Preclinical hybrid in-vivo real-time imaging system (PHiVRIS) Re-submission

虽然众所周知，成像研究可以大大提高动物实验的科学成果，沿着减少所需的动物数量，但这种能力目前还不适用于大多数使用小动物的研究人员。在许多情况下，获得成像系统受到临床前成像设备的高成本的限制。此外，对于研究传染病的研究人员来说，他们必须在生物安全柜内进行研究，没有商业系统可用。低成本紧凑型临床前成像系统，专为标准层流内操作而构建，基于莱斯特大学开发的术中伽马相机，我们提出的成像系统将能够检测伽马辐射、可见光和近红外荧光。这将允许同时采集三种模式的图像，减少小鼠需要麻醉的时间，并确保图像之间精确的空间和时间配准。小动物保持器在成像期间将可旋转高达60度，以提供用于成像的多个视角和动物表面以下的源深度的估计。这个新系统将为更大范围的研究人员提供进行纵向成像研究的机会。通过与结核病研究小组、莱斯特大学和诺丁汉大学的合作，这种新型成像系统的设计将由最终用户指导。这将确保系统的能力符合小动物研究人员的要求。特别是，我们将重点关注从早期阶段检测和监测结核病或其他分枝杆菌肺部感染进展的能力。这种高度传染性和使人衰弱的疾病将被用作原型系统的案例研究。PHiVRIS将把在X射线天文学中得到验证的先进探测器技术转化为下一代生物成像工具，并将提供一种新的独特的成像能力，为可能无法使用传统临床前成像核心设施的animals.to研究人员提供一种创新的活体全身成像方法。

Although it is well known that imaging studies can greatly improve the scientific outcomes of animal experiments, along with reducing the number of animals needed, such capability is not currently available to the majority of researchers using small animal. In many cases access to imaging systems is limited by the high cost of preclinical imaging equipment. In addition, for researchers studying infectious diseases who have to conduct their research within biosafety cabinets, there are no commercial systems available.This proposal will translate advanced detector technologies designed for space science to develop a unique, low cost compact preclinical imaging system purpose-built for operation inside a standard laminar-flow biosafety cabinet or an isolator unit.Based on an intraoperative gamma camera developed by the University of Leicester, our proposed imaging system will be able to detect gamma radiation, visible and near infrared fluorescence. This will allow images in three modalities to be acquired simultaneously, reducing the amount of time mice will need to be anaesthetised and ensuring exact spatial and temporal registration between the images. The small animal holder will be rotatable up to 60 degrees during imaging to provide multiple viewing angles for imaging and an estimation of source depth below the animals surface. This new system will provide an opportunity to conduct longitudinal imaging studies to a far larger range of researchers. Through collaboration with the Tuberculosis Research Group, University of Leicester and the University of Nottingham the design of this novel imaging system will be guided by end users. This will ensure that the capabilities of the system match the requirements of the small animal researcher. In particular, we will be focussing on the ability to detect and monitor the progression of tuberculosis or other mycobacterial lung infection from an early stage. This highly infectious and debilitating disease will be used as a case study for the prototype system. PHiVRIS will translate advanced detector technologies proven in X-ray astronomy, into a next generation tool for bioimaging, and will offer a new and unique imaging capability that will provide an innovative approach to live, whole body imaging of small animals.to researchers who may not have access to traditional pre-clinical imaging core facilities.