Lipophilic dye-compatible brain clearing technique allowing correlative magnetic resonance/high-resolution fluorescence imaging in rat models of glioblastoma.
Animals
Brain Neoplasms
/ blood supply
Cell Line, Tumor
Contrast Media
Disease Models, Animal
Fluorescent Dyes
Glioblastoma
/ blood supply
Humans
Hydrophobic and Hydrophilic Interactions
Image Enhancement
/ methods
Magnetic Resonance Imaging
/ methods
Neovascularization, Pathologic
Neuroimaging
/ methods
Optical Imaging
/ methods
Rats
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
21 10 2020
21 10 2020
Historique:
received:
07
07
2020
accepted:
09
10
2020
entrez:
22
10
2020
pubmed:
23
10
2020
medline:
10
4
2021
Statut:
epublish
Résumé
In this work we optimized a novel approach for combining in vivo MRI and ex vivo high-resolution fluorescence microscopy that involves: (i) a method for slicing rat brain tissue into sections with the same thickness and spatial orientation as in in vivo MRI, to better correlate in vivo MRI analyses with ex-vivo imaging via scanning confocal microscope and (ii) an improved clearing protocol compatible with lipophilic dyes that highlight the neurovascular network, to obtain high tissue transparency while preserving tissue staining and morphology with no significant tissue shrinkage or expansion. We applied this methodology in two rat models of glioblastoma (GBM; U87 human glioma cells and patient-derived human glioblastoma cancer stem cells) to demonstrate how vital the information retrieved from the correlation between MRI and confocal images is and to highlight how the increased invasiveness of xenografts derived from cancer stem cells may not be clearly detected by standard in vivo MRI approaches. The protocol studied in this work could be implemented in pre-clinical GBM research to further the development and validation of more predictive and translatable MR imaging protocols that can be used as critical diagnostic and prognostic tools. The development of this protocol is part of the quest for more efficacious treatment approaches for this devastating and still uncurable disease. In particular, this approach could be instrumental in validating novel MRI-based techniques to assess cellular infiltration beyond the macroscopic tumor margins and to quantify neo-angiogenesis.
Identifiants
pubmed: 33087842
doi: 10.1038/s41598-020-75137-y
pii: 10.1038/s41598-020-75137-y
pmc: PMC7578790
doi:
Substances chimiques
Contrast Media
0
Fluorescent Dyes
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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