PIV-based Investigation of Hemodynamic Factors in Diseased Carotid Artery Bifurcations with Varying Plaque Geometries

Ischemic stroke is often a consequence of complications due to clot formation (i.e. thrombosis) at the site of an atherosclerotic plaque developed in the internal carotid artery. Hemodynamic factors, such as shear-stress forces and flow disturbances, can facilitate the key mechanisms of thrombosis. Atherosclerotic plaques can differ in the severity of stenosis (narrowing), in eccentricity (symmetry), as well as inclusion of ulceration (wall roughness). Therefore, in terms of clinical significance, it is important to investigate how the local hemodynamics of the carotid artery is mediated by the geometry of plaque. Knowledge of thrombosis-associated hemodynamics may provide a basis to introduce advanced clinical diagnostic indices that reflect the increased probability of thrombosis and thus assist with better estimation of stroke risk, which is otherwise primarily assessed based on the degree of narrowing of the lumen. A stereoscopic particle image velocimetry (stereo-PIV) system was configured to obtain instantaneous full-field velocity measurements in life-sized carotid artery models. Extraction of the central-plane and volumetric features of the flow revealed the complexity of the stenotic carotid flow, which increased with increasing stenosis severity and changed with the symmetry of the plaque. Evaluation of the energy content of two models of the stenosed carotid bifurcation provided insight on the expected level of flow instabilities with potential clinical implications. Studies in a comprehensive family of eight models ranging from disease-free to severely stenosed (30%, 50%, 70% diameter reduction) and with two types of plaque symmetry (concentric or eccentric), as well as a single ulcerated stenosed model, clearly demonstrated the significance of plaque geometry in marked alteration of the levels and patterns of downstream flow disturbances and shear stress. Plaque eccentricity and ulceration resulted in enhanced flow disturbances. In addition, shear-stress patterns in those models with eccentric stenosis were suggestive of increased thrombosis potential at the post-stenotic recirculation zone compared to their concentric counterpart plaques

TURBULENCE ACCUMULATION AND AVERAGE IN THE SYMMETRICALLY AND ASYMMETRICALLY STENOSED CAROTID BIFURCATION

Ischemic stroke due to atherosclerotic disease has been studied widely in the recent past. Most studies focus on either the correlation between stroke risk and stenosis severity (narrowing of the plaque in the vessel) or mechanisms affecting platelet activation and aggregation. Shear stress has been identified as a strong indicator for platelet activation/aggregation, resulting in both thrombus formation and plaque growth. This has subsequently been correlated with regions of elevated turbulence. Doppler ultrasound offers a method of characterizing these flow disturbances using a well-established parameter—turbulence intensity (Tl), which is the root mean squared deviation in the spectral mean velocity. Using an in-house in vitro flow system, Doppler spectra are obtained at each of over 1000, 1-mm3 isotropically spaced sites in the central plane of seven Teflon phantoms simulating varying degrees of arterial disease. An average of Tl over a 25 mm2 region of interest, as well as the volume of Tl and the cumulative Tl over the internal carotid artery showed that downstream turbulence increased significantly with both stenosis severity (30% - 650% increase) and plaque asymmetry (10% - 30% increase)

Investigation of Flow Disturbances and Multi-Directional Wall Shear Stress in the Stenosed Carotid Artery Bifurcation Using Particle Image Velocimetry

