Longitudinal Assessment of Amyloid Pathology in Transgenic ArcAβ Mice Using Multi-Parametric Magnetic Resonance Imaging

PLoS One. 2013 Jun 19;8(6):e66097. doi: 10.1371/journal.pone.0066097. Print 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier
  • Brain / blood supply*
  • Brain / diagnostic imaging
  • Cerebral Amyloid Angiopathy / diagnostic imaging*
  • Cerebral Amyloid Angiopathy / genetics
  • Diffusion Magnetic Resonance Imaging / methods*
  • Disease Models, Animal
  • Linear Models
  • Longitudinal Studies
  • Male
  • Mice
  • Mice, Transgenic

Supplementary concepts

  • Amyloid angiopathy

Grants and funding

The work was supported by the Swiss National Science Foundation (grants 3100A0-112835 and 310030-126029 to MR; 310030-132629 to IK), by the German Research Foundation Grant RE 1123/9-2) and by the Carl Zeiss Foundation (dissertation fellowship to FS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.