From time-series to complex networks: Application to the cerebrovascular flow patterns in atrial fibrillation

A network-based approach is presented to investigate the cerebrovascular flow patterns during atrial fibrillation (AF) with respect to normal sinus rhythm (NSR). AF, the most common cardiac arrhythmia with faster and irregular beating, has been recently and independently associated with the increased risk of dementia. However, the underlying hemodynamic mechanisms relating the two pathologies remain mainly undetermined so far; thus the contribution of modeling and refined statistical tools is valuable. Pressure and flow rate temporal series in NSR and AF are here evaluated along representative cerebral sites (from carotid arteries to capillary brain circulation), exploiting reliable artificially built signals recently obtained from an in silico approach. The complex network analysis evidences, in a synthetic and original way, a dramatic signal variation towards the distal/capillary cerebral regions during AF, which has no counterpart in NSR conditions. At the large artery level, networks obtained from both AF and NSR hemodynamic signals exhibit elongated and chained features, which are typical of pseudo-periodic series. These aspects are almost completely lost towards the microcirculation during AF, where the networks are topologically more circular and present random-like characteristics. As a consequence, all the physiological phenomena at microcerebral level ruled by periodicity - such as regular perfusion, mean pressure per beat, and average nutrient supply at cellular level - can be strongly compromised, since the AF hemodynamic signals assume irregular behaviour and random-like features. Through a powerful approach which is complementary to the classical statistical tools, the present findings further strengthen the potential link between AF hemodynamic and cognitive decline.Comment: 12 pages, 10 figure

Integration of anatomical and hemodynamical information in magnetic resonance angiography

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PIV-based Investigation of Hemodynamic Factors in Diseased Carotid Artery Bifurcations with Varying Plaque Geometries

Ischemic stroke is often a consequence of complications due to clot formation (i.e. thrombosis) at the site of an atherosclerotic plaque developed in the internal carotid artery. Hemodynamic factors, such as shear-stress forces and flow disturbances, can facilitate the key mechanisms of thrombosis. Atherosclerotic plaques can differ in the severity of stenosis (narrowing), in eccentricity (symmetry), as well as inclusion of ulceration (wall roughness). Therefore, in terms of clinical significance, it is important to investigate how the local hemodynamics of the carotid artery is mediated by the geometry of plaque. Knowledge of thrombosis-associated hemodynamics may provide a basis to introduce advanced clinical diagnostic indices that reflect the increased probability of thrombosis and thus assist with better estimation of stroke risk, which is otherwise primarily assessed based on the degree of narrowing of the lumen. A stereoscopic particle image velocimetry (stereo-PIV) system was configured to obtain instantaneous full-field velocity measurements in life-sized carotid artery models. Extraction of the central-plane and volumetric features of the flow revealed the complexity of the stenotic carotid flow, which increased with increasing stenosis severity and changed with the symmetry of the plaque. Evaluation of the energy content of two models of the stenosed carotid bifurcation provided insight on the expected level of flow instabilities with potential clinical implications. Studies in a comprehensive family of eight models ranging from disease-free to severely stenosed (30%, 50%, 70% diameter reduction) and with two types of plaque symmetry (concentric or eccentric), as well as a single ulcerated stenosed model, clearly demonstrated the significance of plaque geometry in marked alteration of the levels and patterns of downstream flow disturbances and shear stress. Plaque eccentricity and ulceration resulted in enhanced flow disturbances. In addition, shear-stress patterns in those models with eccentric stenosis were suggestive of increased thrombosis potential at the post-stenotic recirculation zone compared to their concentric counterpart plaques

Methods and Algorithms for Cardiovascular Hemodynamics with Applications to Noninvasive Monitoring of Proximal Blood Pressure and Cardiac Output Using Pulse Transit Time

