Safety of arterial shear wave elastography-ex-vivoassessment of induced strain and strain rates.

Shear wave elastography (SWE) is a promising technique for characterizing carotid plaques and assessing local arterial stiffness. The mechanical stress to which the tissue is subjected during SWE using acoustic radiation force (ARF), leading to strain at a certain strain rate, is still relatively unknown. Because SWE is increasingly used for arterial applications where the mechanical stress could potentially lead to significant consequences, it is important to understand the risks of SWE-induced strain and strain rate. The aim of this study was to investigate the safety of SWE in terms of induced arterial strain and strain rateex-vivoand in a human carotid arteryin-vivo. SWE was performed on six porcine aortae as a model of the human carotid artery using different combinations of ARF push parameters (push voltage: 60/90 V, aperture width: f/1.0/1.5, push length: 100/150/200µs) and distance to push position. The largest induced strain and strain rate were 1.46% and 54 s-1(90 V, f/1.0, 200µs), respectively. Moreover, the SWE-induced strains and strain rates increased with increasing push voltage, aperture, push length, and decreasing distance between the region of interest and the push. In the human carotid artery, the SWE-induced maximum strain was 0.06% and the maximum strain rate was 1.58 s-1, compared with the maximum absolute strain and strain rate of 12.61% and 5.12 s-1, respectively, induced by blood pressure variations in the cardiac cycle. Our results indicate thatex-vivoarterial SWE does not expose the artery to higher strain rate than normal blood pressure variations, and to strain one order of magnitude higher than normal blood pressure variations, at the push settings and distances from the region of interest used in this study.

Hydraulic force is a novel mechanism of diastolic function that may contribute to decreased diastolic filling in HFpEF and facilitate filling in HFrEF.

A hydraulic force generated by blood moving the atrioventricular plane is a novel mechanism of diastolic function. The direction and magnitude of the force is dependent on the geometrical relationship between the left atrium and ventricle and is measured as the short-axis atrioventricular area difference (AVAD). In short, the net hydraulic force acts from a larger area toward a smaller one. It is currently unknown how cardiac remodeling affects this mechanism. The aim of the study was therefore to investigate this diastolic mechanism in patients with pathological or physiological remodeling. Seventy subjects [n = 11 heart failure with preserved ejection fraction (HFpEF), n = 10 heart failure with reduced ejection fraction (HFrEF), n = 7 signs of isolated diastolic dysfunction, n = 10 hypertrophic cardiomyopathy, n = 10 cardiac amyloidosis, n = 18 triathletes, and n = 14 controls] were included. Subjects underwent cardiac MR, and short-axis images of the left atrium and ventricle were delineated. AVAD was calculated as ventricular area minus atrial area and used as an indicator of net hydraulic force. At the onset of diastole, AVAD in HFpEF was -9.2 cm2 (median) versus -4.4 cm2 in controls, P = 0.02. The net hydraulic force was directed toward the ventricle for both but was larger in HFpEF. HFrEF was the only group with a positive median value (11.6 cm2), and net hydraulic force was throughout diastole directed toward the atrium. The net hydraulic force may impede cardiac filling throughout diastole in HFpEF, worsening diastolic dysfunction. In contrast, it may work favorably in patients with dilated ventricles and aid ventricular filling.NEW & NOTEWORTHY It is a previously unrecognized physiological mechanism of the heart that diastolic filling occurs with the help of hydraulics. In patients with heart failure with preserved ejection fraction, atrial dilatation may cause the net hydraulic force to work against cardiac filling, thus further augmenting diastolic dysfunction. In contrast, it may work favorably in patients with dilated ventricles, as in heart failure with reduced ejection fraction.

Cardiac remodeling in aortic and mitral valve disease: a simulation study with clinical validation.

