Cardiovascular diseases (CVDs) are a leading cause of death worldwide. To prevent sudden lethal cardiovascular events, early diagnosis and treatment are crucial. Hemodynamics play a key role in both the development and the management of cardiovascular diseases. In recent decades, physicians and engineers have been working together to understand the interplay between blood flow and various cardiovascular conditions, and to develop flow-based parameters as new biomarkers for clinical guidelines.
Visualizing and quantifying blood flow in opaque moving cavities are challenging. Current in vivo medical imaging techniques, such as 4D-Flow magnetic resonance imaging (4D-Flow MRI), are able to provide non-invasive blood flow information in 3D space and time. However, their accuracy is affected by limited spatial and temporal resolutions. Engineering techniques, i.e., computational fluid dynamics (CFD) simulations and in vitro optical flow measurements using particle image-based techniques, can offer high spatiotemporal resolution flow information but require improved fidelity to accurately represent the complexities of physiological blood flow for patient-specific treatment.
In the past decades, in vitro optical flow measurements were conducted based on simplifications, such as general geometries, steady flow conditions, and rigid walls. To enhance fidelity, in vitro system must mimic the physiological conditions as closely as possible. Moreover, in vitro optical flow measurements primarily used the 2D technique – planar particle image velocimetry (PIV) and pseudo-3D technique –multiplane Stereoscopic PIV (Stereo-PIV) which resolves the 3D velocity field from a series of 2D planar measurements. Given the inherent 3D nature of cardiovascular flows, using advanced volumetric techniques to obtain highly-resolved 3D velocity fields (often called 4D), is highly beneficial.
In this thesis, we first confirmed the superiority of the volumetric technique over 2D and pseudo-3D techniques in in vitro hemodynamic studies by conducting both Tomographic PIV (Tomo-PIV) and multiplane Stereo-PIV measurements on a patient-specific intracranial aneurysm. The obtained flow patterns, velocity, and flow-derived parameters such as vorticity and wall shear stress (WSS) were compared to in vivo 4D-Flow MRI and CFD simulation. The comparative results showed that despite having twice the in-plane resolution of Tomo-PIV, the multiplane Stereo-PIV underpredicted the WSS due to its four times lower spatial resolution in the depth direction compared to Tomo-PIV. The voxel sizes in the depth dimension for multiplane Stereo-PIV measurements are limited by the laser sheet thickness (1 mm), resulting in a significant smoothing effect on the velocity gradients and, consequently, WSS.
Next, we applied advanced 4D particle tracking velocimetry (PTV) technique – Shake-the-Box (STB) to the hemodynamic study. Compared to Tomo-PIV, STB has the advantages of resolving fewer ghost particles in the reconstruction, higher positional accuracy, higher spatial resolution with the same seeding density, and less computational time. The STB was performed on a realistic-shaped, compliant left ventricle (LV) phantom with biological valves. Particle tracks, 4D velocity, and pressure field were resolved. We then conducted a Proper Orthogonal Decomposition (POD) flow analysis based on the obtained velocity field. The STB-resolved flow pattern, velocity, and pressure were validated to those in vivo MRI studies in the literature. To our knowledge, this is the first work that provides cardiovascular flow investigation based on STB measurements. Moreover, we demonstrated the potential of POD as an alternative approach to efficiently visualize and analyze the various scale flow structures and their temporal behaviors in the cardiovascular system.
Finally, we put our focus on improving the bio-fidelity of in vitro modeling. We manufactured a patient-specific, compliant, and low-cost aorta phantom for in vitro optical
flow measurement use. By incorporating a physiological flow-providing system and the STB technique, we assessed the aortic wall movements and aortic hemodynamics. The compliant aorta exhibited distensibility and cyclic strain that were within the reported physiological values in the literature. Flow patterns and wall shear stress (WSS) qualitatively also matched with in vivo 4D-Flow MRI measurements and similar reported cases in the literature. In summary, this work improved in vitro blood flow modeling fidelity by developing a compliant patient-specific artery phantom with physiological wall properties, demonstrating its successful application in particle image-based volumetric flow measurements. This contributes to the availability of high-fidelity experimental cardiovascular flow data for hemodynamic studies as well as for validating medical techniques and computational modeling.
The dissertation ends with a concluding chapter where we highlighted the important findings and the perspective for future works.@en

