Quantitative Fluorescence Assay Using Indocyanine Green in Early Diagnosis of Acute Small Intestinal Ischemia: An Experimental Study

Intraoperative assessment of tissue viability of hollow organs of the gastrointestinal tract during surgical interventions for acute mesenteric ischemia and a number of other surgical operations remains an unsolved problem. Existing methods for determining tissue viability limits in conditions of acute circulatory failure are characterized by a low sensitivity, which determines the choice of surgical treatment tactics for the patient. The aim of the work was to assess the effectiveness of the intraoperative fluorescence visualization technique for ischemic changes in the intestinal wall using a new device “MMC Scope ICG”, which allows using the V / Q-ICG method of research for quantitative angiography with indocyanine green (ICG), performed in the near infrared range. Wistar rats were divided into four groups: 1) 15-minute, 2) 30-minute, 3) 45-minute and 4) 60-minute intestinal ischemia, which after 30 minutes of reperfusion underwent recordings of curves of changes in time of ICG fluorescence brightness in zones with ischemic and reperfusion damage of intestinal tissue in comparison with control areas of healthy intestine. The analysis of relationship between changes in the indicated dynamic curves of indocyanine green fluorescence intensity and typical morphological changes in rat intestinal samples shows direct (positive) relationship between the dynamics of the increase in indocyanine green fluorescence intensity and the degree of morphological changes in the damaged area of the intestine

acute mesenteric ischemia, bowel infarction, near-infrared fluorescence, indocyanine green

1. Acosta S. Mesenteric ischemia. Curr Opin Crit Care. 2015;21(2):171-178. doi: 10.1097/MCC.0000000000000189.

2. Clair D.G., Beach J.M. Mesenteric Ischemia. N Engl J Med. 2016;10;374(10):959-68. doi: 10.1056/NEJMra1503884.

3. Bala M., Catena F., Kashuk J. et al. Acute mesenteric ischemia: updated guidelines of the World Society of Emergency Surgery. World J Emerg Surg. 2022;19;17(1):54. doi: 10.1186/s13017-022-00443-x.

4. Yu H., Kirkpatrick I.D.C. An Update on Acute Mesenteric Ischemia. Can Assoc Radiol J. 2023;74(1):160-171. doi: 10.1177/08465371221094280.

5. Urbanavičius L., Pattyn P., de Putte D.V., Venskutonis D. How to assess intestinal viability during surgery: a review of techniques. World J Gastrointest Surg. 2011; May 27;3(5):59-69. doi: 10.4240/wjgs.v3.i5.59.

6. Desmettre T., Devoisselle J.M., Morton S. Fluorescence Properties and Metabolic Features of Indocyanine Green (ICG) as Related to Angiography. Survey of ophthalmology. 2000;45(1):15-27 doi: 10.1016/S0039-6257(00)00123-5.

7. Rubben A., Eren S., Krein R. at al. Infrared videoangiofluorography of the skin with indocyanine green - rat random cutaneous flap model and results in man. Microvasc Res. 1994;47(2):240-251. doi: 10.1006/mvre.1994.1018.

8. Mizukami A., Furuya S., Takiguchi K. et al.Intraoperative indocyanine green fluorescence for precise resection of nonocclusive mesenteric ischemia: a case report and diagnostic considerations based on pathology findings. Surg Case Rep. 2024;4;10(1):230. doi: 10.1186/s40792-024-02024-3.

9. Miyashita R., Kitazawa M., Tokumaru S. Importance of intraoperative indocyanine green imaging in the management of non-occlusive mesenteric ischemia: a case report. Surg Case Rep. 2023;27;9(1):31. doi: 10.1186/s40792-023-01614-x.

10. Nakagawa Y., Kobayashi K., Kuwabara S. at al. Use of indocyanine green fluorescence imaging to determine the area of bowel resection in non-occlusive mesenteric ischemia: A case report.Int J Surg Case Rep. 2018;51:352-357. doi: 10.1016/j.ijscr.2018.09.024.

11. Irie T., Matsutani T., Hagiwara N., Nomura T. Successful treatment of non-occlusive mesenteric ischemia with indocyanine green fluorescence and open-abdomen management. Clin J Gastroenterol. 2017;10(6):514-518. doi: 10.1007/s12328-017-0779-3.

12. Khalaf M.H., Abdelrahman H., El-Menyar A. at al. Utility of indocyanine green fluorescent dye in emergency general surgery: a review of the contemporary literature. Front Surg. 2024;14;11:1345831. doi: 10.3389/fsurg.2024.1345831.

13. Fransvea P., Fico V., Puccioni C. at al. Application of fluorescence-guided surgery in the acute care setting: a systematic literature review. Langenbecks Arch Surg. 2023;25;408(1):375. doi: 10.1007/s00423-023-03109-7.

14. Gioux S., Choi H.S., Frangioni J.V. Image-guided surgery using invisible near-infrared light: fundamentals of clinical translation. Mol Imaging. 2010;9(5):237-55. PMID: 20868625.

