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.

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.

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.

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.

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.

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.

Validation of a three-dimensional quantitative coronary angiography-based software to calculate fractional flow reserve: the FAST study.

AIMS: The aim of this study was to validate novel software to calculate vessel fractional flow reserve (vFFR) based on 3D-QCA and to assess inter-observer variability in patients who underwent routine preprocedural FFR assessment for intermediate coronary artery stenosis. METHODS AND RESULTS: In vitro validation was performed in an experimental model. Clinical validation was performed in an observational, retrospective, single-centre cohort study. A total of 100 patients presenting with stable angina or non-ST-segment elevation myocardial infarction and an indication to perform FFR between January 2016 and October 2016 were included. vFFR was calculated based on the aortic root pressure along with two angiographic projections and validated against pressure wire-derived FFR. Mean FFR and vFFR were 0.82±0.08 and 0.84±0.07, respectively. A good linear correlation was found between FFR and vFFR (r=0.89; p<0.001). Assessment of vFFR had a low inter-observer variability (r=0.95; p<0.001). The diagnostic accuracy of vFFR in identifying lesions with an FFR ≤0.80 was higher as compared with 3D-QCA: AUC 0.93 (95% CI: 0.88-0.97) vs 0.66 (95% CI: 0.55-0.77), respectively. CONCLUSIONS: The 3D-QCA-derived vFFR has a high linear correlation to invasively measured FFR, a high diagnostic accuracy to detect FFR ≤0.80 and a low inter-observer variability.

Image acquisition stability of fixated musculoskeletal sonography in an exercise setting: a quantitative analysis and comparison with freehand acquisition.

PURPOSE: In dynamic musculoskeletal sonography, probe fixation can contribute to field of view (FOV) consistency, which is necessary for valid analysis of architectural parameters. In this volunteer study, the achieved FOV consistency in fixated ultrasonography was quantified and compared with freehand acquisition. METHODS: During five resting periods during cycling exercise, longitudinal B-mode images of the vastus lateralis (VL) muscle were acquired on one thigh with a fixated probe, and by two trained observers on the other thigh. In each acquisition, the structural similarity compared to the first resting period was determined using the complex wavelet structural similarity index (CW-SSIM). Also, the pennation angle of the VL was measured. Both CW-SSIM and pennation angle were compared between fixated and freehand acquisition. Furthermore, the compression of tissue by the probe fixation was measured. RESULTS: In fixated acquisition, a significantly higher structural similarity (p < 0.05) and an improved repeatability of pennation angle measurement were obtained compared to freehand acquisition. Probe fixation compressed muscle tissue by 12% on average. CONCLUSIONS: Quantification of the structural similarity showed an increase in FOV consistency with sonography compared to freehand acquisition. The demonstrated feasibility of long-term fixated acquisition might be attractive in many medical fields and sports, and for reduction of work-related ergonomic problems among sonographers.

Decoupling the Effect of Shear Stress and Stretch on Tissue Growth and Remodeling in a Vascular Graft.

The success of cardiovascular tissue engineering (TE) strategies largely depends on the mechanical environment in which cells develop a neotissue through growth and remodeling processes. This mechanical environment is defined by the local scaffold architecture to which cells adhere, that is, the microenvironment, and by external mechanical cues to which cells respond, that is, hemodynamic loading. The hemodynamic environment of early developing blood vessels consists of both shear stress (due to blood flow) and circumferential stretch (due to blood pressure). Experimental platforms that recapitulate this mechanical environment in a controlled and tunable manner are thus critical for investigating cardiovascular TE. In traditional perfusion bioreactors, however, shear stress and stretch are coupled, hampering a clear delineation of their effects on cell and tissue response. In this study, we uniquely designed a bioreactor that independently combines these two types of mechanical cues in eight parallel vascular grafts. The system is computationally and experimentally validated, through finite element analysis and culture of tissue constructs, respectively, to distinguish various levels of shear stress (up to 5 Pa) and cyclic stretch (up to 1.10). To illustrate the usefulness of the system, we investigated the relative contribution of cyclic stretch (1.05 at 0.5 Hz) and shear stress (1 Pa) to tissue development. Both types of hemodynamic loading contributed to cell alignment, but the contribution of shear stress overruled stretch-induced cell proliferation and matrix (i.e., collagen and glycosaminoglycan) production. At a macroscopic level, cyclic stretching led to the most linear stress-stretch response, which was not related to the presence of shear stress. In conclusion, we have developed a bioreactor that is particularly suited to further unravel the interplay between hemodynamics and in situ TE processes. Using the new system, this work highlights the importance of hemodynamic loading to the study of developing vascular tissues.

