Aortic flow below and visceral circulation during aortic counterpulsation: Evaluation of an in vitro model.

INTRODUCTION: This study aimed to test a computer-driven cardiovascular model for the evaluation of the visceral flow during intra-aortic balloon pump (IABP) assistance. METHODS: The model includes a systemic and pulmonary circulation as well as a heart contraction model. The straight polyurethane tube aorta had a single visceral while four windkessel components mimicked resistance compliance of the brachiocephalic, renal and sub-mesenteric, pulmonary, and systemic circulation. Twelve flow probes were placed in the circuit to measure pressures and flows with the IABP on and off. RESULTS: With the balloon off, the meantime to reach the steady state was 48 ± 16 s; with the balloon on, this figure was 178 ± 20 s. The stability of pressure and flow signals was obtained after 72 ± 11 min. The number of cycles of stability of the system was 93 [86-103]. Measurements were reliable either with samples of 10 or 20 beats. Bland Altman method demonstrated the reliability of measurements. Finally, all measurements were comparable to published in vivo data. CONCLUSION: The presented mock circulation was reliable and gave values with high accuracy both at baseline and during mechanical assistance. This system allows evaluation of the mesenteric flow during IABP, under different clinical/hemodynamic conditions. Nonetheless, its translational potential needs to be further evaluated.

Ultrasound-based estimation of remaining cardiac function in LVAD-supported ex vivo hearts.

Left ventricular assist devices (LVAD) provide cardiac support to patients with advanced heart failure. Methods that can directly measure remaining LV function following device implantation do not currently exist. Previous studies have shown that a combination of loading (LV pressure) and deformation (strain) measurements enables quantitation of myocardial work. We investigated the use of ultrasound (US) strain imaging and pressure-strain loop analysis in LVAD-supported hearts under different hemodynamic and pump unloading conditions, with the aim of determining LV function with and without LVAD support. Ex vivo porcine hearts (n = 4) were implanted with LVADs and attached to a mock circulatory loop. Measurements were performed at hemodynamically defined "heart conditions" as the hearts deteriorated from baseline. Hemodynamic (including LV pressure) and radio-frequency US data were acquired during a pump-ramp protocol at speeds from 0 (with no pump outflow) to 10 000 revolutions per minute (rpm). Regional circumferential (εcirc ) and radial (εrad ) strains were estimated over each heart cycle. Regional ventricular dyssynchrony was quantitated through time-to-peak strain. Mean change in LV pulse pressure and εcirc between 0 and 10 krpm were -21.8 mm Hg and -7.24% in the first condition; in the final condition -46.8 mm Hg and -19.2%, respectively. εrad was not indicative of changes in pump speed or heart condition. Pressure-strain loops showed a degradation in the LV function and an increased influence of LV unloading: loop area reduced by 90% between 0 krpm in the first heart condition and 10 krpm in the last condition. High pump speeds and degraded condition led to increased dyssynchrony between the septal and lateral LV walls. Functional measurement of the LV while undergoing LVAD support is possible by using US strain imaging and pressure-strain loops. This can provide important information about remaining pump function. Use of novel LV pressure estimation or measurement techniques would be required for any future use in LVAD patients.

Relative contributions from the ventricle and arterial tree to arterial pressure and its amplification: an experimental study.