Hemodynamics and shear forces are associated with pathological changes in the vascular wall and its function, resulting in the focal development of atherosclerosis. Flow complexities that develop in the presence of established plaques create environments favourable to thrombosis formation and potentially plaque rupture leading to stroke. The carotid artery bifurcation is a common site of atherosclerosis development. Recently, the multi-directional nature of shear stress acting on the endothelial layer has been highlighted as a risk factor for atherogenesis, emphasizing the need for accurate measurements of shear stress magnitude as well direction. In the absence of comprehensive patient specific datasets numerical simulations of hemodynamics are limited by modeling assumptions. The objective of this thesis was to investigate the relative contributions of various factors - including geometry, rheology, pulsatility, and compliance – towards the development of disturbed flow and multi-directional wall shear stress (WSS) parameters related to the development of atherosclerosis An experimental stereoscopic particle image velocimetry (PIV) system was used to measure instantaneous full-field velocity in idealized asymmetrically stenosed carotid artery bifurcation models, enabling the extraction of bulk flow features and turbulence intensity (TI). The velocity data was combined with wall location information segmented from micro computed tomography (CT) to obtain phase-averaged maps of WSS magnitude and direction. A comparison between Newtonian and non-Newtonian blood-analogue fluids demonstrated that the conventional Newtonian viscosity assumption underestimates WSS magnitude while overestimating TI. Studies incorporating varying waveform pulsatility demonstrated that the levels of TI and oscillatory shear index (OSI) depend on the waveform amplitude in addition to the degree of vessel constriction. Local compliance resulted in a dampening of disturbed flow due to volumetric capacity of the upstream vessel, however wall tracking had a negligible effect on WSS prediction. While the degree of stenosis severity was found to have a dominant effect on local hemodynamics, comparable relative differences in metrics of flow and WSS disturbances were found due to viscosity model, waveform pulsatility and local vessel compliance

2-D and 3-D high frame-rate Pulse Wave Imaging for the characterization of focal vascular disease

Cardiovascular diseases are major causes of morbidity and mortality in Western-style populations. Atherosclerosis and Abdominal Aortic Aneurysms (AAAs) are two prevalent vascular diseases that may progress without symptoms and contribute to acute cardiovascular events such as stroke and AAA rupture, which are consistently among the leading causes of death worldwide. The imaging methods used in the diagnosis of these diseases, have been reported to present several limitations. Given that both are associated with mechanical changes in the arterial wall, imaging of the arterial mechanical properties may improve early disease detection and patient care. Pulse wave velocity (PWV) refers to the velocity at which arterial waves generated by ventricular ejection travel along the arterial tree. PWV is a surrogate marker of arterial stiffness linked to cardiovascular mortality. The foot-to-foot method that is typically used to calculate PWV suffers from errors of distance measurements and time-delay measurements. Additionally, a single PWV estimate is provided over a relatively long distance, thus inherently lacking the capability to provide regional arterial stiffness measurements. Pulse Wave Imaging (PWI) is a noninvasive, ultrasound-based technique for imaging the propagation of pulse waves along the wall of major arteries and providing a regional PWV value for the imaged artery. The aim of this work was to enable PWI to provide more localized PWV and stiffness measurements within the imaged arterial segment and to further extend it into a 2-D and 3-D technique for the detection and monitoring of focal vascular disease at high temporal and spatial resolution. The improved modality was integrated with blood flow imaging modalities aiming to render PWI a comprehensive methodology for the study of arterial biomechanics in vivo. Spatial information was increased with the introduction of piecewise PWI. This novel technique was used to measure PWV within small sub-regions of the imaged vessel in murine aneurysmal (n = 8) and atherosclerotic aortas (n = 11) in vivo. It provided PWV and stiffness maps while capturing the progressive arterial stiffening caused by atherosclerosis. PWI was further augmented with a sophisticated adaptive algorithm, enabling it to optimally partition the imaged artery into relatively homogeneous segments, automatically isolating arterial stiffness inhomogeneities. Adaptive PWI was validated in silicone phantoms consisting of segments of varying stiffness and then tested in murine aortas in vivo. Subsequently, the conventional tradeoff between spatial and temporal resolution was addressed with a plane wave compounding implementation of PWI, allowing the acquisition of full field of view frames at over 2000 Hz. A GPU-accelerated PWI post-processing framework was developed for the processing of the big bulk of generated data. The parameters of coherent compounding were optimized in vivo. The optimized sequences were then used in the clinic to assess the mechanical properties of atherosclerotic carotids (n=10) and carotids of patients after endarterectomy (n=7), a procedure to remove the plaque and restore blood flow to the brain. In the case of atherosclerotic patients undergoing carotid endarterectomy, the results were compared against the histology of the excised plaques. Investigation of the mechanical properties of plaques was also conducted for the first time with a high-frequency transducer (18.5 MHz). Additionally, 4-D PWI was introduced, utilizing high frame rate 3-D plane wave acquisitions with a 2-D matrix array transducer (16x16 elements, 2.5 MHz). A novel methodology for PWV estimation along the direction of pulse wave propagation was implemented and validated in silicone phantoms. 4-D PWI provided comprehensive views of the pulse wave propagation in a plaque phantom and the results were compared against conventional PWI. Finally, its feasibility was tested in the carotid arteries of healthy human subjects (n=6). PWVs derived in 3-D were within the physiological range and showed good agreement with the results of conventional PWI. Finally, PWI was integrated with flow imaging modalities (Color and Vector Doppler). Thus, full field-of-view, high frame-rate, simultaneous and co-localized imaging of the arterial wall dynamics and color flow as well as 2-D vector flow was implemented. The feasibility of both techniques was tested in healthy subjects (n=6) in vivo. The relationship between the timings of the flow and wall velocities was investigated at multiple locations of the imaged artery. Vector flow velocities were found to be aligned with the vessel’s centerline during peak systole in the common carotid artery and interesting flow patterns were revealed in the case of the carotid bifurcation Consequently, with the aforementioned improvements and the inclusion of 3-D imaging, PWI is expected to provide comprehensive information on the mechanical properties of pathological arteries, providing clinicians with a powerful tool for the early detection of vascular abnormalities undetectable on the B-mode, while also enabling the monitoring of fully developed vascular pathology and of the recovery of post-operated vessels

