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. While data exist on the effects of gravitational and acceleration (G) forces on human physiology, data on the effects of the aerospace environment in unselected members of the public, and particularly in those with clinically significant pathology, are limited. Although short in duration, these high acceleration forces can potentially either impair the experience or, more seriously, pose a risk to health in some individuals. Rather than expose individuals with existing pathology to G forces to collect data, computational modelling might be useful to predict the nature and severity of cardiovascular diseases that are of sufficient risk to restrict access, require modification, or suggest further investigation or training before flight. In this Review, we explore state-of-the-art, zero-dimensional, compartmentalized models of human cardiovascular pathophysiology that can be used to simulate the effects of acceleration forces, homeostatic regulation and ventilation-perfusion matching, using data generated by long-arm centrifuge facilities of the US National Aeronautics and Space Administration and the European Space Agency to risk stratify individuals and help to improve safety in commercial suborbital spaceflight.

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'. This leak model is a function of taper and local pressure, the latter of which may change radically when focal disease is present. This builds upon previous techniques, which either ignore side branch flow, or rely purely on anatomical factors. This study aimed to describe a new, conductivity model of side branch flow and compare this with established anatomical models. METHODS AND RESULTS: The novel technique was used to quantify vFFR, distal absolute flow (Qd) and microvascular resistance (CMVR) in 325 idealised 1D models of coronary arteries, modelled from invasive clinical data. Outputs were compared to an established anatomical model of flow. The conductivity model correlated and agreed with the reference model for vFFR (r = 0.895, p < 0.0001; ＋0.02, 95% CI 0.00 to ＋ 0.22), Qd (r = 0.959, p < 0.0001; -5.2 mL/min, 95% CI -52.2 to ＋13.0) and CMVR (r = 0.624, p < 0.0001; ＋50 Woods Units, 95% CI -325 to ＋2549). CONCLUSION: Agreement between the two techniques was closest for vFFR, with greater proportional differences seen for Qd and CMVR. The conductivity function assumes vessel taper was optimised for the healthy state and that CMVR was not affected by local disease. The latter may be addressed with further refinement of the technique or inferred from complementary image data. The conductivity technique may represent a refinement of current techniques for modelling coronary side-branch flow. Further work is needed to validate the technique against invasive clinical data.

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. The novel GPU simulation was significantly faster than the CPU method (median 31.7 s (Interquartile Range (IQR) 24.0-44.4s) vs. 607.5 s (490-964 s), P < 0.0001). The novel GPU technique was 99.6% (IQR 99.3-99.9) accurate relative to the CPU method. The initial cost of the GPU hardware was greater than the CPU (£4080 vs. £2876), but the median energy consumption per case was significantly less using the GPU method (8.44 (6.80-13.39) Wh vs. 2.60 (2.16-3.12) Wh, P < 0.0001). Conclusion: This study demonstrates that vFFR can be computed using 3D-CFD with up to 28-fold acceleration than previous techniques with no clinically significant sacrifice in accuracy.

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. Methods and results: We used a computational fluid dynamics (CFD) model of human coronary physiology to calculate absolute CMVR based on invasive coronary angiographic images and pressures in 203 coronary arteries from 144 individual patients. CMVR was significantly higher in women than men (860 [650-1,205] vs. 680 [520-865] WU, Z = -2.24, p = 0.025). None of the other major subgroup comparisons yielded any differences in CMVR. Conclusion: CMVR was significantly higher in women compared with men. These sex-specific differences may help to explain the increased prevalence of CMD in women.

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 this study we present a multiscale computational framework to simulate MT procedures. The developed framework can provide quantitative assessment of clinically relevant quantities such as flow in the retrieval path and can be used to find the optimal procedural parameters that are most likely to result in a favorable clinical outcome. The results show the advantage of using BGC during MT and indicate small differences between positioning the aspiration catheter in proximal or distal locations. The framework has significant potential for future expansions and applications to other surgical treatments.

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. Firstly, the multi-digital image correlation analyses were performed, and then the valve leaflet structure was measured under the static condition with fixed opening angles in the water-filled visualization chamber and the pulsatile flow tests simulating paediatric pulmonary flow conditions in the different types of conduit structures; with or without bulging sinuses. The results showed the maximum 3D reconstruction error to be around 0.06 mm. In the steady flow test, the evaluation of opening angles under the different flow rates conditions was achieved. In the pulsatile flow test, each leaflet's opening and closing behaviours were successfully reconstructed simultaneously at the high-frequency recording rate of 960fps. Therefore, the system developed in this study confirms the design evaluation method of an ePTFE valved conduit behaviour with leaflet structures interacting with local fluid dynamics in the vicinity of valves. Clinical Relevance- The system reveals the bulging sinus effects on ePTFE valve leaflet motion by the 3D reconstruction using multi-camera high-speed sequential imaging in vitro.

