Advanced MRI Center, Department of Radiology
Analytical, Diagnostic and Therapeutic Techniques and Equipment | Bioimaging and Biomedical Optics | Neoplasms | Radiology
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.
MRI, fluorescence microscopy, imaging, glioblastoma
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Copyright © The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
DOI of Published Version
Peviani M, Spano G, Pagani A, Brugnara G, Covino C, Galli R, Biffi A, Politi LS. Lipophilic dye-compatible brain clearing technique allowing correlative magnetic resonance/high-resolution fluorescence imaging in rat models of glioblastoma. Sci Rep. 2020 Oct 21;10(1):17974. doi: 10.1038/s41598-020-75137-y. PMID: 33087842; PMCID: PMC7578790. Link to article on publisher's site
Peviani M, Spano G, Pagani A, Brugnara G, Covino C, Galli R, Biffi A, Politi LS. (2020). Lipophilic dye-compatible brain clearing technique allowing correlative magnetic resonance/high-resolution fluorescence imaging in rat models of glioblastoma. Open Access Publications by UMMS Authors. https://doi.org/10.1038/s41598-020-75137-y. Retrieved from https://escholarship.umassmed.edu/oapubs/4439
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.