Evaluation of the diffusion MRI white matter tract integrity model using myelin histology and Monte-Carlo simulations

Zhou, Zihan; Tong, Qiqi; Zhang, Lei; Ding, Qiuping; Lü, Hui; Jonkman, Laura E.; Yao, Junye; He, Hongjian; Zhu, Keqing; Zhong, Jianhui

doi:10.1016/j.neuroimage.2020.117313

Cited by 16 publications

(12 citation statements)

References 62 publications

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“…At the preclinical stage, diffusion metrics appear to behave in opposition to the trend observed in aging and clinical AD (ie, MCI, dementia) of more progressively widespread increases in diffusivity 4,5 due to age-and disease-related neurodegeneration. A unique strength of this paper is our use of WMTI metrics (Fig 3A) [13][14][15][16] that have been validated in model systems [17][18][19][20] to distinguish axonal degeneration (AWF) from gliosis (D e,⊥ ), thereby providing insight into which tissue changes contribute to greater diffusion restriction. The WMTI model is predicated on the well-supported assumption of minimal water exchange between the intra-axonal and extra-axonal compartments over time scales comparable to TE of the diffusion MRI sequence (≈50-100 milliseconds).…”

Section: Discussionmentioning

confidence: 99%

“…In addition to conventional diffusion metrics (ie, FA, MD, mean kurtosis [MK]), we report modeling-derived white matter tract integrity (WMTI) metrics of axonal density (ie, axonal water fraction [AWF]) and gliosis/myelin changes (ie, extra-axonal radial diffusivity [D e,⊥ ]) to distinguish neuronal from glial changes, respectively. We have shown these metrics to be sensitive to white matter changes in aging 14 and across the clinical stages of AD, 15,16 with additional validation from preclinical models [17][18][19][20] indicating the viability of our inferences regarding the mechanisms underlying these changes.…”

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confidence: 86%

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Greater Diffusion Restriction in White Matter in Preclinical Alzheimer Disease

Benitez

Jensen

Thorn

et al. 2022

Annals of Neurology

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Objective: The Alzheimer's continuum is biologically defined by beta-amyloid deposition, which at the earliest stages is superimposed upon white matter degeneration in aging. However, the extent to which these co-occurring changes is characterized is relatively underexplored. The goal of this study was to use diffusional kurtosis imaging (DKI) and biophysical modeling to detect and describe amyloid-related white matter changes in preclinical Alzheimer disease. Methods: Cognitively unimpaired participants ages 45 to 85 years completed brain magnetic resonance imaging, amyloid positron emission tomography (florbetapir), neuropsychological testing, and other clinical measures at baseline in a cohort study. We tested whether beta-amyloid-negative (ABÀ) and -positive (AB+) participants differed on DKIbased conventional (ie, fractional anisotropy [FA], mean diffusivity [MD], mean kurtosis) and modeling (ie, axonal water fraction [AWF], extra-axonal radial diffusivity [D e,⊥ ]) metrics, and whether these metrics were associated with other biomarkers. Results: We found significantly greater diffusion restriction (higher FA/AWF, lower MD/D e,⊥ ) in white matter in AB+ than ABÀ (partial η 2 =0.08-0.19), more notably in the extra-axonal space within primarily late myelinating tracts. Diffusion metrics predicted amyloid status incrementally over age (area under the curve = 0.84) with modest yet selective associations, where AWF (a marker of axonal density) correlated with speed/executive functions and neurodegeneration, whereas D e,⊥ (a marker of gliosis/myelin repair) correlated with amyloid deposition and white matter hyperintensity volume. Interpretation: These results support prior evidence of a nonmonotonic change in diffusion behavior, where an early increase in diffusion restriction is hypothesized to reflect inflammation and myelin repair prior to an ensuing decrease in diffusion restriction, indicating glial and neuronal degeneration.

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Section: Discussionmentioning

confidence: 99%

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confidence: 86%

Greater Diffusion Restriction in White Matter in Preclinical Alzheimer Disease

Benitez

Jensen

Thorn

et al. 2022

Annals of Neurology

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“…Interestingly, radEAD from the WMTI diffusion model was found to be the most important feature for the CC‐specific WM age prediction. WMTI‐radEAD has been related to degree of myelination in both ex vivo (Kelm et al, 2016 ) and in vivo animal histology models (Jelescu et al, 2016 ), as well as in an ex vivo human model of CC (Zhou et al, 2020 ). While this may potentially indicate that the CC association with previous childbirths could be driven by individual differences in myelin‐related ageing processes, the precise underlying neural substrates of diffusion metrics remain to be clarified.…”

Section: Discussionmentioning

confidence: 99%

A history of previous childbirths is linked to women's white matter brain age in midlife and older age

Voldsbekk

Barth

Maximov

et al. 2021

Human Brain Mapping

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Maternal brain adaptations occur in response to pregnancy, but little is known about how parity impacts white matter and white matter ageing trajectories later in life. Utilising global and regional brain age prediction based on multi‐shell diffusion‐weighted imaging data, we investigated the association between previous childbirths and white matter brain age in 8,895 women in the UK Biobank cohort (age range = 54–81 years). The results showed that number of previous childbirths was negatively associated with white matter brain age, potentially indicating a protective effect of parity on white matter later in life. Both global white matter and grey matter brain age estimates showed unique contributions to the association with previous childbirths, suggesting partly independent processes. Corpus callosum contributed uniquely to the global white matter association with previous childbirths, and showed a stronger relationship relative to several other tracts. While our findings demonstrate a link between reproductive history and brain white matter characteristics later in life, longitudinal studies are required to establish causality and determine how parity may influence women's white matter trajectories across the lifespan.

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“…Interestingly, radEAD from the WMTI diffusion model was found to be the most important feature for the CC-specific WM age prediction. WMTI-radEAD has been related to degree of myelination in both ex vivo [117] and in vivo animal histology models [118], as well as in an ex vivo human model of CC [119]. While this may potentially indicate that the CC association with previous childbirths could be driven by individual differences in myelin-related ageing processes, the precise underlying neural substrates of diffusion metrics remain to be clarified.…”

Section: Discussionmentioning

confidence: 99%

A history of previous childbirths is linked to women’s white matter brain age in midlife and older age

Voldsbekk

Barth

Maximov

et al. 2020

Preprint

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Maternal brain adaptations occur in response to pregnancy, but little is known about how parity impacts white matter (WM) microstructure and WM ageing trajectories later in life. Utilising global and regional brain-age prediction based on multi-shell diffusion MRI data, we investigated the association between previous childbirths and WM brain age in 8,895 women in the UK Biobank cohort (age range = 54 - 81 years). The results showed that a higher number of previous childbirths was associated with lower WM brain age, in line with previous studies showing less evident grey matter (GM) brain ageing in parous relative to nulliparous women. Both global WM and GM brain age estimates showed unique contributions to the association with previous childbirths, suggesting partly independent processes. Corpus callosum contributed uniquely to the global WM association with previous childbirths, and showed a stronger relationship relative to several other tracts. While our findings demonstrate a link between reproductive history and brain WM characteristics later in life, longitudinal studies are required to understand how parity influences women’s WM trajectories across the lifespan.

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Evaluation of the diffusion MRI white matter tract integrity model using myelin histology and Monte-Carlo simulations

Cited by 16 publications

References 62 publications

Greater Diffusion Restriction in White Matter in Preclinical Alzheimer Disease

Greater Diffusion Restriction in White Matter in Preclinical Alzheimer Disease

A history of previous childbirths is linked to women's white matter brain age in midlife and older age

A history of previous childbirths is linked to women’s white matter brain age in midlife and older age

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