title: Early detection of human glioma sphere xenografts in mouse brain using diffusion MRI at 14.1 T.
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 T2-weighted or contrast-enhanced T1-weighted MRI at 14.1 T. 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 T2-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.
authors.affiliation: Centre for Biomedical Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. paola.porcari@ncl.ac.uk.|Newcastle Magnetic Resonance Centre, Newcastle University, Newcastle, Upon Tyne, UK. paola.porcari@ncl.ac.uk.
authors.forename: P
authors.initials: P
authors.lastname: Porcari
authors.affiliation: Laboratory of Brain Tumor Biology and Genetics, Service of Neurosurgery and Neuroscience Research Centre, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
authors.forename: M E
authors.initials: ME
authors.lastname: Hegi
authors.affiliation: Centre for Biomedical Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.|Department of Radiology, University of Geneva (UNIGE), Geneva, Switzerland.
authors.forename: H
authors.initials: H
authors.lastname: Lei
authors.affiliation: Laboratory of Brain Tumor Biology and Genetics, Service of Neurosurgery and Neuroscience Research Centre, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
authors.forename: M-F
authors.initials: MF
authors.lastname: Hamou
authors.affiliation: Laboratory of Brain Tumor Biology and Genetics, Service of Neurosurgery and Neuroscience Research Centre, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
authors.forename: I
authors.initials: I
authors.lastname: Vassallo
authors.affiliation: CNR-ISC UOS Roma Sapienza, Physics Department, Sapienza University of Rome, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Capuani
authors.affiliation: Centre for Biomedical Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.|Department of Radiology, University of Geneva (UNIGE), Geneva, Switzerland.|Department of Radiology, University of Lausanne, Lausanne, Switzerland.|LIFMET, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Gruetter
authors.affiliation: Centre for Biomedical Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.|High Field MR Center, Medical University of Vienna, Vienna, Austria.
authors.forename: V
authors.initials: V
authors.lastname: Mlynarik
mesh_terms: D000465:Algorithms; D000818:Animals; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D045744:Cell Line, Tumor; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging* / Q000473:pathology*; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D018874:Spheroids, Cellular / Q000473:pathology
keywords: ADC; FA; MD; MRS; brain tumours; diffusion MRI; human glioma xenografts; immunohistochemistry