Remodeling is an important long-term determinant of cardiac function throughout the progression of heart disease. Numerous biomolecular pathways for mechanosensing and transduction are involved. However, we hypothesize that biomechanical factors alone can explain changes in myocardial volume and chamber size in valve disease. A validated model of the human vasculature and the four cardiac chambers was used to simulate aortic stenosis, mitral regurgitation, and aortic regurgitation. Remodeling was simulated with adaptive feedback preserving myocardial fiber stress and wall shear stress in all four cardiac chambers. Briefly, the model used myocardial fiber stress to determine wall thickness and cardiac chamber wall shear stress to determine chamber volume. Aortic stenosis resulted in the development of concentric left ventricular hypertrophy. Aortic and mitral regurgitation resulted in eccentric remodeling and eccentric hypertrophy, with more pronounced hypertrophy for aortic regurgitation. Comparisons with published clinical data showed the same direction and similar magnitudes of changes in end-diastolic volume index and left ventricular diameters. Changes in myocardial wall volume and wall thickness were within a realistic range in both stenotic and regurgitant valvular disease. Simulations of remodeling in left-sided valvular disease support, in both a qualitative and quantitative manner, that left ventricular chamber size and hypertrophy are primarily determined by preservation of wall shear stress and myocardial fiber stress. NEW & NOTEWORTHY Cardiovascular simulations with adaptive feedback that normalizes wall shear stress and fiber stress in the cardiac chambers could predict, in a quantitative and qualitative manner, remodeling patterns seen in patients with left-sided valvular disease. This highlights how mechanical stress remains a fundamental aspect of cardiac remodeling. This in silico study validated with clinical data paves the way for future patient-specific predictions of remodeling in valvular disease.

Plaque characterization using shear wave elastography-evaluation of differentiability and accuracy using a combined ex vivo and in vitro setup.

Ultrasound elastography has shown potential for improved plaque risk stratification. However, no clear consensus exists on what output metric to use, or what imaging parameters would render optimal plaque differentiation. For this reason we developed a combined ex vivo and in vitro setup, in which the ability to differentiate phantom plaques of varying stiffness was evaluated as a function of plaque geometry, push location, imaging plane, and analysed wave speed metric. The results indicate that group velocity or phase velocity ⩾1 kHz showed the highest ability to significantly differentiate plaques of different stiffness, successfully classifying a majority of the 24 analysed plaque geometries, respectively. The ability to differentiate plaques was also better in the longitudinal views than in the transverse view. Group velocity as well as phase velocities <1 kHz showed a systematic underestimation of plaque stiffness, stemming from the confined plaque geometries, however, despite this group velocity analysis showed lowest deviation in estimated plaque stiffness (0.1 m s-1 compared to 0.2 m s-1 for phase velocity analysis). SWE results were also invariant to SWE push location, albeit apparent differences in signal-to-noise ratio (SNR) and generated plaque particle velocity. With that, the study has reinforced the potential of SWE for successful plaque differentiation; however the results also highlight the importance of choosing optimal imaging settings and using an appropriate wave speed metric when attempting to differentiate different plaque groups.

Hydraulic forces contribute to left ventricular diastolic filling.

Myocardial active relaxation and restoring forces are known determinants of left ventricular (LV) diastolic function. We hypothesize the existence of an additional mechanism involved in LV filling, namely, a hydraulic force contributing to the longitudinal motion of the atrioventricular (AV) plane. A prerequisite for the presence of a net hydraulic force during diastole is that the atrial short-axis area (ASA) is smaller than the ventricular short-axis area (VSA). We aimed (a) to illustrate this mechanism in an analogous physical model, (b) to measure the ASA and VSA throughout the cardiac cycle in healthy volunteers using cardiovascular magnetic resonance imaging, and (c) to calculate the magnitude of the hydraulic force. The physical model illustrated that the anatomical difference between ASA and VSA provides the basis for generating a hydraulic force during diastole. In volunteers, VSA was greater than ASA during 75-100% of diastole. The hydraulic force was estimated to be 10-60% of the peak driving force of LV filling (1-3 N vs 5-10 N). Hydraulic forces are a consequence of left heart anatomy and aid LV diastolic filling. These findings suggest that the relationship between ASA and VSA, and the associated hydraulic force, should be considered when characterizing diastolic function and dysfunction.

Influence of wall thickness and diameter on arterial shear wave elastography: a phantom and finite element study.

