Histologic Analysis of Retrieved Clots in Acute Ischemic Stroke: Correlation with Stroke Etiology and Gradient-Echo MRI

Abstract

Background and purpose: It is unclear whether clot composition analysis is helpful to predict a stroke mechanism in acute large vessel occlusion. In addition, the relationship between early vessel signs on imaging studies and clot compositions has been poorly understood. The purpose of this study was to elucidate the relationship between clot composition and stroke etiology following mechanical thrombectomy and to investigate the effect of varied clot compositions on gradient-echo MR imaging of clots.

Materials and methods: Histopathologic analysis of retrieved clots from 37 patients with acute MCA occlusion was performed. Patients underwent gradient-echo imaging before endovascular therapy. Retrieved clots underwent semiquantitative proportion analysis to quantify red blood cells, fibrin, platelets, and white blood cells by area. Correlations between clot compositions and stroke subtypes and susceptibility vessel signs on gradient-echo imaging were assessed.

Results: Stroke etiology was classified as cardioembolism in 22 patients (59.4%), large-artery atherosclerosis in 8 (21.6%), and undetermined in 7 (18.9%). The clots from cardioembolism had a significantly higher proportion of red blood cells (37.8% versus 16.9%, P = .031) and a lower proportion of fibrin (32.3% versus 48.5%, P = .044) compared with those from large-artery atherosclerosis. The proportion of red blood cells was significantly higher in clots with a susceptibility vessel sign than in those without it (48.0% versus 1.9%, P < .001), whereas the proportions of fibrin (26.4% versus 57.0%, P < .001) and platelets (22.6% versus 36.9%, P = .011) were significantly higher in clots without a susceptibility vessel sign than those with it.

Conclusions: The histologic composition of clots retrieved from cerebral arteries in patients with acute stroke differs between those with cardioembolism and large-artery atherosclerosis. In addition, a susceptibility vessel sign on gradient-echo imaging is strongly associated with a high proportion of red blood cells and a low proportion of fibrin and platelets in retrieved clots.

Fig 1.

Differences in the mean percentages of clot compositions between cardioembolism (CE) and large-artery atherosclerosis (LAA). Red blood cell (A), fibrin (B), platelet (C), and white blood cell (D) composition.

Fig 2.

Differences in the mean percentages of clot compositions relative to a positive susceptibility vessel sign (P-SVS) and a negative susceptibility vessel sign (N-SVS). Red blood cell (A), fibrin (B), platelet (C), and white blood cell (D) composition.

Fig 3.

Brain images from a 53-year-old man with acute MCA occlusion and atrial fibrillation. A, Axial GRE image reveals a positive susceptibility vessel sign (arrow) in the M1 segment of the right MCA. B, Microscopic view of a retrieved clot shows that most thrombi consist of red blood cells in a hematoxylin-eosin stained section (×100 magnification). Magnified images are presented in the bottom right (×400 magnification). C, CD61 immunostained section shows small areas of platelet infiltrations (brown) in the periphery of the clot (×100 magnification).

Fig 4.

Brain images from a 74-year-old man with acute ischemic stroke and underlying atherosclerotic stenosis in the MCA. A, Axial GRE image reveals a negative susceptibility vessel sign (arrow) in the M1 segment of the left MCA. B, Microscopic view of the clot shows that most thrombi consist of organized fibrin aggregates with sparse cellular elements in a hematoxylin-eosin stained section (×100 magnification). Magnified image is presented in the top left (×400 magnification). C, CD61 immunostained section shows abundant infiltrations of platelets (brown) in the central and peripheral portion of the clot (×100 magnification).