Transient Cardiovascular Hemodynamics In A Patient-Specific Arterial System

The ultimate goal of the present study is to aid in the development of tools to assist in the treatment of cardiovascular disease. Gaining an understanding of hemodynamic parameters for medical implants allow clinicians to have some patient-specific proposals for intervention planning. In the present study a full cardiovascular experimental phantom and digital phantom (CFD model) was fabricated to study: (1) the effects of local hemodynamics on global hemodynamics, (2) the effects of transition from bed-rest to upright position, and (3) transport of dye (drug delivery) in the arterial system. Computational three dimensional (3-D) models (designs A, B, and C) stents were also developed to study the effects of stent design on hemodynamic flow and the effects of drug deposition into the arterial wall. The experimental phantom used in the present study is the first system reported in literature to be used for hemodynamic assessment in static and orthostatic posture changes. Both the digital and experimental phantom proved to provide different magnitudes of wall shear and normal stresses in sections where previous studies have only analyzed single arteries. The dye mass concentration study for the digital and experimental cardiovascular phantom proved to be useful as a surrogate for medical drug dispersion. The dye mass concentration provided information such as transition time and drug trajectory paths. For the stent design CFD studies, hemodynamic results (wall shear stress (WSS), normal stress, and vorticity) were assessed to determine if simplified stented geometries can be used as a surrogate for patient-specific geometries and the role of stent design on flow. Substantial differences in hemodynamic parameters were found to exist which confirms the need for patient-specific modeling. For drug eluting stent studies, the total deposition time for the drug into the arterial wall was approximately 3.5 months

Modelling the characteristics of the baroreceptor

A dissertation submitted to the Faculty of Engineering and the Built Environment, University of Witwatersrand in fulfilment of the requirements for the degree of Master of Science in Engineering. 2017The baroreceptor is a stretch receptor which detects changes in pressure in arterial blood vessels. Baroreceptor nerves inform the brainstem of changes in blood pressure, which then influences sympathetic and parasympathetic nervous activity to counteract that change. Due to the relationship between essential hypertension, sympathetic nervous activity and the baroreflex, there is some debate in the literature about whether the baroreflex can act as a long-term controller of blood pressure. This debate has increased in recent years, due to the high prevalence of essential hypertension in all societies and the introduction of new technologies to counteract drug-resistance hypertension. The baroreflex has become a source of debate due to the complex physiological feedback control that regulates blood pressure and due to new stimulating electrical devices, which have shown promising results in reducing drug-resistant essential hypertension. system. This is done through a literature survey extending through experimental and modelling research, where selected mathematical models of the baroreceptor are then analysed and simulated to find the best performing model, so that they may be simulated for an extended frequency response than what would be experimentally possible. The purpose of this investigation is to determine, through simulation, what the sensor static and dynamic characteristics are. Through this characterisation of the sensor behaviour of the baroreceptor in the baroreflex control loop, it is then possible to infer whether the baroreflex can act as a long-term controller of blood pressure. An overview of experimental and analytical investigations on the baroreceptor over the last 70 years is summarised. This overview includes mathematical models, which predict experimental results. A subset of four models from Srinivasen et al., Bugenhagen et al., Beard et al. and Mahdi et al. are selected. These models are implemented in MATLAB and Simulink. The parameters and experimental conditions are integrated into the Simulink models, and the simulated results are compared to the reported experimental data. In this way, each mathematical model is evaluated using secondary data for its ability to simulate the expected behaviour. Thereafter, all simulated models are compared under the same input conditions (a 0-230 mmHg step input over 12 s). These results are used to select the best performing models, based on how well they were parameterised and validated for experimental tests. The best performing models are those of Beard et al. and Bugenhagen et al. They are tested for a wide range of artificial inputs at different frequencies, with sinusoidal inputs which have periods that range from 0.1 s to 10 days and have a 100 mmHg operating point with a 1 mmHg peak amplitude. All modelling techniques studied show that the baroreceptor firing response resets due to the rate of change in strain in the visco-elastic arterial wall. Both tested model frequency responses, although parameterised for different species and for different major vessels, show high sensitivity to inputs in range from 1 s to 1 min 36 s (0.01 Hz 1Hz), and very low sensitivity for changes that are longer than 16 min 36s (0.001 Hz). This extrapolated simulation suggests a zero gain near DC. The simulated frequency response of the best performing baroreceptor models, which were validated against short-term experimental data, indicate that the baroreceptor is only able to sense changes that happen in less than 1 min 16s. The critical analysis of all the simulated baroreceptor models show that this characteristic of the baroreceptor is caused by the visco-elastic layers of the arterial wall, and is likely in all baroreceptors regardless of type or species. It also indicates that under electrical stimulation of the baroreceptor, the input signal from the electrical device bypasses the baroreceptor nerve ending (which is embedded in the arterial wall) and that the electrical signal of the baroreceptor is bypassed by the new stimulated electrical signal of the device. Furthermore, if the sensor can only detect short-term changes, then it is unlikely that the baroreceptor can inform the brainstem on longterm changes to mean arterial blood pressure. Therefore, based on the models examined in this study, this suggests that the baroreceptor is unlikely to be involved in long-term blood pressure control. This analysis of the best performing model is presented to show the limitations of the baroreflex in long term control of blood pressure. It serves as a simulated experiment to rationalise the contentious debate around the role of the baroreflex in long term blood pressure control, and to allow for future improvements that can be made on the baroreceptor model to allow for more extended modelling on sor characteristics. An improvement that could be applied to the best performing baroreceptor models, implemented in this study, is to examine the effects of ageing and inter-species variability on carotid sinus dimensions and visco-elastic wall properties.CK201

