Correlative In Vivo Fluorescence and Micro-Computed Tomographic Imaging of Tissue Structure and Function

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For human and animal bodies to function properly, the tissues and organs that make them up must be organised properly (have the correct tissue architecture). This must happen across many size scales, from individual cells to large organs such as the liver, kidneys, and bones, or blood vessels and nerves supplying the organs. Given cells and tissues are dynamic three-dimensional (3D) structures, we need to see how they fit together in 3D to understand their architecture, how structures connect and vary within the tissue. For example, in Regenerative Medicine, we try to make tissues and organs to repair damaged and diseased tissues and restore the body to its original health. Scaffolds upon which the cells can grow and are guided are used to help organise the cells into the right structures. We are now in a unique position to create new soft and hard tissues (e.g. liver, neural tissue, cartilage, bone) to improve treatments and to better understand normal and abnormal human and animal body function. Similarly, in aging the composition of our bodies changes, and it is important to be able to track and understand how this happens in living animals, so that ultimately we can have the knowledge to better treat a range of diseases, like heart disease, lung disease and cancer.We are applying for an imaging system that will allow us to examine cells, organs and tissues within the body (called Correlative in vivo imaging) to create 3D images at successive time points, without having to kill the animal to look inside it. The system will allow us to label and follow specific cells and molecules within the body and to create 3D image stacks of tissues of interest with a high-resolution micro-computed tomographic (uCT) imaging device. This uses X-rays to non-destructively image large samples and the design of this new instrument allows us to distinguish individual tissue components and how some of their features change over time, in a way that is not currently possible in two dimensions (2D) through a technique called histology, using normal, light microscopy.The imaging system will add to the wide range of existing imaging facilities in Southampton that are supported by 12 expert imaging staff, employed at the Biomedical Imaging Unit (BIU) and the u-VIS X-ray Imaging Centre (u-VIS). The existing expertise in sample preparation and biological image interpretation is essential for these cutting edge imaging techniques to be used effectively. An additional problem in 3D imaging at all scales is the very large digital image datasets that are produced, each taking large amounts of storage, typically; 50-1000Gb (equivalent of 10-200 DVDs each!). On this account, it is pivotal to have dedicated staff in place who will run and make sure that the imaging system performs efficiently and can provide a reliable, streamlined service to all users. The UoS has agreed to fund a Research Support staff member to underpin and provide a sustainable Imaging Service. Provision of the combined preclinical correlative in vivo imaging system, together with our existing leadership team in advanced computing and image processing (state-of-the-art computing hardware, software and expertise already in place at BIU and u-VIS, will allow investigating and understanding tissue architecture and to understand better tissue function. In this project, we will work with our collaborators in the University to develop further correlative in vivo imaging application areas of tissue samples, specifically including processing and analysis workflows for the 3D datasets. Our ability to understand tissue development and formation in its native 3D context has the potential to transform human health over the next 10-30 years. In order to fulfil this promise, as quickly and safely as possible, it is essential we can image the generated structures and tissues in vivo in a longitudinal fashion and at different hierarchical levels of tissue organisation.