Investigation on the Effect of Spatial Compounding on Photoacoustic Images of Carotid Plaques in the In Vivo Available Rotational Range.

Photoacoustic imaging (PAI) is a promising imaging modality due to its high optical specificity. However, the low signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of in vivo PA images are major challenges that prevent PAI from finding its place in clinics. This paper investigates the merit of spatial compounding of PA images in arterial phantoms and the achievable improvements of SNR, when in vivo conditions are mimicked. The analysis of the compounding technique was performed on a polyvinyl alcohol vessel phantom with black threads embedded in its wall. The in vivo conditions were mimicked by limiting the rotation range in ±30°, adding turbid surrounding medium, and filling the lumen with porcine blood. Finally, the performance of the technique was evaluated in ex vivo human carotid plaque samples. Results showed that spatial compounding elevates the SNR by 5-10 dB and CNR by 1-5 dB, depending on the location of the absorbers. This paper elucidates prospective in vivo PA characterization of carotid plaques by proposing a method to enhance PA image quality.

A Novel Angiographic Quantification of Aortic Regurgitation After TAVR Provides an Accurate Estimation of Regurgitation Fraction Derived From Cardiac Magnetic Resonance Imaging.

OBJECTIVES: This study sought to compare a new quantitative angiographic technique to cardiac magnetic resonance-derived regurgitation fraction (CMR-RF) for the quantification of prosthetic valve regurgitation (PVR) after transcatheter aortic valve replacement (TAVR). BACKGROUND: PVR after TAVR is challenging to quantify, especially during the procedure. METHODS: Post-replacement aortograms in 135 TAVR recipients were analyzed offline by videodensitometry to measure the ratio of the time-resolved contrast density in the left ventricular outflow tract to that in the aortic root (videodensitometric aortic regurgitation [VD-AR]). CMR was performed within an interval of ≤30 days (11 ± 6 days) after the procedure. RESULTS: The average CMR-RF was 6.7 ± 7.0% whereas the average VD-AR was 7.0 ± 7.0%. The correlation between VD-AR and CMR-RF was substantial (r = 0.78, p < 0.001). On receiver-operating characteristic curves, a VD-AR ≥10% corresponded to >mild PVR as defined by CMR-RF (area under the curve: 0.94; p < 0.001; sensitivity 100%, specificity 83%), whereas a VD-AR ≥25% corresponded to moderate-to-severe PVR (area under the curve: 0.99; p = 0.004; sensitivity 100%, specificity 98%). Intraobserver reproducibility was excellent for both techniques (for CMR-RF, intraclass correlation coefficient: 0.91, p < 0.001; for VD-AR intraclass correlation coefficient: 0.93, p < 0.001). The difference on rerating was -0.04 ± 7.9% for CMR-RF and -0.40 ± 6.8% for VD-AR. CONCLUSIONS: The angiographic VD-AR provides a surrogate assessment of PVR severity after TAVR that correlates well with the CMR-RF.

Videodensitometric quantification of paravalvular regurgitation of a transcatheter aortic valve: in vitro validation.

