Joseph R. Leach

Flow Residence Time and Regions of Intraluminal Thrombus Deposition in Intracranial Aneurysms

Thrombus formation in intracranial aneurysms, while sometimes stabilizing lesion growth, can present additional risk of thrombo-embolism. The role of hemodynamics in the progression of aneurysmal disease can be elucidated by patient-specific computational modeling. In our previous work, patient-specific computational fluid dynamics (CFD) models were constructed from MRI data for three patients who had fusiform basilar aneurysms that were thrombus-free and then proceeded to develop intraluminal thrombus. In this study, we investigated the effect of increased flow residence time (RT) by modeling passive scalar advection in the same aneurysmal geometries. Non-Newtonian pulsatile flow simulations were carried out in base-line geometries and a new postprocessing technique, referred to as “virtual ink” and based on the passive scalar distribution maps, was used to visualize the flow and estimate the flow RT. The virtual ink technique clearly depicted regions of flow separation. The flow RT at different locations adjacent to aneurysmal walls was calculated as the time the virtual ink scalar remained above a threshold value. The RT values obtained in different areas were then correlated with the location of intra-aneurysmal thrombus observed at a follow-up MR study. For each patient, the wall shear stress (WSS) distribution was also obtained from CFD simulations and correlated with thrombus location. The correlation analysis determined a significant relationship between regions where CFD predicted either an increased RT or low WSS and the regions where thrombus deposition was observed to occur in vivo. A model including both low WSS and increased RT predicted thrombus-prone regions significantly better than the models with RT or WSS alone.

Carotid Atheroma Rupture Observed In Vivo and FSI-Predicted Stress Distribution Based on Pre-rupture Imaging

Atherosclerosis at the carotid bifurcation is a major risk factor for stroke. As mechanical forces may impact lesion stability, finite element studies have been conducted on models of diseased vessels to elucidate the effects of lesion characteristics on the stresses within plaque materials. It is hoped that patient-specific biomechanical analyses may serve clinically to assess the rupture potential for any particular lesion, allowing better stratification of patients into the most appropriate treatments. Due to a sparsity of in vivo plaque rupture data, the relationship between various mechanical descriptors such as stresses or strains and rupture vulnerability is incompletely known, and the patient-specific utility of biomechanical analyses is unclear. In this article, we present a comparison between carotid atheroma rupture observed in vivo and the plaque stress distribution from fluid–structure interaction analysis based on pre-rupture medical imaging. The effects of image resolution are explored and the calculated stress fields are shown to vary by as much as 50% with sub-pixel geometric uncertainty. Within these bounds, we find a region of pronounced elevation in stress within the fibrous plaque layer of the lesion with a location and extent corresponding to that of the observed site of plaque rupture.

Human Cardiac Function Simulator for the Optimal Design of a Novel Annuloplasty Ring with a Sub-valvular Element for Correction of Ischemic Mitral Regurgitation

AbstractIschemic mitral regurgitation is associated with substantial risk of death. We sought to: (1) detail significant recent improvements to the Dassault Systèmes human cardiac function simulator (HCFS); (2) use the HCFS to simulate normal cardiac function as well as pathologic function in the setting of posterior left ventricular (LV) papillary muscle infarction; and (3) debut our novel device for correction of ischemic mitral regurgitation. We synthesized two recent studies of human myocardial mechanics. The first study presented the robust and integrative finite element HCFS. Its primary limitation was its poor diastolic performance with an LV ejection fraction below 20% caused by overly stiff ex vivo porcine tissue parameters. The second study derived improved diastolic myocardial material parameters using in vivo MRI data from five normal human subjects. We combined these models to simulate ischemic mitral regurgitation by computationally infarcting an LV region including the posterior papillary muscle. Contact between our novel device and the mitral valve apparatus was simulated using Dassault Systèmes SIMULIA software. Incorporating improved cardiac geometry and diastolic myocardial material properties in the HCFS resulted in a realistic LV ejection fraction of 55%. Simulating infarction of posterior papillary muscle caused regurgitant mitral valve mechanics. Implementation of our novel device corrected valve dysfunction. Improvements in the current study to the HCFS permit increasingly accurate study of myocardial mechanics. The first application of this simulator to abnormal human cardiac function suggests that our novel annuloplasty ring with a sub-valvular element will correct ischemic mitral regurgitation.

