BACKGROUND AND PURPOSE: Clot perviousness in acute ischemic stroke is a potential CT imaging biomarker for mechanical thrombectomy efficacy. We investigated the association among perviousness, clot cellular composition, and first-pass effect. MATERIALS AND METHODS: In 40 mechanical thrombectomy-treated cases of acute ischemic stroke, we calculated perviousness as the difference in clot density on CT angiography and noncontrast CT. We assessed the proportion of fibrin/platelet aggregates, red blood cells, and white blood cells on clot histopathology. We tested for linear correlation between histologic components and perviousness, differences in components between "high" and "low" pervious clots defined by median perviousness, and differences in perviousness/composition between cases that did and did not achieve a first-pass effect. RESULTS: Perviousness significantly positively and negatively correlated with the percentage of fibrin/platelet aggregates (P ¼ .001) and the percentage of red blood cells (P ¼ .001), respectively. Higher pervious clots had significantly greater fibrin/platelet aggregate content (P ¼ .042). Cases that achieved a first-pass effect (n ¼ 14) had lower perviousness, though not significantly (P ¼ .055). The percentage of red blood cells was significantly higher (P ¼ .028) and the percentage of fibrin/platelet aggregates was significantly lower (P ¼ .016) in cases with a first-pass effect. There was no association between clot density on NCCT and clot composition or first-pass effect. Receiver operating characteristic analysis indicated that clot composition was the best predictor of firstpass effect (area under receiver operating characteristic curve: percentage of fibrin/platelet aggregates ¼ 0.731, percentage of red blood cells ¼ 0.706, perviousness ¼ 0.668). CONCLUSIONS: Clot perviousness on CT is associated with a higher percentage of fibrin/platelet aggregate content. Histologic data and, to a lesser degree, perviousness may have value in predicting first-pass outcome. Imaging metrics that more strongly reflect clot biology than perviousness may be needed to predict a first-pass effect with high accuracy. ABBREVIATIONS: AIS ¼ acute ischemic stroke; AUC ¼ area under the curve; CV ¼ coefficient of variation; FP ¼ fibrin/platelet aggregates; FPE ¼ first-pass effect; MMI ¼ Mattes mutual information; MT ¼ mechanical thrombectomy; mTICI ¼ modified TICI; RBC ¼ red blood cells; ROC ¼ receiver operating characteristic; WBC ¼ white blood cells C T is the most common imaging technique used to evaluate patients with acute ischemic stroke (AIS). Together, NCCT and CTA can provide valuable information about the occlusive clot, such as its location, length, and density. 1-3 One parameter derived from these images is clot permeability, or perviousness, which indicates the amount of contrast that diffuses through the clot tissue. 1,4 Several clinical studies have claimed that perviousness may be an important indicator of how easily occlusive clots can be treated by tPA or mechanical thrombectomy (MT). 1...