Vessel Wall Dynamics Research Articles

Multimodal Study of Murine Cardiovascular Remodeling: Four-Dimensional Ultrasound and Mass Spectrometry Imaging.

Cardiovascular disease (CVD) is the leading cause of death in the United States. Damage inthe cardiovascular system can be due to environmental exposure, trauma, drug toxicity, or numerous other factors.As a result, cardiac tissue and vasculature undergo structural changes and display diminished function. The damage and the resulting remodeling can be detected and quantified with ultrasound (US) imaging at the organ level and mass spectrometry imaging (MSI) at the molecular level. This manuscript describes an innovative methodology for studying murine cardiac pathophysiology, coupling in vivo four-dimensional (4D) ultrasound imaging and analysis with ex vivo matrix-assisted laser desorption/ionization (MADLI) MSI of the heart. 4D ultrasound can provide dynamic volumetric measurements, including radial displacement, surface area strain, and longitudinal strain throughout an entire cardiac cycle. In the vasculature, MSI and ultrasound are used to assess vessel wall compositions, hemodynamics, and vessel wall dynamics. The methodology can be tailored to study a myriad of CV diseases by adjusting functional metrics of interest and/or varying MALDI MSI protocol to target specific molecules. MALDI MSI can be used to study lipids, small metabolites, peptides, and glycans. This protocol outlines the use of MALDI MSI for untargeted lipidomic analysis and the use of ultrasound imaging for cardiovascular hemodynamics and biomechanics.

INVESTIGATION OF THE BLOOD FLOW IN DEFORMABLE VESSELS USING STABILIZED FINITE ELEMENT METHOD

The study and simulation of blood flow in the cardiovascular system have many applications such as pathologies studies, surgical planning, and design of medical devices. Several works within this area consider the problem using a rigid wall assumption, while blood velocity and pressure in large arteries are greatly influenced by vessel wall dynamics. The Coupled Momentum Method (CMM) is based on a strong coupling of degrees-of-freedom of the fluid and the solid domains. This coupling is made by considering that the deformation of the wall, in a variational level, become a boundary condition for the fluid domain. As an advantage, description of motion (Eulerian) may be kept the same and a fixed mesh. In this study, blood is considered a Newtonian fluid and the wall a thin-walled linear elastic. This work is focused on using fluid-structure interaction in 3D geometries to evaluate the blood and vessel dynamics in contrast to the rigid wall formulation what is considered only a fluid dynamic problem. For realistic and physiological parameters, CMM has demonstrated to be a good alternative for the simulation of blood flow in large arteries by virtue of representing more realistic phenomena than a rigid wall model. The results were obtained using FEniCS and Python, and are in agreement with the theoretical and numerical solutions from the literature.

High-Throughput Vascular Screening by ARTSENS Pen During a Medical Camp for Early-Stage Detection of Chronic Kidney Disease.

Intervention in the early stages of cardiovascular and kidney diseases is proven to be more effective in preventing disease progression. Large artery stiffness measurement can be a potential early predictor of future risks. The purpose of the study reported in this work was to demonstrate the feasibility of our ARTSENS® Pen device as a high-throughput vascular screening tool for risk assessment. The study was performed during a medical camp conducted for awareness and early-stage detection of kidney diseases. Screening procedures included biosample tests and blood pressure measurements. Alongside, various clinically relevant measures of the arterial stiffness were evaluated using the ARTSENS® Pen, by measuring vessel wall dynamics via our proprietary image-free ultrasound algorithms. Stiffness measurement from the left common carotid artery on 85 participants could be completed within 4 hours, employing two units of ARTSENS® Pen; this also includes time taken for all the procedures enlisted in the study protocol. The associations of carotid stiffness indices with age-, gender-, and risk factor-dependent variations were established.

