Keuenhof Katharina S, Kavirayani Anoop, Reier Susanne, Geyer Stefan H, Weninger Wolfgang J, Walter Andreas
Department of Chemistry and Molecular Biology, University of Gothenburg, 405 30 Gothenburg, Sweden.
Vienna BioCenter Core Facilities GmbH, Austrian BioImaging/CMI, 1030 Vienna, Austria.
Biomedicines. 2021 Dec 15;9(12):1918. doi: 10.3390/biomedicines9121918.
High-resolution episcopic microscopy (HREM) is a three-dimensional (3D) episcopic imaging modality based on the acquisition of two-dimensional (2D) images from the cut surface of a block of tissue embedded in resin. Such images, acquired serially through the entire length/depth of the tissue block, are aligned and stacked for 3D reconstruction. HREM has proven to be specifically advantageous when integrated in correlative multimodal imaging (CMI) pipelines. CMI creates a composite and zoomable view of exactly the same specimen and region of interest by (sequentially) correlating two or more modalities. CMI combines complementary modalities to gain holistic structural, functional, and chemical information of the entire sample and place molecular details into their overall spatiotemporal multiscale context. HREM has an advantage over in vivo 3D imaging techniques on account of better histomorphologic resolution while simultaneously providing volume data. HREM also has certain advantages over ex vivo light microscopy modalities. The latter can provide better cellular resolution but usually covers a limited area or volume of tissue, with limited 3D structural context. HREM has predominantly filled a niche in the phenotyping of embryos and characterisation of anatomic developmental abnormalities in various species. Under the umbrella of CMI, when combined with histopathology in a mutually complementary manner, HREM could find wider application in additional nonclinical and translational areas. HREM, being a modified histology technique, could also be incorporated into specialised preclinical pathology workflows. This review will highlight HREM as a versatile imaging platform in CMI approaches and present its benefits and limitations.
高分辨率光学切片显微镜技术（HREM）是一种三维（3D）光学切片成像模式，它基于从包埋在树脂中的组织块的切面获取二维（2D）图像。通过在组织块的整个长度/深度上连续获取的此类图像进行对齐和堆叠，以进行三维重建。事实证明，当HREM集成到相关多模态成像（CMI）流程中时，具有特别的优势。CMI通过（顺序地）关联两种或更多种模态，创建完全相同的标本和感兴趣区域的复合且可缩放视图。CMI结合互补模态，以获取整个样本的整体结构、功能和化学信息，并将分子细节置于其整体时空多尺度背景中。由于具有更好的组织形态学分辨率，同时还能提供体积数据，HREM相对于体内三维成像技术具有优势。与离体光学显微镜模态相比，HREM也具有某些优势。后者可以提供更好的细胞分辨率，但通常覆盖的组织面积或体积有限，三维结构背景也有限。HREM在胚胎表型分析和各种物种解剖发育异常的表征方面占据了主要的细分领域。在CMI的框架下，当与组织病理学以相互补充的方式结合时，HREM可能会在更多非临床和转化领域得到更广泛的应用。HREM作为一种改良的组织学技术，也可以纳入专门的临床前病理工作流程中。本综述将重点介绍HREM作为CMI方法中一种通用的成像平台，并阐述其优点和局限性。
