Comparing Glymphatic Function Measures: Diffusion Tensor Image Analysis Along Perivascular Spaces (DTI-ALPS) versus Intrathecal Contrast-Enhanced MRI

Background Diffusion-tensor image (DTI) analysis along the perivascular space (ALPS) is a noninvasive but not well-validated method proposed to evaluate glymphatic function. Purpose To assess ALPS indexes across participant groups and compare them with measures of cerebrospinal fluid (CSF) tracer enrichment and clearance obtained by intrathecal contrast-enhanced MRI (glymphatic MRI [gMRI]). Materials and Methods This secondary analysis of a prospective observational study included participants who underwent clinical work-up for CSF disorders from September 2015 to December 2019. MRI scans were acquired before injection and 24 and 48 hours after intrathecal injection of 0.5 mmol of gadobutrol. DTI scans were preprocessed and segmented using the FMRIB Software Library. Intrathecal contrast-enhanced MRI (ie, gMRI) scans were registered to the baseline T1-weighted image, and cortex and white matter (WM) were segmented with FreeSurfer. ALPS indexes were compared with relative changes in normalized T1-weighted signal intensity at 24 and 48 hours in regions of the cortex, subcortical WM, and deep WM where the ALPS regions of interest are located by using regression analysis. Results A total of 56 participants were included (mean age, 48 years ± 20 [SD]; 36 women): 16 with idiopathic normal pressure hydrocephalus (iNPH), 10 with arachnoid cysts, 11 with idiopathic intracranial hypertension, and 19 reference participants. The ALPS index was lower in the iNPH group than in the reference group (ALPS index, 1.26 and 1.68, respectively; <i>P</i> < .001). Across groups, the ALPS index and degree of CSF tracer enrichment at 24 hours in deep WM were negatively associated (β = -48; <i>P</i> < .001). However, mean tracer enrichment in the ALPS regions of interest was low (10%), in some participants close to 0, whereas enrichment in the cortex ranged from 68% to 81%. Across groups, there was no evidence of associations between the ALPS index and measures of CSF tracer dynamics at 48 hours in any region (|β| ≤ 8; <i>P</i> ≥ .55). Conclusion CSF tracer enhancement in the ALPS regions of interest was sparse across groups, and the association between the ALPS index and gMRI markers of glymphatic function was limited. © The Author(s) 2026. Published by the Radiological Society of North America under a CC BY 4.0 license. <i>Supplemental material is available for this article.</i>