Wehrl Hans F, Bezrukov Ilja, Wiehr Stefan, Lehnhoff Mareike, Fuchs Kerstin, Mannheim Julia G, Quintanilla-Martinez Leticia, Kohlhofer Ursula, Kneilling Manfred, Pichler Bernd J, Sauter Alexander W
Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tuebingen, Tuebingen, Germany.
Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tuebingen, and Department of Empirical Inference, Max-Planck-Institute for Intelligent Systems, Tuebingen, Germany.
Histol Histopathol. 2015 May;30(5):601-13. doi: 10.14670/HH-30.601. Epub 2014 Dec 11.
Especially for neuroscience and the development of new biomarkers, a direct correlation between in vivo imaging and histology is essential. However, this comparison is hampered by deformation and shrinkage of tissue samples caused by fixation, dehydration and paraffin embedding. We used magnetic resonance (MR) imaging and computed tomography (CT) imaging to analyze the degree of shrinkage on murine brains for various fixatives. After in vivo imaging using 7 T MRI, animals were sacrificed and the brains were dissected and immediately placed in different fixatives, respectively: zinc-based fixative, neutral buffered formalin (NBF), paraformaldehyde (PFA), Bouin-Holland fixative and paraformaldehyde-lysine-periodate (PLP). The degree of shrinkage based on mouse brain volumes, radiodensity in Hounsfield units (HU), as well as non-linear deformations were obtained. The highest degree of shrinkage was observed for PLP (68.1%, P < 0.001), followed by PFA (60.2%, P<0.001) and NBF (58.6%, P<0.001). The zinc-based fixative revealed a low shrinkage with only 33.5% (P<0.001). Compared to NBF, the zinc-based fixative shows a slightly higher degree of deformations, but is still more homogenous than PFA. Tissue shrinkage can be monitored non-invasively with CT and MR. Zinc-based fixative causes the smallest degree of brain shrinkage and only small deformations and is therefore recommended for in vivo ex vivo comparison studies.
特别是对于神经科学和新生物标志物的开发，体内成像与组织学之间的直接关联至关重要。然而，这种比较受到固定、脱水和石蜡包埋导致的组织样本变形和收缩的阻碍。我们使用磁共振（MR）成像和计算机断层扫描（CT）成像来分析各种固定剂对小鼠大脑的收缩程度。在使用7T MRI进行体内成像后，处死动物并解剖大脑，然后立即分别将其置于不同的固定剂中：锌基固定剂、中性缓冲福尔马林（NBF）、多聚甲醛（PFA）、Bouin-Holland固定剂和多聚甲醛-赖氨酸-高碘酸盐（PLP）。获得了基于小鼠脑体积、亨氏单位（HU）的放射密度以及非线性变形的收缩程度。观察到PLP的收缩程度最高（68.1%，P<0.001），其次是PFA（60.2%，P<0.001）和NBF（58.6%，P<0.001）。锌基固定剂显示出较低的收缩率，仅为33.5%（P<0.001）。与NBF相比，锌基固定剂的变形程度略高，但仍比PFA更均匀。组织收缩可以通过CT和MR进行无创监测。锌基固定剂导致的脑收缩程度最小，仅产生微小变形，因此推荐用于体内外比较研究。
