Klohs Jan, Politano Igna Wojtyna, Deistung Andreas, Grandjean Joanes, Drewek Anna, Dominietto Marco, Keist Ruth, Schweser Ferdinand, Reichenbach Jürgen R, Nitsch Roger M, Knuesel Irene, Rudin Markus
Institute for Biomedical Engineering, ETH and University of Zurich, Zurich, Switzerland ; Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland.
PLoS One. 2013 Jun 19;8(6):e66097. doi: 10.1371/journal.pone.0066097. Print 2013.
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.
磁共振成像（MRI）可用于监测阿尔茨海默病（AD）的病理变化。这项纵向研究的目的是评估在转基因arcAβ小鼠（一种脑淀粉样变性小鼠模型）中，渐进性淀粉样蛋白相关病理对多个MRI参数的影响。应用扩散加权成像（DWI）、T1映射和定量磁化率映射（QSM，一种基于MRI的新技术）来监测随着时间推移病理导致的结构改变和组织成分变化。通过动态对比增强MRI评估血脑屏障完整性以及用磁化率加权成像和QSM评估脑微出血（CMB）负荷，来研究血管功能和完整性。为每个MRI参数建立线性混合效应模型，以纳入组内和组间（即基因型）的效应，并考虑与疾病病理无关的变化。线性混合效应建模显示所有研究的MRI参数与年龄密切相关。此外，随着时间推移，DWI和QSM显示arcAβ小鼠与野生型小鼠之间存在差异。9月龄的arcAβ小鼠出现明显的CMB；并且CMB负荷反映了疾病阶段。本研究证明了对纵向成像数据进行线性混合效应建模的益处。此外，在AD研究中应进一步利用QSM的诊断效用和CMB负荷评估。