Purpose: Intraventricular blood flow dynamics are associated with cardiac function. Accurate, noninvasive, and easy assessments of hemodynamic quantities (such as velocity, vortex, and pressure) could be an important addition to the clinical diagnosis and treatment of heart diseases. However, the complex time-varying flow brings many challenges to the existing noninvasive image-based hemodynamic assessments. The development of reliable techniques and analysis tools is essential for the application of hemodynamic biomarkers in clinical practice. Methods: In this study, a time-resolved particle tracking method, Shake-the-Box, was applied to reconstruct the flow in a realistic left ventricle (LV) silicone model with biological valves. Based on the obtained velocity, 4D pressure field was calculated using a Poisson equation-based pressure solver. Furthermore, flow analysis by proper orthogonal decomposition (POD) of the 4D velocity field has been performed. Results: As a result of the Shake-the-Box algorithm, we have extracted: (i) particle positions, (ii) particle tracks, and finally, (iii) 4D velocity fields. From the latter, the temporal evolution of the 3D pressure field during the full cardiac cycle was obtained. The obtained maximal pressure difference extracted along the base-to-apex was about 2.7 mmHg, which is in good agreement with those reported in vivo. The POD analysis results showed a clear picture of different scale of vortices in the pulsatile LV flow, together with their time-varying information and corresponding kinetic energy content. To reconstruct 95% of the kinetic energy of the LV flow, only the first six POD modes would be required, leading to significant data reduction. Conclusions: This work demonstrated Shake-the-Box is a promising technique to accurately reconstruct the left ventricle flow field in vitro. The good spatial and temporal resolutions of the velocity measurements enabled a 4D reconstruction of the pressure field in the left ventricle. The application of POD analysis showed its potential in reducing the complexity of the high-resolution left ventricle flow measurements. For future work, image analysis, multi-modality flow assessments, and the development of new flow-derived biomarkers can benefit from fast and data-reducing POD analysis.

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Introduction: Wall shear stress (WSS) is associated with the growth and rupture of an intracranial aneurysm. To reveal their underlying connections, many image-based computational fluid dynamics (CFD) studies have been conducted. However, the methodological validations using both in vivo medical imaging and in vitro optical flow measurements were rarely accompanied in such studies. Methods: In the present study, we performed a comparative assessment on the hemodynamics of a patient-specific intracranial saccular aneurysm using in vivo 4D Flow MRI, in silico CFD, in vitro stereoscopic and tomographic particle imaging velocimetry (Stereo-PIV and Tomo-PIV) techniques. PIV experiments and CFD were conducted under steady state corresponding to the peak systole of 4D Flow MRI. Results: The results showed that all modalities provided similar flow features and overall surface distribution of WSS. However, a large variation in the absolute WSS values was found. 4D Flow MRI estimated a 2- to 4-fold lower peak WSS (3.99 Pa) and a 1.6- to 2-fold lower mean WSS (0.94 Pa) than Tomo-PIV, Stereo-PIV, and CFD. Bland-Altman plots of WSS showed that the differences between PIV-/CFD-based WSS and 4D Flow MRI-based WSS increase with higher WSS magnitude. Such proportional trend was absent in the Bland-Altman comparison of velocity where the resolutions of PIV and CFD datasets were matched to 4D Flow MRI. We also found that because of superior resolution in the out-of-plane direction, WSS estimation by Tomo-PIV was higher than Stereo-PIV. Conclusions: Our results indicated that the differences in spatial resolution could be the main contributor to the discrepancies between each modality. The findings of this study suggest that with current techniques, care should be taken when using absolute WSS values to perform a quantitative risk analysis of aneurysm rupture.

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