Experimental study of the mechanics of the intra-aortic balloon

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.This thesis deals with the mechanics of the Intra-Aortic Balloon Pump (IABP), the most widely used temporary cardiac assist device, whose beneficial action is based on the principle of counterpulsation. The investigation is carried out in vitro in increasingly more realistic setups, including a mock circulatory system with physiological distribution of peripheral resistance and compliance in which IABP counterpulsation was simulated. Pressure and flow measurements show the effect of variables such as intra-luminal pressure, angle and aortic compliance on balloon hemodynamics. These data are complemented by results on the duration of balloon inflation and deflation obtained by means of high-speed camera visualisation. Furthermore, wave intensity analysis is carried out and it is identified as a possible alternative method for the assessment of IABP performance. This work includes two prototypes of intra-aortic balloons of novel shape with the balloon chamber tapering both from and toward the balloon tip. In clinical terms, with reference to the semi-recumbent position in which patients assisted with the IABP are nursed in the intensive care unit, the results presented in this thesis indicate that operating the balloon at an angle compromises the benefit of counterpulsation when assessed in vitro

Neural Recurrent Approches to Noninvasive Blood Pressure Estimation

4This paper presents a comparison between two recurrent neural networks (RNN) for arterial blood pressure (ABP) estimation. ABP is a parameter closely related to the cardiac activity, for this reason its monitoring implies decreasing the risk of heart disease. In order to predict the ABP values (both systolic and diastolic), electrocardiographic (ECG) and photoplethysmographic (PPG) signals are used, separately, as inputs of the networks. To train the artificial neural networks, the synchronized signals are extracted from the Physionet MIMIC database. The output-error Neural networks (NNOE) and the Long Short Term Memory (LSTM) architectures are compared in terms of RMSE and absolute error. NNOE neural network, with ECG signal as input, results the best configuration in terms of both the proposed metrics. The predicted ABP falls within the values of the normative ANSI/AAMI/ ISO 81060-2:2013 for sphygmomanometer certification.partially_openopenAnnunziata Paviglianiti; Vincenzo Randazzo; Giansalvo Cirrincione; Eros PaseroPaviglianiti, Annunziata; Randazzo, Vincenzo; Cirrincione, Giansalvo; Pasero, EROS GIAN ALESSANDR

Arterial pulse wave modeling and analysis for vascular-age studies: a review from VascAgeNet

Aging; Arteriosclerosis; HemodynamicsEnvelliment; Arteriosclerosi; HemodinàmicaEnvejecimiento; Arteriosclerosis; HemodinámicaArterial pulse waves (PWs) such as blood pressure and photoplethysmogram (PPG) signals contain a wealth of information on the cardiovascular (CV) system that can be exploited to assess vascular age and identify individuals at elevated CV risk. We review the possibilities, limitations, complementarity, and differences of reduced-order, biophysical models of arterial PW propagation, as well as theoretical and empirical methods for analyzing PW signals and extracting clinically relevant information for vascular age assessment. We provide detailed mathematical derivations of these models and theoretical methods, showing how they are related to each other. Finally, we outline directions for future research to realize the potential of modeling and analysis of PW signals for accurate assessment of vascular age in both the clinic and in daily life.This article is based upon work from COST Action “Network for Research in Vascular Ageing” (VascAgeNet, CA18216), supported by COST (European Cooperation in Science and Technology, www.cost.eu). This work was supported by British Heart Foundation Grants PG/15/104/31913 (to J.A. and P.H.C.), FS/20/20/34626 (to P.H.C.), and AA/18/6/34223, PG/17/90/33415, SPG 2822621, and SP/F/21/150020 (to A.D.H.); Kaunas University of Technology Grant INP2022/16 (to B.P.); European Research Executive Agency, Marie-Sklodowska Curie Actions Individual Fellowship Grant 101038096 (to S.P.); Istinye University, BAP Project Grant 2019B1 (to S.P.); “la Caixa” Foundation Grant LCF/BQ/PR22/11920008 (to A.G.); and National Institute for Health and Care Research Grant AI AWARD02499 and EU Horizon 2020 Grant H2020 848109 (to A.D.H.)

