The association between human blood clot analogue computed tomography imaging, composition, contraction, and mechanical characteristics

Background Clot composition, contraction, and mechanical properties are likely determinants of endovascular thrombectomy success. A pre-interventional estimation of these properties is hypothesized to aid in selecting the most suitable treatment for different types of thrombi. Here we determined the association between the aforementioned properties and computed tomography (CT) characteristics using human blood clot analogues. MethodsClot analogues were prepared from the blood of 4 healthy human donors with 5 red blood cell (RBC) volume suspensions: 0%, 20%, 40%, 60% and 80% RBCs. Contraction was measured as the weight of the contracted clots as a percentage of the original suspension. The clots were imaged using CT with and without contrast to quantify clot density and density increase. Unconfined compression was performed to determine the high strain compressive stiffness. The RBC content was analysed using H&amp;E staining. Results The 5 RBC suspensions formed only two groups of clots, fibrin-rich (0% RBCs) and RBC-rich (&gt;90% RBCs), as determined by histology. The density of the fibrin-rich clots was significantly lower (31-38HU) compared to the RBC-rich clots (72-89HU), and the density increase of the fibrin-rich clots was significantly higher (82-127HU) compared to the RBC-rich clots (3-17HU). The compressive stiffness of the fibrin-rich clots was higher (178–1624 kPa) than the stiffness of the RBC-rich clots (6–526 kPa). Additionally, the degree of clot contraction was higher for the fibrin-rich clots (89–96%) compared to the RBC-rich clots (11–77%). ConclusionsCT imaging clearly reflects clot RBC content and seems to be related to the clot contraction and stiffness. CT imaging might be a useful tool in predicting the thrombus characteristics. However, future studies should confirm these findings by analysing clots with intermediate RBC and platelet content.</p

The association between human blood clot analogue computed tomography imaging, composition, contraction, and mechanical characteristics

Background Clot composition, contraction, and mechanical properties are likely determinants of endovascular thrombectomy success. A pre-interventional estimation of these properties is hypothesized to aid in selecting the most suitable treatment for different types of thrombi. Here we determined the association between the aforementioned properties and computed tomography (CT) characteristics using human blood clot analogues. MethodsClot analogues were prepared from the blood of 4 healthy human donors with 5 red blood cell (RBC) volume suspensions: 0%, 20%, 40%, 60% and 80% RBCs. Contraction was measured as the weight of the contracted clots as a percentage of the original suspension. The clots were imaged using CT with and without contrast to quantify clot density and density increase. Unconfined compression was performed to determine the high strain compressive stiffness. The RBC content was analysed using H&amp;E staining. Results The 5 RBC suspensions formed only two groups of clots, fibrin-rich (0% RBCs) and RBC-rich (&gt;90% RBCs), as determined by histology. The density of the fibrin-rich clots was significantly lower (31-38HU) compared to the RBC-rich clots (72-89HU), and the density increase of the fibrin-rich clots was significantly higher (82-127HU) compared to the RBC-rich clots (3-17HU). The compressive stiffness of the fibrin-rich clots was higher (178–1624 kPa) than the stiffness of the RBC-rich clots (6–526 kPa). Additionally, the degree of clot contraction was higher for the fibrin-rich clots (89–96%) compared to the RBC-rich clots (11–77%). ConclusionsCT imaging clearly reflects clot RBC content and seems to be related to the clot contraction and stiffness. CT imaging might be a useful tool in predicting the thrombus characteristics. However, future studies should confirm these findings by analysing clots with intermediate RBC and platelet content.</p

The association between in vitro human thrombi composition, mechanics, and computed tomography imaging characteristics