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. Here we compared fractional CBF with the absolute CBF (aCBF in mL/min), measured with a computational method during standard angiography and pressure-wire assessment, on 203 diseased arteries (143 patients). We found a substantial correlation between the two measurements (r 0.89, Cohen's Kappa 0.71). Concordance between fractional and absolute CBF reduction was high when FFR was >0.80 (91%), but reduced when FFR was ≤0.80 (81%), 0.70-0.80 (68%) and, particularly 0.75-0.80 (62%). Discordance was associated with coronary microvascular resistance, vessel diameter and mass of myocardium subtended, all factors to which FFR is agnostic. Assessment of aCBF complements FFR, and may be valuable to assess CBF, particularly in cases within the FFR 'grey-zone'.

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. Parallel analyses involved high-resolution micro-computed tomography scanning followed by computational fluid dynamics simulations to assess wall shear stress distribution. Several stent designs were analysed to assess whether the workflow was robust for diverse strut geometries. Stents had striking effects on fluid flow streamlines, flow separation or funnelling, and the accumulation of particles at areas of complex geometry that were tightly coupled to stent shape. CFD analysis revealed that stents had a major influence on wall shear stress magnitude, direction and distribution and this was highly sensitive to geometry. CONCLUSIONS: Integration of particle tracking with CFD allows assessment of fluid flow and shear stress in stented arteries in unprecedented detail. Deleterious flow perturbations, such as accumulation of particles at struts and non-physiological shear stress, were highly sensitive to individual stent geometry. Novel designs for stents should be tested for mass transport and shear stress which are important effectors of vascular health and repair.

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). We used 1D modelling to simulate pre- and post-stroke velocity and flow wave propagation in a typical arterial network, and Sobol's sensitivity analysis, supported by the use of Gaussian process emulators, to identify biomarkers linked to cerebral perfusion. We showed that values of pulsatility index of the right anterior cerebral artery > 1.6 are associated with poor perfusion and may require immediate intervention. Three additional biomarkers with similar behaviour, all related to pulsatility indices, were identified. These results suggest that flow pulsatility measured at specific locations could be used to effectively estimate distal cerebral perfusion rates, and ultimately improve clinical diagnosis and management of ischaemic stroke.

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. Furthermore, the magnitude of vFFR error arising from reconstruction is unkown. We aimed to validate a method for 3D CA reconstruction and determine the effect this had upon the accuracy of vFFR. Clinically realistic coronary phantom models were created comprosing seven standard stenoses in aluminium and 15 patient-based 3D-printed, imaged with CA, three times, according to standard clinical protocols, yielding 66 datasets. Each was reconstructed using epipolar line projection and intersection. All reconstructions were compared against the real phantom models in terms of minimal lumen diameter, centreline and surface similarity. 3D-printed reconstructions (n = 45) and the reference files from which they were printed underwent vFFR computation, and the results were compared. The average error in reconstructing minimum lumen diameter (MLD) was 0.05 (± 0.03 mm) which was < 1% (95% CI 0.13-1.61%) compared with caliper measurement. Overall surface similarity was excellent (Hausdorff distance 0.65 mm). Errors in 3D CA reconstruction accounted for an error in vFFR of ± 0.06 (Bland Altman 95% limits of agreement). Errors arising from the epipolar line projection method used to reconstruct 3D coronary anatomy from CA are small but contribute to clinically relevant errors when used to compute vFFR.

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. METHODS AND RESULTS: Virtual fractional flow reserve was computed using a proprietary method (VIRTUheart) from the invasive angiograms of patients with coronary artery disease. Each case was processed by an expert (>100 vFFR cases) and a non-expert (<20 vFFR cases) operator and results were compared. The primary outcome was the variability in vFFR between experts and non-experts and the impact this had upon treatment strategy (PCI vs. conservative management). Two hundred and thirty-one vessels (199 patients) were processed. Mean non-expert and expert vFFRs were similar overall [0.76 (0.13) and 0.77 (0.16)] but there was significant variability between individual results (variability coefficient 12%, intraclass correlation coefficient 0.58), with only moderate agreement (κ = 0.46), and this led to a statistically significant change in management strategy in 27% of cases. Variability was significantly lower, and agreement higher, for expert operators; a change in their recommended management occurred in 10% of repeated expert measurements and 14% of inter-expert measurements. CONCLUSION: Virtual fractional flow reserve results are influenced by operator experience of vFFR processing. This had implications for treatment allocation. These results highlight the importance of training and quality assurance to ensure reliable, repeatable vFFR results.