Blood flow simulation during flow‐mediated dilation

AbstractEndothelial dysfunction is known to be the early stage of arteriosclerosis. The flow‐mediated dilation (FMD) test is the most commonly used method to diagnose the endothelial function. The test measures the maximum vasodilation (FMD response) on the brachial artery induced by the increases in blood flow after cuff deflation on the forearm. The vessel diameter must be captured clearly with the ultrasonic probe during the test. The vasodilation is induced in response to changes in the mechanical property of the vessel wall due to the blood flow stimulation. The changes are supposed to affect the pulsatile flow, but the influence of continuous behavior of vascular property on hemodynamics has not been clarified. In this study, in order to clarify the influence of the FMD response on hemodynamics, we propose a mathematical model that can simulate hemodynamics and vasomotor responses. As a result, it was shown that vessel wall dynamics affected the pulsatile flow. This result suggests that the endothelial function can be evaluated from blood flow.

A PSF-Shape-Based Beamforming Strategy for Robust 2D Motion Estimation in Ultrafast Data

This paper presents a framework for motion estimation in ultrafast ultrasound data. It describes a novel approach for determining the sampling grid for ultrafast data based on the system’s point-spread-function (PSF). As a consequence, the cross-correlation functions (CCF) used in the speckle tracking (ST) algorithm will have circular-shaped peaks, which can be interpolated using a 2D interpolation method to estimate subsample displacements. Carotid artery wall motion and parabolic blood flow simulations together with rotating disk experiments using a Verasonics Vantage 256 are used for performance evaluation. Zero-degree plane wave data were acquired using an ATL L5-12 (fc = 9 MHz) transducer for a range of pulse repetition frequencies (PRFs), resulting in 0–600 µm inter-frame displacements. The proposed methodology was compared to data beamformed on a conventionally spaced grid, combined with the commonly used 1D parabolic interpolation. The PSF-shape-based beamforming grid combined with 2D cubic interpolation showed the most accurate and stable performance with respect to the full range of inter-frame displacements, both for the assessment of blood flow and vessel wall dynamics. The proposed methodology can be used as a protocolled way to beamform ultrafast data and obtain accurate estimates of tissue motion.

Model evaluation-based approaches for endothelial function.

In order to develop an evaluation method for the endothelial function from blood flow information, a mathematical model and simulation technique that can simultaneously analyze hemodynamics and vessel wall dynamics were proposed. Experimental observations reveal that the proposed method adequately reproduced blood flow data. There was also confirmation that the method enables access of the internal state of the blood vessels, which is difficult to measure directly.

MR imaging of carotid webs.

We propose a magnetic resonance (MR) imaging protocol for the characterization of carotid web morphology, composition, and vessel wall dynamics. The purpose of this case series was to determine the feasibility of imaging carotid webs with MR imaging. Five patients diagnosed with carotid web on CT angiography were recruited to undergo a 30-min MR imaging session. MR angiography (MRA) images of the carotid artery bifurcation were acquired. Multi-contrast fast spin echo (FSE) images were acquired axially about the level of the carotid web. Two types of cardiac phase resolved sequences (cineFSE and cine phase contrast) were acquired to visualize the elasticity of the vessel wall affected by the web. Carotid webs were identified on MRA in 5/5 (100%) patients. Multi-contrast FSE revealed vessel wall thickening and cineFSE demonstrated regional changes in distensibility surrounding the webs in these patients. Our MR imaging protocol enables an in-depth evaluation of patients with carotid webs: morphology (by MRA), composition (by multi-contrast FSE), and wall dynamics (by cineFSE).

Arterial compliance probe for local blood pulse wave velocity measurement.

Arterial compliance and vessel wall dynamics are significant in vascular diagnosis. We present the design of arterial compliance probes for measurement of local pulse wave velocity (PWV). Two designs of compliance probe are discussed, viz (a) a magnetic plethysmograph (MPG) based probe, and (b) a photoplethysmograph (PPG) based probe. The ability of the local PWV probes to consistently capture carotid blood pulse waves is verified by in-vivo trials on few volunteers. The probes could reliably perform repeatable measurements of local PWV from carotid artery along small artery sections less than 20 mm. Further, correlation between the measured values of local PWV using probes and various measures of blood pressure (BP) was also investigated. The study indicates that such arterial compliance probes have strong potential in cuff less BP monitoring.

