First-in-human orbital tumor surgery guided by nearinfrared II window fluorescence imaging: A feasibility study

Abstract

Precise resection of orbital tumors is a critically important but elusive issue. Fluorescence imaging in the near-infrared II window (NIR-II) holds the potential to provide the surgeons with real-time identification for orbital tumors. Here, for the first time, we evaluated the feasibility and clinical value of NIR-II fluorescence imaging in orbital tumor surgery. To establish the method of NIR-II fluorescence imaging for orbital tumors, we developed a NIR-II fluorescence imaging system and indocyanine green (ICG) served as the fluorescent contrast agent. Twenty-two patients diagnosed with orbital tumors and scheduled for standard-of-care surgery were enrolled in this study. Timecourse NIR-II fluorescence imaging of two patients with superficial orbital tumors showed the optimum imaging time was 2 h post injection of ICG. Fifteen patients were allocated for diagnostic test, which showed that both the in situ and ex vivo NIR-II fluorescence imaging showed better sensitivity and specificity than the surgeon judgment. In the feasibility trial of the remaining five patients, the surgeon encountered 34 suspicious regions and surgical decisions were changed nine times due to NIR-II fluorescence imaging. The resultant seven additional resections were justified by histopathology and the two conservative treatments did not result in recurrence. Based on these findings, we suggested that ICG-based NIR-II fluorescence imaging was feasible to guide precise resection of orbital tumors. A future randomized controlled trial with a larger cohort is encouraged to further verify the clinical value.

Keywords

fluorescence imaging / ICG / NIR-II imaging / orbital tumor

References

[1] N.Weizman, G.Horowitz, Z.Gil, D. M.Fliss, JAMA Otolaryngol. Head Neck Surg. 2013, 139, 841.

[2] M. S.Alam, A.Tongbram, S.Krishnakumar, J.Biswas, B.Mukherjee, Indian J. Ophthalmol. 2019, 67, 1988.

[3] S.Fakurnejad, G.Krishnan, S.van Keulen, N.Nishio, A. C.Birkeland, F. M.Baik, M. J.Kaplan, A. D.Colevas, N. S.van den Berg, E. L.Rosenthal, B. A.Martin, Front. Oncol. 2020, 9, 1476.

[4] R.Liu, Y.Xu, K.Xu, Z.Dai, Aggregate 2021, 2, e23.

[5] C.Wu, J.Gleysteen, N. T.Teraphongphom, Y.Li, E.Rosenthal, Int. J. Oral Sci. 2018, 10, 10.

[6] T.Ishizawa, N.Fukushima, J.Shibahara, K.Masuda, S.Tamura, T.Aoki, K.Hasegawa, Y.Beck, M.Fukayama, N. Kokudo, Cancer 2009, 115, 2491.

[7] A. D.Newton, J. D.Predina, M. H.Shin, L. GFrenzel-Sulyok, C. M. Vollmer, J. A.Drebin, S.Singhal, M. K.Lee, Ann. Surg. 2019, 270, 12.

[8] G.Liberale, S.Vankerckhove, M. G.Caldon, B.Ahmed, M.Moreau, I. E.Nakadi, D.Larsimont, V.Donckier, P.Bourgeois, Ann. Surg. 2016, 264, 1110.

[9] J. Y. KLee, J. T.Pierce, J. P.Thawani, R.Zeh, S.Nie, M.Martinez-Lage, S.Singhal, J. Neurosurg. 2018, 128, 380.

[10] F.Nicoli, D. B.Saleh, B.Baljer, C. D. Chan, T.Beckingsale, K. M.Ghosh, M.Ragbir, K. S.Rankin, Ann. Surg. 2021, 273, e63.

[11] L. J.Lauwerends, P. B. A. A.van Driel, R. J.Baatenburg de Jong, J. A. U.Hardillo, S.Koljenovic, G.Puppels, L.Mezzanotte, C. W. G. M.Löwik, E. L. Rosenthal, A. L.Vahrmeijer, S.Keereweer, Lancet Oncol. 2021, 22, e186.

