Skip to main content
Log in

A new fluorescence imaging technique for visualizing hepatobiliary structures using sodium fluorescein: result of a preclinical study in a rat model

  • Published:
Surgical Endoscopy Aims and scope Submit manuscript

Abstract

Background

Near-infrared fluorescence imaging has been recently applied in the field of hepatobiliary surgery. Our objective was to apply blue light fluorescence imaging to cholangiography and liver mapping during laparoscopic surgery. Therefore, we designed a preclinical study to evaluate the feasibility of using blue light fluorescence for cholangiography and liver mapping in a rat model.

Methods

Sodium fluorescein solution (1 mL to each individual) were administered intravenously to 20 male Sprague–Dawley rats (6 weeks old, 200–250 g), after laparotomy. Whole abdominal organs were observed under blue light (at a wavelength of 440–490 nm) emitted from a commercialized LED curing light.

Results

Immediately after the tracer solution was administered into the circulatory system of the rat, it was possible to visualize the location of the kidneys and the bile duct under blue light emitted from the light source. The liver was vaguely stained green by the tracer, while the ureters were not. After establishing biliary retention via duct clamping in the left lateral segment of the liver, the green color of the segment became distinct by the tracer, which showed vague coloration following release of the clamp.

Conclusion

We established the preclinical basis for using blue light fluorescence cholangiography and liver mapping in this study. The clinical feasibility of these techniques during laparoscopic cholecystectomy and hepatectomy remained to be demonstrated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Rossi EC, Ivanova A, Boggess JF (2012) Robotically assisted fluorescence-guided lymph node mapping with ICG for gynecologic malignancies: a feasibility study. Gynecol Oncol 124:78–82

    Article  PubMed  Google Scholar 

  2. Gray DC, Kim EM, Cotero VE, Bajaj A, Staudinger VP, Hehir CA, Yazdanfar S (2012) Dual-mode laparoscopic fluorescence image-guided surgery using a single camera. Biomed Opt Express 3:1880–1890

    Article  PubMed  PubMed Central  Google Scholar 

  3. Gioux S, Kianzad V, Ciocan R, Gupta S, Oketokoun R, Frangioni JV (2009) High-power, computer-controlled, light-emitting diode-based light sources for fluorescence imaging and image-guided surgery. Mol imaging 8:156–165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Matsui A, Tanaka E, Choi HS, Kianzad V, Gioux S, Lomnes SJ, Frangioni JV (2010) Real-time, near-infrared, fluorescence-guided identification of the ureters using methylene blue. Surgery 148:78–86

    Article  PubMed  PubMed Central  Google Scholar 

  5. Murawa D, Polom K, Rho YS, Murawa P (2013) Developments in near-infrared-guided hepatobiliary, pancreatic and other upper gastrointestinal surgery. Contrast Media Mol Imaging 8:211–219

    Article  CAS  PubMed  Google Scholar 

  6. Landsman ML, Kwant G, Mook GA, Zijlstra WG (1976) Light-absorbing properties, stability, and spectral stabilization of indocyanine green. J Appl Physiol 40:575–583

    Article  CAS  PubMed  Google Scholar 

  7. Way LW, Stewart L, Gantert W, Liu K, Lee CM, Whang K, Hunter JG (2003) Causes and prevention of laparoscopic bile duct injuries: analysis of 252 cases from a human factors and cognitive psychology perspective. Ann Surg 237:460–469

    PubMed  PubMed Central  Google Scholar 

  8. Nuzzo G, Giuliante F, Giovannini I, Ardito F, D’Acapito F, Vellone M, Murazio M, Capelli G (2005) Bile duct injury during laparoscopic cholecystectomy: results of an Italian national survey on 56 591 cholecystectomies. Arch Surg 140:986–992

    Article  PubMed  Google Scholar 

  9. Woods MS, Traverso LW, Kozarek RA, Donohue JH, Fletcher DR, Hunter JG, Oddsdottir M, Rossi RL, Tsao J, Windsor J (1995) Biliary tract complications of laparoscopic cholecystectomy are detected more frequently with routine intraoperative cholangiography. Surg Endosc 9:1076–1080

