Real‐time identification of liver cancers by using indocyanine green fluorescent imaging

Abstract

BACKGROUND: We have often encountered difficulties in identifying small liver cancers during surgery. Fluorescent imaging using indocyanine green (ICG) has the potential to detect liver cancers through the visualization of the disordered biliary excretion of ICG in cancer tissues and noncancerous liver tissues compressed by the tumor. METHODS: ICG had been intravenously injected for a routine liver function test in 37 patients with hepatocellular carcinoma (HCC) and 12 patients with metastasis of colorectal carcinoma (CRC) before liver resection. Surgical specimens were investigated using a near‐infrared light camera system. Among the 49 subjects, the 26 patients examined during the latter period of the study (20 with HCC and 6 with metastasis) underwent ICG‐fluorescent imaging of the liver surfaces before resection. RESULTS: ICG‐fluorescent imaging identified all of the microscopically confirmed HCCs (n = 63) and CRC metastases (n = 28) in surgical specimens. Among the 63 HCCs, 8 tumors (13%, including 5 early HCCs) were not evident grossly unless observed by ICG‐fluorescent imaging. Five false‐positive nodules (4 large regenerative nodules and 1 bile duct proliferation) were identified among the fluorescent lesions. Well‐differentiated HCCs appeared as uniformly fluorescing lesions with higher lesion‐to‐liver contrast than that of moderately or poorly differentiated HCCs (162.6 [71.1‐218.2] per pixel vs 67.7 [‐6.3‐211.2] per pixel, P < .001), while CRC metastases were delineated as rim‐fluorescing lesions. Fluorescent microscopy confirmed that fluorescence originated in the cytoplasm and pseudoglands of HCC cells and in the noncancerous liver parenchyma surrounding metastases. ICG‐fluorescent imaging before resection identified 21 of the 41 HCCs (51%) and all of the 16 metastases that were examined. CONCLUSIONS: ICG‐fluorescent imaging enables the highly sensitive identification of small and grossly unidentifiable liver cancers in real time, enhancing the accuracy of liver resection and operative staging. Cancer 2009. © 2009 American Cancer Society.

Parathyroid gland angiography with indocyanine green fluorescence to predict parathyroid function after thyroid surgery

“…ICG was prepared according to protocols used for abdominal surgery10; the dye was mixed with 10 ml sterile water, and 3·5 ml was injected intravenously. The injection could be repeated until a maximum dose of 5 mg per kg per day was reached.…”

“…Initially used in the detection of macular degeneration8, the technique of angiography using indocyanine green (ICG) has been used to identify sentinel lymph nodes9, to determine the extent of oncological resections10 and to study hepatic function11. Recent studies have also demonstrated its usefulness in evaluating the vascular blood flow of intestinal anastomoses12.…”

A reappraisal of vascular anatomy of the parathyroid gland based on fluorescence techniques

“…Subsequently, ICG angiography has been used to identify sentinel lymph nodes (37), determine the extent of oncologic resections (38), and study hepatic function (39). Recent studies have also demonstrated its usefulness in evaluating the vascular blood flow of intestinal anastomoses (40) and tissue flap reconstructions (41).…”

“…At our center, ICG for thyroid or parathyroid surgery is prepared according to the protocols used for abdominal surgery (38). Briefly, 25 mg ICG is mixed with 10 mL of sterile water (concentration, 2.5 mg/mL), and 3.5 mL is injected intravenously during the procedure by the anesthesia team.…”

Intraoperative molecular imaging to identify lung adenocarcinomas

“…ICG cannot escape the tight junctions of normal capillaries but extravasates from the leaky capillaries of tumors and becomes trapped in that tissue (23). Several groups have demonstrated in human patients that ICG can be used to detect hepatocellular carcinoma (HCC) and colorectal cancer liver metastases (24,25).…”