Development of a synchrotron based non-invasive three-dimensional imaging method for soft tissue engineering in vivo studies

前言：在组织工程(TE)中，生物医学成像技术在生物材料、支架、细胞和工程化组织的表征中发挥着越来越重要的作用。尽管光学显微镜、电子显微镜等常规成像技术已被广泛应用于体外研究，但由于体内成像技术的缺乏，揭示生物材料与体内再生组织之间的相互作用仍然具有挑战性。TE的发展需要在成像技术方面进行一些创新，使其能够实现三维(3D)和在体延时可视化，以及对TE支架进行非侵入性的定量分析。*目标：*我的研究计划的长期目标是为TE和其他生物医学应用推进基于同步加速器(SR)的X射线成像的技术和实用基础。NSERC DG资助的这项研究在未来5年的短期目标是开发一种系统的3D成像方法，用于软组织工程的体内无创研究，具体目标有三：(1)开发一种新的基于SR传播的成像-螺旋CT(PBI-SCT)系统，用于软组织和水凝胶支架的体外无创成像，并对系统进行优化，以获得最佳的空间分辨率和对比度分辨率；(2)为成像系统开发一种支持性的数据处理方法，以处理这些图像数据并量化再生组织和支架的三维结构；以及(3)进一步优化成像系统，使体内成像应用的辐射剂量尽可能低，同时为体内应用保持尽可能高的空间分辨率和对比度分辨率，并具有定量成像能力。*影响：*该项目有几个广泛的影响，将为生物医学科学和社会带来重要的好处。该项目的成功完成将使PBI-SCT成为表征工程组织三维结构的一种高效工具，并将对TE领域产生革命性影响。TE研究的加速将对人类健康产生重大影响，因为它将导致治疗由疾病、创伤或先天性缺陷引起的缺陷的新方法。这项研究还将涉及对研究生的培训，以满足生物医学成像领域对高素质人才日益增长的需求。

INTRODUCTION: ***In tissue engineering (TE), biomedical imaging techniques play an increasingly essential role in the characterization of biomaterials, scaffolds, cells, and engineered tissues. Although conventional imaging techniques, such as light microscopy, electron microscopy, and etc., are widely used in in vitro studies, it is still challenging to reveal the interactions between biomaterials and regenerative tissues in vivo due to the lack of in vivo imaging techniques. Progress in TE requires a number of innovations in imaging techniques which are capable of allowing three-dimensional (3D) and time-lapse in vivo visualization and a non-invasive, quantitative analysis of TE scaffolds.******OBJECTIVES: ***The long-term objective of my research program is to advance the technical and practical basis of synchrotron-based (SR) X-ray imaging for TE and other biomedical applications. The short-term goal for this NSERC DG-funded research in the next 5 years is to develop a systematic 3D imaging method for non-invasive in vivo studies of soft tissue engineering with three specific objectives: (1) develop a novel SR propagation based imaging - spiral computed tomography (PBI-SCT) system for non-invasive ex vivo imaging of soft tissue and hydrogel scaffolds and optimize the system to achieve the best spatial and contrast resolution; (2) develop a supporting data processing method for the imaging system to process those image data and quantify the 3D structure of regrowth tissues and scaffolds; and (3) further optimize the imaging system to have the lowest possible radiation dose for in vivo imaging applications, while maintaining the highest possible spatial and contrast resolution with quantitative imaging capabilities for TE in vivo applications.******IMPACT: ***There are several broad impacts of the project that will yield important benefits to both biomedical science and society. The successful completion of this project will establish the PBI-SCT as a highly effective tool for characterizing the 3D structure of engineered tissues and will have a transformative impact on the field to TE. The acceleration of TE research will have significant impact on human health by leading to new therapeutic approaches for the treatment of defects resulting from disease, trauma or congenital defects. The research will also involve training of graduate students to meet the increasing demand for highly qualified personnel in biomedical imaging.*****