Arterial pressure is an important diagnostic parameter for cardiovascular disease. However, relative contributions of individual ventricular and arterial parameters in generating and augmenting pressure are not understood. Using a novel experimental arterial model, our aim was to characterize individual parameter contributions to arterial pressure and its amplification. A piston-driven ventricle provided programmable stroke profiles into various silicone arterial trees and a bovine aorta. Inotropy was varied in the ventricle, and arterial parameters modulated included wall thickness, taper and diameter, the presence of bifurcation, and a native aorta (bovine) versus silicone. Wave reflection at bifurcations was measured and compared with theory, varying parent-to-child tube diameter ratios, and branch angles. Intravascular pressure-tip wires and ultrasonic flow probes measured pressure and flow. Increasing ventricular inotropy independently augmented pressure amplification from 17% to 61% between the lower and higher systolic gradient stroke profiles in the silicone arterial network and from 10% to 32% in the bovine aorta. Amplification increased with presence of a bifurcation, decreasing wall thickness and vessel taper. Pulse pressure increased with increasing wall thickness (stiffness) and taper angle and decreasing diameter. Theoretical predictions of wave transmission through bifurcations werre similar to measurements (correlation: 0.91, R2 = 0.94) but underestimated wave reflection (correlation: 0.75, R2 = 0.94), indicating energy losses during mechanical wave reflection. This study offers the first comprehensive investigation of contributors to hypertensive pressure and its propagation throughout the arterial tree. Importantly, ventricular inotropy plays a crucial role in the amplification of peripheral pressure wave, which offers opportunity for noninvasive assessment of ventricular health.NEW & NOTEWORTHY The present study distinguishes contributions from cardiac and arterial parameters to elevated blood pressure and pressure amplification. Most importantly, it offers the first evidence that ventricular inotropy, an indicator of ventricular function, is an independent determinant of pressure amplification and could be measured with such established devices such as the SphygmoCor.

Enhancement of Arterial Pressure Pulsatility by Controlling Continuous-Flow Left Ventricular Assist Device Flow Rate in Mock Circulatory System.

Continuous-flow left ventricular assist devices (CF-LVADs) generally operate at a constant speed, which reduces pulsatility in the arteries and may lead to complications such as functional changes in the vascular system, gastrointestinal bleeding, or both. The purpose of this study is to increase the arterial pulse pressure and pulsatility by controlling the CF-LVAD flow rate. A MicroMed DeBakey pump was used as the CF-LVAD. A model simulating the flow rate through the aortic valve was used as a reference model to drive the pump. A mock circulation containing two synchronized servomotor-operated piston pumps acting as left and right ventricles was used as a circulatory system. Proportional-integral control was used as the control method. First, the CF-LVAD was operated at a constant speed. With pulsatile-speed CF-LVAD assistance, the pump was driven such that the same mean pump output was generated. Continuous and pulsatile-speed CF-LVAD assistance provided the same mean arterial pressure and flow rate, while the index of pulsatility increased significantly for both arterial pressure and pump flow rate signals under pulsatile speed pump support. This study shows the possibility of improving the pulsatility of CF-LVAD support by regulating pump speed over a cardiac cycle without reducing the overall level of support.

Intra-Aortic Balloon Pump Support in the Isolated Beating Porcine Heart in Nonischemic and Ischemic Pump Failure.

The blood pressure changes induced by the intra-aortic balloon pump (IABP) are expected to create clinical improvement in terms of coronary perfusion and myocardial oxygen consumption. However, the measured effects reported in literature are inconsistent. The aim of this study was to investigate the influence of ischemia on IABP efficacy in healthy hearts and in shock. Twelve slaughterhouse porcine hearts (hearts 1-12) were connected to an external circulatory system, while physiologic cardiac performance was restored. Different clinical scenarios, ranging from healthy to cardiogenic shock, were simulated by step-wise administration of negative inotropic drugs. In hearts 7-12, severe global myocardial ischemia superimposed upon the decreased contractile states was created. IABP support was applied in all hearts under all conditions. Without ischemia, the IABP induced a mild increase in coronary blood flow and cardiac output. These effects were strongly augmented in the presence of persisting ischemia, where coronary blood flow increased by 49 ± 24% (P < 0.01) and cardiac output by 17 ± 6% (P < 0.01) in case of severe pump failure. As expected, myocardial oxygen consumption increased in case of ischemia (21 ± 17%; P < 0.01), while it slightly decreased without (-3 ± 6%; P < 0.01). In case of progressive pump failure due to persistent myocardial ischemia, the IABP increased hyperemic coronary blood flow and cardiac output significantly, and reversed the progressive hemodynamic deterioration within minutes. This suggests that IABP therapy in acute myocardial infarction is most effective in patients with viable myocardium, suffering from persistent myocardial ischemia, despite adequate epicardial reperfusion.

