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Correlated MRI and ultramicroscopy of brain tumors reveals vast heterogeneity of tumor infiltration and neoangiogenesis in preclinical models and the human disease

Purpose: Diffuse tumor infiltration into the adjacent brain parenchyma is an effective dissemination mechanism of brain tumors. We use correlated magnetic resonance imaging and ultramicroscopy (MR-UM) to investigate tumor infiltration and neoangiogenesis in a translational approach in several precli...

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Published in:Clinical neuroradiology (Munich) 2018-09, Vol.28 (S1), p.S55
Main Authors: Breckwoldt, Michael, Bode, Julia, Sahm, Felix, Solecki, Gergely, Hahn, Artur, Berghoff, Anna, Wick, Wolfgang, HeroldMende, Christel, Heiland, Sabine, Bendszus, Ma, Kurz, Felix Tobias, Winkler, Frank, Tews, Bjorn
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Language:English
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Summary:Purpose: Diffuse tumor infiltration into the adjacent brain parenchyma is an effective dissemination mechanism of brain tumors. We use correlated magnetic resonance imaging and ultramicroscopy (MR-UM) to investigate tumor infiltration and neoangiogenesis in a translational approach in several preclinical brain tumor models and the human disease. Methods: We compare infiltration and neoangiogenesis patterns in four brain tumor models (U87, RCAS/tva, S24, A2058) and brain tumor pathological specimen (IDH WT, IDHR132H, brain metastasis). The MRI protocol included T1w/T2w, DCE and T2*w and was performed on a small animal scanner at 9.4 Tesla (80 [micro]m isotropic resolution). Ultramicroscopy of entire unsectioned brains/brain tumor specimen was performed after tissue clearing (5 [micro]m in plane resolution). Fluorescent labeling of tumor cells and/or the microvasculature was based on the expression of fluorescent proteins (S24-tdtomato, intravital dyes (lectin-FITC) or endogenous contrasts (erythrocytes). Results: The U87MG glioma model resembles the brain metastases model A2058 with an encapsulated growth, extensive neoangiogenesis and profound blood-brain barrier disruption on dynamic contrast enhanced MRI. In contrast S24 experimental gliomas exhibited only minimal blood-brain barrier breakdown but extensive infiltration into the adjacent parenchyma and along white matter tracts to the contralateral hemisphere mimicking IDH wildtype glioblastomas. MR-UM. Conclusion: MR-UM reveals huge morphological diversity of brain tumor models regarding their infiltrative and neoangiogenic capacities and directly compares them to the human disease.
ISSN:1869-1439
DOI:10.1007/S00062-018-0719-8