基于XCT/FMT成像技术的肿瘤组织荧光剂药代动力学关键技术研究

基于荧光分子层析（FMT）成像技术的荧光剂药代动力学参数重建技术在肿瘤早期检测、肿瘤分期、药效评价、动态生物学和病理信息监测等领域具有重要应用价值。目前该技术研究在国内外处于初始阶段，还有大量关键问题亟待解决。本课题针对肿瘤组织体荧光剂药代动力学研究对测量系统灵敏性、快速性、建模精确性以及图像重建技术鲁棒性等关键技术的要求，发展XCT系统与扫描式光子计数型动态FMT系统协同测量方法，建立非均匀组织精确光子传输模型和药代动力学分室模型，并研究其高效数值求解方法。在此基础上，探索基于XCT先验信息支持的FMT先进反演理论以及基于扩展卡尔曼滤波的药代动力学参数重建技术，并研究有效改善图像重建精度、分辨率和稳定性的方法，结合测量系统进行模拟组织体和小动物实验验证，实现小动物模型肿瘤组织的荧光剂药代动力学多参数动态、定量监测。

The imaging technology of fluorophore pharmacokinetic parameters based on the fluorescence molecular tomography (FMT) has some potential applications in the fields of early tumor detection, staging, efficient evaluation and dynamic monitoring of biology and pathology information. At present, the research is at the initial stage at home and abroad, and there are some major problems to be solved. The performances strongly rely on the three fundamental factors: the sensitivity, rapidity of the measurement system, the accuracy of the modeling and the robustness of the image reconstruction. For these purposes, we implement a highly synergistic scheme of XCT and FMT based on photon counting technology and the prototype system with high-sensitivity, high temporally-and spatially-resolutions, develop an accurate model of the photon migration in heterogeneous tissue and compartmental modeling, and research the highly efficient numerical solutions. Based on these, we build a quantitative and robust inversion framework for FMT image reconstruction with the support of XCT structural a-priori and inversion technology of pharmacokinetic parameters based Expended Kalman Filter. In addition, we further research the methods to improve the quantitativeness, resolution and stability of image reconstruction and investigate the proposed methods based on prototype system. The ultimate goal of the research is to obtain the fluorophore pharmacokinetic multi-parameters and develop a quantitative and dynamic tool for small-animal based tumor malignant biology applications.