面向吲哚菁绿药代动力学成像的动态实验系统
|
摘要
为实现小动物吲哚菁绿(ICG)药代动力学成像,设计了一套高灵敏度扩散荧光层析成像系统。该系统采用了基于离散光纤耦合光子计数采集的仿计算机断层成像扫描方式,在保障高灵敏度和大动态范围测量的前提下,可有效提高系统的空间采样分辨率;同时采用了基于光开关切换四通道串-并混和的测量模式,兼顾了测量时间分辨率和系统性价比之间的平衡。为验证实验系统的有效性,设计了可模拟小动物体内ICG代谢规律的动态仿体,并结合实验室开发的荧光剂药代动力学直接重建算法,实现了ICG代谢速率的重建。实验结果表明,该系统具有较高的空间分辨率、灵敏度和量化性。
A highly-sensitive pharmacokinetic diffuse fluorescence tomographic system is proposed to achieve the indocyanine green(ICG)pharmacokinetic imaging of small animals.The system employs a photon-counting technique based on discrete optical fiber measurement of computed tomography scanning mode in the computer tomography,which effectively improves spatial sampling resolution of the system on the premise of high sensitivity and wide dynamic measurement range.Meanwhile,it adopts serial-parallel mixed measurement mode through switching four photomultiplier tube photon-counting channels by optical switch to obtain a balance between time resolution of measurement and cost-effectiveness of the system.We investigate the principle validity of the system by designing a dynamic phantom that can simulate ICG metabolism in living tissue.In addition,combined with the algorithm of fluorescent agent pharmacokinetic imaging developed by our laboratory,the reconstruction of ICG metabolic velocity is realized.Experimental results show that the proposed system has high sensitivity,spatial resolution and quantitativeness.
A highly-sensitive pharmacokinetic diffuse fluorescence tomographic system is proposed to achieve the indocyanine green(ICG)pharmacokinetic imaging of small animals.The system employs a photon-counting technique based on discrete optical fiber measurement of computed tomography scanning mode in the computer tomography,which effectively improves spatial sampling resolution of the system on the premise of high sensitivity and wide dynamic measurement range.Meanwhile,it adopts serial-parallel mixed measurement mode through switching four photomultiplier tube photon-counting channels by optical switch to obtain a balance between time resolution of measurement and cost-effectiveness of the system.We investigate the principle validity of the system by designing a dynamic phantom that can simulate ICG metabolism in living tissue.In addition,combined with the algorithm of fluorescent agent pharmacokinetic imaging developed by our laboratory,the reconstruction of ICG metabolic velocity is realized.Experimental results show that the proposed system has high sensitivity,spatial resolution and quantitativeness.
引文
[1]Zhang G L,Liu F,Zhang B,et al.Imaging of pharmacokinetic rates of indocyanine green in mouse liver with a hybrid fluorescence molecular tomography/X-ray computed tomography system[J].Journal of Biomedical Optics,2013,18(4):040505.
[2]Folkman J.What is the evidence that tumors are angiogenesis dependent?[J].Journal of the National Cancer Institute,1990,82(1):4-6.
[3]Jain R K.Normalization of tumor vasculature:an emerging concept in antiangiogenic therapy[J].Science,2005,307(5706):58-62.
[4]Yu Qian,Guo Yiming,Cui Haizhen,et al.The relevance evaluation of indocyanine green excretion test in the hepatic functional reserve[J].China Journal of Laboratory Diagnosis,2014,18(11):1776-1778.于倩,郭义明,崔海珍,等.吲哚菁绿排泄试验与肝脏储备功能的相关性评价[J].中国实验诊断学,2014,18(11):1776-1778.
[5]Cuccia D J,Bevilacqua F,Durkin A J,et al.In vivo quantification of optical contrast agent dynamics in rat tumors by use of diffuse optical spectroscopy with magnetic resonance imaging coregistration[J].Applied Optics,2003,42(16):2940-2950.
[6]Intes X,Ripoll J,Chen Y,et al.In vivo continuous-wave optical breast imaging enhanced with indocyanine green[J].Medical Physics,2003,30(6):1039-1047.
[7]Alacam B,Yazici B.Direct reconstruction of pharmacokinetic-rate images of optical fluorophores from NIR measurements[J].IEEE Transactions on Medical Imaging,2009,28(9):1337-1353.