Background- A wide variation in composition is found within the thrombi retrieved from acute ischemic stroke patients. The composition of a thrombus and its mechanical properties have a significant influence on the procedural ease and success rate of mechanical retrieval procedures. If the composition and mechanical properties of a thrombus could be determined using admission computed tomography (CT) imaging, the treatment could be adjusted to ensure a good outcome in each case. This study aims to investigate and associate three thrombus characteristics related to this issue: composition, mechanics, and CT imaging characteristics. Methods- Blood was drawn from three healthy volunteers. Analog thrombi of different compositions were prepared by combining red blood cells (RBCs) and platelet-rich plasma (PRP) in five different volumetric ratios: 0% RBCs and 100% PRP, 20% RBCs and 80% PRP, 40% RBCs and 60% PRP, 60% RBCs and 40% PRP, 80% RBCs and 20% PRP. To measure thrombus contraction, the weight of the resulting thrombus was expressed as a percentage of the weight of the original blood mixture. First, CT imaging was performed using micro CT and clinical CT imaging to obtain density and perviousness measurements of the thrombi. Secondly, the thrombi were subjected to a cyclic unconfined compression test to analyse stress-strain behaviour and to determine low and high strain secant moduli as a measure for thrombus stiffness. Lastly, thrombus composition was analysed using histological techniques to quantify RBCs, fibrin and platelet conglomerations, fibrin, and white blood cells. Results- First, a positive linear relationship was found between the relative thrombus weight after contraction and the volumetric RBC ratio (r=0.98, p&lt;0.001). Secondly, with composition analysis, it was found that the thrombi with the 0% 20%, 40%, 60%, and 80% volumetric RBC ratios produced thrombi with non-equivalent compositions of 0.0%, 89.8%, 95.1%, 97.4%, and 99.4% RBCs. This showed that only 0% RBC and RBC-rich (&gt;85% RBC) thrombi were created. Thirdly, on clinical CT imaging, the 0% RBC samples were found to be significantly lower in mean density compared to the RBC-rich thrombi (36 HU and 88 HU respectively, p&lt;0.001). Fourthly, the perviousness was significantly higher for the 0% RBC thrombi compared to the RBC-rich thrombi (An increase of &gt;81 HU and &lt;14 HU respectively, p&lt;0.005). Fifthly, for the mechanics, the secant modulus at high strain decreased with an increasing amount of RBCs in the original volumetric ratio. For donor one the high strain stiffness values were 263, 84, 72, 27, and 13 kPa for an increasing RBC content. Lastly, thrombus stiffness differed per donor. For example, the high strain stiffnesses for 40% RBC thrombi were 72, 432, and 33 kPa between donors. Thrombus density and perviousness on clinical CT imaging were significantly different for the 0% RBC and RBC-rich group (both p&lt;0.001). High strain stiffness was significantly correlated to the contracted thrombus weight (r=-0.68 p=0.006). Conclusions- Both density and perviousness on clinical CT imaging were related to the RBC content of the analog thrombi. For the thrombus mechanics, the high strain stiffness of the thrombi was highly correlated to the relative thrombus weight after contraction and moderately correlated to the RBC content. This implicates that clinical imaging should strive to measure thrombus contraction as well as composition to estimate thrombus mechanics prior to mechanical retrieval.BioMedical Engineerin

A review on the association of thrombus composition with mechanical and radiological imaging characteristics in acute ischemic stroke

Thrombus composition and mechanical properties significantly impact the ease and outcomes of thrombectomy procedures in patients with acute ischemic stroke. A wide variation exists in the composition of thrombi between patients. If a relationship can be determined between the composition of a thrombus and its mechanical behaviour, as well as between the composition of a thrombus and its radiological imaging characteristics, then there is the potential to personalise thrombectomy treatment based on each individual thrombus. This review aims to give an overview of the current literature addressing this issue. Here, we present a scoping review detailing associations between thrombus composition, mechanical behaviour and radiological imaging characteristics. We conducted two searches 1) on the association between thrombus composition and the mechanical behaviour of the tissue and 2) on the association between radiological imaging characteristics and thrombus composition in the acute stroke setting. The review suggests that higher fibrin and lower red blood cell (RBC) content contribute to stiffer thrombi independent of the loading mode. Further, platelet-contracted thrombi are stiffer than non-contracted compositional counterparts. Fibrin content contributes to the elastic portion of viscoelastic behaviour while RBC content contributes to the viscous portion. It is possible to identify fibrin-rich or RBC-rich thrombi with computed tomography and magnetic resonance imaging vessel signs. Standardisation is required to quantify the association between thrombus density on non-contrast computed tomography and the RBC content. The characterisation of the thrombus fibrin network has not been addressed so far in radiological imaging but may be essential for the prediction of device-tissue interactions and distal thrombus embolization. The association between platelet-driven clot contraction and radiological imaging characteristics has not been explicitly investigated. However, evidence suggests that perviousness may be a marker of clot contraction