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Cited by 22Advanced Neuroimaging Techniques and ApplicationsCerebrospinal fluid and hydrocephalusAdvanced MRI Techniques and Applications

Diffusion tensor image analysis along the perivascular space (DTI-ALPS): Redefining its interpretation and role

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Taoka, Toshiaki, Ito, Rintaro, Nakamichi, Rei, Nakane, Toshiki, Naganawa, Shinji·2026·Japanese Journal of Radiology
DOI 10.1007/s11604-026-02035-0PMC PMC13624023
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Abstract

Diffusion tensor image analysis along the perivascular space (DTI-ALPS) was originally developed and defined as a noninvasive diffusion MRI method intended to evaluate glymphatic function and is now widely used in neuroimaging research. However, accumulating evidence suggests that the biological meaning of the ALPS index is more complex than initially assumed as a simple marker of glymphatic function. The ALPS index does not directly measure whole-brain fluid transport but rather reflects localized directional diffusivity based on the Brownian motion of water molecules. Its value is strongly influenced by white matter microstructure, including fiber orientation, crossing fibers, extracellular geometry, and age-related diffusivity changes. In addition, because the ALPS index is a ratio-based measure derived from directional diffusivity components, its alterations may arise from different combinations of numerator and denominator diffusivity changes, indicating that similar ALPS index reductions may reflect distinct underlying microstructural mechanisms. White matter microstructure may represent not merely a confounding factor, but a structural substrate guiding interstitial fluid transport itself. White matter hydraulic permeability exhibits strong anisotropy, and brain fluid transport may occur preferentially along white matter tracts. Thus, the structure dependence of the ALPS index may reflect physiologically relevant interactions between white matter architecture and interstitial fluid dynamics rather than simple measurement bias. In this review, we propose redefining the ALPS index not as a direct marker of glymphatic function, but as a “spatially fixed-point biomarker” evaluating directional diffusivity within anatomically defined regions. Within this framework, the ALPS index can be understood as a composite biomarker reflecting interactions among white matter microstructure, extracellular environment, vascular geometry, and neurofluid-related tissue environment. Because the ALPS index has been associated with aging, sleep, and various diseases, it may function less as a disease-specific marker and more as an adjunctive imaging marker relevant to brain health assessment and the brain tissue environment.

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Cited by

Sorted by citations

Authors
Taoka, T., Ito, R., Nakamichi, R., Nakane, T., & Naganawa, S.
Affiliations
Nagoya University (JP)
Corresponding author
Taoka, Toshiaki
ORCID
Venue
Japanese Journal of Radiology
Publisher
Springer Science and Business Media LLC
Published
2026-06-16
Volume
44
Issue
10
Pages
1707-1725
ISSN
  • 1867-1071 (ISSN-L)
  • 1867-108X
DOI
10.1007/s11604-026-02035-0
PMC
PMC13624023
OpenAlex
W7164839391
Cited by
22
References
1
Citations by year
2026: 22
FWCI
28.56
Type
journal article
Language
en
Open access
Licence
Locations
  • Japanese Journal of Radiology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Japan Society for the Promotion of Science (24K10855, Japan Society for the Promotion of Science, 23K27545)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
Keywords
DTI-ALPS index, perivascular spaces, glymphatic function, white matter microstructure, interstitial fluid flow, aging, sleep
MeSH terms
Glymphatic System, Brain, Humans, Image Interpretation, Computer-Assisted, Diffusion Tensor Imaging, White Matter

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