Hemodynamics in the Stenosed Carotid Bifurcation with Plaque Ulceration

The presence of irregular plaque surface morphology or ulceration of the atherosclerotic lesion has been identified as an independent risk factor for ischemic stroke. Doppler ultrasound (DUS) is the most commonly performed non-invasive technique used to assess patients suspected of having carotid artery disease, but currently does not incorporate the diagnosis of plaque ulceration. Advanced Doppler analyses incorporating quantitative estimates of flow disturbances may result in diagnostic indices that identify plaque ulcerative conditions. A technique for the fabrication of DUS-compatible flow phantoms was developed, using a direct-machining method that is amenable to comprehensive DUS investigations. In vitro flow studies in an ensemble of matched model vessel geometries determined that ulceration as small as 2 mm can generate significant disturbances in the downstream flow field in a moderately stenosed carotid artery, which are detectable using the DUS velocity-derived parameter turbulence intensity (TI) measured with a clinical system. Further experimental results showed that distal TI was significantly elevated (P \u3c 0.001) due to proximal plaque ulceration in the mild and moderately stenosed carotid bifurcation (30%, 50%, 60% diameter reduction), and also increased with stenosis severity. Pulsatile computational fluid dynamics (CFD) models, with simulated particle tracking, demonstrated enhanced flow disruption of the stenotic jet and slight elevations in path-dependent shear exposure parameters in a stenosed carotid bifurcation model with ulceration. In addition, CFD models were used to evaluate the DUS index TI using finite volume sampling

Doctor of Philosophy

dissertationDiffusion tensor MRI (DT-MRI or DTI) has been proven useful for characterizing biological tissue microstructure, with the majority of DTI studies having been performed previously in the brain. Other studies have shown that changes in DTI parameters are detectable in the presence of cardiac pathology, recovery, and development, and provide insight into the microstructural mechanisms of these processes. However, the technical challenges of implementing cardiac DTI in vivo, including prohibitive scan times inherent to DTI and measuring small-scale diffusion in the beating heart, have limited its widespread usage. This research aims to address these technical challenges by: (1) formulating a model-based reconstruction algorithm to accurately estimate DTI parameters directly from fewer MRI measurements and (2) designing novel diffusion encoding MRI pulse sequences that compensate for the higher-order motion of the beating heart. The model-based reconstruction method was tested on undersampled DTI data and its performance was compared against other state-of-the-art reconstruction algorithms. Model-based reconstruction was shown to produce DTI parameter maps with less blurring and noise and to estimate global DTI parameters more accurately than alternative methods. Through numerical simulations and experimental demonstrations in live rats, higher-order motion compensated diffusion-encoding was shown to successfully eliminate signal loss due to motion, which in turn produced data of sufficient quality to accurately estimate DTI parameters, such as fiber helix angle. Ultimately, the model-based reconstruction and higher-order motion compensation methods were combined to characterize changes in the cardiac microstructure in a rat model with inducible arterial hypertension in order to demonstrate the ability of cardiac DTI to detect pathological changes in living myocardium

Validation of a 1D Algorithm That Measures Pulse Wave Velocity to Estimate Compliance in Blood Vessels

The purpose of this research is to determine if it is possible to validate the new 1D method for measuring pulse wave velocity in the aorta in vivo and estimate compliance. Arterial pressure and blood flow characterize the traveling of blood from the heart to the arterial system and have played a significant role in the evaluation of cardiovascular diseases. Blood vessel distensibility can give some information on the evolution of cardiovascular disease. A patient’s aorta cannot be explanted to measure compliance; therefore we are using a flow phantom model to validate the 1D pulse wave velocity technique to estimate compliance

Study of Human Muscle Structure and Function with Velocity Encoded Phase Contrast and Diffusion Tensor Magnetic Resonance Imaging Techniques

