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

Zein-based smart coatings for drug-eluting stents: investigations via static and microfluidic approaches

Coronary heart disease is currently responsible for a significant percentage of global mortality in developed and developing nations alike. This occurrence takes place despite the advancement in medical technology and improved treatment options, such as stenting procedures. Due to complications with restenosis and stent thrombosis that are associated with current commercial stents, there has been a growing interest in stent research and development in order to eradicate the causes of such clinical events. The selection of an antioxidant, non-thrombogenic coating has been a major obstacle to the development of drug-eluting stents (DES), and, to date, a truly biocompatible stent platform remains elusive. Moreover, there is a need to assess stent coatings within an in vitro platform prior to in vivo and clinical studies in order to minimize adverse effects. Even if considerable progress has been made over the last two decades in the development of flow chambers to monitor and study thrombus formation outside of the circulation, blood-material interactions are still little investigated under static and dynamic modes. In order to avoid some of the drawbacks of synthetic polymers, such as their undesirable degradation products, long-lasting presence, or potential biocompatibility issues, the aim of this PhD thesis was to investigate zein as a green and abundant plant-derived protein as a coating material for DES applications. This study aimed to understand the potential uses of zein as a controlled release matrix for drug delivery systems, in addition to developing a microfluidic platform to assess the behavior and hemocompatibility of the proposed plant-based stent coatings under flow conditions

A method to improve the computational efficiency of the Chan-Vese model for the segmentation of ultrasound images

Purpose Advanced image segmentation techniques like the Chan-Vese (CV) models transform the segmentation problem into a minimization problem which is then solved using the gradient descent (GD) optimization algorithm. This study explores whether the computational efficiency of CV can be improved when GD is replaced by a different optimization method. Methods Two GD variants from the literature (Nesterov accelerated, Barzilai-Borwein) and a newly developed hybrid variant of GD were used to improve the computational efficiency of CV by making GD insensitive to local minima. One more variant of GD from the literature (projected GD) was used to address the issue of maintaining the constraint on boundary evolution in CV which also increases computational cost. A novel modified projected GD (Barzilai-Borwein projected GD) was also used to overcome both problems at the same time. The effect of optimization method selection on processing time and the quality of the output was assessed for 25 musculoskeletal ultrasound images (five anatomical areas). Results The Barzilai-Borwein projected GD method was able to significantly reduce computational time (average(±std.dev.) reduction 95.82 % (±3.60 %)) with the least structural distortion in the delineated output relative to the conventional GD (average(±std.dev.) structural similarity index: 0.91(±0.06)). Conclusion The use of an appropriate optimization method can substantially improve the computational efficiency of CV models. This can open the way for real-time delimitation of anatomical structures to aid the interpretation of clinical ultrasound. Further research on the effect of the optimization method on the accuracy of segmentation is needed

Aortic dissection: simulation tools for disease management and understanding

Aortic dissection is a severe cardiovascular pathology in which a tear in the intimal layer of the aortic wall allows blood to flow between the vessel wall layers, forming a 'false lumen'. In type-B aortic dissections, those involving only the descending aorta, the decision to medically manage or surgically intervene is not clear and is highly dependent on the patient. In addition to clinical imaging data, clinicians would benefit greatly from additional physiological data to inform their decision-making process. Computational fluid dynamics methods show promise for providing data on haemodynamic parameters in cardiovascular diseases, which cannot otherwise be predicted or safely measured. The assumptions made in the development of such models have a considerable impact on the accuracy of the results, and thus require careful investigation. Application of appropriate boundary conditions is a challenging but critical component of such models. In the present study, imaging data and invasive pressure measurements from a patient with a type-B aortic dissection were used to assist numerical modelling of the haemodynamics in a dissected aorta. A technique for tuning parameters for coupled Windkessel models was developed and evaluated. Two virtual treatments were modelled and analysed using the developed dynamic boundary conditions. Finally, the influence of wall motion was considered, of which the intimal flap that separates the false lumen from the true lumen, is of particular interest. The present results indicate that dynamic boundary conditions are necessary in order to achieve physiologically meaningful flows and pressures at the boundaries, and hence within the dissected aorta. Additionally, wall motion is of particular importance in the closed regions of the false lumen, wherein rigid wall simulations fail to capture the motion of the fluid due to the elasticity of the vessel wall and intimal flap