Abstract 440: Non-Invasive Quantification of Rat Vasculature Biomechanical Properties Under a Cardiovascular Challenge: Implications in Atherosclerosis Progression

Introduction: Measurements of cyclic strain give insight into vessel wall properties, offer a better understanding of the pathogenesis of atherosclerosis, and can be used in quantifying loss of vessel compliance. Using dobutamine stimulation to increase heart rate and cardiac output provides a clinically relevant means to begin to understand alterations in cyclic strain during a vascular challenge which mimics some aspects of exercise. Similar work has been completed in murine models, but translating these methods to a species that is an order of magnitude larger allows for a better understanding of how these results could allometrically scale to the human condition. We hypothesize that using a pharmacological cardiovascular stimulant will cause cyclic strain shifts that vary between species. Materials and Methods: Cyclic strain was non-invasively quantified using MRI. Young rats and mice were anesthetized using isoflurane and imaged at 7T. 2D and 3D gradient echo data were used to plan ECG-gated acquisitions that included 12 CINE frames across the cardiac cycle, in the infrarenal aorta pre- and post- dobutamine infusion. Vessel strain was quantified in each CINE frame. Results: Baseline strain in rats was 17% and 16%, for males and females respectively (A, C). In mice, baseline strain was 22% in males and 18% in females (B, D). After infusion of dobutamine, strain in rats increased to 26% in males and 27% in females, while in mice strain increased to 36% in males and 32% in females. Conclusions: In conclusion, there are evident variations in cyclic strain under a cardiovascular challenge between species. With this insight, a clearer understanding of the biomechanical forces experienced by the vasculature in different species may lead to improved extrapolation from mouse to human in understanding the effects of atherosclerosis on vessel compliance and developing therapeutic approaches.

Abstract TP125: Intracranial Stenosis Subtypes in Patients Aged 45 Years or Younger

Objective: Using high-resolution magnetic resonance imaging(HRMRI), we sought to examine the proportions of intracranial stenosis subtypes and their clinical relevance in young patients(≤45 years old). Methods: One hundred and twenty-nine consecutive patients (mean age 36±8 years) with middle cerebral artery stenosis and without Moyamoya disease were evaluated by HRMRI. The stenosis was classified as eccentric stenosis, concentric stenosis, and mixed stenosis if both eccentric and concentric stenosis occurred in one vessel. The clinical data and vessel wall properties were analyzed among the subtypes. Results: Eccentric stenosis was found in 86 (69.4%) patients, while concentric stenosis was found in 26 patients (21.0%) and mixed stenosis in 12(9.7%) patients. The patients with eccentric stenosis were older (p<0.001) and more likely had atherosclerosis risk factors (p=0.024). The patients with concentric stenosis were more likely female, and aged 35 years old or younger. All mixed stenosis were high-grade (>70%) stenotic. All concentric stenosis showed constrictive remodeling, while eccentric and mixed stenosis had heterogeneous remodeling types. In 34 patients with available enhanced images, ring enhancement was revealed in 8/9(88.9%) concentric stenosis and 5/5(100%) mixed stenosis, but only in 3/20(15%) eccentric stenosis (P<0.001). Ten of twelve (83.3%) patients with mixed stenosis were symptomatic, more frequently than the patients with eccentric stenosis (57.0%, p=0.072) and the patients with concentric stenosis (50%, p=0.052). Conclusions: The distinct vessel wall features among intracranial stenosis subtypes suggest heterogeneous pathophysiology. Further studies are required to investigate whether mixed stenosis is the most vulnerable subtype in young patients (≤45 years old).

Towards Non-Invasive Pressure Assessment

In clinical practice, ultrasound is frequently applied to non-invasively assess blood velocity, blood volume flow and blood vessel wall properties such as vessel wall thickness and vessel diameter waveforms. To convert these properties into relevant biomechanical properties that are related to cardiovascular disease (CVD), such as elastic modulus and compliance of the vessel wall, local pressure has to be assessed simultaneously with vessel wall thickness and vessel diameter waveforms. Additionally, accurate estimates of vascular impedance (transfer function between pressure and blood flow) can be a valuable tool for the estimation of the condition of the vessel, e.g., to diagnose stenosis. Studies of arterial impedance in humans, however, are hampered by the lack of reliable non-invasive techniques to simultaneously record pressure and flow locally as a function of time. Local pressure assessment together with flow has great potential for improving the ability to diagnose and monitor CVD.

Signs of Accelerated Preclinical Atherosclerosis in Patients with Ankylosing Spondylitis

Objective.Preliminary evidence suggests that ankylosing spondylitis (AS) is associated with an increased cardiovascular (CV) risk. We investigated subclinical atherosclerosis and arterial stiffness in patients with AS compared with controls, and identified CV and AS related risk factors for atherosclerotic disease.Methods.A total of 59 patients with AS who were scheduled for etanercept treatment according to the ASsessments in Ankylosing Spondylitis guidelines and 30 healthy controls were recruited. Subclinical atherosclerosis was assessed as the average intima-media thickness (IMT) of the common carotid artery. Arterial stiffness was determined by distensibility, compliance, and Young’s elastic modulus of the carotid artery.Results.AS patients had a greater IMT (0.62 ± 0.09 mm vs 0.57 ± 0.09 mm in controls; p = 0.02), a difference that remained after adjustment for traditional CV risk factors. AS was associated with higher carotid pulse pressure (47 ± 7 mm Hg vs 44 ± 8 mm Hg in controls; p = 0.04), but this was not due to local vessel wall properties. Among AS patients, age and body mass index (BMI) were determinants of IMT. Age, BMI, total cholesterol, triglycerides, and disease duration were identified as determinants of stiffness indices. No relationship was found between large-vessel properties and higher Bath AS disease indices or C-reactive protein values.Conclusion.AS was associated with subclinical atherosclerosis and arterial stiffness, supporting epidemiological evidence of an increased CV risk in these patients. Whether these differences are due to AS or to a higher prevalence of CV risk factors in patients with AS remains to be determined.

Simulation of Blood Flow in Deformable Arteries Using Subject-Specific Geometry and Variable Vessel Wall Properties

Previous efforts to simulate blood flow in patient-specific models either assumed rigid vessel walls or deformable walls with constant mechanical property [1]. We have developed a new workflow to enable blood flow and vessel dynamics simulations using subject-specific geometry and variable wall properties. The geometric model construction is based on 3D segmentation and geometric processing which greatly reduce human labor and increase the objectivity of the model. Variable wall properties are assigned to the model based on combining centerline-based and surface-based methods. This new approach was successfully applied to simulate blood flow and wall dynamics in models with abdominal, thoracic, and cerebral aneurysms.

Effects of Nonuniform Vessel Wall Properties in Fluid-Structure Interaction Simulations

Aneurysms are a disease that plagues mankind. Clinicians are in a difficult position when trying to gauge what action, if any, needs to be taken after a patient is found to have an aneurysm. Increasingly, doctors rely on computer simulations to determine the transient 3-D hemodynamics within the aneurysm sac. Specifically, ongoing research is being conducted to characterize aneurysms in order to develop criteria which predict high-risk factors leading to aneurysm rupture, using patient-specific geometries [1–4].