AIMS: Videodensitometric assessment of aortography provides a periprocedural quantitation of prosthetic valve regurgitation (PVR) after transcatheter aortic valve implantation. We sought to compare the videodensitometric parameters of PVR severity to the regurgitation fraction (RF) in a controlled in vitro setting. METHODS AND RESULTS: In a mock circulation system, a transcatheter balloon-expandable valve inserted at the aortic valve position was gradually deformed to induce different grades of paravalvular leakage and the RF was measured with a transonic flow probe. Contrast aortography was performed and the following videodensitometric parameters were generated: left ventricle aortic regurgitation (LV-AR), LV outflow tract AR (LVOT-AR), quantitative regurgitation assessment (qRA) index, relative maximum density (relative max), and maximum upslope of the LV time-density curve. The correlation was substantial between videodensitometric parameters (LV-AR, LVOT-AR, qRA index, relative max, and maximum upslope) and RF (r2=0.96, 0.96, 0.93, 0.87, and 0.93; p<0.001 for all). LV-AR (region of interest [ROI]=entire LV) and LVOT-AR (ROI=LVOT) were not different (p=0.51) and were strongly correlated (r2=0.99) with a mean difference of 1.92% (95% limits of agreement: ±2.83). The correlations of LV-AR and LVOT-AR with RF were stronger when more than one cardiac cycle was included in the analysis (one cycle: r2=0.85 and r2=0.83; four cycles: r2=0.96 and r2=0.96, for LV-AR and LVOT-AR, respectively). Including more cycles beyond four did not improve accuracy. CONCLUSIONS: Quantitative assessment of PVR by videodensitometry of aortograms strongly correlates with the actual RF in a controlled in vitro setting. Accuracy is improved by including more than one cardiac cycle in the analysis.

A Numerical Simulation of HeartAssist5 Blood Pump Using an Advanced Turbulence Model.

The need for mechanical assistance of the failing heart has increased with improvements in medicine and a rapidly aging population. In recent decades, significant progress has been made in the development and refinement of ventricular assist devices (VADs). Such devices operate in mixed laminar, transitional, and turbulent flow regime. One tool that assists in the development of VADs by facilitating understanding of the physical and mechanical properties of these flow regimes is computational fluid dynamics (CFD). In our investigation, we tested an advanced turbulence model that is a further development from standard Reynolds-averaged Navier-Stokes (RANS) models. From estimated pump flow rates (Q0) and constant rotation speed (n), pressure head (Δp) was calculated and validated with experimental data. An advanced turbulence model called scale adaptive simulation (SAS) was used in the solving of six different working cases comparing numerical SAS-SST and standard SST-kω models to experimental results.

Ultrasound functional imaging in an ex vivo beating porcine heart platform.

In recent years, novel ultrasound functional imaging (UFI) techniques have been introduced to assess cardiac function by measuring, e.g. cardiac output (CO) and/or myocardial strain. Verification and reproducibility assessment in a realistic setting remain major issues. Simulations and phantoms are often unrealistic, whereas in vivo measurements often lack crucial hemodynamic parameters or ground truth data, or suffer from the large physiological and clinical variation between patients when attempting clinical validation. Controlled validation in certain pathologies is cumbersome and often requires the use of lab animals. In this study, an isolated beating pig heart setup was adapted and used for performance assessment of UFI techniques such as volume assessment and ultrasound strain imaging. The potential of performing verification and reproducibility studies was demonstrated. For proof-of-principle, validation of UFI in pathological hearts was examined. Ex vivo porcine hearts (n = 6, slaughterhouse waste) were resuscitated and attached to a mock circulatory system. Radio frequency ultrasound data of the left ventricle were acquired in five short axis views and one long axis view. Based on these slices, the CO was measured, where verification was performed using flow sensor measurements in the aorta. Strain imaging was performed providing radial, circumferential and longitudinal strain to assess reproducibility and inter-subject variability under steady conditions. Finally, strains in healthy hearts were compared to a heart with an implanted left ventricular assist device, simulating a failing, supported heart. Good agreement between ultrasound and flow sensor based CO measurements was found. Strains were highly reproducible (intraclass correlation coefficients >0.8). Differences were found due to biological variation and condition of the hearts. Strain magnitude and patterns in the assisted heart were available for different pump action, revealing large changes compared to the normal condition. The setup provides a valuable benchmarking platform for UFI techniques. Future studies will include work on different pathologies and other means of measurement verification.