Beat-to-beat variation in pulse wave velocity during breathing maneuvers.

PURPOSE: Thoracic pulse wave velocity (PWV) variation due to modulated trans-mural pressure (TMP) may indicate mechanical properties of the aorta. Our aim was to measure beat-to-beat thoracic PWV and TMP to observe its normal variation during respiratory maneuvers. METHODS: We validated PWV measurements from a real-time velocity projection MRI scan in a pulsatile phantom. A volunteer study showed inter-scan repeatability of steady-state PWV, and observed PWV variation when performing Mueller and Valsalva maneuvers. Synchronized to the real-time projection velocity data, TMP was measured using a mouth piece and pressure sensor arrangement monitoring the intra-thoracic pressure and a single arterial pressure measurement. RESULTS: In the phantom, beat-to-beat PWV derived from real-time projection (5.33 ± 0.32 m s(-1) ) agreed well with experimentally derived PWV using ultrasound probes (5.72 ± 0.50 m s(-1) ). The within-subject PWV variation between scans was 0.28 m s(-1) . Volunteers' PWVs increased during Mueller maneuver (TMP increase of 14.67 ± 10.69 mmHg) by 32% (P < 0.001), and during Valsalva maneuver (TMP decrease of TMP = 17.01 ± 12.91 mmHg), PWV response were inconsistent with an average increase of 14% (P < 0.05). CONCLUSION: Gating TMP to beat-to-beat PWV allows insight into how aortic stiffness varies with strain. However, quantifying nonlinear arterial stiffness requires real-time arterial pressure measurement.

Simulation of changes in myocardial tissue properties during left ventricular assistance with a rotary blood pump.

We considered a mathematical model to investigate changes in geometric and hemodynamic indices of left ventricular function in response to changes in myofiber contractility and myocardial tissue stiffness during rotary blood pump support. Left ventricular assistance with a rotary blood pump was simulated based on a previously published biventricular model of the assisted heart and circulation. The ventricles in this model were based on the one-fiber model that relates ventricular function to myofiber contractility and myocardial tissue stiffness. The simulations showed that indices of ventricular geometry, left ventricular shortening fraction, and ejection fraction had the same response to variations in myofiber contractility and myocardial tissue stiffness. Hemodynamic measures showed an inverse relation compared with geometric measures. Particularly, pulse pressure and arterial dP/dtmax increased when myofiber contractility increased, whereas increasing myocardial tissue stiffness decreased these measures. Similarly, the lowest pump speed at which the aortic valve remained closed increased when myofiber contractility increased and decreased when myocardial tissue stiffness increased. Therefore, simultaneous monitoring of hemodynamic parameters and ventricular geometry indirectly reflects the status of the myocardial tissue. The appropriateness of this strategy will be evaluated in the future, based on in vivo studies.

Exercise hemodynamics during extended continuous flow left ventricular assist device support: the response of systemic cardiovascular parameters and pump performance.

Patients on continuous flow left ventricular assist devices (cf-LVADs) are able to return to an active lifestyle and perform all sorts of physical activities. This study aims to evaluate exercise hemodynamics in patients with a HeartMate II cf-LVAD (HM II). Thirty (30) patients underwent a bicycle exercise test. Along with exercise capacity, systemic cardiovascular responses and pump performance were evaluated at 6 and 12 months after HM II implantation. From rest to maximum exercise, heart rate increased from 87 ± 14 to 140 ± 32 beats/minute (bpm) (P<0.01), while systolic arterial blood pressure increased from 93 ± 12 to 116 ± 21 mm Hg (P<0.01). Total cardiac output (TCO) increased from 4.1 ± 1.1 to 8.5 ± 2.8 L/min (P<0.01) while pump flow increased less, from 5.1 ± 0.7 to 6.4 ± 0.6 L/min (P<0.01). Systemic vascular resistance (SVR) decreased from 1776 ± 750 to 1013 ± 83 dynes.s/cm(5) (P<0.001) and showed the strongest correlation with TCO (r= -0.72; P<0.01). Exercise capacity was affected by older age, while blood pressure increased significantly in men compared with women. Exercise capacity remained consistent at 6 and 12 months after HM II implantation, 51% ± 13% and 52% ± 13% of predicted VO2 max for normal subjects corrected for age and gender. In conclusion, pump flow of the HM II may contribute partially to TCO during exercise, while SVR was the strongest determinant of TCO.

