The three-dimensional micro- and nanostructure of the aortic medial lamellar unit measured using 3D confocal and electron microscopy imaging.

Changes in arterial wall composition and function underlie all forms of vascular disease. The fundamental structural and functional unit of the aortic wall is the medial lamellar unit (MLU). While the basic composition and organization of the MLU is known, three-dimensional (3D) microstructural details are tenuous, due (in part) to lack of three-dimensional data at micro- and nano-scales. We applied novel electron and confocal microscopy techniques to obtain 3D volumetric information of aortic medial microstructure at micro- and nano-scales with all constituents present. For the rat abdominal aorta, we show that medial elastin has three primary forms: with approximately 71% of total elastin as thick, continuous lamellar sheets, 27% as thin, protruding interlamellar elastin fibers (IEFs), and 2% as thick radial struts. Elastin pores are not simply holes in lamellar sheets, but are indented and gusseted openings in lamellae. Smooth muscle cells (SMCs) weave throughout the interlamellar elastin framework, with cytoplasmic extensions abutting IEFs, resulting in approximately 20 degrees radial tilt (relative to the lumen surface) of elliptical SMC nuclei. Collagen fibers are organized as large, parallel bundles tightly enveloping SMC nuclei. Quantification of the orientation of collagen bundles, SMC nuclei, and IEFs reveal that all three primary medial constituents have predominantly circumferential orientation, correlating with reported circumferentially dominant values of physiological stress, collagen fiber recruitment, and tissue stiffness. This high resolution three-dimensional view of the aortic media reveals MLU microstructure details that suggest a highly complex and integrated mural organization that correlates with aortic mechanical properties.

Quantification of particle residence time in abdominal aortic aneurysms using magnetic resonance imaging and computational fluid dynamics.

Hemodynamic conditions are hypothesized to affect the initiation, growth, and rupture of abdominal aortic aneurysms (AAAs), a vascular disease characterized by progressive wall degradation and enlargement of the abdominal aorta. This study aims to use magnetic resonance imaging (MRI) and computational fluid dynamics (CFD) to quantify flow stagnation and recirculation in eight AAAs by computing particle residence time (PRT). Specifically, we used gadolinium-enhanced MR angiography to obtain images of the vessel lumens, which were used to generate subject-specific models. We also used phase-contrast MRI to measure blood flow at supraceliac and infrarenal locations to prescribe physiologic boundary conditions. CFD was used to simulate pulsatile flow, and PRT, particle residence index, and particle half-life of PRT in the aneurysms were computed. We observed significant regional differences of PRT in the aneurysms with localized patterns that differed depending on aneurysm geometry and infrarenal flow. A bulbous aneurysm with the lowest mean infrarenal flow demonstrated the slowest particle clearance. In addition, improvements in particle clearance were observed with increase of mean infrarenal flow. We postulate that augmentation of mean infrarenal flow during exercise may reduce chronic flow stasis that may influence mural thrombus burden, degradation of the vessel wall, and aneurysm growth.

Hemodynamic changes quantified in abdominal aortic aneurysms with increasing exercise intensity using mr exercise imaging and image-based computational fluid dynamics.

Abdominal aortic aneurysm (AAA) is a vascular disease resulting in a permanent, localized enlargement of the abdominal aorta. We previously hypothesized that the progression of AAA may be slowed by altering the hemodynamics in the abdominal aorta through exercise [Dalman, R. L., M. M. Tedesco, J. Myers, and C. A. Taylor. Ann. N.Y. Acad. Sci. 1085:92-109, 2006]. To quantify the effect of exercise intensity on hemodynamic conditions in 10 AAA subjects at rest and during mild and moderate intensities of lower-limb exercise (defined as 33 ± 10% and 63 ± 18% increase above resting heart rate, respectively), we used magnetic resonance imaging and computational fluid dynamics techniques. Subject-specific models were constructed from magnetic resonance angiography data and physiologic boundary conditions were derived from measurements made during dynamic exercise. We measured the abdominal aortic blood flow at rest and during exercise, and quantified mean wall shear stress (MWSS), oscillatory shear index (OSI), and particle residence time (PRT). We observed that an increase in the level of activity correlated with an increase of MWSS and a decrease of OSI at three locations in the abdominal aorta, and these changes were most significant below the renal arteries. As the level of activity increased, PRT in the aneurysm was significantly decreased: 50% of particles were cleared out of AAAs within 1.36 ± 0.43, 0.34 ± 0.10, and 0.22 ± 0.06 s at rest, mild exercise, and moderate exercise levels, respectively. Most of the reduction of PRT occurred from rest to the mild exercise level, suggesting that mild exercise may be sufficient to reduce flow stasis in AAAs.

