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

backgroundThe 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 < 0.05.

resultsInter-observer ICCs were excellent for average-measures (≥ 0.90) and mostly good for single-measures (0.90 > 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

conclusionDTI-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. LEVEL OF EVIDENCE: 2: TECHNICAL EFFICACY: Stage 1.