Autoregulation of coronary blood flow in the isolated beating pig heart.

The isolated beating pig heart model is an accessible platform to investigate the coronary circulation in its truly morphological and physiological state, whereas its use is beneficial from a time, cost, and ethical perspective. However, whether the coronary autoregulation is still intact is not known. Here, we study the autoregulation of coronary blood flow in the working isolated pig heart in response to brief occlusions of the coronary artery, to step-wise changes in left ventricular loading conditions and contractile states, and to pharmacologic vasodilating stimuli. Six slaughterhouse pig hearts (473 ± 40 g) were isolated, prepared, and connected to an external circulatory system. Through coronary reperfusion and controlled cardiac loading, physiological cardiac performance was achieved. After release of a coronary occlusion, coronary blood flow rose rapidly to an equal (maximum) level as the flow during control beats, independent of the duration of occlusion. Moreover, a linear relation was found between coronary blood flow and coronary driving pressure for a wide variation of preload, afterload, and contractility. In addition, intracoronary administration of papaverine did not yield a transient increase in blood flow indicating the presence of maximum coronary hyperemia. Together, this indicates that the coronary circulation in the isolated beating pig heart is in a permanent state of maximum hyperemia. This makes the model excellently suitable for testing and validating cardiovascular devices (i.e., heart valves, stent grafts, and ventricular assist devices) under well-controlled circumstances, whereas it decreases the necessity of sacrificing large mammalians for performing classical animal experiments.

Enabling strain imaging in realistic Eulerian ultrasound simulation methods.

Cardiovascular strain imaging is continually improving due to ongoing advances in ultrasound acquisition and data processing techniques. The phantoms used for validation of new methods are often burdensome to make and lack flexibility to vary mechanical and acoustic properties. Simulations of US imaging provide an alternative with the required flexibility and ground truth strain data. However, the current Lagrangian US strain imaging models cannot simulate heterogeneous speed of sound distributions and higher-order scattering, which limits the realism of the simulations. More realistic Eulerian modelling techniques exist but have so far not been used for strain imaging. In this research, a novel sampling scheme was developed based on a band-limited interpolation of the medium, which enables accurate strain simulation in Eulerian methods. The scheme was validated in k-Wave using various numerical phantoms and by a comparison with Field II. The method allows for simulations with a large range in strain values and was accurate with errors smaller than -60 dB. Furthermore, an excellent agreement with the Fourier theory of US scattering was found. The ability to perform simulations with heterogeneous speed of sound distributions was demonstrated using a pulsating artery model. The developed sampling scheme contributes to more realistic strain imaging simulations, in which the effect of heterogenous acoustic properties can be taken into account.

MarioHeart: Novel In-Vitro Flow Model for Testing Heart Valve Prostheses and Anticoagulant Therapies.