Autonomic Cardiovascular Regulation in Children with Hypoplastic Left Heart Syndrome and the Fontan Circulation

Background: Hypoplastic left heart syndrome (HLHS) is a congenital heart disease phenotype where the left side of the heart is severely underdeveloped and cannot support systemic circulation. Children with HLHS undergo the Fontan operation, where the caval veins are attached to the pulmonary artery, and the right ventricle pumps blood through the aorta. Children with HLHS with Fontan circulation (HLHS-FC) have a reduced exercise tolerance and suffer from autonomic dysfunction. Understanding the role of autonomic dysfunction by studying the exercise pressor reflex through the stimulation of mechano- and metaboreceptors could provide further insight on potential mechanisms contributing to exercise intolerance. We hypothesized than children with HLHS-FC would have an augmented exercise pressor response resulting in increased sympathetic stimulation through mechno- and metaboreflex (handgrip) and metaboreflex only (post-exercise circulatory occlusion, PECO) as defined by change in mean arterial pressure (MAP) versus healthy controls (CTL). Methods and Results: Nine HLHS-FC (f=3, m=6; 134 y) and 9 CTL (f=3, m=6; 133 y) rested supine for 10 minutes to assess heart rate variability (HRV) and resting physiologic parameters, then performed 2 minutes of 40% maximal voluntary contraction isometric handgrip exercise, followed by 3 minutes of PECO on the exercised arm. Continuous blood pressure, heart rate (HR), ventilation, and forearm blood flow (FBF) of the contralateral limb were measured throughout the protocol. Children with HLHS-FC had lower resting heart rate variability (HRV) values of standard deviation of normal R-R intervals (31.932.4 vs. 70.424.0; P = 0.011), root mean square of successive R-R interval differences (31.932.3 vs. 70.324.0; P = 0.011), percentage of consecutive normal R-R intervals that differ by more than 50ms (19.828.2 vs. 44.718.8; P = 0.043), low frequency power percentage (21.85.4 vs. 35.710.4; P = 0.003), high frequency power percentage (31.515.4 vs. 46.89.7; P < 0.023) than CTL. Mean arterial pressure (MAP) increased significantly less during handgrip (55mmHg vs 1610mmHg; P < 0.001) and PECO (45mmHg vs 149mmHg P = 0.002) in HLHS-FC than CTL. There was a blunted exercise HR response in HLHS-FC compared to CTL (67 bpm vs. 248 bpm; P <0.001). Ventilation was lower in HLHS-FC than CTL during handgrip (0.321.15 L/min vs 3.363.94 L/min; P = 0.003). In HLHS-FC FBF increased substantially during PECO when compared to rest (0 mL/min/m2 vs 19.832.6 mL/min/m2; P = 0.012) and handgrip (2.916.7 mL/min/m2 vs 19.832.6 mL/min/m2; P = 0.036). Conclusion: Children with HLHS-FC suffer from autonomic dysfunction, with a sympathovagal balance favouring the sympathetic nervous system, and contrary to our hypothesis, have a blunted exercise pressor reflex response to increased sympathetic stimulation. The exercise pressor reflex may play a key role in the exercise intolerance encountered by children with HLHS-FC

