A spatial imaging-transcriptomics paradigm for deciphering the molecular basis of microscopic MRI in the normal brain and Alzheimer’s disease
Open accessAbstract
Imaging genomics offers powerful links between genetics and neuroimaging phenotypes, but conventional methods often lack spatial correspondence. We introduce spatial imaging-transcriptomics, a paradigm that directly integrates magnetic resonance imaging (MRI) and spatially resolved transcriptomics (ST) with matched resolution from the same brain through spatially co-registered maps. We apply this framework to wild-type and Alzheimer's disease (AD) mouse models to uncover the molecular underpinnings of diffusion MRI. In the normal brain, fractional anisotropy (FA) correlates with myelination processes and oligodendrocytes, whereas diffusivity indices are associated with neurons. Furthermore, we identified the genetic basis for observed cortical gradients in diffusion tensor imaging (DTI). In the AD mouse model, reduced FA is linked to myelin and oligodendrocyte change and β-amyloid deposition. Critically, imaging-defined disease foci can guide differential gene expression analysis to uncover AD-specific genetic alterations. The spatial imaging-transcriptomics paradigm provides an unprecedented high-resolution bridge between neuroimaging and transcriptomics, benefitting the decipherment of complex molecular events in brain disorders.
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Most prior work has focused on DTI metrics and linear associations, which may not fully capture compartment-specific microstructural changes.
“most prior work has focused on DTI metrics and linear associations, 39 , 40 , 41 , 42 which may not fully capture compartment‐specific microstructural changes.”
From Diffusion MRI reveals amyloid plaque–associated cellular signatures through spatial transcriptomic integration (2026) · cites this paper as [39]
In 5xFAD mice, genes with higher expression in gray matter and lower expression in white matter showed significant correlations with diffusion metrics and were predominantly neuronal and oligodendrocyte-associated.
“In 5xFAD mice, genes with higher expression in gray matter and lower expression in white matter showed significant correlations with diffusion metrics and were predominantly neuronal and oligodendrocyte‐associated, consistent with previous findings. 39”
From Diffusion MRI reveals amyloid plaque–associated cellular signatures through spatial transcriptomic integration (2026) · cites this paper as [39]
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Han, X., Hu, R., Ping, X., Chen, J., Liu, J., Liu, Z., Jin, X., Gao, X., Lin, M., Zhao, Y., et al. (2026) · Alzheimer's & Dementia · doi:10.1002/alz.71908
- Authors
- Shen, Y., Shen, Y., Wang, M., Jin, K., Yang, P., Cao, Z., Zhu, Q., Zhao, Z., Li, H., Han, L., Liu, S., Liao, J., Zhang, J., Fan, X., & Wu, D.
- Affiliations
- Zhejiang University (CN)
- Children's Hospital of Zhejiang University (CN)
- First Affiliated Hospital Zhejiang University (CN)
- Corresponding author
- Fan, Xiaohui
- Wu, Dan
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2025-08
- Volume
- 44
- Issue
- 8
- Pages
- 116073
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W4412855907
- Cited by
- 10
- References
- 75
- Citations by year
- 2026: 10
- FWCI
- 5.43
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Ministry of Science and Technology of the People's Republic of China (2021ZD0200202)
- National Natural Science Foundation of China (32427802, U24A200313)
- Zhejiang Province Natural Science Foundation (LQ23C090008)
- Hangzhou Agriculture and Social Development Research Funds (20231203A13)
- Science and Technology Department of Zhejiang Province
- Science and Technology Program of Zhejiang Province (202006140, 2022C03057)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- Alzheimer's disease, diffusion MRI, fractional anisotropy, diffusion tensor imaging, spatial transcriptomics, myelination, oligodendrocytes, amyloid-beta deposition, cortical gradients, disease foci, mouse model, radiogenomics
- MeSH terms
- Alzheimer Disease, Animals, Brain, Disease Models, Animal, Humans, Magnetic Resonance Imaging, Male, Mice, Inbred C57BL, Oligodendroglia, Gene Expression Profiling, Mice, Diffusion Tensor Imaging, Transcriptome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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