A novel synchronised diastolic injection method to reduce contrast volume during aortography for aortic regurgitation assessment: in vitro experiment of a transcatheter heart valve model.

AIMS: In the minimalist transcatheter aortic valve implantation (TAVI) era, the usage of transoesophageal echocardiography has become restricted. Conversely, aortography has gained clinical ground in quantifying prosthetic valve regurgitation (PVR) during the procedure. In a mock circulation system, we sought to compare the contrast volume required and the accuracy of aortographic videodensitometric PVR assessment using a synchronised diastolic and standard (non-synchronised) injection aortography. METHODS AND RESULTS: Synchronised diastolic injection triggered by the signal stemming from the mock circulation was compared with standard non-synchronised injection. A transcatheter heart valve was implanted and was deformed step by step by advancing a screw perpendicularly to the cage of the valve in order to create increasing PVR. Quantitative measurement of PVR was derived from time-density curves of both a reference area (aortic root) and a region of interest (left ventricle) developed by a videodensitometric software. The volume of contrast required for the synchronised diastolic injection was significantly less than in the non-synchronised injection (8.1 [7.9-8.5] ml vs. 19.4 [19.2-19.9] ml, p<0.001). The correlation between the two methods was substantial (Spearman's coefficient rho ranging from 0.991 to 0.968). Intraobserver intra-class correlation coefficient for both methods of injection was 0.999 (95% CI: 0.996-1.000) for the synchronised diastolic and 0.999 (95% CI: 0.996-1.000) for the non-synchronised injection group. The mean difference in the rating was 0.17% and limits of agreement were ±1.64% for both groups. CONCLUSIONS: A short synchronised diastolic injection enables contrast volume reduction during aortography without compromising the accuracy of the quantitative assessment of PVR using videodensitometry.

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.

A Bioreactor to Identify the Driving Mechanical Stimuli of Tissue Growth and Remodeling.

Tissue growth and remodeling are essential processes that should ensure long-term functionality of tissue-engineered (TE) constructs. Even though it is widely recognized that these processes strongly depend on mechanical stimuli, the underlying mechanisms of mechanically induced growth and remodeling are only partially understood. It is generally accepted that cells sense mechanical changes and respond by altering their surroundings, by means of extracellular matrix growth and remodeling, in an attempt to return to a certain preferred mechanical homeostatic state. However, the exact mechanical cues that trigger cells to synthesize and remodel their environment remain unclear. To identify the driving mechanical stimuli of these processes, it is critical to be able to temporarily follow the mechanical state of developing tissues under physiological loading conditions. Therefore, a novel "versatile tissue growth and remodeling" (Vertigro) bioreactor was developed that is capable of tissue culture and mechanical stimulation for a prolonged time period, while simultaneously performing mechanical testing. The Vertigro's unique two-chamber design allows easy, sterile handling of circular 3D TE constructs in a dedicated culture chamber, while a separate pressure chamber facilitates a pressure-driven dynamic loading regime during culture. As a proof-of-concept, temporal changes in the mechanical state of cultured tissues were quantified using nondestructive mechanical testing by means of a classical bulge test, in which the tissue displacement was tracked using ultrasound imaging. To demonstrate the successful development of the bioreactor system, compositional, structural, and geometrical changes were qualitatively and quantitatively assessed using a series of standard analysis techniques. With this bioreactor and associated mechanical analysis technique, a powerful toolbox has been developed to quantitatively study and identify the driving mechanical stimuli of engineered tissue growth and remodeling.