Vandenberghe Michel E, Hérard Anne-Sophie, Souedet Nicolas, Sadouni Elmahdi, Santin Mathieu D, Briet Dominique, Carré Denis, Schulz Jocelyne, Hantraye Philippe, Chabrier Pierre-Etienne, Rooney Thomas, Debeir Thomas, Blanchard Véronique, Pradier Laurent, Dhenain Marc, Delzescaux Thierry
Commissariat à l'Energie Atomique (CEA) - Molecular Imaging Research Center (MIRCen), 92265 Fontenay-Aux-Roses, France.
Brain and Spine Institute (ICM), 75013 Paris, France.
Sci Rep. 2016 Feb 15;6:20958. doi: 10.1038/srep20958.
Histology is the gold standard to unveil microscopic brain structures and pathological alterations in humans and animal models of disease. However, due to tedious manual interventions, quantification of histopathological markers is classically performed on a few tissue sections, thus restricting measurements to limited portions of the brain. Recently developed 3D microscopic imaging techniques have allowed in-depth study of neuroanatomy. However, quantitative methods are still lacking for whole-brain analysis of cellular and pathological markers. Here, we propose a ready-to-use, automated, and scalable method to thoroughly quantify histopathological markers in 3D in rodent whole brains. It relies on block-face photography, serial histology and 3D-HAPi (Three Dimensional Histology Analysis Pipeline), an open source image analysis software. We illustrate our method in studies involving mouse models of Alzheimer's disease and show that it can be broadly applied to characterize animal models of brain diseases, to evaluate therapeutic interventions, to anatomically correlate cellular and pathological markers throughout the entire brain and to validate in vivo imaging techniques.
组织学是揭示人类和疾病动物模型中微观脑结构及病理改变的金标准。然而，由于手动操作繁琐，组织病理学标志物的定量分析通常仅在少数组织切片上进行，因此测量局限于大脑的有限部分。最近开发的三维显微成像技术使得对神经解剖学的深入研究成为可能。然而，对于细胞和病理标志物的全脑分析，仍然缺乏定量方法。在此，我们提出一种现成可用、自动化且可扩展的方法，用于在啮齿动物全脑中对组织病理学标志物进行三维全面定量分析。该方法依赖于块面摄影、连续组织学以及3D-HAPi（三维组织学分析管道），一款开源图像分析软件。我们在涉及阿尔茨海默病小鼠模型的研究中展示了我们的方法，并表明它可广泛应用于表征脑疾病动物模型、评估治疗干预措施、在全脑范围内对细胞和病理标志物进行解剖学关联以及验证体内成像技术。