An innovative numerical approach to resolve the pulse wave velocity in a healthy thoracic aorta model

Aortic dissection and atherosclerosis are highly fatal diseases. The development of both diseases is closely associated with highly complex haemodynamics. Thus, in predicting the onset of cardiac disease, it is desirable to obtain a detailed understanding of the flowfield characteristics in the human cardiovascular circulatory system. Accordingly, in this study, a numerical model of a normal human thoracic aorta is constructed using the geometry information obtained from a phase-contrast magnetic resonance imaging (PC-MRI) technique. The interaction between the blood flow and the vessel wall dynamics is then investigated using a coupled fluid–structure interaction (FSI) analysis. The simulations focus specifically on the flowfield characteristics and pulse wave velocity (PWV) of the blood flow. Instead of using a conventional PC-MRI method to measure PWV, we present an innovative application of using the FSI approach to numerically resolve PWV for the assessment of wall compliance in a thoracic aorta model. The estimated PWV for a normal thoracic aorta agrees well with the results obtained via PC-MRI measurement. In addition, simulations which consider the FSI effect yield a lower predicted value of the wall shear stress at certain locations in the cardiac cycle than models which assume a rigid vessel wall. Consequently, the model provides a suitable basis for the future development of more sophisticated methods capable of performing the computer-aided analysis of aortic blood flows.

Simulation of blood flow in deformable vessels using subject-specific geometry and spatially varying wall properties

Simulation of blood flow using image-based models and computational fluid dynamics has found widespread application to quantifying hemodynamic factors relevant to the initiation and progression of cardiovascular diseases and for planning interventions. Methods for creating subject-specific geometric models from medical imaging data have improved substantially in the last decade but for many problems, still require significant user interaction. In addition, while fluid-structure interaction methods are being employed to model blood flow and vessel wall dynamics, tissue properties are often assumed to be uniform. In this paper, we propose a novel workflow for simulating blood flow using subject-specific geometry and spatially varying wall properties. The geometric model construction is based on 3D segmentation and geometric processing. Variable wall properties are assigned to the model based on combining centerline-based and surface-based methods. We finally demonstrate these new methods using an idealized cylindrical model and two subject-specific vascular models with thoracic and cerebral aneurysms.

Image-Based Modeling of Blood Flow and Vessel Wall Dynamics: Applications, Methods and Future Directions

The objective of our session at the 2008 International Bio-Fluid Symposium and Workshop was to review the state-of-the-art in image-based modeling of blood flow, and identify future directions. Here we summarize progress in the field of image-based modeling of blood flow and vessel wall dynamics from mid-2005 to early 2009. We first describe the tremendous progress made in the application of image-based modeling techniques to elucidate the role of hemodynamics in vascular pathophysiology, plan treatments for congenital and acquired diseases in individual patients, and design and evaluate endovascular devices. We then review the advances that have been made in improving the methodology for modeling blood flow and vessel wall dynamics in image-based models, and consider issues related to extracting hemodynamic parameters and verification and validation. Finally, the strengths and weaknesses of current work in image-based modeling and the opportunities and threats to the field are described. We believe that with a doubling of our efforts toward the clinical application of image-based modeling tools, the next few years could surpass the tremendous gains made in the last few.

Patient-specific modeling of cardiovascular mechanics.

Advances in numerical methods and three-dimensional imaging techniques have enabled the quantification of cardiovascular mechanics in subject-specific anatomic and physiologic models. Patient-specific models are being used to guide cell culture and animal experiments and test hypotheses related to the role of biomechanical factors in vascular diseases. Furthermore, biomechanical models based on noninvasive medical imaging could provide invaluable data on the in vivo service environment where cardiovascular devices are employed and on the effect of the devices on physiologic function. Finally, patient-specific modeling has enabled an entirely new application of cardiovascular mechanics, namely predicting outcomes of alternate therapeutic interventions for individual patients. We review methods to create anatomic and physiologic models, obtain properties, assign boundary conditions, and solve the equations governing blood flow and vessel wall dynamics. Applications of patient-specific models of cardiovascular mechanics are presented, followed by a discussion of the challenges and opportunities that lie ahead.