An efficient two-stage approach for image-based FSI analysis of atherosclerotic arteries

Patient-specific biomechanical modeling of atherosclerotic arteries has the potential to aid clinicians in characterizing lesions and determining optimal treatment plans. To attain high levels of accuracy, recent models use medical imaging data to determine plaque component boundaries in three dimensions, and fluid–structure interaction is used to capture mechanical loading of the diseased vessel. As the plaque components and vessel wall are often highly complex in shape, constructing a suitable structured computational mesh is very challenging and can require a great deal of time. Models based on unstructured computational meshes require relatively less time to construct and are capable of accurately representing plaque components in three dimensions. These models unfortunately require additional computational resources and computing time for accurate and meaningful results. A two-stage modeling strategy based on unstructured computational meshes is proposed to achieve a reasonable balance between meshing difficulty and computational resource and time demand. In this method, a coarsegrained simulation of the full arterial domain is used to guide and constrain a fine-scale simulation of a smaller region of interest within the full domain. Results for a patient-specific carotid bifurcation model demonstrate that the two-stage approach can afford a large savings in both time for mesh generation and time and resources needed for computation. The effects of solid and fluid domain truncation were explored, and were shown to minimally affect accuracy of the stress fields predicted with the two-stage approach.

Computational modeling of flow-altering surgeries in basilar aneurysms.

In cases where surgeons consider different interventional options for flow alterations in the setting of pathological basilar artery hemodynamics, a virtual model demonstrating the flow fields resulting from each of these options can assist in making clinical decisions. In this study, image-based computational fluid dynamics (CFD) models were used to simulate the flow in four basilar artery aneurysms in order to evaluate postoperative hemodynamics that would result from flow-altering interventions. Patient-specific geometries were constructed using MR angiography and velocimetry data. CFD simulations carried out for the preoperative flow conditions were compared to in vivo phase-contrast MRI measurements (4D Flow MRI) acquired prior to the interventions. The models were then modified according to the procedures considered for each patient. Numerical simulations of the flow and virtual contrast transport were carried out in each case in order to assess postoperative flow fields and estimate the likelihood of intra-aneurysmal thrombus deposition following the procedures. Postoperative imaging data, when available, were used to validate computational predictions. In two cases, where the aneurysms involved vital pontine perforator arteries branching from the basilar artery, idealized geometries of these vessels were incorporated into the CFD models. The effect of interventions on the flow through the perforators was evaluated by simulating the transport of contrast in these vessels. The computational results were in close agreement with the MR imaging data. In some cases, CFD simulations could help determine which of the surgical options was likely to reduce the flow into the aneurysm while preserving the flow through the basilar trunk. The study demonstrated that image-based computational modeling can provide guidance to clinicians by indicating possible outcome complications and indicating expected success potential for ameliorating pathological aneurysmal flow, prior to a procedure.

Monitoring Serial Change in the Lumen and Outer Wall of Vertebrobasilar Aneurysms

BACKGROUND AND PURPOSE:Estimation of the stability of fusiform aneurysms of the basilar artery requires precise monitoring of the luminal and outer wall volumes. In this report we describe the use of MR imaging and 3D postprocessing methods to study the evolution of those aneurysms. MATERIALS AND METHODS:Nine patients with fusiform basilar artery aneurysms underwent MR imaging studies covering at least 2 different time points (mean delay between studies, 7.1 ± 4.6 months). Imaging included multisection 2D T1-weighted fast spin-echo and/or 3D steady-state imaging to assess the outer wall and contrast-enhanced MR angiography to study the lumen. The outer and inner walls were extracted using, respectively, a manual delineation (made by 2 observers) and a thresholding technique. The 2 studies were subsequently coregistered at each time point, as well as between differing time points. Volumes of each vessel component were calculated. RESULTS:Mean volume was 6760 ± 6620 mm3 for the outer wall and 2060 ± 1200 mm3 for the lumen. Evolution of the lumen and outer wall was highly variable from 1 patient to another, with a trend toward increase of the vessel wall for the largest aneurysms. Interobserver reproducibility for outer wall delineation was on the order of 90%. CONCLUSION:Combining MR imaging methods to study both the outer wall and lumen with 3D registration tools provides a powerful method for progression of fusiform basilar aneurysmal disease.