An inverse transmission line model of the lower limb arterial system

Includes bibliography. Includes disk in pocket at back of book

Quantifying the Impact of Altered Hemodynamics and Vascular Biomechanics to Changes in Structure and Function in Native and Corrected Aortic Coarctation

Coarctation of the aorta (CoA) is associated with substantial cardiovascular morbidities despite successful treatment through surgical or catheter-based intervention. Although specific mechanisms leading to these morbidities remain elusive, abnormal hemodynamics and vascular biomechanics are implicated. We used a novel animal model that facilitates quantification of CoA-induced hemodynamic and vascular biomechanics alterations and their impact on vascular structure and function, independent of genetic or confounding factors. Rabbits underwent thoracic CoA at 10 weeks of age (~9 human years) to induce a 20 mmHg blood pressure (BP) gradient using permanent or dissolvable suture thereby replicating untreated and corrected CoA. Computational fluid dynamics (CFD) was performed using subject-specific imaging and BP data at 32 weeks to quantify velocity, strain, and wall shear stress (WSS). Vascular structure and function were evaluated at proximal and distal locations by histology, immunohistochemistry, and myograph analysis. Results revealed proximal systolic and mean BP was elevated in CoA compared to corrected and control rabbits leading to vascular remodeling, endothelial dysfunction proximally and distally, and increased stiffness and reduced active force response proximally. Corrected rabbits had reduced but significant medial thickening, endothelial dysfunction, and stiffening limited to the proximal region despite 12 weeks of alleviated systolic and mean BP (~4 human years) after the suture dissolved. Proximal arteries of CoA and corrected groups demonstrated increased non-muscle myosin expression and decreased myosin heavy chain expression, and this dedifferentiation may influence vascular remodeling and aortic stiffening. CFD analysis of untreated CoA rabbits demonstrated significantly reduced WSS proximal to CoA and markedly elevated WSS distally due to the presence of a stenotic velocity jet. Results from corrected rabbits indicate the velocity jet may have persistent effects on hemodynamics, as WSS remained significantly reduced. These hemodynamic and morphological observations are consistent with alterations in human patients. Using these coupled imaging and experimental results, we may determine changes in structure and function specific to CoA and correction and how they are influenced by hemodynamics and vascular biomechanics. We are now poised to augment clinical treatment of CoA through several methods, including investigation of specific cellular mechanisms causing morbidity in CoA and the development of therapies to improve endothelial function and restore vascular stiffness

Arterial pulse wave modelling and analysis for vascular age studies: a review from VascAgeNet

Arterial pulse waves (PWs) such as blood pressure and photoplethysmogram (PPG) signals contain a wealth of information on the cardiovascular (CV) system that can be exploited to assess vascular age and identify individuals at elevated CV risk. We review the possibilities, limitations, complementarity, and differences of reduced-order, biophysical models of arterial PW propagation, as well as theoretical and empirical methods for analyzing PW signals and extracting clinically relevant information for vascular age assessment. We provide detailed mathematical derivations of these models and theoretical methods, showing how they are related to each other. Finally, we outline directions for future research to realize the potential of modeling and analysis of PW signals for accurate assessment of vascular age in both the clinic and in daily life

Uncertainty quantification of viscoelastic parameters in arterial hemodynamics with the a-FSI blood flow model

This work aims at identifying and quantifying uncertainties related to elastic and viscoelastic parameters, which characterize the arterial wall behavior, in one-dimensional modeling of the human arterial hemodynamics. The chosen uncertain parameters are modeled as random Gaussian-distributed variables, making stochastic the system of governing equations. The proposed methodology is initially validated on a model equation, presenting a thorough convergence study which confirms the spectral accuracy of the stochastic collocation method and the second-order accuracy of the IMEX finite volume scheme chosen to solve the mathematical model. Then, univariate and multivariate uncertain quantification analyses are applied to the a-FSI blood flow model, concerning baseline and patient-specific single-artery test cases. A different sensitivity is depicted when comparing the variability of flow rate and velocity waveforms to the variability of pressure and area, the latter ones resulting much more sensitive to the parametric uncertainties underlying the mechanical characterization of vessel walls. Simulations performed considering both the simple elastic and the more realistic viscoelastic constitutive law show that the great uncertainty of the viscosity parameter plays a major role in the prediction of pressure waveforms, enlarging the confidence interval of this variable. In-vivo recorded patient-specific pressure data falls within the confidence interval of the output obtained with the proposed methodology and expectations of the computed pressures are comparable to the recorded waveforms

The effects of obesity and pre-diabetic conditions on ventricular-arterial coupling in women

