Sensitivity analysis of closed-loop one-chamber and four-chamber models with baroreflex.

The baroreflex is one of the most important control mechanisms in the human cardiovascular system. This work utilises a closed-loop in silico model of baroreflex regulation, coupled to pulsatile mechanical models with (i) one heart chamber and 36-parameters and (ii) four chambers and 51 parameters. We perform the first global sensitivity analysis of these closed-loop systems which considers both cardiovascular and baroreflex parameters, and compare the models with their respective unregulated equivalents.

Correction: Integrating particle tracking with computational fluid dynamics to assess haemodynamic perturbation by coronary artery stents.

[This corrects the article DOI: 10.1371/journal.pone.

Computational fluid dynamics and shape analysis enhance aneurysm rupture risk stratification.

Purpose: Accurately quantifying the rupture risk of unruptured intracranial aneurysms (UIAs) is crucial for guiding treatment decisions and remains an unmet clinical challenge. Computational Flow Dynamics and morphological measurements have been shown to differ between ruptured and unruptured aneurysms. It is not clear if these provide any additional information above routinely available clinical observations or not.

Computational modelling of cardiovascular pathophysiology to risk stratify commercial spaceflight.

For more than 60 years, humans have travelled into space. Until now, the majority of astronauts have been professional, government agency astronauts selected, in part, for their superlative physical fitness and the absence of disease. Commercial spaceflight is now becoming accessible to members of the public, many of whom would previously have been excluded owing to unsatisfactory fitness or the presence of cardiorespiratory diseases.

Evaluation of models of sequestration flow in coronary arteries-Physiology versus anatomy?

Background: Myocardial ischaemia results from insufficient coronary blood flow. Computed virtual fractional flow reserve (vFFR) allows quantification of proportional flow loss without the need for invasive pressure-wire testing. In the current study, we describe a novel, conductivity model of side branch flow, referred to as 'leak'.

Rapid virtual fractional flow reserve using 3D computational fluid dynamics.

Aims: Over the last ten years, virtual Fractional Flow Reserve (vFFR) has improved the utility of Fractional Flow Reserve (FFR), a globally recommended assessment to guide coronary interventions. Although the speed of vFFR computation has accelerated, techniques utilising full 3D computational fluid dynamics (CFD) solutions rather than simplified analytical solutions still require significant time to compute.

Methods And Results: This study investigated the speed, accuracy and cost of a novel 3D-CFD software method based upon a graphic processing unit (GPU) computation, compared with the existing fastest central processing unit (CPU)-based 3D-CFD technique, on 40 angiographic cases.

Sex differences in coronary microvascular resistance measured by a computational fluid dynamics model.

Background: Increased coronary microvascular resistance (CMVR) is associated with coronary microvascular dysfunction (CMD). Although CMD is more common in women, sex-specific differences in CMVR have not been demonstrated previously.

Aim: To compare CMVR between men and women being investigated for chest pain.

A multiscale computational framework to evaluate flow alterations during mechanical thrombectomy for treatment of ischaemic stroke.

The treatment of ischaemic stroke increasingly relies upon endovascular procedures known as mechanical thrombectomy (MT), which consists in capturing and removing the clot with a catheter-guided stent while at the same time applying external aspiration with the aim of reducing haemodynamic loads during retrieval. However, uniform consensus on procedural parameters such as the use of balloon guide catheters (BGC) to provide proximal flow control, or the position of the aspiration catheter is still lacking. Ultimately the decision is left to the clinician performing the operation, and it is difficult to predict how these treatment options might influence clinical outcome.

In Vitro Modelling for Bulging Sinus Effects of an Expanded Polytetrafluoroethylene Valved Conduit Based on High-Speed 3D Leaflet Evaluation.