Mechanical heart valve (MHV) prostheses present a risk of thromboembolic complications despite antithrombotic therapy. Further steps in the development of more hemocompatible MHVs and new anticoagulants are impeded due to the lack of adequate in-vitro models. With the development of a novel in-vitro model (MarioHeart), a pulsatile flow similar to the arterial circulation is emulated. The MarioHeart design owns unique features as 1) a single MHV within a torus with low surface/volume ratio, 2) a closed loop system, and 3) a dedicated external control system driving the oscillating rotational motion of the torus. For verification purposes, a blood analog fluid seeded with particles was used to assess fluid velocity and flow rate using a speckle tracking method on high-speed video recordings of the rotating model. The flow rate resembled the physiological flow rate in the aortic root, in both shape and amplitude. Additional in-vitro runs with porcine blood showed thrombi on the MHV associated with the suture ring, which is similar to the in-vivo situation. MarioHeart is a simple design which induces well-defined fluid dynamics resulting in physiologically nonturbulent flow without stasis of the blood. MarioHeart seems suitable for testing the thrombogenicity of MHVs and the potential of new anticoagulants.

Quantitative aortography for assessment of aortic regurgitation in the era of percutaneous aortic valve replacement.

Paravalvular leak (PVL) is a shortcoming that can erode the clinical benefits of transcatheter valve replacement (TAVR) and therefore a readily applicable method (aortography) to quantitate PVL objectively and accurately in the interventional suite is appealing to all operators. The ratio between the areas of the time-density curves in the aorta and left ventricular outflow tract (LVOT-AR) defines the regurgitation fraction (RF). This technique has been validated in a mock circulation; a single injection in diastole was further tested in porcine and ovine models. In the clinical setting, LVOT-AR was compared with trans-thoracic and trans-oesophageal echocardiography and cardiac magnetic resonance imaging. LVOT-AR > 17% discriminates mild from moderate aortic regurgitation on echocardiography and confers a poor prognosis in multiple registries, and justifies balloon post-dilatation. The LVOT-AR differentiates the individual performances of many old and novel devices and is being used in ongoing randomized trials and registries.

Modeling toolchain for realistic simulation of photoacoustic data acquisition.

SIGNIFICANCE: Physics-based simulations of photoacoustic (PA) signals are used to validate new methods, to characterize PA setups and to generate training datasets for machine learning. However, a thoroughly validated PA simulation toolchain that can simulate realistic images is still lacking. AIM: A quantitative toolchain was developed to model PA image acquisition in complex tissues, by simulating both the optical fluence and the acoustic wave propagation. APPROACH: Sampling techniques were developed to decrease artifacts in acoustic simulations. The performance of the simulations was analyzed by measuring the point spread function (PSF) and using a rotatable three-channel phantom, filled with cholesterol, a human carotid plaque sample, and porcine blood. Ex vivo human plaque samples were simulated to validate the methods in more complex tissues. RESULTS: The sampling techniques could enhance the quality of the simulated PA images effectively. The resolution and intensity of the PSF in the turbid medium matched the experimental data well. Overall, the appearance, signal-to-noise ratio and speckle of the images could be simulated accurately. CONCLUSIONS: A PA toolchain was developed and validated, and the results indicate a great potential of PA simulations in more complex and heterogeneous media.

Continuous-flow cardiac assistance: effects on aortic valve function in a mock loop.

BACKGROUND: As the use of left ventricular assist devices (LVADs) to treat end-stage heart failure has become more widespread, leaflet fusion--with resul-tant aortic regurgitation--has been observed more frequently. To quantitatively assess the effects of nonpulsatile flow on aortic valve function, we tested a continuous-flow LVAD in a mock circulatory system (MCS) with an interposed valve. MATERIALS AND METHODS: To mimic the hemodynamic characteristics of LVAD patients, we utilized an MCS in which a Jarvik 2000 LVAD was positioned at the base of a servomotor-operated piston pump (left ventricular chamber). We operated the LVAD at 8000 to 12,000 rpm, changing the speed in 1000-rpm increments. At each speed, we first varied the outflow resistance at a constant stroke volume, then varied the stroke volume at a constant outflow resistance. We measured the left ventricular pressure, aortic pressure, pump flow, and total flow, and used these values to compute the change, if any, in the aortic duty cycle (aortic valve open time) and transvalvular aortic pressure loads. RESULTS: Validation of the MCS was demonstrated by the simulation of physiologic pressure and flow waveforms. At increasing LVAD speeds, the mean aortic pressure load steadily increased, while the aortic duty cycle steadily decreased. Changes were consistent for each MCS experimental setting, despite variations in stroke volume and outflow resistance. CONCLUSIONS: Increased LVAD flow results in an impaired aortic valve-open time due to a pressure overload above the aortic valve. Such an overload may initiate structural changes, causing aortic leaflet fusion and/or regurgitation.

