Mechanistic insights on age-related changes in heart-aorta-brain hemodynamic coupling using a pulse wave model of the entire circulatory system.

Age-related changes in aortic biomechanics can impact the brain by reducing blood flow and increasing pulsatile energy transmission. Clinical studies have shown that impaired cardiac function in patients with heart failure is associated with cognitive impairment. Although previous studies have attempted to elucidate the complex relationship between age-associated aortic stiffening and pulsatility transmission to the cerebral network, they have not adequately addressed the effect of interactions between aortic stiffness and left ventricle (LV) contractility (neither on energy transmission nor on brain perfusion). In this study, we use a well-established and validated one-dimensional blood flow and pulse wave computational model of the circulatory system to address how age-related changes in cardiac function and vasculature affect the underlying mechanisms involved in the LV-aorta-brain hemodynamic coupling. Our results reveal how LV contractility affects pulsatile energy transmission to the brain, even with preserved cardiac output. Our model demonstrates the existence of an optimal heart rate (near the normal human heart rate) that minimizes pulsatile energy transmission to the brain at different contractility levels. Our findings further suggest that the reduction in cerebral blood flow at low levels of LV contractility is more prominent in the setting of age-related aortic stiffening. Maintaining optimal blood flow to the brain requires either an increase in contractility or an increase in heart rate. The former consistently leads to higher pulsatile power transmission, and the latter can either increase or decrease subsequent pulsatile power transmission to the brain.NEW & NOTEWORTHY We investigated the impact of major aging mechanisms of the arterial system and cardiac function on brain hemodynamics. Our findings suggest that aging has a significant impact on heart-aorta-brain coupling through changes in both arterial stiffening and left ventricle (LV) contractility. Understanding the underlying physical mechanisms involved here can potentially be a key step for developing more effective therapeutic strategies that can mitigate the contributions of abnormal LV-arterial coupling toward neurodegenerative diseases and dementia.

Direct 0D-3D coupling of a lattice Boltzmann methodology for fluid-structure aortic flow simulations.

This work introduces a numerical approach and implementation for the direct coupling of arbitrary complex ordinary differential equation- (ODE-)governed zero-dimensional (0D) boundary conditions to three-dimensional (3D) lattice Boltzmann-based fluid-structure systems for hemodynamics studies. In particular, a most complex configuration is treated by considering a dynamic left ventricle- (LV-)elastance heart model which is governed by (and applied as) a nonlinear, non-stationary hybrid ODE-Dirichlet system. Other ODE-based boundary conditions, such as lumped parameter Windkessel models for truncated vasculature, are also considered. Performance studies of the complete 0D-3D solver, including its treatment of the lattice Boltzmann fluid equations and elastodynamics equations as well as their interactions, is conducted through a variety of benchmark and convergence studies that demonstrate the ability of the coupled 0D-3D methodology in generating physiological pressure and flow waveforms-ultimately enabling the exploration of various physical and physiological parameters for hemodynamics studies of the coupled LV-arterial system. The methods proposed in this paper can be easily applied to other ODE-based boundary conditions as well as to other fluid problems that are modeled by 3D lattice Boltzmann equations and that require direct coupling of dynamic 0D boundary conditions.

Thermal and Postural Effects on Fluid Mixing and Irrigation Patterns for Intraventricular Hemorrhage Treatment.

Intraventricular hemorrhage is characterized by blood leaking into the cerebral ventricles and mixing with cerebrospinal fluid. A standard treatment method involves inserting a passive drainage catheter, known as an external ventricular drain (EVD), into the ventricle. EVDs have common adverse complications, including the occlusion of the catheter, that may lead to permanent neural damage or even mortality. In order to prevent such complications, a novel dual-lumen catheter (IRRAflow®) utilizing an active fluid exchange mechanism has been recently developed. However, the fluid dynamics of the exchange system have not been investigated. In this study, convective flow in a three-dimensional cerebral lateral ventricle with an inserted catheter is evaluated using an in-house lattice-Boltzmann-based fluid-solid interaction solver. Different treatment conditions are simulated, including injection temperature and patient position. Thermal and gravitational effects on medication distribution are studied using a dye simulator based on a recently-introduced (pseudo)spectral convection-diffusion equation solver. The effects of injection temperature and patient position on catheter performance are presented and discussed in terms of hematoma irrigation, vortical structures, mixing, and medication volume distribution. Results suggest that cold-temperature injections can increase catheter efficacy in terms of dye distribution and irrigation potential, both of which can be further guided by patient positioning.

