Transport of nitrite from large arteries modulates regional blood flow during stress and exercise

Background: Acute cardiovascular stress increases systemic wall shear stress (WSS)–a frictional force exerted by the flow of blood on vessel walls–which raises plasma nitrite concentration due to enhanced endothelial nitric oxide synthase (eNOS) activity. Upstream eNOS inhibition modulates distal perfusion, and autonomic stress increases both the consumption and vasodilatory effects of endogenous nitrite. Plasma nitrite maintains vascular homeostasis during exercise and disruption of nitrite bioavailability can lead to intermittent claudication. Hypothesis: During acute cardiovascular stress or strenuous exercise, we hypothesize enhanced production of nitric oxide (NO) by vascular endothelial cells raises nitrite concentrations in near-wall layers of flowing blood, resulting in cumulative NO concentrations in downstream arterioles sufficient for vasodilation. Confirmation and implications: Utilizing a multiscale model of nitrite transport in bifurcating arteries, we tested the hypothesis for femoral artery flow under resting and exercised states of cardiovascular stress. Results indicate intravascular transport of nitrite from upstream endothelium could result in vasodilator-active levels of nitrite in downstream resistance vessels. The hypothesis could be confirmed utilizing artery-on-a-chip technology to measure NO production rates directly and help validate numerical model predictions. Further characterization of this mechanism may improve our understanding of symptomatic peripheral artery occlusive disease and exercise physiology

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

A two-scale approach for CFD modeling of endovascular Chemofilter device

Two-scale CFD modeling is used to design and optimize a novel endovascular filtration device for removing toxins from flowing blood. The Chemofilter is temporarily deployed in the venous side of a tumor during the intra-arterial chemotherapy in order to filter excessive chemotherapy drugs such as Doxorubicin from the blood stream. The device chemically binds selective drugs to its surface thus filtering them from blood, after they have had the effect on the tumor and before they reach the heart and other organs. The Chemofilter consists of a porous membrane made of microscale architected materials and is installed on a structure similar to an embolic protection device. Simulations resolving the microscale structure of the device were carried out to determine the permeability of the microcell membrane. The resulting permeability coefficients were then used for macroscale simulations of the flow through the device modeled as a porous material. The microscale simulations indicate that greater number of microcell layers and smaller microcell size result in increased pressure drop across the membrane, while providing larger surface area for drug binding. In the macroscale simulations, the study of idealized prototypes show that the pressure drop can be reduced by increasing the membrane's tip angle and by decreasing the number of membrane's sectors. Such design, however, can conversely affect the overall drug binding. By decreasing the concentration of toxins in the cardiovascular system, the drug dosage can be increased while side effects are reduced, thus improving the effectiveness of treatment

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

Towards Reconstructing Blood Velocity Profiles from Noisy and Sparse Time Resolved Phase Contrast Magnetic Resonance Flow Data

Abstract: Proper orthogonal decomposition (POD) is applied to reconstruct noisy data of blood flow in a carotid artery. In order to show the effectiveness of the method, we applied this method on data obtained by computational fluid dynamics (CFD). The geometry used for this study was generated based on patient specific phase contrast magnetic resonance imaging (PC-MRI) technique. A Gaussian noise was added to a set of CFD data with slightly different boundary condition (BC) than BCs were used to generate the POD, in order to take into account the uncertainty of readying boundary condition from PC-MRI. The results show good agreement with the original CFD data. This method can potentially be developed as a service for PC-MRI providers to generate noise free PCI-MRI images and ultimately can help with further patient specific studies which are based on in vivo velocity profiles. Pressure difference calculations and wall shear stress (WSS) are just two out of many potential outputs of this study

Giant intracranial aneurysms: evolution of management in a contemporary surgical series

BACKGROUND: Many significant microsurgical series of patients with giant aneurysms predate changes in practice during the endovascular era. OBJECTIVE: A contemporary surgical experience is presented to examine changes in management relative to earlier reports, to establish the role of open microsurgery in the management strategy, and to quantify results for comparison with evolving endovascular therapies. METHODS: During a 13-year period, 140 patients with 141 giant aneurysms were treated surgically. One hundred aneurysms (71%) were located in the anterior circulation, and 41 aneurysms were located in the posterior circulation. RESULTS: One hundred eight aneurysms (77%) were completely occluded, 14 aneurysms (10%) had minimal residual aneurysm, and 16 aneurysms (11%) were incompletely occluded with reversed or diminished flow. Three patients with calcified aneurysms were coiled after unsuccessful clipping attempts. Eighteen patients died in the perioperative period (surgical mortality, 13%). Bypass-related complications resulted from bypass occlusion (7 patients), aneurysm hemorrhage due to incomplete aneurysm occlusion (4 patients), or aneurysm thrombosis with perforator or branch artery occlusion (4 patients). Thirteen patients were worse at late follow-up (permanent neurological morbidity, 9%; mean length of follow-up, 23 ± 1.9 months). Overall, good outcomes (Glasgow Outcome Score 5 or 4) were observed in 114 patients (81%), and 109 patients (78%) were improved or unchanged after therapy. CONCLUSION: A heavy reliance on bypass techniques plus indirect giant aneurysm occlusion distinguishes this contemporary surgical experience from earlier ones, and obviates the need for hypothermic circulatory arrest. Experienced neurosurgeons can achieve excellent results with surgery as the first-line management approach and endovascular techniques as adjuncts to surgery