In vitro comparison of support capabilities of intra-aortic balloon pump and Impella 2.5 left percutaneous.

The Impella 2.5 left percutaneous (LP), a relatively new transvalvular assist device, challenges the position of the intra-aortic balloon pump (IABP), which has a long record in supporting patients after myocardial infarction and cardiac surgery. However, while more costly and more demanding in management, the advantages of the Impella 2.5 LP are yet to be established. The aim of this study was to evaluate the benefits of the 40 cc IABP and the Impella 2.5 LP operating at 47,000 rpm in vitro, and compare their circulatory support capabilities in terms of cardiac output, coronary flow, cardiac stroke work, and arterial blood pressure. Clinical scenarios of cardiogenic preshock and cardiogenic shock (CS), with blood pressure depression, lowered cardiac output, and constant heart rate of 80 bpm, were modeled in a model-controlled mock circulation, featuring a systemic, pulmonary, and coronary vascular bed. The ventricles, represented by servomotor-operated piston pumps, included the Frank-Starling mechanism. The systemic circulation was modeled with a flexible tube having close-to-human aortic dimensions and compliance properties. Proximally, it featured a branch mimicking the brachiocephalic arteries and a physiological correct coronary flow model. The rest of the systemic and pulmonary impedance was modeled by four-element Windkessel models. In this system, the enhancement of coronary flow and blood pressure was tested with both support systems under healthy and pathological conditions. Hemodynamic differences between the IABP and the Impella 2.5 LP were small. In our laboratory model, both systems approximately yielded a 10% cardiac output increase and a 10% coronary flow increase. However, since the Impella 2.5 LP provided significantly better left ventricular unloading, the circulatory support capabilities were slightly in favor of the Impella 2.5 LP. On the other hand, pulsatility was enhanced with the IABP and lowered with the Impella 2.5 LP. The support capabilities of both the IABP and the Impella 2.5 LP strongly depended on the simulated hemodynamic conditions. Maximum hemodynamic benefits were achieved when mechanical circulatory support was applied on a simulated scenario of deep CS.

Towards in vivo photoacoustic imaging of vulnerable plaques in the carotid artery.

The main indicator for endarterectomy is the grade of stenosis, which results in severe overtreatment. Photoacoustic imaging (PAI) can provide patient-specific assessment of plaque morphology, and thereby vulnerability. A pilot study of PAI on carotid plaques in patients (n=16) was performed intraoperatively with a hand-held PAI system. By compensating for motion, the photoacoustic (PA) signal-to-noise ratio (SNR) could be increased by 5 dB in vivo. PA signals from hemorrhagic plaques had different characteristics compared to the signals from the carotid blood pool. This study is a key step towards a non-invasive application of PAI to detect vulnerable plaques.

SVD-based filtering to detect intraplaque hemorrhage using single wavelength photoacoustic imaging.

SIGNIFICANCE: Intraplaque hemorrhage (IPH) is an important indicator of plaque vulnerability. Early detection could aid the prevention of stroke. AIM: We aim to detect IPH with single wavelength PA imaging in vivo and to improve image quality. APPROACH: We developed a singular value decomposition (SVD)-based filter to detect the nonstationary and stationary components in ultrasound data. A PA mask was created to detect stationary (IPH) sources. The method was tested ex vivo using phantoms and in vivo in patients. RESULTS: The flow and IPH channels were successfully separated in the phantom data. We can also detect the PA signals from IPH and reject signals from the carotid lumen in vivo. Generalized contrast-to-noise ratio improved in both ex vivo and in vivo in US imaging. CONCLUSIONS: SVD-based filtering can successfully detect IPH using a single laser wavelength, opening up opportunities for more economical and cost-effective laser sources.