The study aimed to develop a pulmonary circulatory system capable of high-speed 3D reconstruction of valve leaflets to elucidate the local hemodynamic characteristics in the valved conduits with bulging sinuses. Then a simultaneous measurement system for leaflet structure and pressure and flow characteristics was designed to obtain valve leaflet dynamic behaviour with different conduit structures. An image preprocessing method was established to obtain the three leaflets behaviour simultaneously for one sequence with two leaflets images from each pair of three high-speed cameras.

Integrating particle tracking with computational fluid dynamics to assess haemodynamic perturbation by coronary artery stents.

Aims: Coronary artery stents have profound effects on arterial function by altering fluid flow mass transport and wall shear stress. We developed a new integrated methodology to analyse the effects of stents on mass transport and shear stress to inform the design of haemodynamically-favourable stents.

Methods And Results: Stents were deployed in model vessels followed by tracking of fluorescent particles under flow.

The Complementary Value of Absolute Coronary Flow in the Assessment of Patients with Ischaemic Heart Disease (the COMPAC-Flow Study).

Fractional flow reserve (FFR) is the current gold-standard invasive assessment of coronary artery disease (CAD). FFR reports coronary blood flow (CBF) as a fraction of a hypothetical and unknown normal value. Although used routinely to diagnose CAD and guide treatment, how accurately FFR predicts actual CBF changes remains unknown.

Determining Clinically-Viable Biomarkers for Ischaemic Stroke Through a Mechanistic and Machine Learning Approach.

Assessment of distal cerebral perfusion after ischaemic stroke is currently only possible through expensive and time-consuming imaging procedures which require the injection of a contrast medium. Alternative approaches that could indicate earlier the impact of blood flow occlusion on distal cerebral perfusion are currently lacking. The aim of this study was to identify novel biomarkers suitable for clinical implementation using less invasive diagnostic techniques such as Transcranial Doppler (TCD).

The importance of three dimensional coronary artery reconstruction accuracy when computing virtual fractional flow reserve from invasive angiography.

Three dimensional (3D) coronary anatomy, reconstructed from coronary angiography (CA), is now being used as the basis to compute 'virtual' fractional flow reserve (vFFR), and thereby guide treatment decisions in patients with coronary artery disease (CAD). Reconstruction accuracy is therefore important. Yet the methods required remain poorly validated.

Operator-dependent variability of angiography-derived fractional flow reserve and the implications for treatment.

Aims: To extend the benefits of physiologically guided percutaneous coronary intervention to many more patients, angiography-derived, or 'virtual' fractional flow reserve (vFFR) has been developed, in which FFR is computed, based upon the images, instead of being measured invasively. The effect of operator experience with these methods upon vFFR accuracy remains unknown. We investigated variability in vFFR results based upon operator experience with image-based computational modelling techniques.

Modeling Approach for An Aortic Dissection with Endovascular Stenting.

Repair of dissected aorta requires remodeling the structure of the media. Modeling approaches specific to endovascular stenting for aortic dissection have been reported. We created a goat model of descending thoracic aortic dissection and reproduced its morphological characteristics in a mock circulatory system.

A novel method for measuring absolute coronary blood flow and microvascular resistance in patients with ischaemic heart disease.

Aims: Ischaemic heart disease is the reduction of myocardial blood flow, caused by epicardial and/or microvascular disease. Both are common and prognostically important conditions, with distinct guideline-indicated management. Fractional flow reserve (FFR) is the current gold-standard assessment of epicardial coronary disease but is only a surrogate of flow and only predicts percentage flow changes.

Subject-specific simulation for non-invasive assessment of aortic coarctation: Towards a translational approach.

We present a multi-scale CFD-based study conducted in a cohort of 11 patients with coarctation of the aorta (CoA). The study explores the potential for implementation of a workflow using non-invasive routinely collected medical imaging data and clinical measurements to provide a more detailed insight into local aortic haemodynamics in order to support clinical decision making. Our approach is multi-scale, using a reduced-order model (1D/0D) and an optimization process for the personalization of patient-specific boundary conditions and aortic vessel wall parameters from non-invasive measurements, to inform a more complex model (3D/0D) representing 3D aortic patient-specific anatomy.

