title: Illuminating necrosis: From mechanistic exploration to preclinical application using fluorescence molecular imaging with indocyanine green.
abstract: Tissue necrosis commonly accompanies the development of a wide range of serious diseases. Therefore, highly sensitive detection and precise boundary delineation of necrotic tissue via effective imaging techniques are crucial for clinical treatments; however, no imaging modalities have achieved satisfactory results to date. Although fluorescence molecular imaging (FMI) shows potential in this regard, no effective necrosis-avid fluorescent probe has been developed for clinical applications. Here, we demonstrate that indocyanine green (ICG) can achieve high avidity of necrotic tissue owing to its interaction with lipoprotein (LP) and phospholipids. The mechanism was explored at the cellular and molecular levels through a series of in vitro studies. Detection of necrotic tissue and real-time image-guided surgery were successfully achieved in different organs of different animal models with the help of FMI using in house-designed imaging devices. The results indicated that necrotic tissue with a 0.6 mm diameter could be effectively detected with precise boundary definition. We believe that the new discovery and the associated imaging techniques will improve personalized and precise surgery in the near future.
authors: Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.|Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China.
authors: Cheng
authors: C
authors: Fang
authors: Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China.|Beijing Key Laboratory of Molecular Imaging, Beijing 100190, China.
authors: Kun
authors: K
authors: Wang
authors: Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors: Chaoting
authors: C
authors: Zeng
authors: Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China.|Beijing Key Laboratory of Molecular Imaging, Beijing 100190, China.
authors: Chongwei
authors: C
authors: Chi
authors: Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China.
authors: Wenting
authors: W
authors: Shang
authors: Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China.
authors: Jinzuo
authors: J
authors: Ye
authors: Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China.
authors: Yamin
authors: Y
authors: Mao
authors: Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors: Yingfang
authors: Y
authors: Fan
authors: Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors: Jian
authors: J
authors: Yang
authors: Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors: Nan
authors: N
authors: Xiang
authors: Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors: Ning
authors: N
authors: Zeng
authors: Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors: Wen
authors: W
authors: Zhu
authors: Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors: Chihua
authors: C
authors: Fang
authors: Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China.|Beijing Key Laboratory of Molecular Imaging, Beijing 100190, China.
authors: Jie
authors: J
authors: Tian
mesh_terms: D000818:Animals; D002056:Burns / Q000150:complications / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D002460:Cell Line; D005260:Female; D005456:Fluorescent Dyes / Q000032:analysis* / Q000378:metabolism; D006614:Hindlimb; D006801:Humans; D007208:Indocyanine Green / Q000032:analysis* / Q000378:metabolism; D008027:Light; D008074:Lipoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000473:pathology / Q000601:surgery; D009336:Necrosis / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology / Q000601:surgery; D061848:Optical Imaging / Q000379:methods*; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D025321:Surgery, Computer-Assisted / Q000379:methods*
chemical_list: D005456:Fluorescent Dyes; D008074:Lipoproteins; D010743:Phospholipids; D007208:Indocyanine Green