Model-based aortic power transfer: A potential measure for quantifying aortic stenosis severity based on measured data.

Current aortic stenosis severity grading is based mainly on the local properties of the stenotic valve, such as pressure gradient or jet velocity. Success rates of valve replacement therapy are still suboptimal, so alternative grading of AS should be investigated. We suggest the efficiency of power transfer from the left ventricle to the aorta, as it takes into account heart, valve and circulatory system. Left ventricular and circulatory power were estimated using a 0D model, which was optimised to patient data: left ventricular and aortic pressure, aortic flow and diastolic left ventricular volume. Optimisation was performed using a data assimilation method. These data were available in rest as well as chemically induced exercise for twelve patients. Using this limited data set, we showed that aortic valve efficiency is highly heterogeneous between patients, but also often dependent on the haemodynamic load. This indicates that power transfer efficiency is a highly interesting metric for further research in aortic stenosis.

Uncertainty in model-based treatment decision support: Applied to aortic valve stenosis.

Patient outcome in trans-aortic valve implantation (TAVI) therapy partly relies on a patient's haemodynamic properties that cannot be determined from current diagnostic methods alone. In this study, we predict changes in haemodynamic parameters (as a part of patient outcome) after valve replacement treatment in aortic stenosis patients. A framework to incorporate uncertainty in patient-specific model predictions for decision support is presented. A 0D lumped parameter model including the left ventricle, a stenotic valve and systemic circulatory system has been developed, based on models published earlier. The unscented Kalman filter (UKF) is used to optimize model input parameters to fit measured data pre-intervention. After optimization, the valve treatment is simulated by significantly reducing valve resistance. Uncertain model parameters are then propagated using a polynomial chaos expansion approach. To test the proposed framework, three in silico test cases are developed with clinically feasible measurements. Quality and availability of simulated measured patient data are decreased in each case. The UKF approach is compared to a Monte Carlo Markov Chain (MCMC) approach, a well-known approach in modelling predictions with uncertainty. Both methods show increased confidence intervals as measurement quality decreases. By considering three in silico test-cases we were able to show that the proposed framework is able to incorporate optimization uncertainty in model predictions and is faster and the MCMC approach, although it is more sensitive to noise in flow measurements. To conclude, this work shows that the proposed framework is ready to be applied to real patient data.

A novel technique for the assessment of mechanical properties of vascular tissue.

Accurate estimation of mechanical properties of the different atherosclerotic plaque constituents is important in assessing plaque rupture risk. The aim of this study was to develop an experimental set-up to assess material properties of vascular tissue, while applying physiological loading and being able to capture heterogeneity. To do so, a ring-inflation experimental set-up was developed in which a transverse slice of an artery was loaded in the radial direction, while the displacement was estimated from images recorded by a high-speed video camera. The performance of the set-up was evaluated using seven rubber samples and validated with uniaxial tensile tests. For four healthy porcine carotid arteries, material properties were estimated using ultrasound strain imaging in whole-vessel-inflation experiments and compared to the properties estimated with the ring-inflation experiment. A 1D axisymmetric finite element model was used to estimate the material parameters from the measured pressures and diameters, using a neo-Hookean and Holzapfel-Gasser-Ogden material model for the rubber and porcine samples, respectively. Reproducible results were obtained with the ring-inflation experiment for both rubber and porcine samples. Similar mean stiffness values were found in the ring-inflation and tensile tests for the rubber samples as 202 kPa and 206 kPa, respectively. Comparable results were obtained in vessel-inflation experiments using ultrasound and the proposed ring-inflation experiment. This inflation set-up is suitable for the assessment of material properties of healthy vascular tissue in vitro. It could also be used as part of a method for the assessment of heterogeneous material properties, such as in atherosclerotic plaques.