The Usefulness of a Three-Microneedle Device for Indocyanine Green Fluorescence Lymphography
Publication: Lymphatic Research and Biology
Volume 21, Issue Number 4
Abstract
Background: Indocyanine green (ICG) fluorescence lymphography is widely used to diagnose lymphedema. There is little consensus on the appropriate injection method for ICG fluorescence lymphangiography. We used a three-microneedle device (TMD) for skin injection of ICG solution and investigated its usefulness.
Methods and Results: Thirty healthy volunteers were injected with ICG solution using a 27-gauge (27G) needle in one foot and a TMD in the other foot. Injection-related pain was evaluated using the Numerical Rating Scale (NRS) and Face Rating Scale (FRS). The skin depth of the injected ICG solution was evaluated by injecting the solution into the skin of amputated lower limbs using a 27G needle or TMD using ICG fluorescence microscopy. The median and interquartile range of the NRS scores was 3 (3–4) and 2 (2–4) in the 27G needle and TMD groups, respectively; that of the FRS scores was 2 (2–3) and 2 (1–2) in the 27G needle and TMD groups, respectively. Injection-related pain was significantly lower with the TMD than with the 27G needle. The lymphatic vessels were similarly visible using both needles. The depth of the ICG solution varied for each injection with a 27G needle (400–1200 μm) and was consistent at ∼300–700 μm below the skin surface using the TMD. Injection depth was significantly different between the 27G needle and the TMD.
Conclusions: Injection-related pain decreased using the TMD, and ICG solution depth was consistent on fluorescence lymphography. A TMD may be useful for ICG fluorescence lymphography.
Clinical Trials Registry (UMIN-CTR; ID: UMIN000033425).
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References
1. Zawieja DC. Contractile physiology of lymphatics. Lymphat Res Biol 2009;7(2):87–96;
2. Hidding JT, Viehoff PB, Beurskens CH, et al. Measurement properties of instruments for measuring of lymphedema: Systematic review. Phys Ther 2016;96(12):1965–1981;
3. Wallace S, Jackson L, Schaffer B, et al. Lymphangiograms: Their diagnostic and therapeutic potential. Radiology 1961;76:179–199;
4. Maegawa J, Mikami T, Yamamoto Y, et al. Types of lymphoscintigraphy and indications for lymphaticovenous anastomosis. Microsurgery 2010;30(6):437–442;
5. Sheehan R, Hreshchyshyn M, Lin RK, et al. The use of lymphography as a diagnostic method. Radiology 1961;76(1):47–53;
6. Unno N, Inuzuka K, Suzuki M, et al. Preliminary experience with a novel fluorescence lymphography using indocyanine green in patients with secondary lymphedema. J Vasc Surg 2007;45(5):1016–1021;
7. Hojo T, Nagao T, Kikuyama M, et al. Evaluation of sentinel node biopsy by combined fluorescent and dye method and lymph flow for breast cancer. Breast 2010;19(3):210–213;
8. Shikayama T. Characteristics of the photodynamic eye camera. In: ICG Fluorescence Imaging and Navigation Surgery. (Kusano M. et al. eds.) Springer: Tokyo; pp. 21–27;
9. Visconti G, Albanese R, Salgarello M. Painless indocyanine green lymphography. J Reconstr Microsurg 2017;33(3):225–226;
10. Suami H, Heydon-White A, Mackie H, et al. Cryogenic numbing to reduce injection discomfort during indocyanine green lymphography. J Reconstr Microsurg 2019;35(2):e1–e2;
11. Fukamizu H, Fujiwara M, Kim T, et al. Development of a three-microneedle device for hypodermic drug delivery and clinical application. Plast Reconstr Surg 2012;130(2):451–455;
12. Ishikawa K, Fukamizu H, Takiguchi T, et al. Application of a three-microneedle device for the delivery of local anesthetics. Patient Prefer Adherence 2015;9:585–588;
13. Achilefu S. The insatiable quest for near-infrared fluorescent probes for molecular imaging. Angew Chem Int Ed Engl 2010;49(51):9816–9818;
14. Hartrick CT, Kovan JP, Shapiro S. The numeric rating scale for clinical pain measurement: A ratio measure? Pain Pract 2003;3(4):310–316;
15. Garra G, Singer AJ, Taira BR, et al. Validation of the Wong-Baker FACES pain rating scale in pediatric emergency department patients. Acad Emerg Med 2010;17(1):50–54;
16. Sano M, Sasaki T, Hirakawa S, et al. Lymphangiogenesis and angiogenesis in abdominal aortic aneurysm. PLoS One 2014;9(3):e89830;
17. Strazar AR, Leynes PG, Lalonde DH. Minimizing the pain of local anesthesia injection. Plast Reconstr Surg 2013;132(3):675–684;
18. Metz BJ. Procedural pediatric dermatology. Dermatol Clin 2013;31(2):337–346;
19. Arendt-Nielsen L, Egekvist H, Bjerring P. Pain following controlled cutaneous insertion of needles with different diameters. Somatosens Mot Res 2006;23(1–2):37–43;
20. Martires KJ, Malbasa CL, Bordeaux JS. A randomized controlled crossover trial: Lidocaine injected at a 90-degree angle causes less pain than lidocaine injected at a 45-degree angle. J Am Acad Dermatol 2011;65(6):1231–1233;
21. Habif TP. Clinical Dermatology: A Color Guide to Diagnosis and Therapy. Mosby: Edinburgh; 2010.
22. Zilinsky I, Bar-Meir E, Zaslansky R, et al. Ten commandments for minimal pain during administration of local anesthetics. J Drugs Dermatol 2005;4(2):212–216.
