title: Longitudinal Assessment of Amyloid Pathology in Transgenic ArcAβ Mice Using Multi-Parametric Magnetic Resonance Imaging.
abstract: Magnetic resonance imaging (MRI) can be used to monitor pathological changes in Alzheimer's disease (AD). The objective of this longitudinal study was to assess the effects of progressive amyloid-related pathology on multiple MRI parameters in transgenic arcAβ mice, a mouse model of cerebral amyloidosis. Diffusion-weighted imaging (DWI), T1-mapping and quantitative susceptibility mapping (QSM), a novel MRI based technique, were applied to monitor structural alterations and changes in tissue composition imposed by the pathology over time. Vascular function and integrity was studied by assessing blood-brain barrier integrity with dynamic contrast-enhanced MRI and cerebral microbleed (CMB) load with susceptibility weighted imaging and QSM. A linear mixed effects model was built for each MRI parameter to incorporate effects within and between groups (i.e. genotype) and to account for changes unrelated to the disease pathology. Linear mixed effects modelling revealed a strong association of all investigated MRI parameters with age. DWI and QSM in addition revealed differences between arcAβ and wt mice over time. CMBs became apparent in arcAβ mice with 9 month of age; and the CMB load reflected disease stage. This study demonstrates the benefits of linear mixed effects modelling of longitudinal imaging data. Moreover, the diagnostic utility of QSM and assessment of CMB load should be exploited further in studies of AD.
authors.affiliation: Institute for Biomedical Engineering, ETH and University of Zurich, Zurich, Switzerland ; Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland.
authors.forename: Jan
authors.initials: J
authors.lastname: Klohs
authors.forename: Igna Wojtyna
authors.initials: IW
authors.lastname: Politano
authors.forename: Andreas
authors.initials: A
authors.lastname: Deistung
authors.forename: Joanes
authors.initials: J
authors.lastname: Grandjean
authors.forename: Anna
authors.initials: A
authors.lastname: Drewek
authors.forename: Marco
authors.initials: M
authors.lastname: Dominietto
authors.forename: Ruth
authors.initials: R
authors.lastname: Keist
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Schweser
authors.forename: Jürgen R
authors.initials: JR
authors.lastname: Reichenbach
authors.forename: Roger M
authors.initials: RM
authors.lastname: Nitsch
authors.forename: Irene
authors.initials: I
authors.lastname: Knuesel
authors.forename: Markus
authors.initials: M
authors.lastname: Rudin
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply* / Q000000981:diagnostic imaging; D016657:Cerebral Amyloid Angiopathy / Q000000981:diagnostic imaging* / Q000235:genetics; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D004195:Disease Models, Animal; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D051379:Mice; D008822:Mice, Transgenic