Andrea Ducci

Transcatheter aortic valves produce unphysiological flows which may contribute to thromboembolic events: An in-vitro study

Purpose Transcatheter aortic valve implantation (TAVI) has been associated with large incidence of ischemic events, whose sources are still unclear. In fact, sub-acute complications cannot be directly related to the severity of the calcification in the host tissues, nor with catheter manipulation during the implant. A potential cause could be local flow perturbations introduced by the implantation approach, resulting in thrombo-embolic consequences. In particular, contrary to the surgical approach, TAVI preserves the presence of the native leaflets, which are expanded in the paravalvular space inside the Valsalva sinuses. The purpose of this study is to verify if this configuration can determine hemodynamic variations which may promote blood cell aggregation and thrombus formation. Methods The study was performed in vitro, on idealized models of the patient anatomy before and after TAVI, reproducing a range of physiological operating conditions on a pulse duplicator. The fluid dynamics in the Valsalva sinuses was analyzed and characterized using phase resolved Particle Image Velocimetry. Results Comparison of the flow downstream the valve clearly indicated major alterations in the fluid mechanics after TAVI, characterized by unphysiological conditions associated with extended stagnation zones at the base of the sinuses. Conclusion The prolonged stasis observed in the Valsalva sinuses for the configuration modelling the presence of transcatheter aortic valves provides a fluid dynamic environment favourable for red blood cell aggregation and thrombus formation, which may justify some of the recently reported thromboembolic and ischemic events. This suggests the adoption of anticoagulation therapies following TAVI, and some caution in the patients׳ selection.

Physiological vortices in the sinuses of Valsalva: An in vitro approach for bio-prosthetic valves

Purpose The physiological flow dynamics within the Valsalva sinuses, in terms of global and local parameters, are still not fully understood. This study attempts to identify the physiological conditions as closely as possible, and to give an explanation of the different and sometime contradictory results in literature. Methods An in vitro approach was implemented for testing porcine bio-prosthetic valves operating within different aortic root configurations. All tests were performed on a pulse duplicator, under physiological pressure and flow conditions. The fluid dynamics established in the various cases were analysed by means of 2D Particle Image Velocimetry, and related with the achieved hydrodynamic performance. Results Each configuration is associated with substantially different flow dynamics, which significantly affects the valve performance. The configuration most closely replicating healthy native anatomy was characterised by the best hemodynamic performance, and any mismatch in size and position between the valve and the root produced substantial modification of the fluid dynamics downstream of the valve, hindering the hydrodynamic performance of the system. The worst conditions were observed for a configuration characterised by the total absence of the Valsalva sinuses. Conclusion This study provides an explanation for the different vortical structures described in the literature downstream of bioprosthetic valves, enlightening the experimental complications in valve testing. Most importantly, the results clearly identify the fluid mechanisms promoted by the Valsalva sinuses to enhance the ejection and closing phases, and this study exposes the importance of an optimal integration of the valve and root, to operate as a single system.

Mode decomposition and Lagrangian structures of the flow dynamics in orbitally shaken bioreactors

In this study, two mode decomposition techniques were applied and compared to assess the flow dynamics in an orbital shaken bioreactor (OSB) of cylindrical geometry and flat bottom: proper orthogonal decomposition and dynamic mode decomposition. Particle Image Velocimetry (PIV) experiments were carried out for different operating conditions including fluid height, h, and shaker rotational speed, N. A detailed flow analysis is provided for conditions when the fluid and vessel motions are in-phase (Fr = 0.23) and out-of-phase (Fr = 0.47). PIV measurements in vertical and horizontal planes were combined to reconstruct low order models of the full 3D flow and to determine its Finite-Time Lyapunov Exponent (FTLE) within OSBs. The combined results from the mode decomposition and the FTLE fields provide a useful insight into the flow dynamics and Lagrangian coherent structures in OSBs and offer a valuable tool to optimise bioprocess design in terms of mixing and cell suspension.

Impact of hydrodynamics on iPSC-derived cardiomyocyte differentiation processes

Cardiomyocytes (CMs), derived from pluripotent stem cells (PSCs), have the potential to be used in cardiac repair. Addition of physical cues, such as electrical and mechanical stimulations, have proven to significantly effect morphology, density, cardiogenesis, maturity and functionality of differentiated CMs. This work combines rigorous fluid dynamics investigation and flow frequency analysis with iPSC differentiation experiments to identify and quantify the flow characteristics leading to a significant increase of differentiation yield. This is towards a better understanding of the physical relationship between frequency modulation and embryoid bodies suspension, and the development of dimensionless correlations applicable at larger scales. Laser Doppler Anemometry and Fast Fourier Transform analysis were used to identify characteristic flow frequencies under different agitation modes. Intermittent agitation resulted in a pattern of low intensity frequencies at reactor scale that could be controlled by varying three identified time components: rotational speed, interval and dwell times. A proof of concept biological study was undertaken, tuning the hydrodynamic environment through variation of dwell time based on the engineering study findings and a significant improvement in CM yield was obtained. This work introduces the concept of fine-tuning the physical hydrodynamic cues within a three-dimensional flow system to improve cardiomyocyte differentiation of iPSC.

Scalar mixing and strain dynamics methodologies for PIV/LIF measurements of vortex ring flows

Fluid mixing operations are central to possibly all chemical, petrochemical, and pharmaceutical industries either being related to biphasic blending in polymerisation processes, cell suspension for biopharmaceuticals production, and fractionation of complex oil mixtures. This work aims at providing a fundamental understanding of the mixing and stretching dynamics occurring in a reactor in the presence of a vortical structure, and the vortex ring was selected as a flow paradigm of vortices commonly encountered in stirred and shaken reactors in laminar flow conditions. High resolution laser induced fluorescence and particle imaging velocimetry measurements were carried out to fully resolve the flow dissipative scales and provide a complete data set to fully assess macro- and micro-mixing characteristics. The analysis builds upon the Lamb-Oseen vortex work of Meunier and Villermaux [“How vortices mix,” J. Fluid Mech. 476, 213–222 (2003)] and the engulfment model of Baldyga and Bourne [“Simplification of micromixing calculations. I. Derivation and application of new model,” Chem. Eng. J. 42, 83–92 (1989); “Simplification of micromixing calculations. II. New applications,” ibid. 42, 93–101 (1989)] which are valid for diffusion-free conditions, and a comparison is made between three methodologies to assess mixing characteristics. The first method is commonly used in macro-mixing studies and is based on a control area analysis by estimating the variation in time of the concentration standard deviation, while the other two are formulated to provide an insight into local segregation dynamics, by either using an iso-concentration approach or an iso-concentration gradient approach to take into account diffusion.