The imaging-quiescent phenotype in thrombolysed acute ischemic stroke: a diffusion-weighted MRI–based deconstruction

Abstract

Standard CT perfusion mismatch and hypoperfusion intensity ratio formulas are undefined when ischemic core or Tmax>6 s equals zero. Such “imaging-quiescent” patients remain uncharacterized. We quantified their prevalence and used DWI to separate CTP-undetected ischemia from DWI-negative presentations. We conducted a single-center retrospective cohort study of 188 consecutive patients receiving intravenous thrombolysis between January 2023 and October 2025. Patients were classified into four CTP phenotypes based on the presence of rCBF<30% core and Tmax>6 s hypoperfusion: A (classic mismatch), B (core without hypoperfusion), C (pure penumbra), and D (imaging-quiescent, both volumes = 0 mL). Group D was further subdivided by post-thrombolysis DWI into D1 (DWI-positive), D2 (DWI-negative), and D3 (DWI unavailable). The primary outcome was 90-day modified Rankin Scale 0–2. Analyses included Kruskal–Wallis tests, multivariable logistic regression, two one-sided tests, and false discovery rate adjustment. Of 188 thrombolysed patients, 168 had classifiable CTP phenotypes and 161 had 90-day mRS data. Group D was the largest phenotype ( n  = 69, 41.1%), with a favorable outcome rate of 84.6%, comparable to Group C (83.9%) and higher than Group A (55.9%). Among 62 Group D patients with DWI, 42 (60.9%) were DWI-positive (D1) and 20 (29.0%) were DWI-negative (D2). D1 patients had higher NIHSS (median 4 vs. 2), more posterior circulation involvement (38.1% vs. 5.0%), and lower favorable outcome rates (80.5% vs. 94.1%); 65% of D2 patients achieved mRS = 0. Group A had 51.4% large-vessel occlusion versus 4.4% in Group D. In multivariable regression (EPV = 17, AUC = 0.823), NIHSS was the strongest predictor of favorable outcome (OR 0.83 per point, 95% CI 0.75–0.91; p  < 0.001). The imaging-quiescent phenotype is not a single entity but a composite of three operationally defined subgroups (D3 reflecting absent MRI data rather than a distinct biological entity), with approximately 30% being DWI-negative, a population enriched for stroke mimics or transient ischemic events. DWI reclassified nearly one-third of CTP-quiescent patients and may improve diagnostic precision. These findings are hypothesis-generating and suggest that post-thrombolysis DWI may improve diagnostic characterization of CTP-quiescent patients; prospective study is required before any change to pre-thrombolysis workflow can be recommended.