Sensitivity of Non-contrast Computed Tomography Net Water Uptake Versus FLAIR-MRI, with MR-DWI Reference Standard, for Early Detection and Physiological Characterization of Ischemic Edema in Hyperacute Stroke.

OBJECTIVE: On non-contrast computed tomography (NCCT), progressive hypoattenuation can be quantified as percent net water uptake (%NWU), whereas relative fluid attenuated inversion recovery (rFLAIR)-magnetic resonance imaging hyperintensity marks later-stage vasogenic edema and blood-brain-barrier disruption. We compared the degree and rate of %NWU versus rFLAIR development and characterized 4 ischemic edema imaging profiles relative to a magnetic resonance (MR)-diffusion-weighted-imaging (MR-DWI) reference standard. METHODS: NCCT and fluid attenuated inversion recovery (FLAIR) images from MR-DWI-positive hyperacute stroke patients were visually rated positive (+) or negative (-) for ischemic hypodensity/hyperintensity and sulcal-effacement (SE), defining 4 edema imaging profiles: (I) NWU-/FLAIR-/SE-, (II) NWU+/FLAIR-/SE-, (III) NWU+/FLAIR+/SE-, and (IV) NWU+/FLAIR+/SE+. %NWU, rFLAIR, and relative apparent diffusion coefficient (rADC) were quantified within the DWI/apparent diffusion coefficient-defined core region-of-interest, normalized to the contralateral mirror region, and compared between groups. RESULTS: Of 53 DWI+ patients, n = 5/17/13/17 were in groups I to IV, with mean onset-to-CT times of 2.4 ± 1.2/2.5 ± 1.6/3.2 ± 1.9/5.0 ± 1.6 hours (p < 0.01), and baseline characteristics were comparable (all p ≥ 0.12). Mean %NWU differed between all groups (1.4 ± 0.3/4.3 ± 4.2/8.0 ± 4.1/13.6 ± 4.3; all pairwise p < 0.012), rADC did not (p = 0.21), and rFLAIR differed only between groups II and III versus group IV (p = 0.02, p = 0.04). %NWU and rFLAIR were uncorrelated (R2 = 0.02, p = 0.48). Fitted %NWU increased monotonically and near-linearly within 4.5 hours post-ictus, whereas rFLAIR rose abruptly only in the late transition to group IV. INTERPRETATION: Quantitative %NWU-CT was more sensitive than rFLAIR for detecting the earliest edematous stages of hyperacute stroke, discriminating early, intermediate, late, and late-severe (SE) stages; rFLAIR increased only in the latest stage. %NWU may, therefore, provide a practical, quantitative CT marker of edema progression, supporting acute triage and risk phenotyping in CT-first pathways, pending prospective validation. ANN NEUROL 2026.