Comparison of in vivo and ex vivo MRI for the detection of structural abnormalities in a mouse model of tauopathy
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With increasingly large numbers of mouse models of human disease dedicated to MRI studies, compromises between in vivo and ex vivo MRI must be fully understood in order to inform the choice of imaging methodology. We investigate the application of high resolution in vivo and ex vivo MRI, in combination with tensor-based morphometry (TBM), to uncover morphological differences in the rTg4510 mouse model of tauopathy. The rTg4510 mouse also offers a novel paradigm by which the overexpression of mutant tau can be regulated by the administration of doxycycline, providing us with a platform on which to investigate more subtle alterations in morphology with morphometry. Both in vivo and ex vivo MRI allowed the detection of widespread bilateral patterns of atrophy in the rTg4510 mouse brain relative to wild-type controls. Regions of volume loss aligned with neuronal loss and pathological tau accumulation demonstrated by immunohistochemistry. When we sought to investigate more subtle structural alterations in the rTg4510 mice relative to a subset of doxycycline-treated rTg4510 mice, ex vivo imaging enabled the detection of more regions of morphological brain changes. The disadvantages of ex vivo MRI may however mitigate this increase in sensitivity: we observed a 10% global shrinkage in brain volume of the post-mortem tissues due to formalin fixation, which was most notable in the cerebellum and olfactory bulbs. However, many central brain regions were not adversely affected by the fixation protocol, perhaps due to our “in-skull” preparation. The disparity between our TBM findings from in vivo and ex vivo MRI underlines the importance of appropriate study design, given the trade-off between these two imaging approaches. We support the utility of in vivo MRI for morphological phenotyping of mouse models of disease; however, for subtler phenotypes, ex vivo offers enhanced sensitivity to discrete morphological changes.
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Ex vivo MRI achieves higher anatomic resolution and better tissue contrast than in vivo study, improving detection of microstructural changes, and maintains consistency with ex vivo spatial transcriptomics data.
“Ex vivo MRI was chosen over an in vivo study to achieve higher anatomic resolution and better tissue contrast, which improves the detection of microstructural changes, 45 , 46 and to maintain consistency with ex vivo spatial transcriptomics data.”
From Diffusion MRI reveals amyloid plaque–associated cellular signatures through spatial transcriptomic integration (2026) · cites this paper as [46]
The Results report higher ex vivo spatial resolution, and the Discussion reports greater gray–white matter contrast than in vivo MRI. The Conclusion says ex vivo MRI may be more sensitive to subtle morphological changes, but the paper does not establish improved detection of microstructural changes. The spatial-transcriptomics rationale follows the citations in the citing sentence and is not attributed to this source. (LLM, conf=0.84)
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- Authors
- Holmes, H. E., Powell, N. M., Ma, D., Ismail, O., Harrison, I. F., Wells, J. A., Colgan, N., O'Callaghan, J. M., Johnson, R. A., Murray, T. K., Ahmed, Z., Heggenes, M., Fisher, A., Cardoso, M. J., Modat, M., O'Neill, M. J., Collins, E. C., Fisher, E. M. C., Ourselin, S., & Lythgoe, M. F.
- Affiliations
- University College London (GB)
- Eli Lilly (United States) (US)
- Eli Lilly (United Kingdom) (GB)
- UCL Queen Square Institute of Neurology (GB)
- Corresponding author
- Holmes, Holly E.
- ORCID
- Venue
- Frontiers in Neuroinformatics
- Publisher
- Frontiers Media SA
- Published
- 2017-03-31
- Volume
- 11
- Pages
- 20-20
- ISSN
- 1662-5196 (ISSN-L)
- PMC
- PMC5374887
- OpenAlex
- W2599826853
- Cited by
- 55
- References
- 63
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 7 · 2023: 8 · 2022: 5 · 2021: 4 · 2020: 6 · 2019: 7 · 2018: 4 · 2017: 1
- FWCI
- 3.61
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Neuroinformatics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Research Portal (King's College London) (submittedVersion, cc-by)
- Funders
- Wellcome Trust (098327)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- tauopathy, in vivo MRI, ex vivo MRI, brain atrophy, tensor-based morphometry, brain morphometry, mouse models of human disease, Alzheimer's disease
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