Dynamic Perviousness Has Predictive Value for Clot Fibrin Content in Acute Ischemic Stroke

Abstract

Dynamic perviousness is a novel imaging biomarker, with clot density measurements at multiple timepoints to allow longer contrast to thrombus interaction. We investigated the correlations between dynamic perviousness and clot composition in the setting of acute ischemic stroke. Thirty-nine patients with large vessel occlusion (LVO) undergoing mechanical thrombectomy (MT) were analyzed. Patients received a three-phase CT imaging pre-thrombectomy and histopathological analysis of retrieved clots. Clot densities for every phase and change in densities between phases were calculated, leading to four patterns of dynamic perviousness: no contrast uptake, early contrast uptake with and without washout and late uptake. Clots were categorized into three groups based on dominant histologic composition: red blood cell (RBC)-rich, fibrin/platelet-rich and mixed. Clot composition was correlated with dynamic perviousness using the Kruskal-Wallis test and Pearson's correlation analysis. The dynamic perviousness categories showed a significant difference between fibrin-rich clots when compared to RBC-rich plus mixed groups. The uptake without washout category had significantly fewer fibrin clots compared to the uptake with washout (p = 0.036), and nearly significantly fewer fibrin clots when compared to the no uptake category (p = 0.057). Contrast uptake with different patterns of contrast washout showed significant differences of the likelihood for fibrin-rich clots.

Keywords: blood clot; histology; permeability; stroke; thrombectomy.

Figure 1

(a) Representative non-contrast CT (NCCT), CT angiography (CTA) and late venous phase CT (CTV) images of our clinical AIS protocol. (b) Illustration of spherical ROIs placed over the clot in all three images for dynamic perviousness calculation.

Figure 2

HE staining of a fibrin-rich clot (A) and the automated quantification map by Orbit^® (B), with blue coding for fibrin platelets, green for red blood cells and yellow for white blood cells, representing a total of 86% fibrin content.

Figure 3

Graphic representation of Pearson correlations between fibrin/platelets (labeled as fibrin in the graph), red blood cells (RBCs) and white blood cells (WBCs). Correlations between fibrin/platelet to RBC, fibrin/platelet to WBC and RBC to WBC grouped into four categories according to the measured contrast agent uptake characteristics are shown. A moderate relationship between RBCs and WBCs in the uptake without washout (r = 0.45) and the uptake with washout category (r = 0.41) is seen. The Pearson correlation coefficient (r) measures the strength and direction of a linear relationship between the two variables.

Figure 4

Comparison between contrast uptake categories and clot types. Significance of p = 0.036 was found only for the fibrin/platelet-rich clots between uptake with and uptake without washout. The uptake with washout category showed significantly more fibrin/platelet-rich clots compared to the uptake without washout category. Comparison between the other uptake categories did not show any significant differences of clot components. Asterisk placed above categories where statistical significance was found.

Figure 5

Comparison of percentages of clot components between the different contrast uptake categories. No significance was found.