Optimization of Second Window Indocyanine Green for Intraoperative Near-Infrared Imaging of Thoracic Malignancy

Andrew D. Newton, Jarrod D. Predina, Christopher J. Corbett, Lydia G. Frenzel-Sulyok, Leilei Xia, E. James Petersson, Andrew Tsourkas, Shuming Nie, Edward J. Delikatny, Sunil Singhal

Research output: Contribution to journalArticle

Abstract

Background: Near-infrared (NIR) imaging using the second time window of indocyanine green (ICG) allows localization of pulmonary, pleural, and mediastinal malignancies during surgery. Based on empirical evidence, we hypothesized that different histologic tumor types fluoresce optimally at different ICG doses. Study Design: Patients with thoracic tumors biopsy-proven or suspicious for malignancy were enrolled in an NIR imaging clinical trial. Patients received a range of ICG doses 1 day before surgery: 1 mg/kg (n = 8), 2 mg/kg (n = 8), 3 mg/kg (n = 13), 4 mg/kg (n = 8), and 5 mg/kg (n = 8). Intraoperatively, NIR imaging was performed. The endpoint was to identify the highest tumor-to-background fluorescence ratio (TBR) for each tumor type at each dose. Final pathology confirmed tumor histology. Results: Of 45 patients, 41 had malignancies (18 non-small cell lung cancers [NSCLC], 3 pulmonary neuroendocrine tumors, 13 thoracic metastases, 4 thymomas, 3 mesotheliomas). At doses of 4 to 5 mg/kg, the TBR from primary NSCLC vs other malignancies was no different (2.70 vs 3.21, p = 1.00). At doses of 1 to 3 mg/kg, the TBR was greater for the NSCLCs (3.19 vs 1.49, p = 0.0006). Background fluorescence from the heart or ribs was observed in 1 of 16 cases at 1 to 2 mg/kg, 5 of 13 cases at 3 mg/kg, and 14 of 16 cases at 4 to 5 mg/kg; this was a major determinant of dose optimization. Conclusions: This is the first study to demonstrate that the optimal NIR contrast agent dose varies by tumor histology. Lower dose ICG (2 to 3 mg/kg) is superior for nonprimary lung cancers, and high dose ICG (4 to 5 mg/kg) is superior for lung cancers. This will have major implications as more intraoperative imaging trials surface in other specialties, will significantly reduce costs and may facilitate wider application.

Original languageEnglish (US)
Pages (from-to)188-197
Number of pages10
JournalJournal of the American College of Surgeons
Volume228
Issue number2
DOIs
StatePublished - Feb 2019

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Indocyanine Green
Thorax
Neoplasms
Fluorescence
Non-Small Cell Lung Carcinoma
Lung Neoplasms
Histology
Lung
Thymoma
Neuroendocrine Tumors
Mesothelioma
Ribs
Ambulatory Surgical Procedures
Contrast Media
Clinical Trials
Pathology
Neoplasm Metastasis
Biopsy
Costs and Cost Analysis

ASJC Scopus subject areas

  • Surgery

Cite this

Newton, A. D., Predina, J. D., Corbett, C. J., Frenzel-Sulyok, L. G., Xia, L., Petersson, E. J., ... Singhal, S. (2019). Optimization of Second Window Indocyanine Green for Intraoperative Near-Infrared Imaging of Thoracic Malignancy. Journal of the American College of Surgeons, 228(2), 188-197. https://doi.org/10.1016/j.jamcollsurg.2018.11.003

Optimization of Second Window Indocyanine Green for Intraoperative Near-Infrared Imaging of Thoracic Malignancy. / Newton, Andrew D.; Predina, Jarrod D.; Corbett, Christopher J.; Frenzel-Sulyok, Lydia G.; Xia, Leilei; Petersson, E. James; Tsourkas, Andrew; Nie, Shuming; Delikatny, Edward J.; Singhal, Sunil.

In: Journal of the American College of Surgeons, Vol. 228, No. 2, 02.2019, p. 188-197.

