973 research outputs found

    The effects of running, cycling, and duathlon exercise performance on cardiac function, haemodynamics and regulation

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    This thesis examined the effects of prolonged exercise, specifically Olympic Distance (OD)duathlon upon ultrasound derived indices of cardiac function, cardiac autonomic regulation measured via heart rate variability (HRV), and high-sensitivity cardiac troponin T (hs-cTnT)release. The primary aims were to (1) ascertain the influence of Olympic distance (OD) duathlon performance on cardiac function; (2) to investigate potential relationships between autonomic regulation, hs-cTnT release, and cardiac function, and (3) to investigate the effect of the individual legs of an OD duathlon on post-exercise cardiac function and to quantify the potential performance reserve of highly-trained endurance athletes when completing standalone legs of the duathlon. Findings from a systematic review and meta-analysis(Chapter 1) on research that performed serial echocardiographic and troponin measurements before and after exercise, intensity predicted changes in post-exercise cardiac troponin release and diastolic function. The findings agreed with previous meta-analyses using a more recent sample of studies; however, the recommendation for future studies to implement advanced cardiac imaging techniques, such as myocardial speckle tracking into their data collection would provide a more sensitive measure of post-exercise cardiac function. Whilst a large degree of heterogeneity in the results exists, this was in part explained by study exercise heart rate, participant age, and the prevalence of cardiac troponin release above the clinical detection threshold. The study performed in Chapter 3 was the first to investigate the effects of OD duathlon exercise on immediate and 24 hours post-exercise cardiac function. Additionally, a second OD duathlon was performed by participants with intra-leg measurements of cardiac function. In a highly trained cohort, there was evidence of transient post-exercise reductions in cardiac function and elevated serum high-sensitivity cardiac troponin T (hs-cTnT) above the clinical reference value, which was largely resolved within 24h of recovery. This study also demonstrated the reliability of lab-based duathlon exercise in a highly trained cohort and identified the pacing features of experienced multi-sport athletes that partially explained the different findings between the running and cycling legs of the duathlon. By investigating each leg of the duathlon individually (10k run, 5k run, 40k cycle), both at duathlon race-pace (DM) and maximal (Max) intensity on separate occasions, the performance reserve of the highly-trained cohort was quantified and further explored. The studies presented in Chapters 4 and 5 revealed that experienced duathletes were able to improve their speed across each leg by between 5-15% in a laboratory setting, compared to the duathlon effort. Additionally, the maximal effort 10k run leg provoked the most persistent changes to cardiac function that were present at 6h of recovery. Changes in cardiac function post DM 10k confirmed the findings of Chapter 3 that the greatest magnitude of cardiac perturbations occur following the initial 10k run leg. Aside from the Max 10k run and 40k cycle trials, all perturbations had resolved within 6h of recovery after each bout of exercise, highlighting the importance of recovery following maximal intensity efforts. The lack of 6h and 24h recovery data in Chapter 4, and Chapters 5 and 6, respectively is a shortcoming of these findings and therefore limits interpretation in the context of providing athletic guidance. Future research in this area should endeavour to include 6h and 24h recovery measures as standard, as multi-sport athletes typically perform multiple daily training sessions. The implications of substantial cardiac fatigue accumulation over many years of endurance training history are still unclear, and athletes may benefit from preventingits occurrence

    4D FLOW CMR in congenital heart disease

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    This thesis showed that the use of a cloud-based reconstruction applicationwith advanced eddy currents correction, integrated with interactiveimaging evaluation tools allowed for remote visualization and interpretationof 4D flow data and that was sufficient for gross visualizationof aortic valve regurgitation. Further, this thesis demonstrated that bulkflow and pulmonary regurgitation can be accurately quantified using 4Dflow imaging analyzed. Peak systolic velocity over the pulmonary valvemay be underestimated. However, the measurement of peak systolicvelocity can be optimized if measured at the level of highest velocity inthe pulmonary artery. Also correlated against invasive measurements (inan animal model), this thesis shows that aorta flow and pulmonary flowcan be accurately and simultaneously measured by 4D flow MRI.When applied in clinical practice, 4D flow has extra advantages, of beingable to visualize flow pattern, vorticity and to predict aortic growth. InASD patients it can measure shunt volume directly following the septumframe by frame. In Fontan patients in can visualize better than standardMRI the Fontan circuit and it can measure flow at multiple points alongthe Fontan circuit. We observed in our Fontan population that shunt lesionswere very common, most of the time via veno-venous collaterals.Further using advanced computations, we showed that WSS angle wasthe only independent predictor of aortic growth in BAV patients. We alsoshowed the feasibility of GLS analysis on 4D flow MRI and presented anintegrative approach in which flow and functional data are acquired inone sequence.From the technical point of view, 4D flow MRI has proved to complementthe traditional components of the standard cardiac MR exams, enablingin-depth insights into hemodynamics. At this moment it proved its addedvalue, but in most of the cases it is not able yet to replace the standardexam. This is still due to long scanning times and relatively longpost-processing times.<br/

