Macro-to-molecular correlative X-ray imaging of strain during spinal joint loading

项目摘要(请以下列格式填写摘要，并注明标题。1)简要描述研究背景，包括潜在影响生物组织在动态机械环境中运作。人体对这些力量的反应是由从最小（分子）到最大（器官）的生物物理过程层次所介导的。纤维复合材料的力学生物学对生理功能至关重要，其在疾病或损伤中的多尺度结构/力学变化往往对功能丧失至关重要。这些疾病的治疗带来了巨大的医疗负担。生物工程的挑战是确定完整组织在生理负荷下分子、纤维和细胞基质长度尺度上的相关3D变形和结构变化，以及这些在衰老、损伤和疾病中如何变化。器官的x射线照射可以在基质中建立胶原纤维束的三维地图（断层扫描或CT），分辨率为微米级。在小一百倍的尺寸下，这些相同的x射线可以通过干涉与构成纤维的分子相互作用，形成类似衍射光栅的图像（小角度散射或SAXS）。当一个明亮的x射线束（就像在同步加速器中可用的那种）可用时，这些方法可以用来动态研究负载引起的生物物理变化。如果CT和SAXS这两种技术的信息能够结合起来，我们将拥有一个前所未有的从分子到宏观尺度的组织生物物理学可视化。该项目旨在使用带有SAXS的相衬CT对组织的多尺度生物物理学进行成像，以帮助理解椎间盘等器官的行为，这对姿势和预防背痛至关重要。2)目的和目标总体目的是获得组织的多尺度生物物理学的新见解，以帮助理解椎间盘的生物力学行为。要实现这一目标，具体目标是：1。在完整的椎间盘上使用相衬断层扫描和数字体积相关来测量纤维结构。2. 利用原位生物力学加载与成像相结合，以生理相关的方式开发和成像破坏天然组织基质结构的有害加载方案。3. 利用数字体积相关分析这些损伤系统，以预测完整受伤关节的微力学功能改变，为人体健康和疾病的功能提供新的见解。3)研究方法的新颖性本项目将开发新的有害加载方案，以生理相关的方式破坏天然组织基质结构并动态成像。4)与EPSRC的战略和研究领域保持一致该项目与EPSRC工程大挑战医疗保健技术重点优化治疗和开发未来疗法保持一致，通过跨领域能力主题新颖成像技术。通过对组织进行多尺度生物物理分析，该项目为“理解生命物理大挑战”提供了支持。这项研究与EPSRC研究领域生物物理学（生长）和肌肉骨骼生物力学（维持）保持一致。本博士学位是伦敦大学学院（UCL），伦敦玛丽女王大学（QMUL），钻石光源（www.diamond.ac.uk）， ESRF (www.esrf.eu)，曼彻斯特大学和俄勒冈州立大学（美国）合作的一部分。

Project Summary (Please complete the summary in the following format with headings present. Should be 4,000 characters Maximum):1) Brief description of the context of the research including potential impactBiological tissues operate in a dynamic mechanical environment. The body's response to these forces is mediated by a hierarchy of biophysical processes from the smallest (molecular) to the largest (organ) level. The mechanobiology of fibrillar composites is critical for physiological function, and their multiscale structural/ mechanical changes in disease or injury are often critical to loss of function. Treatment for these conditions imposes a huge healthcare burden. The bioengineering challenge is to determine the correlated 3D deformation and structural changes at the molecular-, fibrillar-, and cell-matrix length-scales under physiological load in intact tissue, and how these alter in ageing, injury and disease. X-ray illumination of an organ can build up a 3D map of the collagen fibre bundles in the matrix (tomography or CT) with micron-level resolution. At a hundred times smaller size, these same X-rays can interact with the molecules making up the fibres via interference, building up a picture like a diffraction grating (small angle scattering or SAXS). When a brilliant X-ray beam (like the kind available at synchrotrons) is available, these methods can be used to study load-induced biophysical changes dynamically. If the information from these two techniques - CT and SAXS - could be combined, we would have an unprecedented molecular-to-macroscale visualisation of tissue biophysics.This project aims to use phase-contrast CT with SAXS to image the multiscale biophysics of tissues to help understand the behaviour of organs like the intervertebral disc, which is crucially important for posture and preventing back pain. 2) Aims and ObjectivesThe overall aims is to gain new insights into multiscale biophysics of tissues to help understand the biomechanical behaviour of intervertebral disc. To achieve this the specific objects are to: 1. use phase contrast tomography and digital volume correlation on intact intervertebral discs to measure the fibre-structure. 2. To use in situ biomechanical loading coupled with imaging to develop and image injurious loading protocols which disrupt the native tissue matrix structure in physiologically relevant ways. 3. To analyse these injury-systems using digital volume correlation to predict the functional alterations in micromechanics in intact, injured joints, providing new insights into the function of the human body in health and disease.3) Novelty of Research MethodologyThis project will develop new injurious loading protocols which disrupt the native tissue matrix structure in physiologically relevant ways and image these dynamically. 4) Alignment to EPSRC's strategies and research areasThe project aligns with the EPSRC Engineering Grand Challenge Healthcare Technologies foci Optimising Treatment and Developing Future Therapies, via the Cross-cutting capabilities theme Novel imaging technologies. By taking a step-change in multiscale biophysical analysis of tissues, this project supports the Grand Challenge Understanding the Physics of Life. This research is aligned to EPSRC research areas Biophysics (Grow) and Musculoskeletal Biomechanics (Maintain). 5) Any companies or collaborators involvedThis PhD is part of a collaboration between University College London (UCL), Queen Mary University of London (QMUL), Diamond Light Source (www.diamond.ac.uk), ESRF (www.esrf.eu), the University of Manchester and Oregon State University (USA).