cancer Sci. 2022;113(4):1125–1139. PMID: 35100484 https://doi.org/10.1111/cas.15283