Clot permeability and histopathology: is a clot’s perviousness on CT imaging correlated with its histologic composition?

Abstract

BackgroundClot perviousness in large vessel occlusion has been shown to be associated with improved recanalization outcomes with mechanical thrombectomy and intravenous thrombolysis.ObjectiveTo evaluate the association between clot perviousness based on thrombus attenuation increase (TAI) on CT, and histologic composition of clots in acute ischemic stroke (AIS).MethodsA retrospective review was completed of patients with AIS secondary to large vessel occlusion, non-contrast CT (NCCT) and CT angiography (CTA) images, and histologic analysis of the retrieved clot. TAI was measured by subtracting clot attenuation on NCCT from the attenuation on CTA. Up to 3 regions of interest (ROIs) were evaluated on each clot; the average attenuation was used for analysis if multiple ROIs were assessed. Pervious clots were defined as TAI ≥10 Hounsfield units (HUs); impervious clots had TAI <10 HU. Histopathologic analyses of clots were assessed for relative compositions of red blood cells (RBCs), white blood cells (WBCs), fibrin, and platelets/other.Results57 patients were included. Pervious clots were more likely to be RBC rich (p=0.04); impervious clots were more likely to be fibrin and WBC rich (p=0.01 for both). Pervious clots also had greater RBC density than impervious clots (49.8% and 33.0%, respectively; p=0.006); fibrin density of pervious clots was lower than that of impervious clots (17.8% and 23.2%, respectively; p=0.02).ConclusionClot perviousness, assessed on NCCT and CTA imaging, is associated with higher RBC density and lower fibrin density, offering a possible explanation for the higher rates of successful thrombectomy and favorable clinical outcome seen in such patients.

Increased Perviousness on CT for Acute Ischemic Stroke is Associated with Fibrin/Platelet-Rich Clots

“…Only 1 other study has explored the relationship between clot composition and perviousness in MT-treated patients with AIS. In a study of n = 57 patients, Benson et al 20 dichotomized both perviousness and clot composition (RBC-rich versus FP-rich) and found that the pervious group consisted of a higher fraction of clots in the RBC-rich group. This contradictory result is likely because unlike in our study and that of Berndt et al, 19 Benson et al 20 did not directly investigate the association between clot composition and perviousness (both of which are continuous variables).…”

“…Due to their statistical methods, it is difficult to reliably interpret these findings. One must be careful when dichotomizing variables, especially with both independent and dependent variables as in Benson et al, 20 because dichotomization is known to reduce statistical power and increase the risk of false-positive results. 21 Thus, we chose to first perform Pearson correlation analysis to assess the relationship between perviousness and clot composition in our study in an unbiased manner.…”

“…11,27 Poorer MT device integration in FP-rich thrombi may be due to the high static coefficient of friction, as demonstrated by Gunning et al 28 This can result in increased adherence to the vessel wall and decreased compressibility of fibrin-rich clots. 20 Conversely, high RBC density has been associated with successful recanalization after thrombectomy and reduced thrombectomy procedure time. 27 While clot biology was significantly related to FPE, we did not find a statistically significant association between perviousness and FPE, even though perviousness and clot composition were correlated with each other.…”

Thrombus Imaging Using 3D Printed Middle Cerebral Artery Model and Preclinical Imaging Techniques: Application to Thrombus Targeting and Thrombolytic Studies

“…Clot perviousness, associated with densities of major components including red blood cells, white blood cells, fibrin, and platelet conglomerates, plays an important role in responsiveness to therapy. Higher red blood cells content and lower fibrin density are associated with higher clot perviousness [ 33 ]. Similarly, permeability of clots would probably have an impact on the efficacy of clot imaging using nanoparticle-based targeted contrast agents.…”

Biomechanics and hemodynamics of stent-retrievers

“…113 Current research into identifying thrombus compositions by histopathology and/or imaging is being conducted in hopes of developing a more holistic and personalized approach to stroke treatment. [114][115][116][117][118][119] These data may provide insights to predict which patients will benefit from endovascular therapy, but it does not solve the need for newer technologies and devices to tackle these hard-to-remove, resistant clots. Future research will focus on the interactions of the clot with the device and the vessel wall.…”