面向荧光剂药代动力学的动态扩散荧光层析系统
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摘要
为捕捉生物组织体内快速变化的荧光信号,并借鉴扩散荧光层析在穿透深度、高灵敏度等方面的优势,设计了一套具备快速实时采样能力的动态扩散荧光层析成像在体测量系统.该系统采用多光源-探测器布配方案,结合光电倍增管探测器与锁相光子计数检测技术,具有高空间采样密度、高探测灵敏度、大动态测量范围以及高性价比等优势.有效性评估实验表明:该系统具备良好的稳定性和很强的环境光抑制能力,频率串扰率低于1.39%.仿体成像实验表明:该系统能够有效地对单个和多个目标体成像.活体健康小鼠吲哚菁绿肝代谢实验进一步表明:该系统可有效捕捉小鼠体内快速变化的荧光信号,能够用于荧光剂药代动力学研究.
To capture the fast-changing fluorescence information during a finite metabolism process in vivo,a dynamic system with the ability of parallel detection was developed based on the merits of high penetration depth and sensitivity of diffuse fluorescence tomography.It adopts the mode of muti-source and muti-detector,and combines photo-multiplier tube detector and lock-in photon-counting technique to achieve high spatial sampling density,high sensitivity,wide dynamic range,as well as better costeffectiveness.The assessment results show that this system has good performances in stability and ambient light suppression,and the crosstalk-rate of frequency belows 1.39%.The phantom experiment demonstrates the favorable abilities of imaging single and multiple targets.Furtherly,the in vivo experiment on indocyanine green metabolism in healthy mouse liver demonstrates the capability of capturing the fast-changing fluorescence signals in small animals for fluorescence pharmacokinetic study.
To capture the fast-changing fluorescence information during a finite metabolism process in vivo,a dynamic system with the ability of parallel detection was developed based on the merits of high penetration depth and sensitivity of diffuse fluorescence tomography.It adopts the mode of muti-source and muti-detector,and combines photo-multiplier tube detector and lock-in photon-counting technique to achieve high spatial sampling density,high sensitivity,wide dynamic range,as well as better costeffectiveness.The assessment results show that this system has good performances in stability and ambient light suppression,and the crosstalk-rate of frequency belows 1.39%.The phantom experiment demonstrates the favorable abilities of imaging single and multiple targets.Furtherly,the in vivo experiment on indocyanine green metabolism in healthy mouse liver demonstrates the capability of capturing the fast-changing fluorescence signals in small animals for fluorescence pharmacokinetic study.
引文
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[15] ZHANG Yan-qi,ZHANG Li-min,YIN Guo-yan,et al.Assessing indocyanine green pharmacokinetics in mouse liver with a dynamic diffuse fluorescence tomography system[J].Journal of Biophotonics,2018,11(10):e201800041.
[2] MARKUS R,RALPH W.Molecular imaging in drug discovery and development[J].Nature Reviews Drug Discovery,2003,2(2):123-131.
[3] GAO Feng,ZHAO Hui-juan,TANIKAWA Y,et al.A linear,featured-data scheme for image reconstruction in timedomain fluorescence molecular tomography[J].Optics Express,2006,14(16):7109-7024.
[4] ZHANG Li-min,GAO Feng,HE Hui-yuan,et al.Three-dimensional scheme for time-domain fluorescence molecular tomography based on Laplace transforms with noise-robust factors[J].Optics Express,2008,16(10):7214-7223.
[5] PATWARDHAN S V,BLOCH S R,ACHILEFU S,et al.Time-dependent whole-body fluorescence tomography of probe bio-distributions in mice[J].Optics Express,2005,13(7):2564-2577.
[6] SCHULZ R B,RIPOLL J,NTZIACHRISTOS V,et al.Experimental fluorescence tomography of tissues with noncontact measurements[J].IEEE Transactions on Medical Imaging,2004,23(4):492-500.
[7] ALACAMB,YAZICI B,INTES X,et al.Pharmacokinetic-rate images of indocyanine green for breast tumors using near-infrared optical methods[J].Physics in Medicine and Biology,2008,53(4):837-859.
[8] ALACAM B,MEMBER S,YAZICI B,et al.Extended kalman filtering for the modeling and analysis of ICG pharmacokinetics in cancerous tumors using NIR optical methods[J].IEEE Transactions on Biomedical Engineering,2006,53(10):1861-1871.
[9] SCHULZ R B,ALE A,SARANTOPOULOS A,et al.Hybrid system for simultaneous fluorescence and x-ray computed tomography[J].IEEE Transactions on Medical Imaging,2010,29(2):465-473.
[10] LIU Xin,ZHANG Bin,LUO Jian-wen,et al.4-D reconstruction for dynamic fluorescence diffuse optical tomography[J].IEEE Transactions on Medical Imaging,2012,31(11):2120-2132.
[11] LIU Xin,GUO Xiao-lian,LIU Fei,et al.Imaging of indocyanine green perfusion in mouse liver with fluorescence diffuse optical tomography[J].IEEE Transactions on Biomedical Engineering,2011,58(8):2139-2143.
[12] CHEN Wei-ting,WANG Xin,WANG Bing-yuan,et al.Lock-in-photon-counting-based highly-sensitive and largedynamic imaging system for continuous-wave diffuse optical tomography[J].Biomedical Optics Express,2016,7(2):499-511.
[13] ZHANG Yan-qi,WANG Xin,YIN Guyan,et al.Dynamic experimental system for indocyanine green pharmacokinetic imaging[J].Chinese Journal of Laser,2017,44(1):238-244.张雁琦,王欣,尹国艳,等.面向吲哚菁绿药代动力学成像的动态实验系统[J].中国激光,2017,44(1):238-244.
[14] WANG Xin,ZHANG Yan-qi,ZHANG Li-min,et al.Direct reconstruction in CT-analogous pharmacokinetic diffuse fluorescence tomography:two-dimensional simulative and experimental validations[J].Journal of Biomedical Optics,2016,21(4):046007.
[15] ZHANG Yan-qi,ZHANG Li-min,YIN Guo-yan,et al.Assessing indocyanine green pharmacokinetics in mouse liver with a dynamic diffuse fluorescence tomography system[J].Journal of Biophotonics,2018,11(10):e201800041.