Li Li1,2, Yang Du2, Xinjian Chen3, Jie Tian4. 1. School of Electronic and Information Engineering, Soochow University, No. 1 Ten Azusa Street, Suzhou, 215006, China. 2. CAS Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, No. 95 Zhongguancun East Road, Haidian District, Beijing, 100190, China. 3. School of Electronic and Information Engineering, Soochow University, No. 1 Ten Azusa Street, Suzhou, 215006, China. xjchen@suda.edu.cn. 4. CAS Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, No. 95 Zhongguancun East Road, Haidian District, Beijing, 100190, China. tian@ieee.org.
Abstract
PURPOSE: Malignant gliomas are major causes of cancer-related mortality and morbidity. Traditional surgery usually leads to incomplete resection of gliomas resulting in the high incidence of tumor recurrence. Advanced medical imaging technology, such as fluorescence imaging-guided surgery, combined with tumor-specific imaging probes allows the identification of tumor margins and improved surgery. However, there are two pressing issues that need to be addressed: first, few fluorescence imaging probes can specifically target gliomas; second, fluorescence molecular imaging (FMI) cannot get the in-depth information of deep-seated gliomas; both of which affect the complete removal of the gliomas. PROCEDURES: In this study, the biodistribution of smart matrix metalloproteinase (MMP) targeting near-infrared (NIR) fluorescent probe MMPSense 750 FAST (MMP-750) was examined in both U87MG-GFP-fLuc glioma xenograft and orthotopic mouse models using FMI. Then, CT and FMI images of orthotopic gliomas were acquired for the reconstruction of fluorescence molecular tomography (FMT) using a randomly enhanced adaptive subspace pursuit (REASP) algorithm. Furthermore, the resection of orthotopic glioma was performed using the fluorescence surgical navigation system after the injection of the MMP-750 probe. After surgery, bioluminescence imaging (BLI) and hematoxylin and eosin staining were carried out to confirm the precision resection of the tumor. RESULTS: FMI results showed that the MMP-750 probe can specifically target U87MG glioma in vivo. FMT presented the spatial information of the orthotopic glioma using the REASP reconstruction algorithm. Furthermore, MMP-750 could effectively delineate the tumor margin during glioma surgery leading to a complete resection of the tumors. CONCLUSIONS: The smart MMP-750 specifically targets the glioma and FMT of MMP-750 provides 3D information for the spatial localization of the glioma. MMP-750 can work as an ideal fluorescence probe for guiding the intraoperative surgical resection of the glioma, possessing clinical translation.
PURPOSE:Malignant gliomas are major causes of cancer-related mortality and morbidity. Traditional surgery usually leads to incomplete resection of gliomas resulting in the high incidence of tumor recurrence. Advanced medical imaging technology, such as fluorescence imaging-guided surgery, combined with tumor-specific imaging probes allows the identification of tumor margins and improved surgery. However, there are two pressing issues that need to be addressed: first, few fluorescence imaging probes can specifically target gliomas; second, fluorescence molecular imaging (FMI) cannot get the in-depth information of deep-seated gliomas; both of which affect the complete removal of the gliomas. PROCEDURES: In this study, the biodistribution of smart matrix metalloproteinase (MMP) targeting near-infrared (NIR) fluorescent probe MMPSense 750 FAST (MMP-750) was examined in both U87MG-GFP-fLuc glioma xenograft and orthotopic mouse models using FMI. Then, CT and FMI images of orthotopic gliomas were acquired for the reconstruction of fluorescence molecular tomography (FMT) using a randomly enhanced adaptive subspace pursuit (REASP) algorithm. Furthermore, the resection of orthotopic glioma was performed using the fluorescence surgical navigation system after the injection of the MMP-750 probe. After surgery, bioluminescence imaging (BLI) and hematoxylin and eosin staining were carried out to confirm the precision resection of the tumor. RESULTS: FMI results showed that the MMP-750 probe can specifically target U87MG glioma in vivo. FMT presented the spatial information of the orthotopic glioma using the REASP reconstruction algorithm. Furthermore, MMP-750 could effectively delineate the tumor margin during glioma surgery leading to a complete resection of the tumors. CONCLUSIONS: The smart MMP-750 specifically targets the glioma and FMT of MMP-750 provides 3D information for the spatial localization of the glioma. MMP-750 can work as an ideal fluorescence probe for guiding the intraoperative surgical resection of the glioma, possessing clinical translation.
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