Imaging photoplethysmography: towards effective physiological measurements

Since its conception decades ago, Photoplethysmography (PPG) the non-invasive opto-electronic technique that measures arterial pulsations in-vivo has proven its worth by achieving and maintaining its rank as a compulsory standard of patient monitoring. However successful, conventional contact monitoring mode is not suitable in certain clinical and biomedical situations, e.g., in the case of skin damage, or when unconstrained movement is required. With the advance of computer and photonics technologies, there has been a resurgence of interest in PPG and one potential route to overcome the abovementioned issues has been increasingly explored, i.e., imaging photoplethysmography (iPPG). The emerging field of iPPG offers some nascent opportunities in effective and comprehensive interpretation of the physiological phenomena, indicating a promising alternative to conventional PPG. Heart and respiration rate, perfusion mapping, and pulse rate variability have been accessed using iPPG. To effectively and remotely access physiological information through this emerging technique, a number of key issues are still to be addressed. The engineering issues of iPPG, particularly the influence of motion artefacts on signal quality, are addressed in this thesis, where an engineering model based on the revised Beer-Lambert law was developed and used to describe opto-physiological phenomena relevant to iPPG. An iPPG setup consisting of both hardware and software elements was developed to investigate its reliability and reproducibility in the context of effective remote physiological assessment. Specifically, a first study was conducted for the acquisition of vital physiological signs under various exercise conditions, i.e. resting, light and heavy cardiovascular exercise, in ten healthy subjects. The physiological parameters derived from the images captured by the iPPG system exhibited functional characteristics comparable to conventional contact PPG, i.e., maximum heart rate difference was <3 bpm and a significant (p < 0.05) correlation between both measurements were also revealed. Using a method for attenuation of motion artefacts, the heart rate and respiration rate information was successfully assessed from different anatomical locations even in high-intensity physical exercise situations. This study thereby leads to a new avenue for noncontact sensing of vital signs and remote physiological assessment, showing clear and promising applications in clinical triage and sports training. A second study was conducted to remotely assess pulse rate variability (PRV), which has been considered a valuable indicator of autonomic nervous system (ANS) status. The PRV information was obtained using the iPPG setup to appraise the ANS in ten normal subjects. The performance of the iPPG system in accessing PRV was evaluated via comparison with the readings from a contact PPG sensor. Strong correlation and good agreement between these two techniques verify the effectiveness of iPPG in the remote monitoring of PRV, thereby promoting iPPG as a potential alternative to the interpretation of physiological dynamics related to the ANS. The outcomes revealed in the thesis could present the trend of a robust non-contact technique for cardiovascular monitoring and evaluation

Studies of adipose tissue in humans with special reference to innervation by the sympathetic nervous system

PhDThis thesis reports the effects in vivo of the sympathetic nervous system (SNS) in human subcutaneous abdominal white adipose tissue (WAT) and other tissues involved in energy storage and utilisation. Cannulation of superficial veins draining skin, abdominal subcutaneous WAT and deep forearm muscle combined with isotope turnover methodology and tissue blood flow estimation was used to investigate the behaviour of these tissues under varying experimental conditions. Glucose infusion study: This examined differential substrate uptake and utilisation in the three tissues. WAT was responsible for only a small amount of glucose disposal and deep forearm muscle took up but did not release NEFA. Skin was a net exporter of lactate. Results confirm the relative purity of the venous effluent from these tissues. Sympathetic Nervous System study: This examined whole body, WAT and forearm muscle SNS activity in lean and obese individuals under fasting and postprandial conditions. Whereas whole body SNS activity was increased in the obese, regional heterogeneity of SNS activity was evidenced by reduced SNS activity in WAT. Adipose tissue blood flow was significantly reduced in the obese. This may underlie abnormal lipolysis and/or blood flow regulation in obesity. 7 Pulsatility Studies: These studies examined whether lipolysis and leptin production in human WAT is uniform or pulsatile. Novel control datasets were used to test the robustness of a widely used pulse detection algorithm. Whereas NEFA release appeared truly pulsatile, apparent leptin ‘pulses’ occurred with similar frequency in the control datasets and appear likely simply to reflect variability. Anatomical studies: Confocal immuno-fluorescence microscopy was used to demonstrate innervation of WAT in man for the first time. Such innervation appears confined to the microvasculature and suggests that the defective SNS activity within WAT is likely to affect adipose tissue biology primarily through defective regulation of adipose tissue blood flow

