White matter characterization with diffusional kurtosis imaging
Open accessAbstract
Diffusional kurtosis imaging (DKI) is a clinically feasible extension of diffusion tensor imaging that probes restricted water diffusion in biological tissues using magnetic resonance imaging. Here we provide a physically meaningful interpretation of DKI metrics in white matter regions consisting of more or less parallel aligned fiber bundles by modeling the tissue as two non-exchanging compartments, the intra-axonal space and extra-axonal space. For the b-values typically used in DKI, the diffusion in each compartment is assumed to be anisotropic Gaussian and characterized by a diffusion tensor. The principal parameters of interest for the model include the intra- and extra-axonal diffusion tensors, the axonal water fraction and the tortuosity of the extra-axonal space. A key feature is that these can be determined directly from the diffusion metrics conventionally obtained with DKI. For three healthy young adults, the model parameters are estimated from the DKI metrics and shown to be consistent with literature values. In addition, as a partial validation of this DKI-based approach, we demonstrate good agreement between the DKI-derived axonal water fraction and the slow diffusion water fraction obtained from standard biexponential fitting to high b-value diffusion data. Combining the proposed WM model with DKI provides a convenient method for the clinical assessment of white matter in health and disease and could potentially provide important information on neurodegenerative disorders.
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Interpreting MRI alterations in AD remains challenging because MRI contrasts reflect complex, combined contributions from cellular composition, microstructural organization, and biochemical changes rather than disease-specific processes alone, and provide only indirect measurements of underlying physiological mechanisms.
“Interpreting MRI alterations in AD remains challenging because MRI contrasts reflect complex, combined contributions from cellular composition, microstructural organization, and biochemical changes rather than disease‐specific processes alone, 26 , 79 , 80 and provide only indirect measurements of underlying physiological mechanisms. 81”
From Diffusion MRI reveals amyloid plaque–associated cellular signatures through spatial transcriptomic integration (2026) · cites this paper as [26]
The Introduction (page unavailable) says diffusion MRI is affected by tissue barriers, their orientation and permeability, and various cell types; it also notes that diffusion tensor imaging lacks specificity to histological features. This supports the microstructural-complexity point, but the paper does not establish the claim about biochemical changes or interpreting MRI alterations specifically in Alzheimer’s disease. The separate claim about indirect measurements is attached to citation 81, not this source. (LLM, conf=0.83)
Experimental — accuracy not yet measuredDKI extends DTI by quantifying non-Gaussian diffusion and is therefore sensitive to microstructural heterogeneity and restricted diffusion arising from complex tissue architecture.
“DKI extends DTI by quantifying non‐Gaussian diffusion and is therefore sensitive to microstructural heterogeneity and restricted diffusion arising from complex tissue architecture.”
From Diffusion MRI reveals amyloid plaque–associated cellular signatures through spatial transcriptomic integration (2026) · cites this paper as [26]
Recent years have seen a marked proliferation of biophysical models with the explicit aim of clinically feasible data acquisition.
“Recent years have seen a marked proliferation of biophysical models with the explicit aim of clinically feasible data acquisition (single-diffusion encoding, b-values up to 2000-3000 s/mm 2 , diffusion time 20-100 ms) (Fieremans et al., 2011;Hansen et al., 2017;Kaden et al., 2016;Zhang et al., 2012).”
From NODDI in clinical research (2020) · cites this paper as Fieremans et al., 2011
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White matter biomarkers from fast protocols using axially symmetric diffusion kurtosis imaging
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Lampinen, B., Szczepankiewicz, F., Lätt, J., Knutsson, L., Mårtensson, J., Björkman-Burtscher, I. M., van Westen, D., Sundgren, P. C., Ståhlberg, F., & Nilsson, M. (2023) · NeuroImage · doi:10.1016/j.neuroimage.2023.120338 · Cited by 38 · see citing works
Applying microstructural models to understand the role of white matter in cognitive development
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Chung, S., Wang, X., Fieremans, E., Rath, J. F., Amorapanth, P., Foo, F.-Y. A., Morton, C. J., Novikov, D. S., Flanagan, S. R., & Lui, Y. W. (2019) · American Journal of Neuroradiology · doi:10.3174/ajnr.a6146 · Cited by 31 · see citing works
Self-citationHan, 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
- Fieremans, E., Jensen, J. H., & Helpern, J. A.
- Affiliations
- New York University (US)
- NYU Langone Health (US)
- Corresponding author
- Fieremans, Els
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2011-09
- Volume
- 58
- Issue
- 1
- Pages
- 177-188
- ISSN
- 1053-8119 (ISSN-L)
- PMC
- PMC3136876
- OpenAlex
- W2142018683
- Cited by
- 561
- References
- 71
- Citations by year
- 2026: 25 · 2025: 42 · 2024: 39 · 2023: 30 · 2022: 49 · 2021: 51 · 2020: 52 · 2019: 50 · 2018: 62 · 2017: 43 · 2016: 39 · 2015: 28 · 2014: 20 · 2013: 20 · 2012: 8
- FWCI
- 12.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute for Health and Care Research
- National Institutes of Health
- National Institute on Aging (R01AG027852, P30AG008051)
- National Institute of Biomedical Imaging and Bioengineering (R01EB007656)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Physical Sciences › Physics and Astronomy › Nuclear and High Energy Physics › NMR spectroscopy and applications
- Keywords
- diffusion kurtosis imaging, white matter, restricted diffusion, biexponential fitting, diffusion tensor imaging, neurodegenerative diseases
- MeSH terms
- Adult, Algorithms, Axons, Body Water, Brain, Data Interpretation, Statistical, Female, Humans, Image Processing, Computer-Assisted, Male, Models, Neurological, Nerve Fibers, Normal Distribution, Diffusion Tensor Imaging
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