    Article  CAS  PubMed  Google Scholar 

  10. Carroll BJ, Friedman RL, Liberman MA, Phillips EH (1996) Routine cholangiography reduces sequelae of common bile duct injuries. Surg Endosc 10:1194–1197

    Article  CAS  PubMed  Google Scholar 

  11. Sheffield KM, Han Y, Kuo YF, Townsend CM Jr, Goodwin JS, Riall TS (2012) Variation in the use of intraoperative cholangiography during cholecystectomy. J Am Coll Surg 214:668–679 [discussion 679–681]

    Article  PubMed  PubMed Central  Google Scholar 

  12. Ishizawa T, Tamura S, Masuda K, Aoki T, Hasegawa K, Imamura H, Beck Y, Kokudo N (2009) Intraoperative fluorescent cholangiography using indocyanine green: a biliary road map for safe surgery. J Am Coll Surg 208:e1-4

    Article  PubMed  Google Scholar 

  13. Ishizawa T, Bandai Y, Ijichi M, Kaneko J, Hasegawa K, Kokudo N (2010) Fluorescent cholangiography illuminating the biliary tree during laparoscopic cholecystectomy. Br J Surg 97:1369–1377

    Article  CAS  PubMed  Google Scholar 

  14. Ishizawa T, Kaneko J, Inoue Y, Takemura N, Seyama Y, Aoki T, Beck Y, Sugawara Y, Hasegawa K, Harada N, Ijichi M, Kusaka K, Shibasaki M, Bandai Y, Kokudo N (2011) Application of fluorescent cholangiography to single-incision laparoscopic cholecystectomy. Surg Endosc 25:2631–2636

    Article  PubMed  Google Scholar 

  15. Verbeek FP, Schaafsma BE, Tummers QR, van der Vorst JR, van der Made WJ, Baeten CI, Bonsing BA, Frangioni JV, van de Velde CJ, Vahrmeijer AL, Swijnenburg RJ (2014) Optimization of near-infrared fluorescence cholangiography for open and laparoscopic surgery. Surg Endosc 28:1076–1082

    Article  PubMed  PubMed Central  Google Scholar 

  16. Ishizawa T, Bandai Y, Kokudo N (2009) Fluorescent cholangiography using indocyanine green for laparoscopic cholecystectomy: an initial experience. Arch Surg 144:381–382

    Article  PubMed  Google Scholar 

  17. Sherwinter DA (2012) Identification of anomalous biliary anatomy using near-infrared cholangiography. J gastrointest Surg 16:1814–1815

    Article  PubMed  Google Scholar 

  18. van den Bos J, Schols RM, Luyer MD, van Dam RM, Vahrmeijer AL, Meijerink WJ, Gobardhan PD, van Dam GM, Bouvy ND, Stassen LP (2016) Near-infrared fluorescence cholangiography assisted laparoscopic cholecystectomy versus conventional laparoscopic cholecystectomy (FALCON trial): study protocol for a multicentre randomised controlled trial. BMJ open 6:e011668

    Article  PubMed  PubMed Central  Google Scholar 

  19. Hasegawa K, Kokudo N, Imamura H, Matsuyama Y, Aoki T, Minagawa M, Sano K, Sugawara Y, Takayama T, Makuuchi M (2005) Prognostic impact of anatomic resection for hepatocellular carcinoma. Ann Surg 242:252–259

    Article  PubMed  PubMed Central  Google Scholar 

  20. Topal B, Aerts R, Penninckx F (2007) Laparoscopic intrahepatic Glissonian approach for right hepatectomy is safe, simple, and reproducible. Surg Endosc 21:2111

    Article  CAS  PubMed  Google Scholar 

  21. Machado MA, Makdissi FF, Galvao FH, Machado MC (2008) Intrahepatic Glissonian approach for laparoscopic right segmental liver resections. Am J Surg 196:e38-42

