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@ARTICLE{Hahn:144589,
author = {A. Hahn and J. Bode$^*$ and T. Krüwel$^*$ and G.
Solecki$^*$ and S. Heiland and M. Bendszus and B. Tews$^*$
and F. Winkler$^*$ and M. Breckwoldt$^*$ and F. T. Kurz},
title = {{G}lioblastoma multiforme restructures the topological
connectivity of cerebrovascular networks.},
journal = {Scientific reports},
volume = {9},
number = {1},
issn = {2045-2322},
address = {[London]},
publisher = {Macmillan Publishers Limited, part of Springer Nature},
reportid = {DKFZ-2019-02032},
pages = {11757},
year = {2019},
abstract = {Glioblastoma multiforme alters healthy tissue vasculature
by inducing angiogenesis and vascular remodeling. To fully
comprehend the structural and functional properties of the
resulting vascular network, it needs to be studied
collectively by considering both geometric and topological
properties. Utilizing Single Plane Illumination Microscopy
(SPIM), the detailed capillary structure in entire healthy
and tumor-bearing mouse brains could be resolved in three
dimensions. At the scale of the smallest capillaries, the
entire vascular systems of bulk U87- and GL261-glioblastoma
xenografts, their respective cores, and healthy brain
hemispheres were modeled as complex networks and quantified
with fundamental topological measures. All individual vessel
segments were further quantified geometrically and modular
clusters were uncovered and characterized as meta-networks,
facilitating an analysis of large-scale connectivity. An
inclusive comparison of large tissue sections revealed that
geometric properties of individual vessels were altered in
glioblastoma in a relatively subtle way, with high intra-
and inter-tumor heterogeneity, compared to the impact on the
vessel connectivity. A network topology analysis revealed a
clear decomposition of large modular structures and
hierarchical network organization, while preserving most
fundamental topological classifications, in both tumor
models with distinct growth patterns. These results augment
our understanding of cerebrovascular networks and offer a
topological assessment of glioma-induced vascular
remodeling. The findings may help understand the emergence
of hypoxia and necrosis, and prove valuable for therapeutic
interventions such as radiation or antiangiogenic therapy.},
cin = {V077 / B320 / D170 / L101},
ddc = {600},
cid = {I:(DE-He78)V077-20160331 / I:(DE-He78)B320-20160331 /
I:(DE-He78)D170-20160331 / I:(DE-He78)L101-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:31409816},
pmc = {pmc:PMC6692362},
doi = {10.1038/s41598-019-47567-w},
url = {https://inrepo02.dkfz.de/record/144589},
}