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Cited by 209Advanced Neuroimaging Techniques and ApplicationsFunctional Brain Connectivity StudiesAdvanced MRI Techniques and Applications

White matter microstructure across the adult lifespan: A mixed longitudinal and cross-sectional study using advanced diffusion models and brain-age prediction

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Beck, Dani, de Lange, Ann-Marie G., Maximov, Ivan I., Richard, Geneviève, Andreassen, Ole A., Nordvik, Jan E., Westlye, Lars T.·2021·NeuroImage
DOI 10.1016/j.neuroimage.2020.117441

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Abstract

The macro- and microstructural architecture of human brain white matter undergoes substantial alterations throughout development and ageing. Most of our understanding of the spatial and temporal characteristics of these lifespan adaptations come from magnetic resonance imaging (MRI), including diffusion MRI (dMRI), which enables visualisation and quantification of brain white matter with unprecedented sensitivity and detail. However, with some notable exceptions, previous studies have relied on cross-sectional designs, limited age ranges, and diffusion tensor imaging (DTI) based on conventional single-shell dMRI. In this mixed cross-sectional and longitudinal study (mean interval: 15.2 months) including 702 multi-shell dMRI datasets, we combined complementary dMRI models to investigate age trajectories in healthy individuals aged 18 to 94 years (57.12% women). Using linear mixed effect models and machine learning based brain age prediction, we assessed the age-dependence of diffusion metrics, and compared the age prediction accuracy of six different diffusion models, including diffusion tensor (DTI) and kurtosis imaging (DKI), neurite orientation dispersion and density imaging (NODDI), restriction spectrum imaging (RSI), spherical mean technique multi-compartment (SMT-mc), and white matter tract integrity (WMTI). The results showed that the age slopes for conventional DTI metrics (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity [AD], radial diffusivity [RD]) were largely consistent with previous research, and that the highest performing advanced dMRI models showed comparable age prediction accuracy to conventional DTI. Linear mixed effects models and Wilk's theorem analysis showed that the 'FA fine' metric of the RSI model and 'orientation dispersion' (OD) metric of the NODDI model showed the highest sensitivity to age. The results indicate that advanced diffusion models (DKI, NODDI, RSI, SMT mc, WMTI) provide sensitive measures of age-related microstructural changes of white matter in the brain that complement and extend the contribution of conventional DTI.

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  • These measures reflect a composite of axonal organization, myelin, extracellular water, fiber geometry, and cerebrovascular injury.

    “However, these measures reflect a composite of axonal organization, myelin, extracellular water, fiber geometry, and cerebrovascular injury (Beck et al., 2021; Jones et al., 2013).”

    From 40 Years of diffusion MRI in the brain: From history to emerging frontiers (2026) · cites this paper as Beck et al., 2021

    The discussion passage indexed under Table 5 says diffusion measures can be influenced by axonal density, myelination, extracellular conditions, and fibre architecture. It also mentions blood vessels and perivascular spaces, but does not establish that the measures reflect cerebrovascular injury. No page number was supplied for the indexed passage. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Beck, D., de Lange, A.-M. G., Maximov, I. I., Richard, G., Andreassen, O. A., Nordvik, J. E., & Westlye, L. T.
Affiliations
  • Oslo University Hospital (NO)
  • CatoSenteret (NO)
Corresponding author
  • Beck, Dani
  • Westlye, Lars T.
ORCID
Venue
NeuroImage
Publisher
Elsevier BV
Published
2021-01
Volume
224
Pages
117441
ISSN
1053-8119 (ISSN-L)
DOI
10.1016/j.neuroimage.2020.117441
OpenAlex
W3092037825
Cited by
209
References
11
Citations by year
2026: 26 · 2025: 43 · 2024: 47 · 2023: 35 · 2022: 36 · 2021: 18 · 2020: 4
FWCI
11.37
Type
journal article
Language
en
Open access
Licence
Locations
  • NeuroImage (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
Funders
  • EkstraStiftelsen Helse og Rehabilitering
  • Stiftelsen Kristian Gerhard Jebsen
  • Horizon 2020
  • Helse Sør-Øst RHF
  • Norges Forskningsråd
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
Keywords
white matter microstructure, brain aging, brain development, brain age prediction, NODDI, restriction spectrum imaging, white matter tract integrity, fractional anisotropy, age trajectories
MeSH terms
Adolescent, Adult, Aged, Aged, 80 and over, Aging, Brain, Cross-Sectional Studies, Female, Humans, Image Processing, Computer-Assisted, Longitudinal Studies, Male, Middle Aged, Anisotropy, Diffusion Magnetic Resonance Imaging, Young Adult, Diffusion Tensor Imaging, White Matter

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