Effects of vessel wall mechanics on non-invasive evaluation of cardiovascular intrinsic frequencies.

Intrinsic Frequency (IF) is a systems-based approach that provides valuable information for hemodynamic monitoring of the left ventricle (LV), the arterial system, and their coupling. Recent clinical studies have demonstrated the clinical significance of this method for prognosis and diagnosis of cardiovascular diseases. In IF analysis, two dominant instantaneous frequencies (ω1 and ω2) are extracted from arterial pressure waveforms. The value of ω1 is related to the dynamics of the LV and the value of ω2 is related to the dynamics of vascular function. This work investigates the effects of vessel wall mechanics on the accuracy and applicability of IFs extracted from vessel wall displacement waveforms compared to IFs extracted from pressure waveforms. In this study, we used a computational approach employing a fluid-structure interaction finite element method for various wall mechanics governed by linearly elastic, hyperelastic, and viscoelastic models. Results show that for vessels with elastic wall behavior, the error between displacement-based and pressure-based IFs is negligible. In the presence of stenosis or aneurysm in elastic arteries, the maximum errors associated with displacement-based IFs is less than 2%. For non-linear elastic and viscoelastic arteries, errors are more pronounced (where the former reaches up to 11% and the latter up to 27%). Our results ultimately suggest that displacement-based computations of ω1 and ω2 are accurate in vessels that exhibit elastic behavior (such as carotid arteries) and are suitable surrogates for pressure-based IFs. This is clinically significant because displacement-based IFs can be measured non-invasively.

Accuracy and applicability of non-invasive evaluation of aortic wave intensity using only pressure waveforms in humans.

Background.Wave intensity (WI) analysis is a well-established method for quantifying the energy carried in arterial waves, providing valuable clinical information about cardiovascular function. The primary drawback of this method is the need for concurrent measurements of both pressure and flow waveforms.Objective. We have for the first time investigated the accuracy of a novel methodology for estimating wave intensity employing only single pressure waveform measurements; we studied both carotid- and radial-based estimations in a large heterogeneous cohort.Approach.Tonometry was performed alongside Doppler ultrasound to acquire measurements of both carotid and radial pressure waveforms as well as aortic flow waveforms in 2640 healthy and diseased participants (1439 female) in the Framingham Heart Study. Patterns consisting of two forward waves (Wf1, Wf2) and one backward wave (Wb1) along with reflection metrics were compared with those obtained from exact WI analysis.Main Results. Carotid-based estimates correlated well for forward peak amplitudes (Wf1,r = 0.85,p < 0.05; Wf2,r = 0.72,p < 0.05) and peak time (Wf1,r = 0.94,p < 0.05; Wf2,r = 0.98,p < 0.05), and radial-based estimates correlated fairly to poorly for amplitudes (Wf1,r = 0.62,p < 0.05; Wf2,r = 0.42,p < 0.05) and peak time (Wf1,r = 0.04,p = 0.10; Wf2,r = 0.75,p < 0.05). In all cases, estimated Wb1 measures were not correlated. Reflection metrics were well correlated for healthy patients (r = 0.67,p < 0.05), moderately correlated for valvular disease (r = 0.59,p < 0.05) and fairly correlated for CVD (r = 0.46,p < 0.05) and heart failure (r = 0.49,p < 0.05).Significance. These findings indicate that pressure-only WI produces accurate results only when forward contributions are of primary interest and only for carotid pressure waveforms. The pressure-only WI estimations of this work provide an important opportunity to further the goal of uncovering clinical insights through wave analysis affordably and non-invasively.

Scalability of cardiovascular intrinsic frequencies: Validations in preclinical models and non-invasive clinical studies.

