Real-Time Fluorescence Imaging in Thoracic Surgery

Fig. 1. Intraoperative fluorescence imaging systems. (A) Dual-channel FLARE imaging system [14,15], (B) endoscopic imaging system [19], (C) multiscale multispectral imaging system [10,13], and (D) da Vinci Surgical System [40]. NIR, near-infrared; CCD, charge-coupled device; LED, light emitting diode; FLARE, Fluorescence-Assisted Resection and Exploration.

Fig. 2. The NIR window and NIR fluorophores for image-guided surgery. (A) In vivo penetration of fluorescence light and photon travel according to wavelength [9], and (B) chemical structures and optical properties of NIR fluorophores for MB, ICG, and ZW800-1 [15]. NIR, near-infrared; MB, methylene blue; ICG, indocyanine green.

Fig. 3. Dual-channel imaging of cartilage and bone. (A) Chemical structures of C700-OMe [22] and P800SO3 [23] for cartilage- and bone-specific imaging, respectively. (B) Simultaneous cartilage and bone imaging in mice (top) and pigs (bottom). Scale bars=1 cm. C700-SO3 and P800-SO3 were injected intravenously 4 hours prior to imaging [22].

Fig. 4. Intraoperative imaging of vasculature and nerves. (A) Atherosclerotic (top) and normal (bottom) arteries from a rabbit injected with 1.5 mg/kg of ICG 45 minutes prior to imaging [49]. Scale bar=2 cm. (B) Intraoperative cardiac imaging using IR786-labeled bone marrow stem cells in a Yorkshire pig [1]. (C) Intraoperative imaging of brachial plexus and sciatic nerve 4 hours post-injection of Ox4 (200 nmol) in Sprague-Dawley rats [56]. Arrowheads indicate fluorescence signals in nervous tissue and bundles. Scale bars=1 cm. NIR, near-infrared; MB, methylene blue; ICG, indocyanine green.

Fig. 5. Clinical imaging of the thymus in young child patients and preclinical imaging of the thymus in rodents and pigs. (A) CT scan shows a thymus with enlarged lymph nodes and a thymic mass with a necrotic core [59]. CT, computed tomography. (B) Ultrasound of a normal thymus (arrows) with smooth borders and echotexture between liver and thyroid [59]. AA, aortic arch; PA, pulmonary artery. (C) A CT/sagittal positron emission tomography scan showing a normal thymus in a young patient with Burkitt lymphoma injected with 18F-FDG [59]. Arrows indicate thymic tissues without FDG avidity. FDG, fludeoxyglucose. (D) Chemical structure of Ox170 and intraoperative thymus imaging in mice. Dose-dependent imaging of Ox170 was obtained 4 hours after an intravenous injection [29]. (E) 10 μmol of Ox170 was injected into 35-kg Yorkshire pigs 8 hours prior to imaging [29]. Th, thymus (arrowhead); He, heart; Lu, lung; LN, lymph node; Ne, nerve; Tr, trachea; TG, thyroid gland (arrow). Scale bars=1 cm.

Fig. 6. Intraoperative tumor-specific imaging in lungs. (A) Adenocarcinomas in a lung tumor mouse model injected with 6CQNIR fluorophores (20 nmol) 6 hours prior to imaging [62]. Cancerous lung tissues highlighted with increased fluorescence (white dashed circle) were then analyzed by hematoxylin and eosin (H&E) staining. Scale bars=100 μm. (B) Preoperative CT and intraoperative fluorescence imaging of thymic carcinosarcoma [63]. An anterior mediastinal mass was resected in a patient with primary sarcoma via NIR fluorescence image guidance after injecting ICG 24 hours prior to resection (5 mg/kg). (C) Thoracoscopic tumor imaging highlighted by a percutaneous injection of ICG (0.5 mL; <0.125 mg/mL) 15 minutes prior to imaging into lung cancer patients [65]. Lobectomy of primary lung cancer was performed in all patients. Resected tumor specimen with lung nodule highlighted in yellow circle. (D) NIR imaging was used to detect a pulmonary nodule tumor 24 hours after injection of 5 mg/kg of ICG during open thoracotomy [66]. H&E staining was performed on resected tumors and an NIR microscopy image was taken under a 760-nm light source at ×100 magnification. NIR, near-infrared; ICG, indocyanine…

Fig. 7. SLN resection in mice, pigs, and humans using small-molecule fluorophores. (A) Chemical structures of ICG, ESNF14, and ZW800-3a. (B) 100 nmol (0.1 mL, 1 mg/mL) of ICG solution was injected into the armpit of a mouse 10 minutes prior to imaging and resection. NIR, color, and merged images obtained before and after resection of SLNs [78]. (C) NIR fluorescence-guided SLN mapping and resection was performed in humans 10–15 minutes after injection of ICG (1–2 mL, 2.5 mg/mL) [78]. (D) Dual-channel intraoperative NIR imaging of pan lymph nodes and SLN mapping. ESNF14 (5 nmol) was injected intradermally (NIR #1, red) and 320 nmol of ZW800-3a (NIR #2, lime green) was injected intravenously into the same Yorkshire pig 5 minutes and 4 hours before imaging, respectively [31]. Circle indicates SLN; arrowheads indicate pan lymph nodes. SLN, sentinel lymph node; ICG, indocyanine green; NIR, near-infrared.