    Article  PubMed  Google Scholar 

  22. Hu JX, Dai WD, Miao XY, Zhong DW, Huang SF, Wen Y, Xiong SZ (2009) Anatomic resection of segment VIII of liver for hepatocellular carcinoma in cirrhotic patients based on an intrahepatic Glissonian approach. Surgery 146:854–860

    Article  PubMed  Google Scholar 

  23. Machado MA, Makdissi FF, Surjan RC, Herman P, Teixeira AR, Machado MC (2009) Laparoscopic resection of left liver segments using the intrahepatic Glissonian approach. Surg Endosc 23:2615–2619

    Article  CAS  PubMed  Google Scholar 

  24. Ahn KS, Han HS, Yoon YS, Cho JY, Kim JH (2011) Laparoscopic anatomical S5 segmentectomy by the Glissonian approach. J Laparoendosc Adv Surg Tech A 21:345–348

    Article  PubMed  Google Scholar 

  25. Herman P, Kruger J, Lupinacci R, Coelho F, Perini M (2013) Laparoscopic bisegmentectomy 6 and 7 using a Glissonian approach and a half-Pringle maneuver. Surg Endosc 27:1840–1841

    Article  PubMed  Google Scholar 

  26. Machado MA, Surjan RC, Makdissi FF (2014) Intrahepatic glissonian approach for single-port laparoscopic liver resection. J Laparoendosc Adv Surg Tech A 24:534–537

    Article  PubMed  Google Scholar 

  27. Ho KM, Han HS, Yoon YS, Cho JY, Choi YR, Jang JS, Kwon SU, Kim S, Choi JK (2016) Laparoscopic anatomical segment 2 segmentectomy by the Glissonian approach. J Laparoendosc Adv Surg Tech A 27:818–822

    Article  PubMed  Google Scholar 

  28. Machado MA, Surjan RC, Basseres T, Schadde E, Costa FP, Makdissi FF (2016) The laparoscopic Glissonian approach is safe and efficient when compared with standard laparoscopic liver resection: results of an observational study over 7 years. Surgery 160:643–651

    Article  PubMed  Google Scholar 

  29. Choi H, Han HS, Yoon YS, Cho JY, Choi Y, Jang JY (2017) Laparoscopic anatomic segment 6 liver resection using the Glissonian approach. Surg Laparosc 27:e22–e25

  30. Jang JY, Han HS, Yoon YS, Cho JY, Choi Y, Lee W, Shin HK, Choi HL (2017) Three-dimensional laparoscopic anatomical segment 8 liver resection with Glissonian approach. Ann Surg Oncol 24:1606–1609

    Article  PubMed  Google Scholar 

  31. Aoki T, Yasuda D, Shimizu Y, Odaira M, Niiya T, Kusano T, Mitamura K, Hayashi K, Murai N, Koizumi T, Kato H, Enami Y, Miwa M, Kusano M (2008) Image-guided liver mapping using fluorescence navigation system with indocyanine green for anatomical hepatic resection. World J Surg 32:1763–1767

    Article  PubMed  Google Scholar 

  32. Miyata A, Ishizawa T, Tani K, Shimizu A, Kaneko J, Aoki T, Sakamoto Y, Sugawara Y, Hasegawa K, Kokudo N (2015) Reappraisal of a dye-staining technique for anatomic hepatectomy by the concomitant use of indocyanine green fluorescence imaging. J Am Coll Surg 221:e27-36

    Article  PubMed  Google Scholar 

  33. Inoue Y, Arita J, Sakamoto T, Ono Y, Takahashi M, Takahashi Y, Kokudo N, Saiura A (2015) Anatomical liver resections guided by 3-dimensional parenchymal staining using fusion indocyanine green fluorescence imaging. Ann Surg 262:105–111

    Article  PubMed  Google Scholar 

  34. Ishizawa T, Fukushima N, Shibahara J, Masuda K, Tamura S, Aoki T, Hasegawa K, Beck Y, Fukayama M, Kokudo N (2009) Real-time identification of liver cancers by using indocyanine green fluorescent imaging. Cancer 115:2491–2504

