Combined indocyanine green and medical glue enables stable and precise position in animal studies: promising for fluorescence-guided pulmonary ground glass nodule resection

BACKGROUND: Accurate preoperative localization of pulmonary nodules is crucial for surgical treatment. The use of indocyanine green (ICG) for localization is prone to thoracic contamination and spread, resulting in the eventual failure of localization. By using medical glue combined with ICG, we can accurately and permanently locate various tissues in animal study, which can provide evidences for clinical translations. METHODS: A series of medical glue and ICG volume ratios of 2:3, 3:3, 4:3, 6:3, and 9:3 were mixed and injected immediately into subcutaneous tissues of BALB/c nude mice; either medical glue or ICG was injected singly in the control group. Fluorescence intensity over time and boundary sharpness were investigated to determine the optimal ratio. Then, fluorescence guided resection of tissue was performed ex vivo on the pig intestine utilizing optimal ratio. Further, localization agents with the optimal ratio were injected into the organs of living mice, and fluorescence imaging for accurate positioning was performed 24 hours later. RESULTS: The localization agents with a volume ratio of 4:3 showed the best boundary sharpness and the strongest photostability. With the guidance of fluorescence navigation, the marked tissues were accurately separated and removed from the surrounding tissue both on mice and on pig intestines. In the organs of living mice, the localization agents (ratio 4:3) realized accurate positioning of marked tissues. Additionally, the medical glue limited the diffusion of ICG, promising to enable more stable and precise positioning of the nodules during surgery. CONCLUSIONS: The combination of ICG and medical glue presents a superior approach when compared to the individual use of either ICG or medical glue. This technique offers enhanced precision and durability and sealed the wound, thereby mitigating the risk of pneumothorax following puncture procedures. This innovative technique optimizes the properties of medical adhesive to augment tissue density while harnessing the real-time fluorescent endoscopic marking capabilities of ICG during surgical interventions. By employing this innovative technique, it holds significant promise for augmenting the accuracy of pulmonary nodule localization in thoracoscopic surgery within future clinical applications.