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Background and ObjectivesThe effect of mechanical thrombectomy (MT) on functional outcome in patients with ischemic stroke with low ASPECTS is still uncertain. ASPECTS rating is based on the presence of ischemic hypoattenuation relative to normal; however, the degree of hypoattenuation, which directly reflects net uptake of water, is currently not considered an imaging biomarker in stroke triage. We hypothesized that the effect of thrombectomy on functional outcome in low ASPECTS patients depends on early lesion water uptake.MethodsFor this multicenter observational study, patients with anterior circulation stroke with ASPECTS ≤5 were consecutively analyzed. Net water uptake (NWU) was assessed as a quantitative imaging biomarker in admission CT. The primary end point was the rate of favorable functional outcome defined as modified Rankin Scale score 0–3 at day 90. The effect of recanalization on functional outcome was analyzed according to the degree of NWU within the early infarct lesion.ResultsA total of 254 patients were included, of which 148 (58%) underwent MT. The median ASPECTS was 4 (interquartile range [IQR] 3–5), and the median NWU was 11.4% (IQR 8.9%–15.1%). The rate of favorable outcome was 27.6% in patients with low NWU (p< 0.0001). In multivariable logistic regression analysis, NWU was an independent predictor of outcome, whereas vessel recanalization (modified thrombolysis in cerebral infarction ≥2b) was only significantly associated with better outcomes if NWU was lower than 12.6%. In inverse-probability weighting analysis, recanalization was associated with 20.7% (p= 0.01) increase in favorable outcome in patients with low NWU compared with 9.1% (p= 0.06) in patients with high NWU.DiscussionEarly NWU was independently associated with clinical outcome and might serve as an indicator of futile MT in low ASPECTS patients. NWU could be tested as a tool to select low ASPECTS patients for MT.Trial Registration InformationThe study is registered within theClinicalTrials.govProtocol Registration and Results System (NCT04862507).