    Article  PubMed  Google Scholar 

  35. Ishizawa T, Masuda K, Urano Y, Kawaguchi Y, Satou S, Kaneko J, Hasegawa K, Shibahara J, Fukayama M, Tsuji S, Midorikawa Y, Aburatani H, Kokudo N (2014) Mechanistic background and clinical applications of indocyanine green fluorescence imaging of hepatocellular carcinoma. Ann Surg Oncol 21:440–448

    Article  PubMed  Google Scholar 

  36. Hutteman M, Mieog JS, van der Vorst JR, Dijkstra J, Kuppen PJ, van der Laan AM, Tanke HJ, Kaijzel EL, Que I, van de Velde CJ, Lowik CW, Vahrmeijer AL (2011) Intraoperative near-infrared fluorescence imaging of colorectal metastases targeting integrin alpha(v)beta(3) expression in a syngeneic rat model. Eur J Surg Oncol 37:252–257

    Article  CAS  PubMed  Google Scholar 

  37. van der Vorst JR, Hutteman M, Mieog JS, de Rooij KE, Kaijzel EL, Lowik CW, Putter H, Kuppen PJ, Frangioni JV, van de Velde CJ, Vahrmeijer AL (2012) Near-infrared fluorescence imaging of liver metastases in rats using indocyanine green. J Surg Res 174:266–271

    Article  PubMed  Google Scholar 

  38. van der Vorst JR, Schaafsma BE, Hutteman M, Verbeek FP, Liefers GJ, Hartgrink HH, Smit VT, Lowik CW, van de Velde CJ, Frangioni JV, Vahrmeijer AL (2013) Near-infrared fluorescence-guided resection of colorectal liver metastases. Cancer 119:3411–3418

    Article  PubMed  PubMed Central  Google Scholar 

  39. Lee CM, Park S, Park SH, Jung SW, Choe JW, Sul JY, Jang YJ, Mok YJ, Kim JH (2017) Sentinel node mapping using a fluorescent dye and visible light during laparoscopic gastrectomy for early gastric cancer: result of a prospective study from a single institute. Ann Surg 265:766–773

    Article  PubMed  Google Scholar 

  40. Roberts HW, Donati-Bourne JF, Wilson VL, Wilton JC (2013) The use of live fluorescence staining techniques in surgery: a review. J Invest Surg 26:283–293

    Article  PubMed  Google Scholar 

  41. Dip FD, Nahmod M, Anzorena FS, Moreira A, Sarotto L, Ampudia C, Kalaskar SN, Ferraina P, Rosenthal RJ, Wexner SD (2014) Novel technique for identification of ureters using sodium fluorescein. Surg Endosc 28:2730–2733

    Article  PubMed  Google Scholar 

  42. FDA drug database. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ebb3883c-71f6-4fd0-a7e6-0ba8e1136dd9

  43. Kono Y, Ishizawa T, Tani K, Harada N, Kaneko J, Saiura A, Bandai Y, Kokudo N (2015) Techniques of fluorescence cholangiography during laparoscopic cholecystectomy for better delineation of the bile duct anatomy. Medicine 94:e1005

    Article  PubMed  PubMed Central  Google Scholar 

  44. Ishizawa T, Saiura A, Kokudo N (2016) Clinical application of indocyanine green-fluorescence imaging during hepatectomy. Hepatobiliary Surg Nutr 5:322–328

    Article  PubMed  PubMed Central  Google Scholar 

  45. Tsutsui N, Yoshida M, Kitajima M, Suzuki Y (2016) Laparoscopic cholecystectomy using the PINPOINT endoscopic fluorescence imaging system with intraoperative fluorescent imaging: a case report. Int J Surg Case Rep 21:129–132

    Article  PubMed  PubMed Central  Google Scholar 

  46. Tanaka M, Inoue Y, Mise Y, Ishizawa T, Arita J, Takahashi Y, Saiura A (2016) Laparoscopic deroofing for polycystic liver disease using laparoscopic fusion indocyanine green fluorescence imaging. Surg Endosc 30:2620–2623

