基于干细胞移植的缺血模型混合成像及血管新生定量研究

The project provides the novel imaging tools and evaluation methods for therapeutic stem cell transplantation of promoting angiogenesis in biological research, the use of home-developed bioluminescence tomography system and development of stem cells continuously tracking, and 3D visualization monitoring, tracking stem cells survival, migration and apoptosis in small animals in vivo. At the same time, simultaneous monitor of stem cell treatments to promote angiogenesis in vivo, noninvasive, continuous long-term quantitative monitoring angiogenesis, which using self-developed high-resolution micro-CT imaging system, the method of contrast enhancement imaging of small animals as well as data and image processing method. In this research, to obtain quantitative in vivo tracking method through the reconstructed stem cell based on bioluminescence tomography and the characterization of the relationship between the total light energy and the total number of stem cells. The establishment of a micro-CT angiography imaging and blood vessel segmentation and vascular quantitative assessment programme in three-dimensional space, and realization the three-dimensional space analysis of spatial angiogenesis and in vivo tracking stem cells in the location, a sparse principal component analysis technique was employed to analyze the topological parameters and to assess the different stage of angiogenesis of the mouse hindlimb ischemia model, to evaluate the stem cell transplantation to promote angiogenesis in the temporal and spatialon quantitative factors objectively and effectively. In this study, It provides a series of imaging methods and quantitative evaluation programme for stem cell transplantation and the biological research of angiogenesis.

本项目针对治疗性干细胞移植促进血管新生的生物学研究在成像方面的重要需求，利用自主研发的生物发光断层成像及高分辨率micro-CT混合成像系统对干细胞进行在体连续示踪，并实现三维可视化监测，追踪干细胞在小动物体内的存活、迁移情况；与此同时，通过小动物造影成像、数据融合，同步监测干细胞干预下促进血管新生的情况；对血管新生的定量变化指标进行在体、无创、连续长程的监测，并对体数据的多种特征进行稀疏PCA分析，得到综和了多种血管参数的血管新生定量评价方法。在本课题研究中提出了生物发光断层成像重建光源的总能量与干细胞总数量的关系，获取在体定量示踪的方法；建立了三维空间血管定量评估体系，并实现空间血管新生与干细胞三维空间在体示踪的融合对比分析，客观地评价干细胞移植对促进血管新生在时空上的定量指标。本研究提出的系列成像方法及定量评价体系为干细胞移植及血管新生的生物学研究提供了新的成像手段和评价方法。

本项目为了解决干细胞治疗过程中干细胞移植到体内后的在体三维定量示踪问题，研究了干细胞聚集部位及其周围的血管新生情况并建立起了干细胞移植治疗的三维空间在体示踪与血管新生的疗效评估方法。通过建立稳定表达荧光素酶的干细胞与小鼠下肢缺血模型，利用生物发光断层成像对干细胞进行在体成像和定量研究。基于高分辨率micro-CT结构影像，研究了小鼠下肢血管的分割方法，包括骨骼的自动分割方法，基于Vesselness方法的血管自动分割方法，断裂血管的拼接方法。研究了小鼠下肢缺血模型中血管参数定量评价方法，提出空间血管体积因数长程评估干细胞治疗后的微血管网络密度，提出基于稀疏PCA和聚合提升树技术的血管新生参数在体定量评估方法，提出多分辨率血管网络的定量分析方法。本研究提出的系列成像方法及定量评价体系为干细胞移植及血管新生的生物学研究提供了新的成像手段和评价方法。

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