Implanted imaging laboratories for deep-tissue in vivo imaging

体内显微成像的使用广泛用于生物医学中使用动物模型进行的基础研究，用于药物发现和跟踪疾病进展。然而，深层组织成像是高度侵入性的，因此动物的终止通常发生在每次测量之后。对于涉及多个时间点测试的实验，例如用于研究疾病进展或细胞迁移的实验，每个时间点终止一只动物可能需要使用大量动物才能获得可靠的研究结果。此外，这只提供了现象的快照，阻碍了对细胞命运和功能的理解。我们将开发一种多模式、微型显微镜，并开发通过外科手术将显微镜植入动物体内的技术，以便在更长的时间内进行多模式显微成像。显微镜将足够小，并配置为最大限度地干扰动物舒适。例如，显微镜物镜将用水泥固定在脊椎或关节周围的骨骼上，光学图像导向器将图像传输到探测器阵列，这些探测器阵列可以远程位于体腔内，对动物的不适感最小或没有。研究项目将提供以下优势，与NC3R的目标一致：-对于纵向研究，牺牲的动物数量将明显按比例减少。-每次纵向测量只使用一只动物提供的改进控制，将使以更少的动物获得可靠的研究结果。-在正常动物行为期间的实时成像将为某些实验提供更高的数据质量，并将减少与麻醉相关的动物压力。考虑到前两个方面，我们的目标是减少使用的动物数量在涉及脊髓和关节组织的光谱成像和荧光成像的三个正在进行的研究方案中，每个方案的纵向研究增加了十倍。

The use of in vivo microscopic imaging is widespread for fundamental research using animal models in biomedicine, for drug discovery and tracking disease progression. Deep-tissue imaging is, however, highly invasive and so termination of the animal normally occurs after each measurement. For experiments involving testing with multiple timepoints, for example for studying disease progression or cell migration, termination of an animal for each timepoint can require the use of a large number of animals to achieve a reliable research outcome. Furthermore this provides only snapshots of phenomena, hampering understanding of cell fate and function. We will develop a multi-modal, miniaturised microscope and develop techniques for surgically implanting the microscope into an animal for multimodal microscopic imaging over extended time periods. The microscope will be sufficiently small and configured to be minimally intrusive for animal comfort. For example the microscope objective will be anchored with cement to vertebrae or bones around joints and optical image guides will transmit images to detector arrays that can be remotely located within body cavities with minimal or no discomfort to the animal. The microscope can be recovered at the end of the study.The research project will provide the following advantages that align with the aims of NC3Rs:-For longitudinal studies there will be a clear proportionate reduction in the number of animals sacrificed.-The improved control provided by the use of only a single animal for each longitudinal measurement will enable reliable research outcomes to be achieved with fewer animals.-Real-time imaging during normal animal behaviour will provide for improved quality of data for certain experiments and will reduce the animal stress associated with anaesthesia.Taking these two first aspects into account we aim to reduce the number of animals used by a factor of ten for longitudinal studies in each of three active research programmes involving spectral imaging and fluorescence imaging of the spinal cord and of joint tissue.