Moving shear stress towards the clinic: preclinical comparison of optical coherence tomography-based versus angiography-based time-averaged wall shear stress estimations

Introduction Identification of coronary atherosclerotic plaques at risk of causing future acute coronary syndromes remains a major unmet clinical challenge. The addition of vessel biomechanics to intracoronary imaging derived evaluation of plaque morphology, improves identification of plaques likely to develop high risk features. We and others have developed a framework for intracoronary imaging (optical coherence tomography [OCT]) based 3D reconstructions of coronary arteries for computational fluid dynamics (CFD) simulations of shear stress, which are considered the current gold standard approach for quantification of coronary arterial haemodynamics. However, these approaches are time consuming and computationally intensive, resulting in a barrier to clinical uptake. Purpose Determination of time averaged wall shear stress (TAWSS) based on 3D coronary geometries from non-invasive 3D Quantitative Coronary Angiography (3D-QCA) has recently been developed (Pie Medical Imaging, Netherlands), which enables results of shear stress simulations to be available within 30 minutes. We sought to compare TAWSS determined from 3D-QCA with gold standard OCT-based CFD simulations in both normal and stenotic arteries in minipigs. Methods 15 normal and 5 stenotic minipig coronary arteries were studied. Anatomically matched 3D arterial geometries were reconstructed from 3D-QCA and OCT using common centrelines. Boundary conditions for simulations included directly measured inlet blood velocities; parabolic inlet flow profiles, zero pressure outlet; no-slip arterial walls; blood density: 1.05 g/ml; blood dynamic viscosity: 0.035 g/cm.s. Blood was modelled as Newtonian. 3D-QCA TAWSS was obtained with a Kratos Multi-Physics CFD solver. OCT-based simulations were performed using Abaqus/CFD v6.14. TAWSS was calculated for 80 axially matched segments for both methods (1200 and 400 paired comparisons for normal and stenotic arteries, respectively). Data were analysed using Bland-Altman and Wilcoxon matched-pairs signed ranked tests. Results Computation times for 3D-QCA and OCT-based CFD were approximately 30 minutes and 2 hours respectively. Axial profiles of TAWSS were similar between the two methods and there was agreement in TAWSS magnitudes and narrow 95% limits of agreement (Figure 1 and Figure 2). Using co-registered TAWSS maps generated by each method, we find similar spatial regional distributions of TAWSS in both normal and stenotic arteries. Conclusions Our data suggest that 3D-QCA based TAWSS is feasible in both normal and stenotic arteries. Spatial TAWSS distributions between the two methods are similar with agreement in matched TAWSS comparisons, though there are some small systematic differences in the absolute values of TAWSS, due to different resultant arterial geometries. These encouraging data suggest that further clinical evaluation of rapid TAWSS from 3D-QCA is warranted, which may facilitate clinical adoption of TAWSS assessment. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Medical Research Council

Serum Bilirubin Levels and Extent of Symptomatic Intracranial Atherosclerotic Stenosis in Acute Ischemic Stroke: A Cross-Sectional Study

Background: Bilirubin plays a paradoxical role in the pathological mechanism of stroke. To date, few clinical studies have investigated the effect of serum bilirubin on symptomatic intracranial atherosclerotic stenosis (sICAS). This study aims to evaluate the connection between serum bilirubin and sICAS.Methods: From September 2015 to May 2020, 1,156 sICAS patients without hepatobiliary diseases admitted to our hospital were included. Patients were distributed into none-mild (0–49%), moderate (50–69%) and severe-occlusion sICAS groups (70–100%) by the degree of artery stenosis. Moderate and severe-occlusion sICAS patients were classified into three groups by the number of stenotic arteries (single-, two- and multiple-vessel stenosis). The relationship between serum bilirubin levels and sICAS was analyzed by logistic regression analysis.Results: In univariable analyses, sICAS patients with severe and multiple atherosclerotic stenoses had lower levels of total bilirubin (Tbil), direct bilirubin (Dbil), and indirect bilirubin (Ibil). In multinomial logistic regression analyses, when compared with the highest tertile of bilirubin, lower levels of Tbil, Dbil, and Ibil showed higher risks of severe-occlusion sICAS (95% CI: 2.018–6.075 in tertile 1 for Tbil; 2.380–7.410 in tertile 1 for Dbil; 1.758–5.641 in tertile 1 for Ibil). Moreover, the logistic regression analyses showed that lower levels of Tbil, Dbil, and Ibil were related to multiple (≥3) atherosclerotic stenoses (95% CI: 2.365–5.298 in tertile 1 and 2.312–5.208 in tertile 2 for Tbil; 1.743–3.835 in tertile 1 and 1.416–3.144 in tertile 2 for Dbil; 2.361–5.345 in tertile 1 and 1.604–3.545 in tertile 2 for Ibil) when compared with tertile 3.Conclusions: Our findings suggest that lower bilirubin levels may indicate severe and multiple intracranial atherosclerotic stenoses.