Advanced health monitoring and diagnostics technology are essential to reduce the unrivaled number of human fatalities due to cardiovascular diseases (CVDs). Traditionally, gold standard CVD diagnosis involves direct measurements of the aortic blood pressure (central BP) and flow by cardiac catheterization, which can lead to certain complications. Understanding the inner-workings of the cardiovascular system through patient-specific cardiovascular modeling can provide new means to CVD diagnosis and relating treatment. BP and flow waves propagate back and forth from heart to the peripheral sites, while carrying information about the properties of the arterial network. Their speed of propagation, magnitude and shape are directly related to the properties of blood and arterial vasculature. Obtaining functional and anatomical information about the arteries through clinical measurements and medical imaging, the digital twin of the arterial network of interest can be generated. The latter enables prediction of BP and flow waveforms along this network. Point of care devices (POCDs) can now conduct in-home measurements of cardiovascular signals, such as electrocardiogram (ECG), photoplethysmogram (PPG), ballistocardiogram (BCG) and even direct measurements of the pulse transit time (PTT). This vital information provides new opportunities for designing accurate patient-specific computational models eliminating, in many cases, the need for invasive measurements. One of the main efforts in this area is the development of noninvasive cuffless BP measurement using patient’s PTT. Commonly, BP prediction is carried out with regression models assuming direct or indirect relationships between BP and PTT. However, accounting for the nonlinear FSI mechanics of the arteries and the cardiac output is indispensable. In this work, a monotonicity-preserving quasi-1D FSI modeling platform is developed, capable of capturing the hyper-viscoelastic vessel wall deformation and nonlinear blood flow dynamics in arbitrary arterial networks. Special attention has been dedicated to the correct modeling of discontinuities, such as mechanical properties mismatch associated with the stent insertion, and the intertwining dynamics of multiscale 3D and 1D models when simulating the arterial network with an aneurysm. The developed platform, titled Cardiovascular Flow ANalysis (CardioFAN), is validated against well-known numerical, in vitro and in vivo arterial network measurements showing average prediction errors of 5.2%, 2.8% and 1.6% for blood flow, lumen cross-sectional area, and BP, respectively. CardioFAN evaluates the local PTT, which enables patient-specific calibration and its application to input signal reconstruction. The calibration is performed based on BP, stroke volume and PTT measured by POCDs. The calibrated model is then used in conjunction with noninvasively measured peripheral BP and PTT to inversely restore the cardiac output, proximal BP and aortic deformation in human subjects. The reconstructed results show average RMSEs of 1.4% for systolic and 4.6% for diastolic BPs, as well as 8.4% for cardiac output. This work is the first successful attempt in implementation of deterministic cardiovascular models as add-ons to wearable and smart POCD results, enabling continuous noninvasive monitoring of cardiovascular health to facilitate CVD diagnosis

Automatic identification of characteristic points related to pathologies in electrocardiograms to design expert systems

Electrocardiograms (ECG) record the electrical activity of the heart through 12 main signals called shunts. Medical experts examine certain segments of these signals in where they believe the cardiovascular disease is manifested. This fact is an important determining factor for designing expert systems for cardiac diagnosis, as it requires the direct expert opinion in order to locate these specific segments in the ECG. The main contributions of this paper are: (i) to propose a model that uses the full ECG signal to identify key characteristic points that define cardiac pathology without medical expert intervention and (ii) to present an expert system based on artificial neural networks capable of detecting bundle branch block disease using the previous approach. Cardiologists have validated the proposed model application and a comparative analysis is performed using the MIT-BIH arrhythmia database.Spanish project TSI-020302-2010-136 University of Málaga: 81434547001-

Measuring blood flow and pro-inflammatory changes in the rabbit aorta

Atherosclerosis is a chronic inflammatory disease that develops as a consequence of progressive entrapment of low density lipoprotein, fibrous proteins and inflammatory cells in the arterial intima. Once triggered, a myriad of inflammatory and atherogenic factors mediate disease progression. However, the role of pro-inflammatory activity in the initiation of atherogenesis and its relation to altered mechanical stresses acting on the arterial wall is unclear. Estimation of wall shear stress (WSS) and the inflammatory mediator NF-κB is consequently useful. In this thesis novel ultrasound tools for accurate measurement of spatiotemporally varying 2D and 3D blood flow, with and without the use of contrast agents, have been developed. This allowed for the first time accurate, broad-view quantification of WSS around branches of the rabbit abdominal aorta. A thorough review of the evidence for a relationship between flow, NF-κB and disease was performed which highlighted discrepancies in the current literature and was used to guide the study design. Subsequently, methods for the measurement and colocalization of the spatial distribution of NF-κB, arterial permeability and nuclear morphology in the aorta of New Zealand White rabbits were developed. It was demonstrated that endothelial pro-inflammatory changes are spatially correlated with patterns of WSS, nuclear morphology and arterial permeability in vivo in the rabbit descending and abdominal aorta. The data are consistent with a causal chain between WSS, macromolecule uptake, inflammation and disease, and with the hypothesis that lipids are deposited first, through flow-mediated naturally occurring transmigration that, in excessive amounts, leads to subsequent inflammation and disease.Open Acces

Computational Physiology

This open access volume compiles student reports from the 2021 Simula Summer School in Computational Physiology. Interested readers will find herein a number of modern approaches to modeling excitable tissue. This should provide a framework for tools available to model subcellular and tissue-level physiology across scales and scientific questions. In June through August of 2021, Simula held the seventh annual Summer School in Computational Physiology in collaboration with the University of Oslo (UiO) and the University of California, San Diego (UCSD). The course focuses on modeling excitable tissues, with a special interest in cardiac physiology and neuroscience. The majority of the school consists of group research projects conducted by Masters and PhD students from around the world, and advised by scientists at Simula, UiO and UCSD. Each group then produced a report that addreses a specific problem of importance in physiology and presents a succinct summary of the findings. Reports may not necessarily represent new scientific results; rather, they can reproduce or supplement earlier computational studies or experimental findings. Reports from eight of the summer projects are included as separate chapters. The fields represented include cardiac geometry definition (Chapter 1), electrophysiology and pharmacology (Chapters 2–5), fluid mechanics in blood vessels (Chapter 6), cardiac calcium handling and mechanics (Chapter 7), and machine learning in cardiac electrophysiology (Chapter 8)