Photoacoustic tomography of human hepatic malignancies using intraoperative indocyanine green fluorescence imaging.
Recently, fluorescence imaging following the preoperative intravenous injection of indocyanine green has been used in clinical settings to identify hepatic malignancies during surgery. The aim of this study was to evaluate the ability of photoacoustic tomography using indocyanine green as a contrast agent to produce representative fluorescence images of hepatic tumors by visualizing the spatial distribution of indocyanine green on ultrasonographic images. Indocyanine green (0.5 mg/kg, intravenous) was preoperatively administered to 9 patients undergoing hepatectomy. Intraoperatively, photoacoustic tomography was performed on the surface of the resected hepatic specimens (n = 10) under excitation with an 800 nm pulse laser. In 4 hepatocellular carcinoma nodules, photoacoustic imaging identified indocyanine green accumulation in the cancerous tissue. In contrast, in one hepatocellular carcinoma nodule and five adenocarcinoma foci (one intrahepatic cholangiocarcinoma and 4 colorectal liver metastases), photoacoustic imaging delineated indocyanine green accumulation not in the cancerous tissue but rather in the peri-cancerous hepatic parenchyma. Although photoacoustic tomography enabled to visualize spatial distribution of ICG on ultrasonographic images, which was consistent with fluorescence images on cut surfaces of the resected specimens, photoacoustic signals of ICG-containing tissues decreased approximately by 40% even at 4 mm depth from liver surfaces. Photoacoustic tomography using indocyanine green also failed to identify any hepatocellular carcinoma nodules from the body surface of model mice with non-alcoholic steatohepatitis. In conclusion, photoacoustic tomography has a potential to enhance cancer detectability and differential diagnosis by ultrasonographic examinations and intraoperative fluorescence imaging through visualization of stasis of bile-excreting imaging agents in and/or around hepatic tumors. However, further technical advances are needed to improve the visibility of photoacoustic signals emitted from deeply-located lesions.
Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
Akinori
A
Miyata
Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
Takeaki
T
Ishizawa
Laboratory of Chemical Biology and Molecular Imaging, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
Mako
M
Kamiya
Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
Atsushi
A
Shimizu
Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
Junichi
J
Kaneko
Department of Gastroenterology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
Hideaki
H
Ijichi
Department of Pathology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
Junji
J
Shibahara
Department of Pathology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
Masashi
M
Fukayama
Genome Science Division, Research Center for Advanced Science & Technology, the University of Tokyo, Tokyo, Japan.
Yutaka
Y
Midorikawa
Laboratory of Chemical Biology and Molecular Imaging, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
Yasuteru
Y
Urano
Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
Norihiro
N
Kokudo
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D005453:Fluorescence; D006801:Humans; D007208:Indocyanine Green; D007430:Intraoperative Care; D008099:Liver / Q000473:pathology / Q000601:surgery; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000601:surgery; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D061088:Photoacoustic Techniques / Q000295:instrumentation / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D041622:Tomography, Optical / Q000295:instrumentation / Q000379:methods*; D014183:Transplantation, Heterologous
D007208:Indocyanine Green