AIMS: Cardiovascular intrinsic frequencies (IFs) are associated with cardiovascular health and disease, separately capturing the systolic and diastolic information contained in a single (uncalibrated) arterial waveform. Previous clinical investigations related to IF have been restricted to studying chronic conditions, and hence its applicability for acute cardiovascular diseases has not been explored. Studies of cardiovascular complications such as acute myocardial infarction are difficult to perform in humans due to the high-risk and invasive nature of such procedures. Although they can be performed in preclinical (animal) models, the corresponding interpretation of IF measures and how they ultimately translate to humans is unknown. Hence, we studied the scalability of IF across species and sensor platforms. MATERIALS AND METHODS: Scaled values of the two intrinsic frequencies ω1 and ω2 (corresponding to systolic and diastolic dynamics, respectively) were extracted from carotid waveforms acquired either non-invasively (via tonometry, Vivio or iPhone) in humans or invasively in rabbits and rats. KEY FINDINGS: The scaled IF parameters for all species were found to fall within the same physiological ranges carrying similar statistical characteristics, even though body sizes and corresponding heart rates of the species were substantially different. Additionally, results demonstrated that all non-invasive sensor platforms were significantly correlated with each other for scaled IFs, suggesting that such analysis is device-agnostic and can be applied to upcoming wearable technologies. SIGNIFICANCE: Ultimately, our results found that IFs are scalable across species, which is particularly valuable for the training of IF-based artificial intelligence systems using both preclinical and clinical data.

Anatomy of strike-slip fault tsunami genesis.

Tsunami generation from earthquake-induced seafloor deformations has long been recognized as a major hazard to coastal areas. Strike-slip faulting has generally been considered insufficient for triggering large tsunamis, except through the generation of submarine landslides. Herein, we demonstrate that ground motions due to strike-slip earthquakes can contribute to the generation of large tsunamis (>1 m), under rather generic conditions. To this end, we developed a computational framework that integrates models for earthquake rupture dynamics with models of tsunami generation and propagation. The three-dimensional time-dependent vertical and horizontal ground motions from spontaneous dynamic rupture models are used to drive boundary motions in the tsunami model. Our results suggest that supershear ruptures propagating along strike-slip faults, traversing narrow and shallow bays, are prime candidates for tsunami generation. We show that dynamic focusing and the large horizontal displacements, characteristic of strike-slip earthquakes on long faults, are critical drivers for the tsunami hazard. These findings point to intrinsic mechanisms for sizable tsunami generation by strike-slip faulting, which do not require complex seismic sources, landslides, or complicated bathymetry. Furthermore, our model identifies three distinct phases in the tsunamic motion, an instantaneous dynamic phase, a lagging coseismic phase, and a postseismic phase, each of which may affect coastal areas differently. We conclude that near-source tsunami hazards and risk from strike-slip faulting need to be re-evaluated.

Dynamic Effects of Aortic Arch Stiffening on Pulsatile Energy Transmission to Cerebral Vasculature as A Determinant of Brain-Heart Coupling.

Aortic stiffness increases with age and is a robust predictor of brain pathology including Alzheimer's and other dementias. Aging causes disproportionate stiffening of the aorta compared with the carotid arteries, reducing protective impedance mismatches at their interface and affecting transmission of destructive pulsatile energy to the cerebral circulation. Recent clinical studies have measured regional stiffness within the aortic arch using pulse wave velocity (PWV) and have found a stronger association with cerebrovascular events than global stiffness measures. However, effects of aortic arch PWV on the transmission of harmful excessive pulsatile energy to the brain is not well-understood. In this study, we use an energy-based analysis of hemodynamic waves to quantify the effect of aortic arch stiffening on transmitted pulsatility to cerebral vasculature, employing a computational approach using a one-dimensional model of the human vascular network. Results show there exists an optimum wave condition-occurring near normal human heart rates-that minimizes pulsatile energy transmission to the brain. This indicates the important role of aortic arch biomechanics on heart-brain coupling. Our results also suggest that energy-based indices of pulsatility combining pressure and flow data are more sensitive to increased stiffness than using flow or pressure pulsatility indices in isolation.

A physiologically relevant, simple outflow boundary model for truncated vasculature.

A realistic outflow boundary condition model for pulsatile flow in a compliant vessel is studied by taking into account physiological effects: compliance, resistance, and wave reflection of the downstream vasculature. The new model extends the computational domain with an elastic tube terminated in a rigid contraction. The contraction ratio, the length, and elasticity of the terminal tube can be adjusted to represent effects of the truncated vasculature. Using the wave intensity analysis method, we apply the model to the test cases of a straight vessel and the aorta and find good agreement with the physiological characteristics of blood flow and pressure. The model is suitable for cardiac transient (non-periodic) events and easily employed using so-called black box software.