Obesity is associated with an increased risk of developing type 2 diabetes and women with diabetes have a higher relative-risk of cardiovascular mortality than men. Polycystic ovary syndrome (PCOS) is a common condition that is associated with obesity and confers a particularly high risk of diabetes. There is a need to identify cardiovascular dysfunction in the pre-diabetic stage because, once diabetes is evident, it is difficult to improve the prognosis. Left ventricular hypertrophy (LVH) and diastolic dysfunction are well-established consequences of obesity, but the mechanisms which underpin these findings are not well-defined. Measurements of ventricular-arterial coupling characterise the load which the ventricle must overcome to eject blood. This thesis investigated whether quantitative measures of ventricular-arterial coupling could explain the development of LVH and diastolic dysfunction in young women at risk of diabetes. Two methods of quantifying ventricular-arterial coupling were used (i) a comparison of arterial and ventricular end-systolic elastance, and (ii) the amplitude and timing of wave reflections in the carotid artery using wave intensity. Increases in elastance were associated with general and central obesity. In contrast, increased wave reflections were predominantly associated with fat around the organs and with worse metabolic health. Arterial elastance and wave reflections were independent contributors of left ventricular mass but did not independently contribute to diastolic function. Women with PCOS had similar cardiovascular risk, elastance and diastolic function to matched controls. However, they had a lower odds-ratio of LVH which appeared to be explained by lower amplitude wave reflections. There may be an aspect of PCOS which mitigates the effects of obesity and pre-diabetic states on the pulsatile loading of the left ventricle. The quantification of ventricular-arterial coupling provides new insights to the effects of obesity and pre-diabetic states on sub-clinical cardiovascular disease

Ultrasonic Pulse Wave Imaging for in vivo Assessment of Vascular Wall Dynamics and Characterization of Arterial Pathologies

Arterial diseases such as hypertension, carotid stenosis, and abdominal aortic aneurysm (AAA) may progress silently without symptoms and contribute to acute cardiovascular events such as heart attack, stroke, and aneurysm rupture, which are consistently among the leading causes of death worldwide. The arterial pulse wave, regarded as one of the fundamental vital signs of clinical medicine, originates from the heart and propagates throughout the arterial tree as a pressure, flow velocity, and wall displacement wave, giving rise to the natural pulsation of the arteries. The dynamic properties of the pulse wave are intimately related to the physical state of the cardiovascular system. Thus, the assessment of the arterial wall dynamics driven by the pulse wave may provide valuable insights into vascular mechanical properties for the early detection and characterization of arterial pathologies. The focus of this dissertation was to develop and clinically implement Pulse Wave Imaging (PWI), an ultrasound elasticity imaging-based method for the visualization and spatio-temporal mapping of the pulse wave propagation at any accessible arterial location. Motion estimation algorithms based on cross-correlation of the ultrasound radio-frequency (RF) signals were used to track the arterial walls and capture the pulse wave-induced displacements over the cardiac cycle. PWI facilitates the image-guided measurement of clinically relevant pulse wave features such as propagation speed (pulse wave velocity, or PWV), uniformity, and morphology as well as derivation of the pulse pressure waveform. A parametric study investigating the performance of PWI in two canine aortas ex vivo and 10 normal, healthy human arteries in vivo established the optimal image acquisition and signal processing parameters for reliable measurement of the PWV and wave propagation uniformity. Using this framework, three separate clinical feasibility studies were conducted in patients diagnosed with hypertension, AAA, and carotid stenosis. In a pilot study comparing hypertensive and aneurysmal abdominal aortas with normal controls, the AAA group exhibited significantly higher PWV and lower wave propagation uniformity. A “teetering” motion upon pulse wave arrival was detected in the smaller aneurysms ( 5.5 cm in diameter). While no significant difference in PWV or propagation uniformity was observed between normal and hypertensive aortas, qualitative differences in the pulse wave morphology along the imaged aortic segment may be an indicator of increased wave reflection caused by elevated blood pressure and/or arterial stiffness. Pulse Wave Ultrasound Manometry (PWUM) was introduced as an extension of the PWI method for the derivation of the pulse pressure (PP) waveform in large central arteries. A feasibility study in 5 normotensive, 9 pre-hypertensive, and 5 hypertensive subjects indicated that a significantly higher PP in the hypertensive group was detected in the abdominal aorta by PWUM but not in the peripheral arteries by alternative devices (i.e. a radial applanation tonometer and the brachial sphygmomanometer cuff). A relatively strong positive correlation between aortic PP and both radial and brachial PP was observed in the hypertensive group but not in the normal and pre-hypertensive groups, confirming the notion that PP variation throughout the arterial tree may not be uniform in relatively compliant arteries. The application of PWI in 10 stenotic carotid arteries identified phenomenon such as wave convergence, elevated PWV, and decreased cumulative displacement around and/or within regions of atherosclerotic plaque. Intra-plaque mapping of the PWV and cumulative strain demonstrated the potential to quantitatively differentiate stable (i.e. calcified) and vulnerable (i.e. lipid) plaque components. The lack of correlation between quantitative measurements (PWV, modulus, displacement, and strain) and expected plaque stiffness illuminates to need to consider several physiological and imaging-related factors such as turbulent flow, wave reflection, imaging location, and the applicability of established theoretical models in vivo. PWI presents a highly translational method for visualization of the arterial pulse wave and the image-guided measurement of several clinically relevant pulse wave features. The aforementioned findings collectively demonstrated the potential of PWI to detect, diagnose, and characterize vascular disease based on qualitative and quantitative information about arterial wall dynamics under pathological conditions