title: In vivo quantitative whole-brain diffusion tensor imaging analysis of APP/PS1 transgenic mice using voxel-based and atlas-based methods.
abstract: BACKGROUND
  Diffusion tensor imaging (DTI) has been applied to characterize the pathological features of Alzheimer's disease (AD) in a mouse model, although little is known about whether these features are structure specific. Voxel-based analysis (VBA) and atlas-based analysis (ABA) are good complementary tools for whole-brain DTI analysis. The purpose of this study was to identify the spatial localization of disease-related pathology in an AD mouse model.
  
  
  METHODS
  VBA and ABA quantification were used for the whole-brain DTI analysis of nine APP/PS1 mice and wild-type (WT) controls. Multiple scalar measurements, including fractional anisotropy (FA), trace, axial diffusivity (DA), and radial diffusivity (DR), were investigated to capture the various types of pathology. The accuracy of the image transformation applied for VBA and ABA was evaluated by comparing manual and atlas-based structure delineation using kappa statistics. Following the MR examination, the brains of the animals were analyzed for microscopy.
  
  
  RESULTS
  Extensive anatomical alterations were identified in APP/PS1 mice, in both the gray matter areas (neocortex, hippocampus, caudate putamen, thalamus, hypothalamus, claustrum, amygdala, and piriform cortex) and the white matter areas (corpus callosum/external capsule, cingulum, septum, internal capsule, fimbria, and optic tract), evidenced by an increase in FA or DA, or both, compared to WT mice (p < 0.05, corrected). The average kappa value between manual and atlas-based structure delineation was approximately 0.8, and there was no significant difference between APP/PS1 and WT mice (p > 0.05). The histopathological changes in the gray matter areas were confirmed by microscopy studies. DTI did, however, demonstrate significant changes in white matter areas, where the difference was not apparent by qualitative observation of a single-slice histological specimen.
  
  
  CONCLUSIONS
  This study demonstrated the structure-specific nature of pathological changes in APP/PS1 mouse, and also showed the feasibility of applying whole-brain analysis methods to the investigation of an AD mouse model.
authors: Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.|The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, 217D Traylor Building, 720 Rutland Avenue, Baltimore, MD, 21205, USA.
authors: Yuan-Yuan
authors: YY
authors: Qin
authors: The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, 217D Traylor Building, 720 Rutland Avenue, Baltimore, MD, 21205, USA.
authors: Mu-Wei
authors: MW
authors: Li
authors: Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.
authors: Shun
authors: S
authors: Zhang
authors: Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.
authors: Yan
authors: Y
authors: Zhang
authors: Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.
authors: Ling-Yun
authors: LY
authors: Zhao
authors: Wuhan Center for Magnetic Resonance, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, China.
authors: Hao
authors: H
authors: Lei
authors: The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, 217D Traylor Building, 720 Rutland Avenue, Baltimore, MD, 21205, USA. koishi@mri.jhu.edu.
authors: Kenichi
authors: K
authors: Oishi
authors: Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China. zhuwenzhen@hotmail.com.
authors: Wen-Zhen
authors: WZ
authors: Zhu
mesh_terms: D000465:Algorithms; D000544:Alzheimer Disease / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001921:Brain / Q000473:pathology* / Q000502:physiology; D056324:Diffusion Tensor Imaging / Q000379:methods*; D004195:Disease Models, Animal; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D021621:Imaging, Three-Dimensional / Q000379:methods*; D051379:Mice; D008822:Mice, Transgenic; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D016564:Amyloid beta-Protein Precursor
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