ArticleResearch square2026
Diffusion-relaxation MRI as virtual histology: separable microstructural signatures of AD pathology in ex vivo human brain.
Article in Research square, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cognitive decline in Alzheimer's disease (AD) reflects progressive disruption of cellular and microstructural organization, yet the biological specificity of conventional MRI signals remains poorly understood. Multidimensional diffusion-relaxation MRI (MD-MRI) resolves sub-voxel tissue heterogeneity and may offer a framework for linking imaging signals to underlying neuropathology. We tested the hypothesis that neuronal, glial, and white matter pathologies in AD occupy separable regions of diffusion-relaxation space and generate spatially organized signatures associated with cognitive impairment. We integrated ex vivo MD-MRI with co-registered histology from 12 human donors spanning a range of Braak stages and pathological severity. Nested cross-validated elastic net models predicted voxelwise Aβ, pTau, microglia, and myelin burden from the multidimensional diffusion-relaxation density distribution. Regional associations were assessed across hippocampal subfields and white matter, and MRI-predicted pathology was related to ante-mortem Mini-Mental State Examination scores. Distinct diffusion-relaxation components were preferentially associated with different pathological markers, indicating separable microstructural signatures. MRI-derived predictions corresponded significantly with histological measures of myelin (ρ = 0.77), pTau (ρ = 0.62), and microglia (ρ = 0.61), with weaker correspondence for Aβ (ρ = 0.45). Regionally, predicted pathology recapitulated known patterns of selective vulnerability, with elevated pTau and microglial signal in hippocampal subfields and dominant myelin-associated signal in white matter (p < 0.0001). Higher predicted hippocampal pTau was strongly associated with worse cognitive performance (ρ = -0.88, p = 0.0014), with a moderate association in white matter (ρ = -0.66, p = 0.036). These findings demonstrate that AD-related pathological processes manifest as distinct, spatially organized diffusion-relaxation signatures, providing mechanistic insight into the microstructural basis of MRI contrasts. As clinically feasible MD-MRI protocols continue to emerge, translation of these signatures to in vivo imaging may enable more biologically informed assessment of neurodegeneration.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.