Tissue-specific diffusion abnormalities and localized free-water reductions in hypertension despite no detectable group difference in the DTI-ALPS index

Background: Essential hypertension (HTN) is an established risk factor for cerebral small vessel disease and cognitive decline. Although conventional diffusion tensor imaging (DTI) has identified white matter (WM) abnormalities in HTN, these metrics are often confounded by extracellular free-water (FW) contamination and cannot distinguish tissue microstructural abnormalities from extracellular fluid shifts. This study applied a free-water elimination (FWE) model in combination with the diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index to investigate tissue-specific microstructural alterations, extracellular fluid shifts, and glymphatic function in both WM and cortical gray matter (GM). Methods: Single-shell diffusion magnetic resonance imaging (MRI) data were acquired from 30 patients with HTN and 30 age- and sex-matched healthy controls (HCs). Tissue-specific DTI metrics, including free-water-corrected fractional anisotropy (FAt) and free-water-corrected mean diffusivity (MDt), as well as FW fractional volume maps, were derived. The DTI-ALPS index was calculated to assess glymphatic clearance. Tract-based spatial statistics (TBSS) and gray matter-based spatial statistics (GBSS) were used to evaluate between-group differences. Results: > 0.05). However, alongside conventional diffusion abnormalities, patients with HTN exhibited widespread reductions in FAt and increases in MDt across both WM and GM skeletons. In addition, HTN patients showed a localized reduction in FW fractional volume, predominantly in the corpus callosum. Systolic blood pressure (SBP) was negatively correlated with conventional FA in white matter, and with both FA and FAt in cortical GM across extensive regions. No significant correlations were found with Mini-Mental State Examination (MMSE) scores. Conclusions: These cross-sectional findings suggest that, in HTN, tissue-specific diffusion abnormalities and localized fluid shifts are detectable even in the absence of statistically significant group differences in the DTI-ALPS index. This divergence indicates that FWE metrics may serve as sensitive neuroimaging indicators for evaluating hypertensive brain involvement.