In vivo quantitative whole‐brain diffusion tensor imaging analysis of APP/PS1 transgenic mice using voxel‐based and atlas‐based methods
Abstract
Introduction 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.Conclusion 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.
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Significant directional alignment between MRI and transcriptional changes likely reflects co-occurring neuronal loss, dendritic degeneration, axonal disruption, and myelin damage, together with cellular responses to neuroinflammation and neuropathology.
“Significant directional alignment between MRI and transcriptional changes likely reflects co‐occurring neuronal loss, dendritic degeneration, axonal disruption, and myelin damage, 85 , 86 , 87 together with cellular responses to neuroinflammation and neuropathology. 69”
From Diffusion MRI reveals amyloid plaque–associated cellular signatures through spatial transcriptomic integration (2026) · cites this paper as [85]
The authors' dMRI results are generally consistent with those reported using other mouse models of AD.
“Our dMRI results are generally consistent with those reported using other mouse models of AD [31–35].”
From Brain microstructure abnormalities in the 3xTg-AD mouse – A diffusion MRI and morphology correlation study (2022) · cites this paper as [34]
Previous DTI studies have demonstrated WM integrity impairment in various types of AD mouse models.
“Previous DTI studies have demonstrated WM integrity impairment in various types of AD mouse models (Qin et al., 2013; Massalimova et al., 2020; Bergamino et al., 2023).”
From Multimodal MRI combined with RNA sequencing reveals pathological signatures in the 9-month-old 3×Tg-AD mouse brain (2026) · cites this paper as Qin et al., 2013
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- Authors
- Qin, Y.-Y., Li, M.-W., Zhang, S., Zhang, Y., Zhao, L.-Y., Lei, H., Oishi, K., & Zhu, W.-Z.
- Affiliations
- Johns Hopkins University (US)
- Tongji Hospital (CN)
- Chinese Academy of Sciences (CN)
- Corresponding author
- Oishi, Kenichi
- Zhu, Wen-Zhen
- Venue
- Neuroradiology
- Published
- 2013-05-05
- Volume
- 55
- Issue
- 8
- Pages
- 1027-1038
- ISSN
- 0028-3940 (ISSN-L)
- 1432-1920
- OpenAlex
- W1978593493
- Cited by
- 42
- References
- 75
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 6 · 2021: 4 · 2020: 4 · 2019: 5 · 2018: 5 · 2017: 1 · 2016: 3 · 2015: 5 · 2014: 1 · 2013: 1
- FWCI
- 2.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuroradiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- diffusion tensor imaging, APP/PS1 mice, mouse models of Alzheimer's disease, voxel-based analysis, fractional anisotropy, axial diffusivity, radial diffusivity, white matter pathology, gray matter pathology, hippocampus, corpus callosum, histopathology validation
- MeSH terms
- Algorithms, Alzheimer Disease, Animals, Brain, Disease Models, Animal, Humans, Image Enhancement, Image Interpretation, Computer-Assisted, Mice, Transgenic, Sensitivity and Specificity, Reproducibility of Results, Amyloid beta-Protein Precursor, Imaging, Three-Dimensional, Mice, Diffusion Tensor Imaging
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