On Coupling a Lumped Parameter Heart Model and a Three-Dimensional Finite Element Aorta Model

Aortic flow and pressure result from the interactions between the heart and arterial system. In this work, we considered these interactions by utilizing a lumped parameter heart model as an inflow boundary condition for three-dimensional finite element simulations of aortic blood flow and vessel wall dynamics. The ventricular pressure-volume behavior of the lumped parameter heart model is approximated using a time varying elastance function scaled from a normalized elastance function. When the aortic valve is open, the coupled multidomain method is used to strongly couple the lumped parameter heart model and three-dimensional arterial models and compute ventricular volume, ventricular pressure, aortic flow, and aortic pressure. The shape of the velocity profiles of the inlet boundary and the outlet boundaries that experience retrograde flow are constrained to achieve a robust algorithm. When the aortic valve is closed, the inflow boundary condition is switched to a zero velocity Dirichlet condition. With this method, we obtain physiologically realistic aortic flow and pressure waveforms. We demonstrate this method in a patient-specific model of a normal human thoracic aorta under rest and exercise conditions and an aortic coarctation model under pre- and post-interventions.

Implantation of paclitaxel-eluting stent impairs the vascular compliance of arteries in porcine coronary stenting model

Background The impaired compliance of large and medium-sized muscular arteries has been shown to correlate with the risk of adverse cardiovascular events. We assessed coronary artery distensibility using simultaneous intracoronary ultrasound and pressure wire measurements in porcine coronary arteries after implantation of paclitaxel-eluting (PES) and bare metal stents (BMS) and compared this with the histopathology of the arterial wall injury. Methods PES and BMS were implanted into porcine left coronary arteries under general anesthesia. At 1-month follow-up (FUP) the endothelium-dependent and endothelium-independent vascular compliances were measured after intracoronary infusion of 10 −6 M acetylcholine for 2.5 min, and intracoronary bolus of 100 μg nitroglycerine, respectively. The arterial stiffness index, distensibility and reflexion index were calculated in stented arteries ( n = 25 PES and n = 25 BMS), and correlated with histopathologic and histomorphometric changes of the vessel wall. Results In spite of smaller neointimal area, the fibrin deposition, medial thickening, vascular wall inflammation scores and arterial remodeling index were elevated and endothelialization was impaired in arteries with PES. Arteries with PES exhibited significantly worse endothelium-dependent vascular compliance: the stiffness ( p < 0.001) and reflexion index ( p < 0.001) were significantly higher and the distensibility index ( p < 0.001) lower as compared with the arteries with BMS. The endothelium-independent vascular reaction was similarly impaired in arteries with PES, as the stiffness index ( p < 0.001) and the distensibility index ( p < 0.001) differed significantly between the PES and BMS groups. Incomplete endothelialization ( r = 0.617, p < 0.001) was significantly associated with the endothelium-dependent increased vascular stiffness. The increased fibrin score ( r = 0.646, p < 0.001), vessel wall inflammation ( r = 0.657, p < 0.001) and medial thickening ( r = 0.672, p < 0.001) correlated significantly with the endothelium-independent stiffness index. Conclusions Implantation of PES impairs the coronary artery wall structure and the endothelium-dependent and independent vessel wall dynamics more than does the implantation of BMS.

On the stability of the coupling of 3D and 1D fluid-structure interaction models for blood flow simulations

We consider the coupling between three-dimensional (3D) and one-dimensional (1D) fluid-structure interaction (FSI) models describing blood flow inside compliant vessels. The 1D model is a hyperbolic system of partial differential equations. The 3D model consists of the Navier-Stokes equations for incompressible Newtonian fluids coupled with a model for the vessel wall dynamics. A non standard formulation for the Navier-Stokes equations is adopted to have suitable boundary conditions for the coupling of the models. With this we derive an energy estimate for the fully 3D-1D FSI coupling. We consider several possible models for the mechanics of the vessel wall in the 3D problem and show how the 3D-1D coupling depends on them. Several comparative numerical tests illustrating the coupling are presented.

