Thrombus Permeability in Admission Computed Tomographic Imaging Indicates Stroke Pathogenesis Based on Thrombus Histology

Berndt, M.; Friedrich, B.; Maegerlein, C.; Moench, S.; Hedderich, D.; Lehm, M.; Zimmer, C.; Straeter, A.; Poppert, H.; Wunderlich, S.; Schirmer, L.; Oberdieck, P.; Kaesmacher, Johannes; Boeckh-Behrens, T. (2018). Thrombus Permeability in Admission Computed Tomographic Imaging Indicates Stroke Pathogenesis Based on Thrombus Histology. Stroke, 49(11), pp. 2674-2682. Lippincott Williams & Wilkins 10.1161/strokeaha.118.021873

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Background and Purpose- Intracranial thrombi can be characterized according to their permeability as measured by contrast agent penetration. Thrombus composition and its associated pathogenesis are important factors affecting treatment and secondary prevention. We aimed to explore the histopathologic factors explaining the heterogeneity of thrombus permeability measures and evaluated potential correlations with stroke pathogenesis. Methods- Thrombus densities were measured in thin-slice noncontrast computed tomography and automatically aligned computed tomographic angiography images of 133 patients with large-vessel occlusions of the middle cerebral artery. Change in thrombus attenuation (Deltat) and corrected void fraction (epsilon; attenuation increase corrected for contralateral artery densities) were calculated. First, these thrombus perviousness measures were correlated with histological thrombus components (especially fractions of fibrin-platelet accumulation and red blood cells) and stroke pathogenesis (n=32). For validation, an association between perviousness and pathogenesis was assessed in a second, independent cohort (n=101). Results- Thrombus perviousness estimates were correlated with both fibrin/platelets fractions (Deltat: r=0.43, P=0.016/epsilon: r=0.45, P=0.01) and inversely with red blood cells counts (Deltat: r=-0.46, P=0.01/epsilon: r=-0.49, P=0.006). In the first cohort, Deltat was substantially higher in samples from patients with cardioembolic stroke pathogenesis as compared with noncardioembolic-derived thrombi ( P=0.026). In the validation cohort, thrombus perviousness measures differed significantly between cardioembolic (Deltat: median interquartile range=12.53 8.70-17.90; epsilon: median interquartile range=0.054 0.036-0.082) and noncardioembolic thrombi (Deltat: median interquartile range=3.2 2.17-6.44, P<0.001; epsilon: median interquartile range=0.020 0.011-0.027, P<0.001) and were associated with pathogenesis (Deltat: beta=0.45, P=0.016/epsilon: beta=83.6, P=0.013) in a binary logistic regression model. Conclusions- Permeable thrombi showed a strong correlation with lower fractions of red blood cells counts and more fibrin/platelets conglomerations, concurrent with an association with cardioembolic origin. This novel information about thrombus perviousness may be valuable as a new and simple to acquire imaging marker for identifying stroke pathogenesis using early and readily available imaging.

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