Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden; Austrian BioImaging/CMI, Vienna BioCenter Core Facilities GmbH (VBCF), Vienna, Austria; Center for Biomedical Research, Medical University of Vienna, Vienna, Austria.
Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in the AUVA trauma research center, Austrian BioImaging/CMI, Vienna, Austria; Core Facility Hard Tissue and Biomaterial Research, Karl Donath Laboratory, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria.
Methods Cell Biol. 2021;162:389-415. doi: 10.1016/bs.mcb.2020.10.002. Epub 2020 Dec 2.
In imaging, penetration depth comes at the expense of lateral resolution, which restricts the scope of 3D in-vivo imaging of small animals at micrometer resolution. Bioimaging will need to expand beyond correlative light and electron microscopy (CLEM) approaches to combine insights about in-vivo dynamics in a physiologically relevant 3D environment with ex-vivo information at micrometer resolution (or beyond) within the spatial, structural and biochemical contexts. Our report demonstrates the immense potential for biomedical discovery and diagnosis made available by bridging preclinical in-vivo imaging with ex-vivo biological microscopy to zoom in from the whole organism to individual structures and by adding localized spectroscopic information to structural and functional information. We showcase the use of two novel imaging pipelines to zoom into mural lesions (occlusions/hyperplasia and micro-calcifications) in murine vasculature in a truly correlative manner, that is using exactly the same animal for all integrated imaging modalities. This correlated multimodality imaging (CMI) approach includes well-established technologies such as Positron Emission Tomography (microPET), Autoradiography, Magnetic Resonance Imaging (microMRI) and Computed Tomography (microCT), and imaging approaches that are more novel in the biomedical setting, such as X-Ray Fluorescence Spectroscopy (microXRF) and High Resolution Episcopic Microscopy (HREM). Although the current pipelines are focused on mural lesions, they would also be beneficial in preclinical and clinical investigations of vascular diseases in general.
在成像中，穿透深度是以牺牲横向分辨率为代价的，这限制了在微米分辨率下对小动物进行三维体内成像的范围。生物成像将需要超越相关的光镜和电子显微镜（CLEM）方法，将体内动态的相关见解与在微米分辨率（或更高分辨率）下的体外信息结合起来，在空间、结构和生化背景下进行整合。我们的报告展示了通过将临床前体内成像与体外生物显微镜相结合，从整个生物体缩小到单个结构，并通过增加局部光谱信息来增加结构和功能信息，从而为生物医学发现和诊断提供了巨大的潜力。我们展示了使用两种新颖的成像管道以真正相关的方式放大到小鼠血管中的壁损伤（阻塞/增生和微钙化），即使用完全相同的动物进行所有集成成像模式。这种相关的多模态成像（CMI）方法包括正电子发射断层扫描（microPET）、放射自显影、磁共振成像（microMRI）和计算机断层扫描（microCT）等成熟技术，以及在生物医学环境中更新颖的成像方法，如 X 射线荧光光谱（microXRF）和高分辨率透视显微镜（HREM）。尽管当前的管道集中在壁损伤上，但它们也将有益于血管疾病的临床前和临床研究。