Computational Fluid Dynamics modeling of contrast transport in basilar aneurysms following flow-altering surgeries.

In vivo measurement of blood velocity fields and flow descriptors remains challenging due to image artifacts and limited resolution of current imaging methods; however, in vivo imaging data can be used to inform and validate patient-specific computational fluid dynamics (CFD) models. Image-based CFD can be particularly useful for planning surgical interventions in complicated cases such as fusiform aneurysms of the basilar artery, where it is crucial to alter pathological hemodynamics while preserving flow to the distal vasculature. In this study, patient-specific CFD modeling was conducted for two basilar aneurysm patients considered for surgical treatment. In addition to velocity fields, transport of contrast agent was simulated for the preoperative and postoperative conditions using two approaches. The transport of a virtual contrast passively following the flow streamlines was simulated to predict post-surgical flow regions prone to thrombus deposition. In addition, the transport of a mixture of blood with an iodine-based contrast agent was modeled to compare and verify the CFD results with X-ray angiograms. The CFD-predicted patterns of contrast flow were qualitatively compared to in vivo X-ray angiograms acquired before and after the intervention. The results suggest that the mixture modeling approach, accounting for the flow rates and properties of the contrast injection, is in better agreement with the X-ray angiography data. The virtual contrast modeling assessed the residence time based on flow patterns unaffected by the injection procedure, which makes the virtual contrast modeling approach better suited for prediction of thrombus deposition, which is not limited to the peri-procedural state

Numerical simulation of pre- and postsurgical flow in a giant basilar aneurysm

Computational modeling of the flow in cerebral aneurysms is an evolving technique that may play an important role in surgical planning. In this study, we simulated the flow in a giant basilar aneurysm before and after surgical takedown of one vertebral artery. Patient-specific geometry and flowrates obtained from magnetic resonance (MR) angiography and velocimetry were used to simulate the flow prior to and after the surgery. Numerical solutions for steady and pulsatile flows were obtained. Highly three-dimensional flows, with strong secondary flows, were computed in the aneurysm in the presurgical and postsurgical conditions. The computational results predicted that occlusion of a vertebral artery would result in a significant increase of the slow flow region formed in the bulge of the aneurysm, where increased particle residence time and velocities lower than 2.5 cm/s were computed. The region of slow flow was found to have filled with thrombus following surgery. Predictions of numerical simulation methods are consistent with the observed outcome following surgical treatment of an aneurysm. The study demonstrates that computational models may provide hypotheses to test in future studies, and might offer guidance for the interventional treatment of cerebral aneurysms. Copyright © 2008 by ASME

Computational Fluid Dynamics modeling of contrast transport in basilar aneurysms following flow-altering surgeries

In vivo measurement of blood velocity fields and flow descriptors remains challenging due to image artifacts and limited resolution of current imaging methods; however, in vivo imaging data can be used to inform and validate patient-specific computational fluid dynamics (CFD) models. Image-based CFD can be particularly useful for planning surgical interventions in complicated cases such as fusiform aneurysms of the basilar artery, where it is crucial to alter pathological hemodynamics while preserving flow to the distal vasculature. In this study, patient-specific CFD modeling was conducted for two basilar aneurysm patients considered for surgical treatment. In addition to velocity fields, transport of contrast agent was simulated for the preoperative and postoperative conditions using two approaches. The transport of a virtual contrast passively following the flow streamlines was simulated to predict post-surgical flow regions prone to thrombus deposition. In addition, the transport of a mixture of blood with an iodine-based contrast agent was modeled to compare and verify the CFD results with X-ray angiograms. The CFD-predicted patterns of contrast flow were qualitatively compared to in vivo X-ray angiograms acquired before and after the intervention. The results suggest that the mixture modeling approach, accounting for the flow rates and properties of the contrast injection, is in better agreement with the X-ray angiography data. The virtual contrast modeling assessed the residence time based on flow patterns unaffected by the injection procedure, which makes the virtual contrast modeling approach better suited for prediction of thrombus deposition, which is not limited to the peri-procedural state