Tuning multidomain hemodynamic simulations to match physiological measurements.

In recent years, considerable progress has been made in creating more realistic models of the cardiovascular system, often based on patient-specific anatomic data, whereas comparatively little progress has been made on incorporating measured physiological data. We have developed a method to systematically adjust the parameters of three-element windkessel outlet boundary conditions of three-dimensional blood flow models such that desired features of pressure and flow waveforms are achieved. This tuning method was formulated as the solution of a nonlinear system of equations and employed a quasi-Newton method that was informed by a reduced-order model. The three-dimensional hemodynamic models were solved using a stabilized finite-element method incorporating deformable vessel walls. The tuning method was applied to an idealized common carotid artery, an idealized iliac arterial bifurcation, and a patient-specific abdominal aorta. The objectives for the abdominal aortic model were values of the maximum and minimum of the pressure waveform, an indicator of the pressure waveform's shape, and the mean, amplitude, and diastolic mean of the flow waveform for an infrarenal measurement plane. The hemodynamic models were automatically generated and tuned by custom software with minimal user input. This approach enables efficient development of cardiovascular models for applications including detailed evaluation of cardiovascular mechanics, simulation-based design of medical devices, and patient-specific treatment planning.

Evaluation of a novel Y-shaped extracardiac Fontan baffle using computational fluid dynamics.

OBJECTIVES: The objective of this work is to evaluate the hemodynamic performance of a new Y-graft modification of the extracardiac conduit Fontan operation. The performance of the Y-graft design is compared to two designs used in current practice: a t-junction connection of the venae cavae and an offset between the inferior and superior venae cavae. METHODS: The proposed design replaces the current tube grafts used to connect the inferior vena cava to the pulmonary arteries with a Y-shaped graft. Y-graft hemodynamics were evaluated at rest and during exercise with a patient-specific model from magnetic resonance imaging data together with computational fluid dynamics. Four clinically motivated performance measures were examined: Fontan pressures, energy efficiency, inferior vena cava flow distribution, and wall shear stress. Two variants of the Y-graft were evaluated: an "off-the-shelf" graft with 9-mm branches and an "area-preserving" graft with 12-mm branches. RESULTS: Energy efficiency of the 12-mm Y-graft was higher than all other models at rest and during exercise, and the reduction in efficiency from rest to exercise was improved by 38%. Both Y-graft designs reduced superior vena cava pressures during exercise by as much as 5 mm Hg. The Y-graft more equally distributed the inferior vena cava flow to both lungs, whereas the offset design skewed 70% of the flow to the left lung. The 12-mm graft resulted in slightly larger regions of low wall shear stress than other models; however, minimum shear stress values were similar. CONCLUSIONS: The area-preserving 12-mm Y-graft is a promising modification of the Fontan procedure that should be clinically evaluated. Further work is needed to correlate our performance metrics with clinical outcomes, including exercise intolerance, incidence of protein-losing enteropathy, and thrombus formation.

Morphometry-based impedance boundary conditions for patient-specific modeling of blood flow in pulmonary arteries.

Patient-specific computational models could aid in planning interventions to relieve pulmonary arterial stenoses common in many forms of congenital heart disease. We describe a new approach to simulate blood flow in subject-specific models of the pulmonary arteries that consists of a numerical model of the proximal pulmonary arteries created from three-dimensional medical imaging data with terminal impedance boundary conditions derived from linear wave propagation theory applied to morphometric models of distal vessels. A tuning method, employing numerical solution methods for nonlinear systems of equations, was developed to modify the distal vasculature to match measured pressure and flow distribution data. One-dimensional blood flow equations were solved with a finite element method in image-based pulmonary arterial models using prescribed inlet flow and morphometry-based impedance at the outlets. Application of these methods in a pilot study of the effect of removal of unilateral pulmonary arterial stenosis induced in a pig showed good agreement with experimental measurements for flow redistribution and main pulmonary arterial pressure. Next, these methods were applied to a patient with repaired tetralogy of Fallot and predicted insignificant hemodynamic improvement with relief of the stenosis. This method of coupling image-based and morphometry-based models could enable increased fidelity in pulmonary hemodynamic simulation.