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4269074 
Journal Article 
Comparison ofIn VivoandEx VivoMRI for the Detection of Structural Abnormalities in a Mouse Model of Tauopathy 
Holmes, HE; Powell, NM; Ma, D; Ismail, O; Harrison, IF; Wells, JA; Colgan, N; O'Callaghan, JM; Johnson, RA; Murray, TK; Ahmed, Z; Heggenes, M; Fisher, A; Cardoso, MJ; Modat, M; O'Neill, MJ; Collins, EC; Fisher, EM; Ourselin, S; Lythgoe, MF 
2017 
11 
20 
English 
28408879 
WOS:000397960400001 
With increasingly large numbers of mouse models of human disease dedicated to MRI studies, compromises betweenin vivoandex vivoMRI must be fully understood in order to inform the choice of imaging methodology. We investigate the application of high resolutionin vivoandex vivoMRI, in combination with tensor-based morphometry (TBM), to uncover morphological differences in the rTg4510 mouse model of tauopathy. The rTg4510 mouse also offers a novel paradigm by which the overexpression of mutant tau can be regulated by the administration of doxycycline, providing us with a platform on which to investigate more subtle alterations in morphology with morphometry. Bothin vivoandex vivoMRI allowed the detection of widespread bilateral patterns of atrophy in the rTg4510 mouse brain relative to wild-type controls. Regions of volume loss aligned with neuronal loss and pathological tau accumulation demonstrated by immunohistochemistry. When we sought to investigate more subtle structural alterations in the rTg4510 mice relative to a subset of doxycycline-treated rTg4510 mice,ex vivoimaging enabled the detection of more regions of morphological brain changes. The disadvantages ofex vivoMRI may however mitigate this increase in sensitivity: we observed a 10% global shrinkage in brain volume of the post-mortem tissues due to formalin fixation, which was most notable in the cerebellum and olfactory bulbs. However, many central brain regions were not adversely affected by the fixation protocol, perhaps due to our "in-skull" preparation. The disparity between our TBM findings fromin vivoandex vivoMRI underlines the importance of appropriate study design, given the trade-off between these two imaging approaches. We support the utility ofin vivoMRI for morphological phenotyping of mouse models of disease; however, for subtler phenotypes,ex vivooffers enhanced sensitivity to discrete morphological changes.