Quantitative, non-invasive and local measurements of arterial mechanical properties could be highly beneficial for early diagnosis of cardiovascular disease and follow up of treatment. Arterial shear wave elastography (SWE) and wave velocity dispersion analysis have previously been applied to measure arterial stiffness. Arterial wall thickness (h) and inner diameter (D) vary with age and pathology and may influence the shear wave propagation. Nevertheless, the effect of arterial geometry in SWE has not yet been systematically investigated. In this study the influence of geometry on the estimated mechanical properties of plates (h = 0.5-3 mm) and hollow cylinders (h = 1, 2 and 3 mm, D = 6 mm) was assessed by experiments in phantoms and by finite element method simulations. In addition, simulations in hollow cylinders with wall thickness difficult to achieve in phantoms were performed (h = 0.5-1.3 mm, D = 5-8 mm). The phase velocity curves obtained from experiments and simulations were compared in the frequency range 200-1000 Hz and showed good agreement (R 2 = 0.80 ± 0.07 for plates and R 2 = 0.82 ± 0.04 for hollow cylinders). Wall thickness had a larger effect than diameter on the dispersion curves, which did not have major effects above 400 Hz. An underestimation of 0.1-0.2 mm in wall thickness introduces an error 4-9 kPa in hollow cylinders with shear modulus of 21-26 kPa. Therefore, wall thickness should correctly be measured in arterial SWE applications for accurate mechanical properties estimation.

Shear Wave Elastography Quantifies Stiffness in Ex Vivo Porcine Artery with Stiffened Arterial Region.

Five small porcine aortas were used as a human carotid artery model, and their stiffness was estimated using shear wave elastography (SWE) in the arterial wall and a stiffened artery region mimicking a stiff plaque. To optimize the SWE settings, shear wave bandwidth was measured with respect to acoustic radiation force push length and number of compounded angles used for motion detection with plane wave imaging. The mean arterial wall and simulated plaque shear moduli varied from 41 ± 5 to 97 ± 10 kPa and from 86 ± 13 to 174 ± 35 kPa, respectively, over the pressure range 20-120 mmHg. The results revealed that a minimum bandwidth of approximately 1500 Hz is necessary for consistent shear modulus estimates, and a high pulse repetition frequency using no image compounding is more important than a lower pulse repetition frequency with better image quality when estimating arterial wall and plaque stiffness using SWE.

Contribution of the Arterial System and the Heart to Blood Pressure during Normal Aging - A Simulation Study.

During aging, systolic blood pressure continuously increases over time, whereas diastolic pressure first increases and then slightly decreases after middle age. These pressure changes are usually explained by changes of the arterial system alone (increase in arterial stiffness and vascular resistance). However, we hypothesise that the heart contributes to the age-related blood pressure progression as well. In the present study we quantified the blood pressure changes in normal aging by using a Windkessel model for the arterial system and the time-varying elastance model for the heart, and compared the simulation results with data from the Framingham Heart Study. Parameters representing arterial changes (resistance and stiffness) during aging were based on literature values, whereas parameters representing cardiac changes were computed through physiological rules (compensated hypertrophy and preservation of end-diastolic volume). When taking into account arterial changes only, the systolic and diastolic pressure did not agree well with the population data. Between 20 and 80 years, systolic pressure increased from 100 to 122 mmHg, and diastolic pressure decreased from 76 to 55 mmHg. When taking cardiac adaptations into account as well, systolic and diastolic pressure increased from 100 to 151 mmHg and decreased from 76 to 69 mmHg, respectively. Our results show that not only the arterial system, but also the heart, contributes to the changes in blood pressure during aging. The changes in arterial properties initiate a systolic pressure increase, which in turn initiates a cardiac remodelling process that further augments systolic pressure and mitigates the decrease in diastolic pressure.

Arterial Stiffness Estimation by Shear Wave Elastography: Validation in Phantoms with Mechanical Testing.

Arterial stiffness is an independent risk factor found to correlate with a wide range of cardiovascular diseases. It has been suggested that shear wave elastography (SWE) can be used to quantitatively measure local arterial shear modulus, but an accuracy assessment of the technique for arterial applications has not yet been performed. In this study, the influence of confined geometry on shear modulus estimation, by both group and phase velocity analysis, was assessed, and the accuracy of SWE in comparison with mechanical testing was measured in nine pressurized arterial phantoms. The results indicated that group velocity with an infinite medium assumption estimated shear modulus values incorrectly in comparison with mechanical testing in arterial phantoms (6.7 ± 0.0 kPa from group velocity and 30.5 ± 0.4 kPa from mechanical testing). To the contrary, SWE measurements based on phase velocity analysis (30.6 ± 3.2 kPa) were in good agreement with mechanical testing, with a relative error between the two techniques of 8.8 ± 6.0% in the shear modulus range evaluated (40-100 kPa). SWE by phase velocity analysis was validated to accurately measure stiffness in arterial phantoms.