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. It cannot assess absolute (volumetric) flow or microvascular disease. The aim of this study was to develop and validate a novel method that predicts absolute coronary blood flow and microvascular resistance (MVR) in the catheter laboratory. METHODS AND RESULTS: A computational fluid dynamics (CFD) model was used to predict absolute coronary flow (QCFD) and coronary MVR using data from routine invasive angiography and pressure-wire assessment. QCFD was validated in an in vitro flow circuit which incorporated patient-specific, three-dimensional printed coronary arteries; and then in vivo, in patients with coronary disease. In vitro, QCFD agreed closely with the experimental flow over all flow rates [bias +2.08 mL/min; 95% confidence interval (error range) -4.7 to +8.8 mL/min; R2 = 0.999, P < 0.001; variability coefficient <1%]. In vivo, QCFD and MVR were successfully computed in all 40 patients under baseline and hyperaemic conditions, from which coronary flow reserve (CFR) was also calculated. QCFD-derived CFR correlated closely with pressure-derived CFR (R2 = 0.92, P < 0.001). This novel method was significantly more accurate than Doppler-wire-derived flow both in vitro (±6.7 vs. ±34 mL/min) and in vivo (±0.9 vs. ±24.4 mmHg). CONCLUSIONS: Absolute coronary flow and MVR can be determined alongside FFR, in absolute units, during routine catheter laboratory assessment, without the need for additional catheters, wires or drug infusions. Using this novel method, epicardial and microvascular disease can be discriminated and quantified. This comprehensive coronary physiological assessment may enable a new level of patient stratification and management.

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. The purpose of this study was to examine a newly developed aortic stent which was capable of installing to the aortic dissected lesion for biomedical hemodynamics point of view. In this study, we examined the changes in hemodynamics of dissected lesions and the amelioration by endovascular stent intervention. Firstly, we performed animal experiments with the dissected aorta and examined the effects of stenting on volumetric changes in the false lumen. Secondly, we made several types of 3-D stereolithographic dissected aortic models with silicone rubber membrane between the false and the true lumens. Then, the hemodynamic characteristics in each model were evaluated in the pulsatile flow conditions in a mock circulatory system. These modelling approaches enabled the quantitative examination of post-therapeutic effects of stenting followed by elucidating of hemodynamic changes in the vicinity of stents, which may follow the management of clinical amelioration of interventional treatment with aortic stenting.Clinical Relevance- This study represents a modelling approach of the dissected aorta for endovascular intervention using stenting followed by the examination of false lumen volumetric changes resulting in the deterioration of pressure increase in diseased lesions.

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. The reliability of the modelling approach is investigated by comparing 3D/0D model pressure drop estimation with measured peak gradients recorded during diagnostic cardiac catheterization and 2D PC-MRI flow rate measurements in the descending aorta. The current study demonstrated that the proposed approach requires low levels of user interaction, making it suitable for the clinical setting. The agreement between computed blood pressure drop and catheter measurements is 10  ±  8 mmHg at the coarctation site. The comparison between CFD derived and catheter measured pressure gradients indicated that the model has to be improved, suggesting the use of time varying pressure waveforms to further optimize the tuning process and modelling assumptions.

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. In this study, an experimental framework for multimodal strain imaging in an in vitro porcine heart was developed. Specifically, the aim of this work was to analyse displacement and strain in the heart by means of 3D digital image correlation (3D-DIC) and US-2D-STE. Over a single cardiac cycle, displacement values obtained from the two techniques were in strong correlation, although systematically larger displacements were observed with 3D-DIC. Notwithstanding an absolute comparison of the strain measurements was not possible to achieve between the two methods, maximum principal strain directions computed with 3D-DIC were consistent with the longitudinal and circumferential strain distribution measured with US-2D-STE. 3D-DIC confirmed its high repeatability in quantifying displacement and strain over multiple cardiac cycles, unlike US-2D-STE which is affected by accumulated errors over time (i.e. drift). To conclude, this study demonstrates the potential of 3D-DIC to perform dynamic measurement of displacement and strain during heart deformations and supports future applications of this method in ex vivo beating heart platforms, which replicate more fully the complex contraction of the heart.

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. The vortex ring is the flow of choice because it offers patterns comparable to physiological flows and is stable, predictable, reproducible and controllable. This design employs a piston/cylinder system for vortex ring generation, coupled to an imaging tank full of fluid, for vortex propagation. The phantom is motor-driven and by varying piston speed, piston displacement and orifice size, vortex rings with different characteristics can be produced. Two measurement methods, namely Laser-PIV and an optical/video technique, were used to test the phantom under a combination of configurations. Vortex rings with a range of travelling velocities (approximately 1-80 cm/s) and different output-orifice diameters (10-25 mm) were produced with reproducibility typically better than ±10%. Although ultrasound compatibility has been demonstrated, longer-term ambitions include adapting the design to support comparative studies with different modalities, such as MRA and X-ray-CTA.

