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7139419 
Journal Article 
Microscopic DTI accurately identifies early glioma cell migration: correlation with multimodal imaging in a new glioma stem cell model 
Gimenez, U; Perles-Barbacaru, AT; Millet, A; Appaix, F; El-Atifi, M; Pernet-Gallay, K; van Der Sanden, B; Berger, F; Lahrech, H; , 
2016 
1 
NMR in Biomedicine
ISSN: 0952-3480
EISSN: 1099-1492 
WILEY-BLACKWELL 
HOBOKEN 
1553-1562 
27717043 
WOS:000386617100007 
Monitoring glioma cell infiltration in the brain is critical for diagnosis and therapy. Using a new glioma Glio6 mouse model derived from human stem cells we show how diffusion tensor imaging (DTI) may predict glioma cell migration/invasion.In vivo multiparametric MRI was performed at one, two and three months of Glio6 glioma growth (Glio6 (n=6), sham (n=3)). This longitudinal study reveals the existence of a time window to study glioma cell/migration/invasion selectively. Indeed, at two months only Glio6 cell invasion was detected, while tumor mass formation, edema, blood-brain barrier leakage and tumor angiogenesis were detected later, at three months. To robustly confirm the potential of DTI for detecting glioma cell migration/invasion, a microscopic 3D-DTI (80m isotropic spatial resolution) technique was developed and applied to fixed mouse brains (Glio6 (n=6), sham (n=3)). DTI changes were predominant in the corpus callosum (CC), a known path of cell migration. Fractional anisotropy (FA) and perpendicular diffusivity (D) changes derived from ex vivo microscopic 3D-DTI were significant at two months of tumor growth. In the caudate putamen an FA increase of +38% (p<0.001) was observed, while in the CC a-28% decrease in FA (p<0.005) and a+95% increase in D-perpendicular to (p<0.005) were observed. In the CC, DTI changes and fluorescent Glio6 cell density obtained by two-photon microscopy in the same brains were correlated (p<0.001, r=0.69), validating FA and D-perpendicular to as early quantitative biomarkers to detect glioma cell migration/invasion. The origin of DTI changes was assessed by electron microscopy of the same tract, showing axon bundle disorganization. During the first two months, Glio6 cells display a migratory phenotype without being associated with the constitution of a brain tumor mass. This offers a unique opportunity to apply microscopic 3D-DTI and to validate DTI parameters FA and D-perpendicular to as biomarkers for glioma cell invasion.