Research output: Contribution to journalArticle

Newton, AD, Predina, JD, Corbett, CJ, Frenzel-Sulyok, LG, Xia, L, Petersson, EJ, Tsourkas, A, Nie, S, Delikatny, EJ & Singhal, S 2019, 'Optimization of Second Window Indocyanine Green for Intraoperative Near-Infrared Imaging of Thoracic Malignancy', Journal of the American College of Surgeons, vol. 228, no. 2, pp. 188-197. https://doi.org/10.1016/j.jamcollsurg.2018.11.003
Newton, Andrew D. ; Predina, Jarrod D. ; Corbett, Christopher J. ; Frenzel-Sulyok, Lydia G. ; Xia, Leilei ; Petersson, E. James ; Tsourkas, Andrew ; Nie, Shuming ; Delikatny, Edward J. ; Singhal, Sunil. / Optimization of Second Window Indocyanine Green for Intraoperative Near-Infrared Imaging of Thoracic Malignancy. In: Journal of the American College of Surgeons. 2019 ; Vol. 228, No. 2. pp. 188-197.
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abstract = "Background: Near-infrared (NIR) imaging using the second time window of indocyanine green (ICG) allows localization of pulmonary, pleural, and mediastinal malignancies during surgery. Based on empirical evidence, we hypothesized that different histologic tumor types fluoresce optimally at different ICG doses. Study Design: Patients with thoracic tumors biopsy-proven or suspicious for malignancy were enrolled in an NIR imaging clinical trial. Patients received a range of ICG doses 1 day before surgery: 1 mg/kg (n = 8), 2 mg/kg (n = 8), 3 mg/kg (n = 13), 4 mg/kg (n = 8), and 5 mg/kg (n = 8). Intraoperatively, NIR imaging was performed. The endpoint was to identify the highest tumor-to-background fluorescence ratio (TBR) for each tumor type at each dose. Final pathology confirmed tumor histology. Results: Of 45 patients, 41 had malignancies (18 non-small cell lung cancers [NSCLC], 3 pulmonary neuroendocrine tumors, 13 thoracic metastases, 4 thymomas, 3 mesotheliomas). At doses of 4 to 5 mg/kg, the TBR from primary NSCLC vs other malignancies was no different (2.70 vs 3.21, p = 1.00). At doses of 1 to 3 mg/kg, the TBR was greater for the NSCLCs (3.19 vs 1.49, p = 0.0006). Background fluorescence from the heart or ribs was observed in 1 of 16 cases at 1 to 2 mg/kg, 5 of 13 cases at 3 mg/kg, and 14 of 16 cases at 4 to 5 mg/kg; this was a major determinant of dose optimization. Conclusions: This is the first study to demonstrate that the optimal NIR contrast agent dose varies by tumor histology. Lower dose ICG (2 to 3 mg/kg) is superior for nonprimary lung cancers, and high dose ICG (4 to 5 mg/kg) is superior for lung cancers. This will have major implications as more intraoperative imaging trials surface in other specialties, will significantly reduce costs and may facilitate wider application.",
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AU - Newton, Andrew D.

AU - Predina, Jarrod D.

AU - Corbett, Christopher J.

AU - Frenzel-Sulyok, Lydia G.

AU - Xia, Leilei

AU - Petersson, E. James

AU - Tsourkas, Andrew

AU - Nie, Shuming

AU - Delikatny, Edward J.

AU - Singhal, Sunil

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N2 - Background: Near-infrared (NIR) imaging using the second time window of indocyanine green (ICG) allows localization of pulmonary, pleural, and mediastinal malignancies during surgery. Based on empirical evidence, we hypothesized that different histologic tumor types fluoresce optimally at different ICG doses. Study Design: Patients with thoracic tumors biopsy-proven or suspicious for malignancy were enrolled in an NIR imaging clinical trial. Patients received a range of ICG doses 1 day before surgery: 1 mg/kg (n = 8), 2 mg/kg (n = 8), 3 mg/kg (n = 13), 4 mg/kg (n = 8), and 5 mg/kg (n = 8). Intraoperatively, NIR imaging was performed. The endpoint was to identify the highest tumor-to-background fluorescence ratio (TBR) for each tumor type at each dose. Final pathology confirmed tumor histology. Results: Of 45 patients, 41 had malignancies (18 non-small cell lung cancers [NSCLC], 3 pulmonary neuroendocrine tumors, 13 thoracic metastases, 4 thymomas, 3 mesotheliomas). At doses of 4 to 5 mg/kg, the TBR from primary NSCLC vs other malignancies was no different (2.70 vs 3.21, p = 1.00). At doses of 1 to 3 mg/kg, the TBR was greater for the NSCLCs (3.19 vs 1.49, p = 0.0006). Background fluorescence from the heart or ribs was observed in 1 of 16 cases at 1 to 2 mg/kg, 5 of 13 cases at 3 mg/kg, and 14 of 16 cases at 4 to 5 mg/kg; this was a major determinant of dose optimization. Conclusions: This is the first study to demonstrate that the optimal NIR contrast agent dose varies by tumor histology. Lower dose ICG (2 to 3 mg/kg) is superior for nonprimary lung cancers, and high dose ICG (4 to 5 mg/kg) is superior for lung cancers. This will have major implications as more intraoperative imaging trials surface in other specialties, will significantly reduce costs and may facilitate wider application.

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