ADDITION OF REMESHING TECHNIQUE TO THE STENT IMPLANTATION SOFTWARE AND ITS EFFECT ON THE SIMULATION OUTCOME

Stent implanation is one of the clinical treatments of stenotic arteries. This clinical procedure requires careful planning that considers the geometry of the artery of the particular patient. The numerical simulation can be very useful to analyze the state of the arterial wall during and after this intervention. The numerical model considered within this paper simulates the expansion of the stent and subsequent deformation of the arterial wall using finite element method. This model was validated in literature against clinical data. Within the implementation, the tetrahedral finite elements were used. But, this type of elements can cause inaccuracies and instability during simulations. Within this paper, the stent implantation software was improved by implementing hexahedral finite element mesh and applying an additional remeshing technique in order to ensure better prediction of forces exerted on stent and stress within arterial wall. The benefits of these additions are demonstrated on the simulation of stent implantation with patient-specific coronary artery. This software can be used to analyze quickly the effect of different stent size and position on the state of the arterial wall after the intervention. It represents a valuable and reliable tool for the clinicians that can help them determine the outcome of the stenting intervention and thus improve the patient-specific pre-operative planning process.

In vitro Biomodels in Stenotic Arteries to Perform Blood Analogues Flow Visualizations and Measurements: A Review

Cardiovascular diseases are one of the leading causes of death globally and the most common pathological process is atherosclerosis. Over the years, these cardiovascular complications have been extensively studied by applying in vivo, in vitro and numerical methods (in silico). In vivo studies represent more accurately the physiological conditions and provide the most realistic data. Nevertheless, these approaches are expensive, and it is complex to control several physiological variables. Hence, the continuous effort to find reliable alternative methods has been growing. In the last decades, numerical simulations have been widely used to assess the blood flow behavior in stenotic arteries and, consequently, providing insights into the cardiovascular disease condition, its progression and therapeutic optimization. However, it is necessary to ensure its accuracy and reliability by comparing the numerical simulations with clinical and experimental data. For this reason, with the progress of the in vitro flow measurement techniques and rapid prototyping, experimental investigation of hemodynamics has gained widespread attention. The present work reviews state-of-the-art in vitro macro-scale arterial stenotic biomodels for flow measurements, summarizing the different fabrication methods, blood analogues and highlighting advantages and limitations of the most used techniques.

Modeling Blood Pulsatile Turbulent Flow in Stenotic Coronary Arteries

Atherosclerosis is a potentially serious illness where arteries become clogged with fatty substances called plaques. Over the years, this pathological condition has been deeply studied and computational fluid dynamics has played an important role in investigating the blood flow behavior. Commonly, the blood flow is assumed to be laminar and a Newtonian fluid. However, under a stenotic condition, the blood behaves as a non-Newtonian fluid and the pulsatile blood flow through coronary arteries could result in a transition from laminar to turbulent flow condition. The present study aims to analyze and compare numerically the blood flow behavior, applying the k-ω SST model and a laminar assumption. The effects of Newtonian and non-Newtonian (Carreau) models were also studied. In addition, the effect of the stenosis degree on velocity fields and wall shear stress based descriptors were evaluated. According to the results, the turbulent model is shown to give a better overall representation of pulsatile flow in stenotic arteries. Regarding, the effect of non-Newtonian modeling, it was found to be more significant in wall shear stress measurements than in velocity profiles. In addition, the appearance of recirculation zones in the 50% stenotic model was observed during systole, and a low TAWSS and high OSI were detected downstream of the stenosis which, in turn, are risk factors for plaque formation. Finally, the turbulence intensity measurements allowed to distinguish regions of recirculating and disturbed flow.

Balloon Angioplasty and Stenting

In 1964, Charles Dotter and Melvin Judkins performed the first successful transluminal angioplasty of a superficial femoral artery stenosis. Since then, techniques of revascularization have been the cornerstone of interventional radiology (IR) practices. Angioplasty became a more recognized therapy in the mid-1970s, and in the ensuing 40 years, there have been continual advancements in this technology, resulting in highly sophisticated devices that are now available in IR suites around the world. The array of materials available is constantly evolving, as are the various uses of balloons and stents. In addition to their use in restoring patency of occluded or stenotic arteries and veins, balloons and stents are employed to restore patency in other structures, including bile ducts and ureters. In this chapter, properties of these commonly used tools and indications for their use are discussed in detail.