Modelling the heart with the atrioventricular plane as a piston unit.

Medical imaging and clinical studies have proven that the heart pumps by means of minor outer volume changes and back-and-forth longitudinal movements in the atrioventricular (AV) region. The magnitude of AV-plane displacement has also shown to be a reliable index for diagnosis of heart failure. Despite this, AV-plane displacement is usually omitted from cardiovascular modelling. We present a lumped-parameter cardiac model in which the heart is described as a displacement pump with the AV plane functioning as a piston unit (AV piston). This unit is constructed of different upper and lower areas analogous with the difference in the atrial and ventricular cross-sections. The model output reproduces normal physiology, with a left ventricular pressure in the range of 8-130 mmHg, an atrial pressure of approximatly 9 mmHg, and an arterial pressure change between 75 mmHg and 130 mmHg. In addition, the model reproduces the direction of the main systolic and diastolic movements of the AV piston with realistic velocity magnitude (∼10 cm/s). Moreover, changes in the simulated systolic ventricular-contraction force influence diastolic filling, emphasizing the coupling between cardiac systolic and diastolic functions. The agreement between the simulation and normal physiology highlights the importance of myocardial longitudinal movements and of atrioventricular interactions in cardiac pumping.

Closed-loop real-time simulation model of hemodynamics and oxygen transport in the cardiovascular system.

BACKGROUND: Computer technology enables realistic simulation of cardiovascular physiology. The increasing number of clinical surgical and medical treatment options imposes a need for better understanding of patient-specific pathology and outcome prediction. METHODS: A distributed lumped parameter real-time closed-loop model with 26 vascular segments, cardiac modelling with time-varying elastance functions and gradually opening and closing valves, the pericardium, intrathoracic pressure, the atrial and ventricular septum, various pathological states and including oxygen transport has been developed. RESULTS: Model output is pressure, volume, flow and oxygen saturation from every cardiac and vascular compartment. The model produces relevant clinical output and validation of quantitative data in normal physiology and qualitative directions in simulation of pathological states show good agreement with published data. CONCLUSION: The results show that it is possible to build a clinically relevant real-time computer simulation model of the normal adult cardiovascular system. It is suggested that understanding qualitative interaction between physiological parameters in health and disease may be improved by using the model, although further model development and validation is needed for quantitative patient-specific outcome prediction.

Evaluation of the brain network organization from EEG signals: a preliminary evidence in stroke patient.

Synchronous brain activity in motor cortex in perception or in complex cognitive processing has been the subject of several studies. The advanced analysis of cerebral electro-physiological activity during the course of planning (PRE) or execution of movement (EXE) in a high temporal resolution could reveal interesting information about the brain functional organization in patients following stroke damage. High-power (128 channels) electroencephalography registration was carried out on 8 healthy subjects and on a patient with stroke with capsular lacuna in the right hemisphere. For activation of motor cortex, the finger tapping paradigm was used. In this preliminary study, we tested a theoretical graph approach to characterize the task-related spectral coherence. All of the obtained brain functional networks were analyzed by the connectivity degree, the degree distribution, and efficiency parameters in the Theta, Alpha, Beta, and Gamma bands during the PRE and EXE intervals. All the brain networks were found to hold a regular and ordered topology. However, significant differences (P < 0.01) emerged between the patient with stroke and the control subjects, independently of the neural processes related to the PRE or EXE periods. In the Beta (13-29 Hz) and Gamma (30-40 Hz) bands, the significant (P < 0.01) decrease in global- and local-efficiency in the patient's networks, reflected a lower capacity to integrate communication between distant brain regions and a lower tendency to be modular. This weak organization is principally due to the significant (P < 0.01 Bonferroni corrected) increase in disconnected nodes together with the significant increase in the links in some other crucial vertices.