Computational Models of Vascular Mechanics

Many of the world’s leading causes of death involve pathology of the vasculature, both arterial and venous. In addition to the biochemical and genetic factors governing vascular health and disease, mechanics strongly modulates the form and function of the vessel wall. Biomechanical analysis is being increasingly used to not only elucidate key disease processes, but also to predict disease progression and response to therapeutic and surgical intervention on a patient-specific basis. This chapter reviews some of the recent advances in computational vascular mechanics, with references to key works in constitutive modeling, fluid-structure interaction, image-based modeling, and atherosclerotic plaque mechanics.

Numerical Modeling of the Flow in Cerebral Aneurysms Can Predict Thrombus Deposition Regions Following Vascular Interventions

Giant intracranial aneurysms present a grave danger of hemorrhage, cerebral compression, and thromboembolism. Fusiform aneurysms present a particular challenge for interventional treatment since these lesions cannot be completely removed from the circulation by clipping or coiling without sacrificing flow to the distal vasculature. In some cases, these lesions can be treated by interventions eliminating pathological hemodynamics, such as indirect aneurysm occlusion or deployment of a flow diverter stent (FDS). The first approach consists of proximal occlusion, distal occlusion, or trapping, sometimes performed with a bypass supplying flow from collateral circulation. In the second approach, a flow diverter device is used to reconstruct the parent vessel geometry and redirect the flow away from the aneurysmal sac. This is achieved due to the denser struts of an FDS relative to a standard stent, which provide resistance to the flow across its walls. Both interventional approaches often result in thrombus deposition (TD) in the aneurysm sac that is considered protective. Despite their advantages, these treatments introduce complications related to thrombotic occlusion of vital perforators or branch arteries. A virtual model, that could predict TD regions that result from flow alteration could help evaluate various treatment options. In addition to biochemical factors, an important role in the TD process may be played by hemodynamics. Previous studies demonstrated that flow regions with elevated TD potential are characterized by low velocities and near-wall shear stresses as well as increased flow residence time [1, 2]. The current study extends this patient-specific CFD methodology to predict TD regions following vascular interventions, such as proximal vessel occlusion and FDS deployment.Copyright

Patient Specific FEM Analysis of the Atherosclerotic Carotid Bifurcation

Introduction Atherosclerosis in the carotid bifurcation is a highly variable disease that, in its stable form, can cause a dangerous reduction of blood flow to the brain. Should the plaque rupture or ulcerate, the patient is likely to experience a thrombotic or embolic stroke. Stroke is the 3 rd leading cause of death in the western world, and approximately 10-15% of these cases develop from carotid atherosclerosis. 1 In addition to the complex biochemistry involved in the initiation, progression, and acute insult of carotid disease, the mechanical environment of the carotid bifurcation may also play a pivotal role in these disease states. The finite element method can be used to interrogate the local mechanical environment of the carotid bifurcation throughout the cardiac cycle. The complex time-dependent stress and strain fields can thus be estimated to derive an understanding of the vessel’s mechanical response that may be used within the contexts of various failure criteria and conditioning of the materials present. In addition to the strictly solid-loading approach, fluid-structure interaction (FSI) simulations can be used to include the wall-pressure perturbations induced by flow in more stenotic vessels. 2 With a sufficiently fine fluid mesh, wall-shear-stress may also be measured, allowing characterization of the mechanical signals relevant to the intimal endothelium. 3 While much has been learned from idealized cases, patient-specific analyses are important due to the compounding effects of highly irregular geometry, nonlinear materials, and variable pressure loading. It is hoped that the further development of such analyses will lead to a useful predictive capacity that can be employed in a clinical setting. Methods In this work, CT angiograms of the carotid vessels are segmented using in-house software such that the contours of vessel wall, calcification, lipids, and the vessel lumen may be obtained at intervals of 0.5mm from 20mm above and below the bifurcation. The smoothed