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Early detection of human glioma sphere xenografts in mouse brain using diffusion MRI at 14.1T

Lookup NU author(s): Dr Paola Porcari

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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).

Abstract

Glioma models have provided important insights into human brain cancers. Among the investigative tools, MRI has allowed their characterization and diagnosis. In this study, we investigated whether diffusion MRI might be a useful technique for early detection and characterization of slow-growing and diffuse infiltrative gliomas, such as the proposed new models, LN-2669GS and LN-2540GS glioma sphere xenografts. Tumours grown in these models are not visible in conventional T-2-weighted or contrast-enhanced T-1-weighted MRI at 14.1T. Diffusion-weighted imaging and diffusion tensor imaging protocols were optimized for contrast by exploring long diffusion times sensitive for probing the microstructural alterations induced in the normal brain by the slow infiltration of glioma sphere cells. Compared with T-2-weighted images, tumours were properly identified in their early stage of growth using diffusion MRI, and confirmed by localized proton MR spectroscopy as well as immunohistochemistry. The first evidence of tumour presence was revealed for both glioma sphere xenograft models three months after tumour implantation, while no necrosis, oedema or haemorrhage were detected either by MRI or by histology. Moreover, different values of diffusion indices, such as mean diffusivity and fractional anisotropy, were obtained in tumours grown from LN-2669GS and LN-2540GS glioma sphere lines. These observations highlighted diverse tumour microstructures for both xenograft models, which were reflected in histology. This study demonstrates the ability of diffusion MRI techniques to identify and investigate early stages of slow-growing, invasive tumours in the mouse brain, thus providing a potential imaging biomarker for early detection of tumours in humans.

Publication metadata

Author(s): Porcari P, Hegi ME, Lei H, Hamou MF, Vassallo I, Capuani S, Gruetter R, Mlynarik V

Publication type: Article

Publication status: Published

Journal: NMR in Biomedicine

Year: 2016

Volume: 29

Issue: 11

Pages: 1577-1589

Print publication date: 01/11/2016

Online publication date: 15/09/2016

Acceptance date: 28/07/2016

Date deposited: 22/02/2017

ISSN (print): 0952-3480

ISSN (electronic): 1099-1492

Publisher: Wiley-Blackwell Publishing Ltd.

URL: http://dx.doi.org/10.1002/nbm.3610

DOI: 10.1002/nbm.3610

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