ReviewFrontiers in neuroscience2021
Potential Pitfalls of Using Fractional Anisotropy, Axial Diffusivity, and Radial Diffusivity as Biomarkers of Cerebral White Matter Microstructure.
Review in Frontiers in neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers, 4 of them syntheses that pooled it.
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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.
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Who cites it
160 citing papers in PubMed, 4 syntheses or guidelines pooled it, 209 citations in OpenAlex.
- Early life adversity and white matter microstructural organization-a systematic review.Brain imaging and behavior · 2025Pooled it
- The application of diffusion tensor imaging in patients with mild cognitive impairment: a systematic review and meta-analysis.Frontiers in neurology · 2025Pooled it
- Uncovering the hidden effects of repetitive subconcussive head impact exposure: A mega-analytic approach characterizing seasonal brain microstructural changes in contact and collision sports athletes.Human brain mapping · 2024Pooled it
- An ALE meta-analytic review of musical expertise.Scientific reports · 2022Pooled it
- Reversible white matter changes following a 4-week high phenylalanine exposure in adults with phenylketonuria.Journal of inherited metabolic disease · 2025Trial
- Long-term follow-up of a randomized controlled trial of choline for neurodevelopment in fetal alcohol spectrum disorder: corpus callosum white matter microstructure and neurocognitive outcomes.Journal of neurodevelopmental disorders · 2022Trial
- Substance use involvement moderates the effect of cortisol response on white-matter microstructure longitudinally.Dialogues in clinical neuroscience · 2026Article
- Differential cerebral white matter tract alterations in generalized anxiety disorder revealed by ultra-high-field 7 T diffusion-weighted imaging.Journal of affective disorders · 2026Article
- Reproducibility of diffusion, shape, and connectivity metrics across scanners: Implications for multi-site tractography.NeuroImage · 2026Article
- Longitudinal spatial changes of the contralesional corticospinal tract in high-grade glioma: a within-patient DTI tractography study.Journal of neuro-oncology · 2026Article
- Occupational stress and white matter integrity: a methodological perspective : Short title: White matter integrity and burnout: considerations.Brain structure & function · 2026Article
- Spatial organization of AQP4 water channel expression in the human brain.Science advances · 2026Article
- Disentangling pontine fiber geometry and microstructure in ARSACS using advanced MRI.NeuroImage. Clinical · 2026Article
- The Association Between Loss of Consciousness and the Default Mode Network at the Chronic Stage of Diffuse Axonal Injury: A Diffusion Tensor Imaging Study.Journal of clinical medicine · 2026Article
- Anatomical white matter tracts span the cortical hierarchy to support cognitive diversity.Nature human behaviour · 2026Article
- Divergent recovery trajectories after mild traumatic brain injury are characterized by distinct acute profiles of neurofilament light, 4R-tau, and white matter diffusivity.Journal of neurology · 2026Article
- Corpus callosum fractional anisotropy from routine diffusion tensor imaging predicts dementia in older adults beyond clinical risk factors.GeroScience · 2026Article
- Creativity: a (white) matter of connectivity.Cerebral cortex (New York, N.Y. : 1991) · 2026Article
- Longitudinal Associations of Structural and Functional Brain Connectivity With Dimensions of Psychopathology in Adolescence.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2026Article
- Article
100 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) are commonly used as MRI biomarkers of white matter microstructure in diffusion MRI studies of neurodevelopment, brain aging, and neurologic injury/disease. Some of the more frequent practices include performing voxel-wise or region-based analyses of these measures to cross-sectionally compare individuals or groups, longitudinally assess individuals or groups, and/or correlate with demographic, behavioral or clinical variables. However, it is now widely recognized that the majority of cerebral white matter voxels contain multiple fiber populations with different trajectories, which renders these metrics highly sensitive to the relative volume fractions of the various fiber populations, the microstructural integrity of each constituent fiber population, and the interaction between these factors. Many diffusion imaging experts are aware of these limitations and now generally avoid using FA, AD or RD (at least in isolation) to draw strong reverse inferences about white matter microstructure, but based on the continued application and interpretation of these metrics in the broader biomedical/neuroscience literature, it appears that this has perhaps not yet become common knowledge among diffusion imaging end-users. Therefore, this paper will briefly discuss the complex biophysical underpinnings of these measures in the context of crossing fibers, provide some intuitive "thought experiments" to highlight how conventional interpretations can lead to incorrect conclusions, and suggest that future studies refrain from using (over-interpreting) FA, AD, and RD values as standalone biomarkers of cerebral white matter microstructure.
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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 OpenQuestion graph.