23. Ong EL, Lim NL, Koay CK. Towards a pain-free venepuncture. Anaesthesia 2000;55(3):260–262;
24. Kudo M. Initial injection pressure for dental local anesthesia: Effects on pain and anxiety. Anesth Prog 2005;52(3):95–101;
25. Cepeda MS, Tzortzopoulou A, Thackrey M, et al. Adjusting the pH of lidocaine for reducing pain on injection. Cochrane Database Syst Rev 2010;(12):CD006581;
26. Frank SG, Lalonde DH. How acidic is the lidocaine we are injecting, and how much bicarbonate should we add? Can J Plast Surg 2012;20(2):71–73;
27. Bennett CT. Activity of osmosensitive neurons: Plasma osmotic pressure thresholds. Physiol Behav 1973;11(3):403–406;
28. Setnikar I, Paterlini MR. Osmotic pressure and tolerance of injectable solutions. J Am Pharm Assoc Am Pharm Assoc 1960;49:5–7;
29. Akita S, Unno N, Maegawa J, et al. HAMAMATSU-ICG study: Protocol for a phase III, multicentre, single-arm study to assess the usefulness of indocyanine green fluorescent lymphography in assessing secondary lymphoedema. Contemp Clin Trials Commun 2020;19:100595;
30. Hara H, Mihara M. Multilymphosome injection indocyanine green lymphography can detect more lymphatic vessels than lymphoscintigraphy in lymphedematous limbs. J Plast Reconstr Aesthet Surg 2020;73(6):1025–1030;
31. Yamamoto T, Narushima M, Doi K, et al. Characteristic indocyanine green lymphography findings in lower extremity lymphedema: The generation of a novel lymphedema severity staging system using dermal backflow patterns. Plast Reconstr Surg 2011;127(5):1979–1986;
32. Yoon JA, Shin MJ, Kim JH. Indocyanine green lymphography and lymphoscintigraphy severity stage showed strong correlation in lower limb lymphedema. Lymphat Res Biol 2021;19(1):80–85;
33. Yoshida S, Koshima I, Imai H, et al. Indocyanine green lymphography findings in older patients with lower limb lymphedema. J Vasc Surg Venous Lymphat Disord 2020;8(2):251–258;
34. Klingelhoefer E, Schiltz D, Ranieri M, et al. Video tutorial for indocyanine green lymphography in lymphatic surgery. Plast Reconstr Surg Glob Open 2020;8:e2609.
35. Suami H, Thompson B, Mackie H, et al. A new indocyanine green fluorescence lymphography protocol for diagnostic assessment of lower limb lymphoedema. J Plast Reconstr Aesthet Surg 2022;75(11):3946–3955;
36. Narushima M, Yamamoto T, Ogata F, et al. Indocyanine green lymphography findings in limb lymphedema. J Reconstr Microsurg 2016;32:72–79.
37. Costa Ede P, Rodrigues EB, Farah ME, et al. Vital dyes and light sources for chromovitrectomy: Comparative assessment of osmolarity, pH, and spectrophotometry. Invest Ophthalmol Vis Sci 2009;50:385–391.
38. Hu D, Phan TT, Cherry GW, et al. Dermal oedema assessed by high frequency ultrasound in venous leg ulcers. Br J Dermatol 1998;138(5):815–820;
39. Lubach D, Ludemann W, Berens von Rautenfeld D. Recent findings on the angioarchitecture of the lymph vessel system of human skin. Br J Dermatol 1996;135(5):733–737;
40. Sano M, Hirakawa S, Suzuki M, et al. Potential role of transforming growth factor-beta 1/Smad signaling in secondary lymphedema after cancer surgery. Cancer Sci 2020;111(7):2620–2634;
41. Sano M, Hirakawa S, Sasaki T, et al. Role of subcutaneous adipose tissues in the pathophysiology of secondary lymphedema. Lymphat Res Biol 2022;
42. Sano M, Hirakawa S, Yamanaka Y, et al. Development of a noninvasive skin evaluation method for lower limb lymphedema. Lymphat Res Biol 2020;18(1):7–15;
Information & Authors
Information
Published In
Lymphatic Research and Biology
Volume 21 • Issue Number 4 • August 2023
Pages: 396 - 402
PubMed: 36802287
Copyright
Copyright 2023, Mary Ann Liebert, Inc., publishers.
History
Published online: 22 August 2023
Published in print: August 2023
Published ahead of print: 21 February 2023
Authors
Authors' Contributions
Y.E., M.S., T.K., and T.S. conceived and designed the study. Y.E., M.S., T.K., T.S., K.K., Y.Y., H.Ts., N.I., and E.N. acquired the data. Y.E., M.S., T.K., and T.S. analyzed and interpreted the data. Y.E. and M.S. wrote the article. K.I., H.Ta., and N.U. supervised this project. All authors critically revised and approved the article and agreed to be accountable for all aspects of this work.
Author Disclosure Statement
No competing financial interests exist.
Funding Information
This work was supported by JSPS KAKENHI (grant number 15K21052 awarded to Masaki Sano and grant number 21K16493 awarded to Takafumi Kayama).
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