Illuminating necrosis: From mechanistic exploration to preclinical application using fluorescence molecular imaging
Cheng Fang1,2, Kun Wang2,3, Chaoting Zeng1
1Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
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.
Insights
Indocyanine green (ICG) effectively targets necrotic tissue by interacting with lipoproteins and phospholipids. This breakthrough enables precise detection and image-guided surgery for improved patient outcomes.
Area of Science:
- Biomedical Imaging
- Molecular Imaging
- Surgical Technology
Background:
- Tissue necrosis is a hallmark of many severe diseases, necessitating accurate detection and delineation for effective clinical management.
- Current imaging modalities lack the sensitivity and precision required for identifying necrotic tissue boundaries.
- Fluorescence molecular imaging (FMI) offers potential, but a lack of specific necrosis-avid probes limits its clinical application.
Purpose of the Study:
- To investigate the potential of indocyanine green (ICG) as a necrosis-avid fluorescent probe for enhanced tissue imaging.
- To elucidate the cellular and molecular mechanisms underlying ICG's selective accumulation in necrotic tissues.
- To demonstrate the feasibility of using ICG-based FMI for real-time image-guided surgery in preclinical models.
Main Methods:
- In vitro studies were conducted to explore the interaction of ICG with lipoproteins and phospholipids at cellular and molecular levels.
- Fluorescence molecular imaging (FMI) techniques were employed using custom-designed imaging devices.
- Preclinical studies in various animal models were performed to assess the detection and delineation capabilities of ICG for necrotic tissue.
Main Results:
- ICG demonstrated high avidity for necrotic tissue, attributed to its interaction with lipoprotein and phospholipids.
- The mechanism of ICG's necrosis targeting was elucidated through in vitro cellular and molecular investigations.
- FMI with ICG successfully enabled real-time image-guided surgery, accurately detecting necrotic tissue as small as 0.6 mm in diameter with precise boundary definition.
Conclusions:
- Indocyanine green is a promising necrosis-avid fluorescent agent for clinical applications.
- ICG-based FMI facilitates precise detection and delineation of necrotic tissue, improving surgical accuracy.
- This approach holds significant potential for advancing personalized and precise surgical interventions in the future.
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