Investigation of the baroreflex of the rat : steady state and dynamic features

The baroreflex is one of the most important feedback systems in the body to maintain blood pressure variation within the homeostatic range. In this dissertation, the important features of the carotid and aortic baroreflexes have been extensively investigated on ventilated, central nervous system intact, neuromuscular blocked (NMB) rats using different control system and signal processing tools. Studies have demonstrated that sinoaortic denervation (SAD) caused substantial increases in the blood pressure variability. Comparing the pre- and post-SAD blood pressure spectra, there was a significant increase of power in the very low frequency region (0.00195 -0.2 Hz), and a significant decrease of power in the low frequency region (0.2 - 0.6 Hz) after SAD. The dominant power change after SAD was in the very low frequency region of the blood pressure spectra. The carotid and aortic baroreflexes were accessed by volumetric manipulation of the carotid sinus and electrical manipulation of the aortic depressor nerve (ADN) using step and sinusoidal stimulations. Myelinated ADN-A fibers and myelinated + unmyelinated ADN-A+C fibers were accessed separately in the experiments. Results showed that the baroreflex functions as a \u27low-pass\u27 filter, with -3dB cutoff frequency at approximately \u3c0. I Hz. The major working area of the baroreflex system is in the VLF region of the blood pressure spectra. The estimated system transportation lag was 1.07s, which would cause the baroreflex system to oscillate at frequencies around 0.4 Hz. Analyses demonstrated that it is not likely that the baroreflex is activated only occasionally, such as in response to postural shifts, but operates continuously to bring the blood pressure into balance. It is theoretically and experimentally demonstrated that the absolute gain of the open-loop baroreflex system can be predicted by the ratio of the pre-and post- blood pressure amplitude spectra

Multimodal Signal Processing for Diagnosis of Cardiorespiratory Disorders

This thesis addresses the use of multimodal signal processing to develop algorithms for the automated processing of two cardiorespiratory disorders. The aim of the first application of this thesis was to reduce false alarm rate in an intensive care unit. The goal was to detect five critical arrhythmias using processing of multimodal signals including photoplethysmography, arterial blood pressure, Lead II and augmented right arm electrocardiogram (ECG). A hierarchical approach was used to process the signals as well as a custom signal processing technique for each arrhythmia type. Sleep disorders are a prevalent health issue, currently costly and inconvenient to diagnose, as they normally require an overnight hospital stay by the patient. In the second application of this project, we designed automated signal processing algorithms for the diagnosis of sleep apnoea with a main focus on the ECG signal processing. We estimated the ECG-derived respiratory (EDR) signal using different methods: QRS-complex area, principal component analysis (PCA) and kernel PCA. We proposed two algorithms (segmented PCA and approximated PCA) for EDR estimation to enable applying the PCA method to overnight recordings and rectify the computational issues and memory requirement. We compared the EDR information against the chest respiratory effort signals. The performance was evaluated using three automated machine learning algorithms of linear discriminant analysis (LDA), extreme learning machine (ELM) and support vector machine (SVM) on two databases: the MIT PhysioNet database and the St. Vincent’s database. The results showed that the QRS area method for EDR estimation combined with the LDA classifier was the highest performing method and the EDR signals contain respiratory information useful for discriminating sleep apnoea. As a final step, heart rate variability (HRV) and cardiopulmonary coupling (CPC) features were extracted and combined with the EDR features and temporal optimisation techniques were applied. The cross-validation results of the minute-by-minute apnoea classification achieved an accuracy of 89%, a sensitivity of 90%, a specificity of 88%, and an AUC of 0.95 which is comparable to the best results reported in the literature

Ocular and systemic vascular dysfunction in neurodegenerative disease

The important role played by vascular factors in the pathogenesis of neurodegenerative disease has been increasingly realised over recent years. The nature and impact of ocular and systemic vascular dysfunction in the pathogenesis of comparable neurodegenerative diseases such as glaucoma and Alzheimer’s disease (AD) has however never been fully explored. The aim of this thesis was therefore to investigate the presence of macro- and micro-vascular alterations in both glaucoma and AD and to explore the relationships between these two chronic, slowly progressive neurodegenerative diseases. The principle sections and findings of this work were: 1. Is the eye a window to the brain? Retinal vascular dysfunction in Alzheimer’s disease · Mild newly diagnosed AD patients demonstrated ocular vascular dysfunction, in the form of an altered retinal vascular response to flicker light, which correlated with their degree of cognitive impairment. 2. Ocular and systemic vascular abnormalities in newly diagnosed normal tension glaucoma (NTG) patients · NTG patients demonstrated an altered retinal arterial constriction response to flicker light along with an increased systemic arterial stiffness and carotid artery intima-media thickness (IMT). These findings were not replicated by healthy age matched controls. 3. Ocular vascular dysregulation in AD compares to both POAG and NTG · AD patients demonstrated altered retinal arterial reactivity to flicker light which was comparable to that of POAG patients and altered baseline venous reactivity which was comparable to that of NTG patients. Neither alteration was replicated by healthy controls. 4. POAG and NTG: two separate diseases or one continuous entity? The vascular perspective · POAG and NTG patients demonstrated comparable alterations in nocturnal systolic blood pressure (SBP) variability, ocular perfusion pressure, retinal vascular reactivity, systemic arterial stiffness and carotid IMT. · Nocturnal SBP variability was found to correlate with both retinal artery baseline diameter fluctuation and carotid IMT across the glaucoma groups