The disproportionate loss of muscle force with aging and disuse atrophy compared to the loss of muscle mass is not yet completely understood. In addition to well-established neural and contractile determinants of force loss, remodeling of the extracellular matrix (ECM) has been recently shown in animal models to be another important contributor. In-vivo human studies exploring the structural remodeling of the ECM and its functional consequences are lacking due to the paucity of appropriate imaging techniques. This study focuses on the development and application of advanced Magnetic Resonance Imaging (MRI) methods to elucidate the mechanisms of loss of force with aging and disuse atrophy with the focus on ECM. Functional changes are investigated by strain and strain rate tensor mapping of muscle under different contraction paradigms using Velocity Encoded Phase-Contrast MRI. Methodological advances include improvements in hardware and software control of the dynamic studies. To overcome the limitation of long scan times, compressed sensing MR acquisition and reconstruction framework to reduce scan times to under a minute were developed. A multi-step automated analysis pipeline to extract 3D strain/strain rate tensors from the velocity images was implemented to process the large dynamic volumes. Strain indices reflecting the material properties of the ECM were shown to correlate with force loss leading to a hypothesis that shear strain may serve as a surrogate marker for lateral transmission of force. Diffusion tensor imaging has been applied previously to study skeletal muscle fiber architecture. The resolution of the images precludes direct inferences to be made about the microstructure. To address this limitation, bicompartmental and Random Permeable Barrier models of diffusion were applied to the diffusion data obtained with spin-echo and custom-developed stimulated echo echo-planar-imaging sequences respectively. Model derived parameters (fiber diameter, wall permeability) obtained from fitting time-dependent diffusion data were in physiologically reasonable range, with potential for tracking age related changes in muscle microstructure. The developed imaging and modeling techniques were applied to a cohort of young/senior subjects and to longitudinal tracking of disuse atrophy induced by Unilateral Limb Suspension. These studies may potentially provide the causal link between age- and disuse-related structural remodeling and its functional consequences

Validation of 4D Flow based relative pressure maps in aortic flows

While the clinical gold standard for pressure difference measurements is invasive catheterization, 4D Flow MRI is a promising tool for enabling a non-invasive quantification, by linking highly spatially resolved velocity measurements with pressure differences via the incompressible Navier–Stokes equations. In this work we provide a validation and comparison with phantom and clinical patient data of pressure difference maps estimators. We compare the classical Pressure Poisson Estimator (PPE) and the new Stokes Estimator (STE) against catheter pressure measurements under a variety of stenosis severities and flow intensities. Specifically, we use several 4D Flow data sets of realistic aortic phantoms with different anatomic and hemodynamic severities and two patients with aortic coarctation. The phantom data sets are enriched by subsampling to lower resolutions, modification of the segmentation and addition of synthetic noise, in order to study the sensitivity of the pressure difference estimators to these factors. Overall, the STE method yields more accurate results than the PPE method compared to catheterization data. The superiority of the STE becomes more evident at increasing Reynolds numbers with a better capacity of capturing pressure gradients in strongly convective flow regimes. The results indicate an improved robustness of the STE method with respect to variation in lumen segmentation. However, with heuristic removal of the wall-voxels, the PPE can reach a comparable accuracy for lower Reynolds’ numbers

Hemodynamic Effects of Entry and Exit Tear Size in Aortic Dissection Evaluated with In Vitro Magnetic Resonance Imaging and Fluid-Structure Interaction Simulation

Understanding the complex interplay between morphologic and hemodynamic features in aortic dissection is critical for risk stratification and for the development of individualized therapy. This work evaluates the effects of entry and exit tear size on the hemodynamics in type B aortic dissection by comparing fluid-structure interaction (FSI) simulations with in vitro 4D-flow magnetic resonance imaging (MRI). A baseline patient-specific 3D-printed model and two variants with modified tear size (smaller entry tear, smaller exit tear) were embedded into a flow- and pressure-controlled setup to perform MRI as well as 12-point catheter-based pressure measurements. The same models defined the wall and fluid domains for FSI simulations, for which boundary conditions were matched with measured data. Results showed exceptionally well matched complex flow patterns between 4D-flow MRI and FSI simulations. Compared to the baseline model, false lumen flow volume decreased with either a smaller entry tear (-17.8 and -18.5 %, for FSI simulation and 4D-flow MRI, respectively) or smaller exit tear (-16.0 and -17.3 %). True to false lumen pressure difference (initially 11.0 and 7.9 mmHg, for FSI simulation and catheter-based pressure measurements, respectively) increased with a smaller entry tear (28.9 and 14.6 mmHg), and became negative with a smaller exit tear (-20.6 and -13.2 mmHg). This work establishes quantitative and qualitative effects of entry or exit tear size on hemodynamics in aortic dissection, with particularly notable impact observed on FL pressurization. FSI simulations demonstrate acceptable qualitative and quantitative agreement with flow imaging, supporting its deployment in clinical studies.Comment: Judith Zimmermann and Kathrin B\"aumler contributed equall

Hemodynamic wall shear stress in models of atherosclerotic plaques using phase contrast magnetic resonance velocimetry and computational fluid dynamics

Thesis made openly available per email from author, 5/4/2018.Ph.D.Don P. Gidden