[8]Wang X,Wu L H,Yi X,et al.Performance enhancement of pharmacokinetic diffuse fluorescence tomography by use of adaptive extended Kalman filtering[J].Computational and Mathematical Methods in Medicine,2015,2015:739459.
[9]Saxena V,Sadoqi M,Shao J.Polymeric nanoparticulate delivery system for indocyanine green:biodistribution in healthy mice[J].International Journal of Pharmaceutics,2006,308(1):200-204.
[10]Wang X,Zhang Y Q,Zhang L M,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.
[11]Li Jiao,Gao Feng,Yi Xi,et al.A methodological and experimental investigation on time-domain diffuse fluorescence tomography of analytic based on two-dimensional circular scheme[J].Chinese J Lasers,2010,37(11):2743-2748.李娇,高峰,易茜,等.基于二维圆域解析模型的时域扩散荧光层析原理与实验研究[J].中国激光,2010,37(11):2743-2748.
[12]Liu X,Guo X L,Liu F,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.
[13]Zhang Limin,Gao Feng,Li Jiao,et al.Reconstructing three-dimensional fluorescent parameters using time-resolved data based on transmittance and reflection measurements[J].Chinese J Lasers,2009,36(10):2552-2556.张丽敏,高峰,李娇,等.基于透射和反射时间分辨测量数据的荧光参数三维重建[J].中国激光,2009,36(10):2552-2556.
[2]Folkman J.What is the evidence that tumors are angiogenesis dependent?[J].Journal of the National Cancer Institute,1990,82(1):4-6.
[3]Jain R K.Normalization of tumor vasculature:an emerging concept in antiangiogenic therapy[J].Science,2005,307(5706):58-62.
[4]Yu Qian,Guo Yiming,Cui Haizhen,et al.The relevance evaluation of indocyanine green excretion test in the hepatic functional reserve[J].China Journal of Laboratory Diagnosis,2014,18(11):1776-1778.于倩,郭义明,崔海珍,等.吲哚菁绿排泄试验与肝脏储备功能的相关性评价[J].中国实验诊断学,2014,18(11):1776-1778.
[5]Cuccia D J,Bevilacqua F,Durkin A J,et al.In vivo quantification of optical contrast agent dynamics in rat tumors by use of diffuse optical spectroscopy with magnetic resonance imaging coregistration[J].Applied Optics,2003,42(16):2940-2950.
[6]Intes X,Ripoll J,Chen Y,et al.In vivo continuous-wave optical breast imaging enhanced with indocyanine green[J].Medical Physics,2003,30(6):1039-1047.
[7]Alacam B,Yazici B.Direct reconstruction of pharmacokinetic-rate images of optical fluorophores from NIR measurements[J].IEEE Transactions on Medical Imaging,2009,28(9):1337-1353.
[8]Wang X,Wu L H,Yi X,et al.Performance enhancement of pharmacokinetic diffuse fluorescence tomography by use of adaptive extended Kalman filtering[J].Computational and Mathematical Methods in Medicine,2015,2015:739459.
[9]Saxena V,Sadoqi M,Shao J.Polymeric nanoparticulate delivery system for indocyanine green:biodistribution in healthy mice[J].International Journal of Pharmaceutics,2006,308(1):200-204.
[10]Wang X,Zhang Y Q,Zhang L M,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.
[11]Li Jiao,Gao Feng,Yi Xi,et al.A methodological and experimental investigation on time-domain diffuse fluorescence tomography of analytic based on two-dimensional circular scheme[J].Chinese J Lasers,2010,37(11):2743-2748.李娇,高峰,易茜,等.基于二维圆域解析模型的时域扩散荧光层析原理与实验研究[J].中国激光,2010,37(11):2743-2748.
[12]Liu X,Guo X L,Liu F,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.
[13]Zhang Limin,Gao Feng,Li Jiao,et al.Reconstructing three-dimensional fluorescent parameters using time-resolved data based on transmittance and reflection measurements[J].Chinese J Lasers,2009,36(10):2552-2556.张丽敏,高峰,李娇,等.基于透射和反射时间分辨测量数据的荧光参数三维重建[J].中国激光,2009,36(10):2552-2556.