15. Kudszus S., Roesel C., Schachtrupp A., Höer J.J.Intraoperative laser fluorescence angiography in colorectal surgery: a noninvasive analysis to reduce the rate of anastomotic leakage. Langenbecks Arch Surg. 2010;395(8):1025-30. doi: 10.1007/s00423-010-0699-x.

16. Nerup N., Preisler L., Svendsen M.B. et al. Quantification of fluorescence angiography in a porcine model. Langenbeck’s Arch Surg 2017;402(4):655-662. doi: 10.1007/s00423-016-1531-z.

17. Degett T.H., Andersen H.S., Gogenur I. Indocyanine green fluorescence angiography for intraoperative assessment of gastrointestinal anastomotic perfusion: a systematic review of clinical trials. Langenbeck’s Arch Surg. 2016;401(6):767-75. doi: 10.1007/s00423-016-1400-9.

18. Jansen S.M., de Bruin D.M., van Berge Henegouwen M.I. et al. Optical techniques for perfusion monitoring of the gastric tube after esophagectomy: a review of technologies and thresholds. Dis Esophagus. 2018;1;31(6). doi: 10.1093/dote/dox161.

19. Ladak F., Dang J.T., Switzer N. at al. Indocyanine green for the prevention of anastomotic leaks following esophagectomy: a meta-analysis. Surg Endo. 2019;33(2):384-394. doi: 10.1007/s00464-018-6503-7.

20. Slooter M.D., Eshuis W.J., Cuesta M.A. et al. Fluorescent imaging using indocyanine green during esophagectomy to prevent surgical morbidity: a systematic review and meta-analysis. J Thorac Dis 2019;11(Suppl 5): S755-S765. doi: 10.21037/jtd.2019.01.30.

21. Arezzo A., Bonino M.A., Ris F. et al.Intraoperative use of fluorescence with indocyanine green reduces anastomotic leak rates in rectal cancer surgery: an individual participant data analysis. Surg Endosc 2020;34(10):4281-4290. doi: 10.1007/s00464-020-07735-w.

22. Miyashita R., Tokutake A., Nimori S., Goto H. Importance of intraoperative indocyanine green imaging in the management of non-occlusive mesenteric ischemia: a case report. Surg Case Rep. 2023;27;9(1):31. doi: 10.1186/s40792-023-01614-x.

23. Watt-Boolsen S. Non-occlusive intestinal infarction. Acta Chir Scand. 1977;143:365-369.

24. Diana M., Halvax P., Dallemagne B. et al. Real-time navigation by fluorescence-based enhanced reality for precise estimation of future anastomotic site in digestive surgery. Surg Endosc. 2014;28(11):3108-18. doi: 10.1007/s00464-014-3592-9.

25. Son G.M., Kwon M.S., Kim Y. Quantitative analysis of colon perfusion pattern using indocyanine green (ICG) angiography in laparoscopic colorectal surgery. Surg Endosc. 2019;33(5):1640-1649. doi: 10.1007/s00464-018-6439-y.

26. Wada T., Kawada K., Takahashi R. et al. ICG fluorescence imaging for quantitative evaluation of colonic perfusion in laparoscopic colorectal surgery. Surg Endosc. 2017;31(10):4184-4193. doi: 10.1007/s00464-017-5475-3.

27. Lütken C.D., Achiam M.P., Osterkamp J. at al. Quantification of fluorescence angiography: Toward a reliable intraoperative assessment of tissue perfusion - A narrative review. Langenbecks Arch Surg. 2021;406(2):251-259. doi: 10.1007/s00423-020-01966-0.

28. Diana M, Noll E., Diemunsch P. Enhanced-reality video fluorescence: a real-time assessment of intestinal viability. Ann Surg. 2014;259(4):700-7. doi: 10.1097/SLA.0b013e31828d4ab3.

29. Matsui A., Winer J.H., Laurence R.G., Frangioni J.V. Predicting the survival of experimental ischaemic small bowel using intraoperative near-infrared fluorescence angiography. Br J Surg. 2011;98(12):1725-34. doi: 10.1002/bjs.7698.

30. Duprée A., Rieß H., von Kroge P.H. at al.Intraoperative quality assessment of tissue perfusion with indocyanine green (ICG) in a porcine model of mesenteric ischemia. PLoS One. 2021;20;16(7): e0254144. doi: 10.1371/journal.pone.0254144.

31. Chiu C.J., McArdle A.H., Brown R. at al.Intestinal mucosal lesion in low-flow states. I. A morphological, hemodynamic, and metabolic reappraisal. Arch Surg. 1970;101(4):478-483. doi: 10.1001/archsurg.1970.01340280030009.

32. Karliczek A., Harlaar N.J., Zeebregts C.J. at al. Surgeons lack predictive accuracy for anastomotic leakage in gastrointestinal surgery.Int J Colorectal Dis. 2009;24(5):569-576. doi: 10.1007/s00384-009-0658-6.