    Article  PubMed  Google Scholar 

  47. Novotny HR, Alvis DL (1961) A method of photographing fluorescence in circulating blood in the human retina. Circulation 24:82–86

    Article  CAS  PubMed  Google Scholar 

  48. Stein MR, Parker CW (1971) Reactions following intravenous fluorescein. Am J Ophthalmol 72:861–868

    Article  CAS  PubMed  Google Scholar 

  49. Kwiterovich KA, Maguire MG, Murphy RP, Schachat AP, Bressler NM, Bressler SB, Fine SL (1991) Frequency of adverse systemic reactions after fluorescein angiography: results of a prospective study. Ophthalmology 98:1139–1142

    Article  CAS  PubMed  Google Scholar 

  50. Karhunen U, Raitta C, Kala R (1986) Adverse reactions to fluorescein angiography. Acta Ophthalmol 64:282–286

    Article  CAS  Google Scholar 

  51. Goetz M, Kiesslich R, Dienes HP, Drebber U, Murr E, Hoffman A, Kanzler S, Galle PR, Delaney P, Neurath MF (2008) In vivo confocal laser endomicroscopy of the human liver: a novel method for assessing liver microarchitecture in real time. Endoscopy 40:554–562

    Article  CAS  PubMed  Google Scholar 

  52. Mohsen AA, Elbasiouny MS, Fawzy YS (2013) Fluorescence-guided laparoscopic cholecystectomy: a new technique for visualization of biliary system by using fluorescein. Surg Innov 20:105–108

    Article  PubMed  Google Scholar 

  53. Mohsen A, Elbasiouny MS, El-Shazli M, Azmy O, Amr A (2016) Evaluation of the effectiveness of fluorescent visualization of bile ducts using fluorescein and ultraviolet a at laparoscopic cholecystectomy. Surg Innov 23:261–265

    Article  PubMed  Google Scholar 

  54. Lee S, Charters AC, Chandler JG, Orloff MJ (1973) A technique for orthotopic liver transplantation in the rat. Transplantation 16:664–669

    Article  CAS  PubMed  Google Scholar 

  55. Kamada N, Calne RY (1979) Orthotopic liver transplantation in the rat. Technique using cuff for portal vein anastomosis and biliary drainage. Transplantation 28:47–50

    Article  CAS  PubMed  Google Scholar 

  56. Liu YY, Kong SH, Diana M, Legner A, Wu CC, Kameyama N, Dallemagne B, Marescaux J (2016) Near-infrared cholecysto-cholangiography with indocyanine green may secure cholecystectomy in difficult clinical situations: proof of the concept in a porcine model. Surg Endosc 30:4115–4123

    Article  PubMed  Google Scholar 

  57. Ishizawa T, Zuker NB, Kokudo N, Gayet B (2012) Positive and negative staining of hepatic segments by use of fluorescent imaging techniques during laparoscopic hepatectomy. Arch Surg 147:393–394

    Article  PubMed  Google Scholar 

  58. Ishizawa T, Gumbs AA, Kokudo N, Gayet B (2012) Laparoscopic segmentectomy of the liver: from segment I to VIII. Ann Surg 256:959–964

    Article  PubMed  Google Scholar 

Download references

Funding

This paper was conducted by 2016 Korea University Ansan Hospital R&D support project through the support of Vice President for Medical Affairs of Korea University special research funds (No. K1613811).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Chang Min Lee.

Ethics declarations

Disclosures

Sam-Youl Yoon, Chang Min Lee, Tae-Jin Song, Hyung Joon Han, and Seonghan Kim have no conflict of interest or financial ties to disclose.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yoon, SY., Lee, C.M., Song, TJ. et al. A new fluorescence imaging technique for visualizing hepatobiliary structures using sodium fluorescein: result of a preclinical study in a rat model. Surg Endosc 32, 2076–2083 (2018). https://doi.org/10.1007/s00464-017-5904-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00464-017-5904-3

Keywords

Navigation