Breckwoldt Michael O, Bode Julia, Sahm Felix, Krüwel Thomas, Solecki Gergely, Hahn Artur, Wirthschaft Peter, Berghoff Anna S, Haas Maximilian, Venkataramani Varun, von Deimling Andreas, Wick Wolfgang, Herold-Mende Christel, Heiland Sabine, Platten Michael, Bendszus Martin, Kurz Felix T, Winkler Frank, Tews Björn
Neuroradiology Department, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Front Neurosci. 2019 Jan 10;12:1004. doi: 10.3389/fnins.2018.01004. eCollection 2018.
Diffuse tumor infiltration into the adjacent parenchyma is an effective dissemination mechanism of brain tumors. We have previously developed correlated high field magnetic resonance imaging and ultramicroscopy (MR-UM) to study neonangiogenesis in a glioma model. In the present study we used MR-UM to investigate tumor infiltration and neoangiogenesis in a translational approach. We compare infiltration and neoangiogenesis patterns in four brain tumor models and the human disease: whereas the U87MG glioma model resembles brain metastases with an encapsulated growth and extensive neoangiogenesis, S24 experimental gliomas mimic wildtype glioblastomas, exhibiting infiltration into the adjacent parenchyma and along white matter tracts to the contralateral hemisphere. MR-UM resolves tumor infiltration and neoangiogenesis longitudinally based on the expression of fluorescent proteins, intravital dyes or endogenous contrasts. Our study demonstrates the huge morphological diversity of brain tumor models regarding their infiltrative and neoangiogenic capacities and further establishes MR-UM as a platform for translational neuroimaging.
肿瘤向邻近实质的弥漫性浸润是脑肿瘤一种有效的播散机制。我们之前开发了相关的高场磁共振成像和超微显微镜技术（MR-UM）来研究胶质瘤模型中的新生血管生成。在本研究中，我们采用MR-UM以转化医学的方法来研究肿瘤浸润和新生血管生成。我们比较了四种脑肿瘤模型及人类疾病中的浸润和新生血管生成模式：U87MG胶质瘤模型类似于脑转移瘤，呈包膜样生长且有广泛的新生血管生成；而S24实验性胶质瘤则模拟野生型胶质母细胞瘤，表现为向邻近实质浸润并沿白质束延伸至对侧半球。MR-UM可基于荧光蛋白、活体染料或内源性对比剂的表达纵向解析肿瘤浸润和新生血管生成情况。我们的研究证明了脑肿瘤模型在浸润和新生血管生成能力方面存在巨大的形态学差异，并进一步确立了MR-UM作为转化神经影像学平台的地位。
