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This study explores how orientational differences in projection and association fibers affect the DTI-ALPS index.

May 15, 2026Journal of Magnetic Resonance Imaging1 citations

MRI Diffusion Tensor Image Analysis Along the Perivascular Space: Effects of Mean Tract Orientation Divergence

DBDávid BognárTranslational Research in Oncology GOGergely OrsiUniversity of Pecs CBCsirmaz BenedekUniversity of Pecs

Key Points

This study explores how orientational differences in projection and association fibers affect the DTI-ALPS index.
Evaluated diffusion tensor imaging using a 3 T MRI with diffusion-weighted spin-echo echo-planar imaging
Calculated DTI-ALPS index using three observer methods
Employed statistical tests including intraclass correlation coefficients and Spearman correlation
Inter-observer reliability was high with ICCs ≥ 0.90 for average measures
Higher ALPS values obtained by methods that minimized bias from fiber orientation deviations
Significant differences noted in left versus right DTI-ALPS indices across methods

Abstract

BACKGROUND: The diffusion tensor image analysis along the perivascular space (DTI-ALPS) index is an established term, and ongoing research aims to explore underlying mechanisms. HYPOTHESIS: DTI-ALPS measures are influenced by subject-specific orientational differences of the projection and association fibers. STUDY TYPE: Prospective. SUBJECTS: Forty-four healthy adults (age: 22.1 ± 1.9 years; 19 males). FIELD STRENGTH/SEQUENCE: 3 T/diffusion-weighted spin-echo echo-planar imaging. ASSESSMENT: DTI-ALPS index was calculated by three methods using delineations of four observers (17-, 4-, 5-, 3-years of experience): (1) following vector registration to an atlas (Method 1); (2) after achieving zero projection for the relevant tracts by x-axis rotation (Method 2); and (3) based on the second and third diffusion tensor eigenvalues (Method 3). Effects of deviation from the expected anatomical orientation of ALPS-associated tracts were also analyzed. STATISTICAL TESTS: Intraclass correlation coefficients (ICCs) were calculated among observers and methods. Friedman and Wilcoxon tests were used, respectively, for inter-method and inter-hemispheric comparisons. Spearman correlation and multiple-linear regression assessed whether tract orientation deviation introduced bias in ALPS estimation. Significance level was p ICC ≥ 0.80). ALPS values differed significantly among methods, with significantly higher values for methods reducing bias due to deviation from the expected anatomical orientation of ALPS-associated tracts (bilateral DTI-ALPS index averaged across observers: 1.49 ± 0.13 vs. 1.59 ± 0.13 and 1.66 ± 0.13 for Methods 1-3 respectively). Left DTI-ALPS index was significantly higher than the right for all 3 methods (averaged values across observers: 1.54 ± 0.14 vs. 1.44 ± 0.13; 1.65 ± 0.14 vs. 1.52 ± 0.13; 1.73 ± 0.14 vs. 1.59 ± 0.13). Inter-method ICCs showed good-to-excellent consistency across all method pairs (≥ 0.80), but absolute ICCs were not always acceptable. Deviations from the expected orientation of ALPS-associated tracts significantly affected ALPS values, especially for the left projection pathway (Spearman's rho: -0.503 to -0.376 for the bilateral index). DATA CONCLUSION: DTI-ALPS measures based on diffusion along Cartesian axes are influenced by off-axis orientation of ALPS-associated fibers, indicating that the DTI-ALPS index is statistically significantly confounded by non-glymphatic factors. TECHNICAL EFFICACY: Stage 1.

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