Measurement of in vitro cardiac deformation by means of 3D digital image correlation and ultrasound 2D speckle-tracking echocardiography.

Ultrasound-based 2D speckle-tracking echocardiography (US-2D-STE) is increasingly used to assess the functionality of the heart. In particular, the analysis of cardiac strain plays an important role in the identification of several cardiovascular diseases. However, this imaging technique presents some limitations associated with its operating principle that result in low accuracy and reproducibility of the measurement.

A complex flow phantom for medical imaging: ring vortex phantom design and technical specification.

Cardiovascular fluid dynamics exhibit complex flow patterns, such as recirculation and vortices. Quantitative analysis of these complexities supports diagnosis, leading to early prediction of pathologies. Quality assurance of technologies that image such flows is challenging but essential, and to this end, a novel, cost-effective, portable, complex flow phantom is proposed and the design specifications are provided.

Full-field analysis of epicardial strain in an in vitro porcine heart platform.

The quantitative assessment of cardiac strain is increasingly performed to provide valuable insights on heart function. Currently, the most frequently used technique in the clinic is ultrasound-based speckle tracking echocardiography (STE). However, verification and validation of this modality are still under investigation and further reference measurements are required to support this activity.

Computer model for the cardiovascular system: development of an e-learning tool for teaching of medical students.

Background: This study combined themes in cardiovascular modelling, clinical cardiology and e-learning to create an on-line environment that would assist undergraduate medical students in understanding key physiological and pathophysiological processes in the cardiovascular system.

Methods: An interactive on-line environment was developed incorporating a lumped-parameter mathematical model of the human cardiovascular system. The model outputs were used to characterise the progression of key disease processes and allowed students to classify disease severity with the aim of improving their understanding of abnormal physiology in a clinical context.

Computational fluid dynamics modelling in cardiovascular medicine.

This paper reviews the methods, benefits and challenges associated with the adoption and translation of computational fluid dynamics (CFD) modelling within cardiovascular medicine. CFD, a specialist area of mathematics and a branch of fluid mechanics, is used routinely in a diverse range of safety-critical engineering systems, which increasingly is being applied to the cardiovascular system. By facilitating rapid, economical, low-risk prototyping, CFD modelling has already revolutionised research and development of devices such as stents, valve prostheses, and ventricular assist devices.

Measurement of in vitro and in vivo stent geometry and deformation by means of 3D imaging and stereo-photogrammetry.

Purpose: To quantify variability of in vitro and in vivo measurement of 3D device geometry using 3D and biplanar imaging.

Methods: Comparison of stent reconstruction is reported for in vitro coronary stent deployment (using micro-CT and optical stereo-photogrammetry) and in vivo pulmonary valve stent deformation (using 4DCT and biplanar fluoroscopy). Coronary stent strut length and inter-strut angle were compared in the fully deployed configuration.

From histology and imaging data to models for in-stent restenosis.

The implantation of stents has been used to treat coronary artery stenosis for several decades. Although stenting is successful in restoring the vessel lumen and is a minimally invasive approach, the long-term outcomes are often compromised by in-stent restenosis (ISR). Animal models have provided insights into the pathophysiology of ISR and are widely used to evaluate candidate drug inhibitors of ISR.

Uncertainty assessment of imaging techniques for the 3D reconstruction of stent geometry.

This paper presents a quantitative assessment of uncertainty for the 3D reconstruction of stents. This study investigates a CP stent (Numed, USA) used in congenital heart disease applications with a focus on the variance in measurements of stent geometry. The stent was mounted on a model of patient implantation site geometry, reconstructed from magnetic resonance images, and imaged using micro-computed tomography (CT), conventional CT, biplane fluoroscopy and optical stereo-photogrammetry.