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

Area of Science:

• Neuroimaging
• Biomarker Development
• Diffusion MRI

Background:

• Diffusion tensor image analysis along the perivascular space (DTI-ALPS) was initially proposed as a measure of glymphatic function.
• Emerging evidence indicates the ALPS index is influenced by white matter microstructure and is not a direct measure of whole-brain fluid transport.

Purpose of the Study:

• To re-evaluate the biological meaning of the ALPS index.
• To propose a redefined framework for interpreting the ALPS index as a spatially fixed-point biomarker.

Main Methods:

• Review of existing literature on DTI-ALPS and its relationship with glymphatic function and white matter microstructure.
• Analysis of the ALPS index as a ratio-based measure influenced by directional diffusivity and Brownian motion.

Main Results:

• The ALPS index is significantly influenced by white matter microstructure (fiber orientation, extracellular geometry, age-related changes).
• ALPS index alterations can result from various microstructural changes, indicating distinct underlying mechanisms.
• White matter microstructure plays a crucial role in interstitial fluid transport, suggesting the ALPS index reflects interactions between architecture and fluid dynamics.

Conclusions:

• The ALPS index should be redefined as a spatially fixed-point biomarker evaluating directional diffusivity in specific anatomical regions.
• The ALPS index serves as a composite biomarker reflecting interactions between white matter microstructure, extracellular environment, vascular geometry, and neurofluid dynamics.
• The ALPS index is a valuable adjunctive marker for brain health assessment, reflecting broader aspects of the brain tissue environment rather than a specific disease marker.