Evaluation of Intraoperative Near-Infrared Fluorescence Visualization of the Lung Tumor Margin With Indocyanine Green Inhalation

Abstract

Identification of the tumor margin during surgery is important for precise minimal resection of lung tumors. Intravenous injection of indocyanine green (ICG) has several limitations when used for intraoperative visualization of lung cancer.OBJECTIVES To describe a technique for intraoperative visualization of lung tumor margin using ICG inhalation and evaluate the clinical applicability of the technique in mouse and rabbit lung tumor models as well as lung specimens of patients with lung tumors. DESIGN, SETTING, AND PARTICIPANTSIn lung tumor models of both mice and rabbits, the distribution of inhaled ICG in the lung tumor margin was investigated in vivo and ex vivo using a near-infrared imaging system. Lung tumor margin detection via inhalation of ICG was evaluated by comparing the results obtained with those of the intravenous injection method (n = 32, each time point for 4 mice). Based on preclinical data, use of ICG inhalation to help detect the tumor margin in patients with lung cancer was also evaluated (n = 6). This diagnostic study was conducted from May 31, 2017, to March 30, 2019. MAIN OUTCOMES AND MEASURESThe use of tumor margin detection by inhaled ICG was evaluated by comparing the inhaled formulation with intravenous administration of ICG. RESULTSFrom 10 minutes after inhalation of ICG to 24 hours, the distribution of ICG in the lungs was significantly higher than that in other organs (signal to noise ratio in the lungs: 39 486.4; interquartile range [IQR], 36 983.74-43 592.5). Ex vivo and histologic analysis showed that, in both lung tumor models, inhaled ICG was observed throughout the healthy lung tissue but was rarely found in tumor tissue. The difference in the fluorescent signal between healthy and tumor lung tissues was associated with the mechanical airway obstruction caused by the tumor and with alveolar macrophage uptake of the inhaled ICG in healthy tissues. Inhalation at a 20-fold lower dose of ICG had a 2-fold higher efficiency for tumor margin detection than did the intravenous injection (2.9; IQR, 2.7-3.2; P < .001). CONCLUSIONS AND RELEVANCEThe results of this study suggest that lung-specific inhalation delivery of ICG is feasible and may be useful for the intraoperative visualization of lung tumor margin in clinical practice.

Near-infrared fluorescent imaging with indocyanine green in rabbit and patient specimens of esophageal cancer

“…The signal greater than 1 means the intensity of tumor is higher than the normal, and the tumor has signal. Also, it can be easily distinguished the cancer and normal tissue by the fluorescent when the signal of TNR is higher than 2 (14). All specimens were evaluated by the experimenter as formalin-fixed and paraffin-embedded sections stained with hematoxylin and eosin (H&E) and subsequently confirmed through pathology of the permanent sections in all cases.…”

Near-Infrared Fluorescence Tumor-Targeted Imaging in Lung Cancer: A Systematic Review

“…The peak absorption of ICG is 780 nm and, after binding to plasma proteins, emits light at 805 nm [ 126 ]. ICG was described as a fluorescent agent in lung cancer [ 65 , 66 , 67 , 68 , 69 , 70 , 71 ]. One of these studies is a preclinical trial, four are clinical trials, and two are a combination of both.…”

“…In all of these studies, ICG was administered intravenously; however, the possibility of intraoperative imaging using ICG inhalation has also been studied in a preclinical setting [ 71 ]. Fluorescence should be visible only in healthy lung tissue and not in tumor tissue because the tumor causes airflow obstruction and the destruction of alveoli.…”

Lobectomy Versus Segmentectomy in Patients with Stage T (&gt;2 cm and ≤3 cm) N0M0 Non-small Cell Lung Cancer: A Propensity Score Matching Study

“…Segmentectomy requires more anatomic complexity and variation than lobectomy. This procedure also involves precise lesion positioning during surgery and the identi cation of lung boundaries [17,18,19].…”