On Causes

But let us inquire what are the causes of these things which happened to them. — Hippocrates 1 The idea of risk factors for vascular disease has evolved from a dichotomous to continuous hazard analysis and from the consideration of a few factors to mechanistic investigation of many interrelated risks. However, confusion still abounds regarding issues of association and causation. Originally, the simple presence of tobacco abuse, hypertension, and/or hypercholesterolemia were tallied, and the cumulative score was predictive of subsequent coronary artery disease.2 Since then, dose responses have been defined for these and other factors and it has been suggested that almost 300 factors place patients at risk; these factors include elevations in plasma homocysteine. Recent studies shed interesting light on the mechanism of this potentially causal relationship, which was first noted in 1969.3 Aside from putative effects on vessel wall dynamics, there is now direct evidence that homocysteine is atherogenic. Twenty-fold increases in plasma homocysteine achieved by dietary manipulation of apoE–/– mice increased aortic root lesion size 2-fold and produced a prolonged chronic inflammatory mural response accompanied by elevations in vascular cell adhesion molecule-1 and tumor necrosis factor-α.4 In long term follow-up, homocysteine levels elevated by dietary supplementation with methionine or homocysteine promoted lesion size and plaque fibrosis in these atherosclerosis-prone mice early in life, but without influencing ultimate plaque burden as the animals aged.5 A number of mechanisms were proposed by which homocysteine achieved this effect, including promotion of inflammation, regulation of lipoprotein metabolism, and modification of critical biochemical pathways and metabolites including nitric oxide (NO).6 See p 2569 In the present issue of Circulation , Stuhlinger et al7 advance these mechanistic insights one critical step further by defining homocystine’s effects at an enzymatic level. The group led by Lentz published …

An integrated system for the non-invasive assessment of vessel wall and hemodynamic properties of large arteries by means of ultrasound

Objectives: To integrate methods for non-invasive assessment of vessel wall properties (diastolic diameter, distension waveform and intima-media thickness) and hemodynamic properties (blood flow velocity and shear rate distribution) of large arteries by means of dedicated ultrasound signal processing. Methods: we have developed an arterial laboratory (ART-lab) system. ART-lab consists of software running on a standard personal computer, equipped with a data acquisition card for the acquisition of radio frequency (RF) ultrasound signals obtained with a conventional echo scanner. It operates either (1) off-line or (2) in real-time. Real-time operation is restricted to the assessment of vessel wall properties because of limitations in computational power. Results: This paper provides an overview of ART-lab ultrasound radio frequency data acquisition and dedicated RF-signal processing methods. The capabilities of the system are illustrated with some typical applications. Conclusions: ART-lab in real-time mode is a useful tool for monitoring arterial vessel wall dynamics, while off-line it can be employed to investigate the elastic vessel wall properties in combination with hemodynamics, such as blood flow velocity and shear rate distribution.

Effect of hypertonic saline on vascular responses to angiotensin II in pregnancy

Refractoriness to infused angiotensin II is characteristic or normal human and ovine pregnancy; the mechanisms responsible are unclear. In this study, we sought to ascertain in gravid sheep whether hypertonic saline solution alters the vascular responses to angiotensin II, as in gravid women, and to compare the responses of the systemic and uteroplacental vasculature. Dose-response curves were determined. Mean arterial pressure and systemic vascular resistance increased in a dose-dependent fashion before and after hypertonic saline solution; responses were greater after hypertonic saline solution (p < 0.01). Responses of cardiac output, heart rate, uterine vascular resistance, and uterine blood flow also were dose-dependent, but were unchanged after hypertonic saline solution. Plasma renin activity fell 45% after hypertonic saline solution. Treatment with hypertonic saline solution results in increased pressor responses to angiotensin II that are not a reflection of altered baroreceptor or chemoreceptor reflexes or of the response in the uteroplacental vascular bed. Rather, the increased systemic vascular responsiveness to angiotensin II after hypertonic saline solution appears to be a reflection of other mechanisms, such as alterations in vessel wall dynamics or receptor affinity.

Department of Surgery, Bristol Royal Infirmary, U.K.

Recent developments in ultrasound techniques have made it possible to investigate patients with arterial disease non-invasively by using Doppler blood velocity signal analysis. Since January 1979, 189 patients were pre-stroke syndromes have been investigated by using pulsed Doppler and real-time B-mode ultrasound imaging and waveform analysis. The results were that both imaging systems were highly (more than 92%) sensitive and specific when compared with conventional carotid arteriography. The ultrasound systems detected turbulence and could also be used to measure the distensibility of the arterial wall. The results show that varying grades of carotid stenosis can be demonstrated by two ultrasonic imaging systems, and that lateral scans are particularly helpful.