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. The aim of this work was to enable these reference measurements using a dynamic beating heart simulator to ensure reproducible, controlled, and realistic haemodynamic conditions and to validate the reliability of optical-based three-dimensional digital image correlation (3D-DIC) for a dynamic full-field analysis of epicardial strain. Specifically, performance assessment of 3D-DIC was carried out by evaluating the accuracy and repeatability of the strain measurements across multiple cardiac cycles in a single heart and between five hearts. Moreover, the ability of this optical method to differentiate strain variations when different haemodynamic conditions were imposed in the same heart was examined. Strain measurements were successfully accomplished in a region of the lateral left ventricle surface. Results were highly repeatable over heartbeats and across hearts (intraclass correlation coefficient = 0.99), whilst strain magnitude was significantly different between hearts, due to change in anatomy and wall thickness. Within an individual heart, strain variations between different haemodynamic scenarios were greater than the estimated error of the measurement technique. This study demonstrated the feasibility of applying 3D-DIC in a dynamic passive heart simulator. Most importantly, non-contact measurements were obtained at a high spatial resolution (~ 1.5 mm) allowing resolution of local variation of strain on the epicardial surface during ventricular filling. The experimental framework developed in this paper provides detailed measurement of cardiac strains under controlled conditions, as a reference for validation of clinical cardiac strain imaging modalities.

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. Access to the on-line environment was offered to students at all stages of undergraduate training as an adjunct to routine lectures and tutorials in cardiac pathophysiology. Student feedback was collected on this novel on-line material in the course of routine audits of teaching delivery. RESULTS: Medical students, irrespective of their stage of undergraduate training, reported that they found the models and the environment interesting and a positive experience. After exposure to the environment, there was a statistically significant improvement in student performance on a series of 6 questions based on cardiovascular medicine, with a 33% and 22% increase in the number of questions answered correctly, p < 0.0001 and p < 0.001 respectively. CONCLUSIONS: Considerable improvement was found in students' knowledge and understanding during assessment after exposure to the e-learning environment. Opportunities exist for development of similar environments in other fields of medicine, refinement of the existing environment and further engagement with student cohorts. This work combines some exciting and developing fields in medical education, but routine adoption of these types of tool will be possible only with the engagement of all stake-holders, from educationalists, clinicians, modellers to, most importantly, medical students.

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. Combined with cardiovascular imaging, CFD simulation enables detailed characterisation of complex physiological pressure and flow fields and the computation of metrics which cannot be directly measured, for example, wall shear stress. CFD models are now being translated into clinical tools for physicians to use across the spectrum of coronary, valvular, congenital, myocardial and peripheral vascular diseases. CFD modelling is apposite for minimally-invasive patient assessment. Patient-specific (incorporating data unique to the individual) and multi-scale (combining models of different length- and time-scales) modelling enables individualised risk prediction and virtual treatment planning. This represents a significant departure from traditional dependence upon registry-based, population-averaged data. Model integration is progressively moving towards 'digital patient' or 'virtual physiological human' representations. When combined with population-scale numerical models, these models have the potential to reduce the cost, time and risk associated with clinical trials. The adoption of CFD modelling signals a new era in cardiovascular medicine. While potentially highly beneficial, a number of academic and commercial groups are addressing the associated methodological, regulatory, education- and service-related challenges.

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. Local (inter-strut angle) and global (dog-boning ratio) measures of stent deformation were reported during stent deployment. Pulmonary valve stent geometry was assessed throughout the cardiac cycle by reconstruction of stent geometry and measurement of stent diameter. RESULTS: Good agreement was obtained between methods for assessment of coronary stent geometry with maximum disagreement of +/- 0.03 mm (length) and +/- 3 degrees (angle). The stent underwent large, non-uniform, local deformations during balloon inflation, which did not always correlate with changes in stent diameter. Three-dimensional reconstruction of the pulmonary valve stent was feasible for all frames of the fluoroscopy and for 4DCT images, with good correlation between the diameters calculated from the two methods. The largest compression of the stent during the cardiac cycle was 6.98% measured from fluoroscopy and 7.92% from 4DCT, both in the most distal ring. CONCLUSIONS: Quantitative assessment of stent geometry reconstructed from biplanar imaging methods in vitro and in vivo has shown good agreement with geometry reconstructed from 3D techniques. As a result of their short image acquisition time, biplanar methods may have significant advantages in the measurement of dynamic 3D stent deformation.