[12] G.Hong, A. L.Antaris, H.Dai, Nat. Biomed. Eng. 2017, 1, 0010.

[13] G.Deng, S.Zhang, X.Peng, L. Liu, Y.Tan, P.Gong, B. Z.Tang, L.Cai, P. Zhang, Chem. Biomed. Imaging 2024.

[14] J. A.Carr, D.Franke, J. R.Caram, C. F.Perkinson, M.Saif, V.Askoxylakis, M.Datta, D.Fukumura, R. K.Jain, M. G.Bawendi, O. T.Bruns, Proc. Natl. Acad. Sci. USA 2018, 115, 4465.

[15] Z.Hu, C.Fang, B.Li, Z.Zhang, C.Cao, M. Cai, S.Su, X.Sun, X.Shi, T.Zhou, Y. Zhang, C.Chi, P.He, X.Xia, Y.Chen, S. S. Gambhir, Z.Cheng, J.Tian, Nat. Biomed. Eng. 2020, 4, 259.

[16] E.Rosenthal, J.Warram, K.Bland, K.Zinn, Ann. Surg. 2015, 261, 46.

[17] J. Y.Lee, J. P.Thawani, J.Pierce, R.Zeh, M.Martinez-Lage, M.Chanin, O.Venegas, S.Nims, K.Learned, J. Keating, S.Singhal, Neurosurgery 2016, 79, 856.

[18] Y. S.Modi, A.Epstein, S.Bhaleeya, J. W.Harbour, T.Albini, J. Ophthal. Inflamm. Infect. 2013, 3, 58.

[19] A.Invernizzi, C.Mapelli, F.Viola, M.Cigada, L.Cimino, R.Ratiglia, G.Staurenghi, A.Gupta, Retina 2015, 35, 525.

[20] J.Yokoyama, M.Fujimaki, S.Ohba, T.Anzai, R.Yoshii, S.Ito, M.Kojima, K.Ikeda, OncoTargets Ther. 2013, 6, 325.

[21] S.van Keulen, N.Nishio, S.Fakurnejad, N. S.van den Berg, G. Lu, A.Birkeland, B. A.Martin, T.Forouzanfar, D. A.Colevas, E. L.Rosenthal, J. Am. Coll. Surg. 2019, 229, 560.

[22] S.van Keulen, N.Nishio, S.Fakurnejad, A.Birkeland, B. A.Martin, G.Lu, Q.Zhou, S. U.Chirita, T.Forouzanfar, A. D.Colevas, N. S.van den Berg, E. L.Rosenthal, J. Nucl. Med. 2019, 60, 758.

[23] W. S.Tummers, J. M.Warram, N. S.van den Berg, S. E.Miller, R. J.Swijnenburg, A. L.Vahrmeijer, E. L.Rosenthal, Theranostics 2018, 8, 5336.

[24] B.Shen, Z.Zhang, X.Shi, C. Cao, Z.Hu, N.Ji, J.Tian, Eur. J. Nucl. Med. Mol. Imaging 2021, 48, 3482.

[25] F.Dip, L.Boni, M.Bouvet, T. Carus, M.Diana, J.Falco, G. C.Gurtner, T.Ishizawa, N.Kokudo, E.Lo Menzo, P. S.Low, J.Masia, D.Muehrcke, F. A.Papay, C.Pulitano, S.Schneider-Koraith, D.Sherwinter, G.Spinoglio, L.Stassen, Y.Urano, A.Vahrmeijer, E.Vibert, J.Warram, S. D.Wexner, K.White, R. J.Rosenthal, Ann. Surg. 2022, 275, 685.

[26] W.Stummer, U.Pichlmeier, T.Meinel, O. D.Wiestler, F.Zanella, H. J.Reulen, Lancet Oncol. 2006, 7, 392.

[27] Y.Liao, Z.Peng, X.Liu, Y. Hu, J.Zhang, Interdiscip. Med. 2023, 1, e20230024.

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2024 The Author(s). Interdisciplinary Medicine published by Wiley-VCH GmbH on behalf of Nanfang Hospital, Southern Medical University.