The Atheroprotective Nature of Helical Flow in Coronary Arteries

Arterial hemodynamics is markedly characterized by the presence of helical flow patterns. Previous observations suggest that arterial helical blood flow is of physiological significance, and that its quantitative analysis holds promise for clinical applications. In particular, it has been reported that distinguishable helical flow patterns are potentially atheroprotective in the carotid bifurcation as they suppress flow disturbances. In this context, there is a knowledge gap about the physiological significance of helical flow in coronary arteries, a prominent site of atherosclerotic plaque formation. This study aimed at the quantitative assessment of helical blood flow in coronary arteries, and to investigate its possible associations with vascular geometry and with atherogenic wall shear stress (WSS) phenotypes in a representative sample of 30 swine coronary arteries. This study demonstrates that in coronary arteries: (1) the hemodynamics is characterized by counter-rotating bi-helical flow structures; (2) unfavorable conditions of WSS are strongly and inversely associated with helicity intensity (r=-0.91; p<0.001), suggesting an atheroprotective role for helical flow in the coronary tree; (3) vascular torsion dictates helical flow features (r=0.64; p<0.001). The findings of this work support future studies on the role of helical flow in atherogenesis in coronary arteries

Temporal and spatial changes in wall shear stress during atherosclerotic plaque progression in mice

Wall shear stress (WSS) is involved in atherosclerotic plaque initiation, yet its role in plaque progression remains unclear. We aimed to study (i) the temporal and spatial changes in WSS over a growing plaque and (ii) the correlation between WSS and plaque composition, using animal-specific data in an atherosclerotic mouse model. Tapered casts were placed around the right common carotid arteries (RCCA) of ApoE−/− mice. At 5, 7 and 9 weeks after cast placement, RCCA geometry was reconstructed using contrast-enhanced micro-CT. Lumen narrowing was observed in all mice, indicating the progression of a lumen intruding plaque. Next, we determined the flow rate in the RCCA of each mouse using Doppler Ultrasound and computed WSS at all time points. Over time, as the plaque developed and further intruded into the lumen, absolute WSS significantly decreased. Finally at week 9, plaque composition was histologically characterized. The proximal part of the plaque was small and eccentric, exposed to relatively lower WSS. Close to the cast a larger and concentric plaque was present, exposed to relatively higher WSS. Lower WSS was significantly correlated to the accumulation of macrophages in the eccentric plaque. When pooling data of all animals, correlation between WSS and plaque composition was weak and no longer statistically significant. In conclusion, our data showed that in our mouse model absolute WSS strikingly decreased during disease progression, which was significantly correlated to plaque area and macrophage content. Besides, our study demonstrates the necessity to analyse individual animals and plaques when studying correlations between WSS and plaque composition