    Novel 129Xe Magnetic Resonance Imaging and Spectroscopy Measurements of Pulmonary Gas-Exchange

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    Gas-exchange is the primary function of the lungs and involves removing carbon dioxide from the body and exchanging it within the alveoli for inhaled oxygen. Several different pulmonary, cardiac and cardiovascular abnormalities have negative effects on pulmonary gas-exchange. Unfortunately, clinical tests do not always pinpoint the problem; sensitive and specific measurements are needed to probe the individual components participating in gas-exchange for a better understanding of pathophysiology, disease progression and response to therapy. In vivo Xenon-129 gas-exchange magnetic resonance imaging (129Xe gas-exchange MRI) has the potential to overcome these challenges. When participants inhale hyperpolarized 129Xe gas, it has different MR spectral properties as a gas, as it diffuses through the alveolar membrane and as it binds to red-blood-cells. 129Xe MR spectroscopy and imaging provides a way to tease out the different anatomic components of gas-exchange simultaneously and provides spatial information about where abnormalities may occur. In this thesis, I developed and applied 129Xe MR spectroscopy and imaging to measure gas-exchange in the lungs alongside other clinical and imaging measurements. I measured 129Xe gas-exchange in asymptomatic congenital heart disease and in prospective, controlled studies of long-COVID. I also developed mathematical tools to model 129Xe MR signals during acquisition and reconstruction. The insights gained from my work underscore the potential for 129Xe gas-exchange MRI biomarkers towards a better understanding of cardiopulmonary disease. My work also provides a way to generate a deeper imaging and physiologic understanding of gas-exchange in vivo in healthy participants and patients with chronic lung and heart disease

    Measurement of left ventricular deformation using 3D echocardiography

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    Bakgrunn: 3D speckle tracking ekkokardiografi (STE) er en hjerteultralydmetode som gir mulighet for måling av deformasjonsparametere, som strain, rotasjon, tvist og torsjon. Den største begrensningen for 3D STE er lav tids- og romlig oppløsning. Økes den ene oppløsingen vil den andre bli redusert. I tillegg vil andre faktorer som antall flettede bilder, sektorstørrelse og dybde påvirke begge oppløsningene. Denne avhandlingen har hatt som mål å finne tilstander og opptaksinnstillinger for å optimalisere nøyaktigheten til 3D STE-parametere i et kontrollert miljø. Videre har det vært som mål å finne regional deformasjon fra 3D STE i en klinisk studie på pasienter med aortaklaffestenose (AS) ved bruk av optimaliserte innstillinger. Materiale og metode: Studie 1 og 2 utforsket nøyaktigheten til 3D STE ved bruk av et in vitro-oppsett med et fantom av venstre ventrikkel. Studie 1 sammenlignet 3D STE strain mot sonomikromertri som gullstandard i longitudinell, sirkumferensiell og radiell retning. Ved å bruke et annet fantom i studie 2 ble 3D STE tvist sammenlignet mot sonomikrometri tvist for å finne nøyaktigheten til 3D STE tvistmålinger. Studie 3 inkluderte 85 pasienter med variabel grad av AS i en tverrsnittstudie. 3D ekkokardiografi ble utført og 3D STE-parametere ble sammenlignet mellom grupper av pasienter med mild, moderat og alvorlig AS. Resultater: Studie 1 fant godt samsvar mellom 3D STE og sonomikrometri med optimalt volum rate på 36,6 volumer per sekund (VPS) ved bruk av 6 sammenflettede bilder. I studie 2 hadde 3D STE godt samsvar ved bruk av både 4 og 6 sammenflettede bilder med volum rater på henholdsvis 20,3 og 17,1 VPS. Studie 3 fant lavere global longitudinal strain i pasienter med alvorlig AS sammenlignet med mild AS. Basal og midtre longitudinal strain var også lavere i alvorlig sammenlignet med mild AS. Apikal-basal ratio var høyere for moderat i forhold til mild AS. Maks apikal-basal tvist var høyere hos pasienter med alvorlig sammenlignet med mild og moderat AS. Konklusjon: Måling av venstre ventrikkelfunksjon med 3D STE er mest nøyaktig med volum rater < 40 VPS. Høy romlig oppløsning virker å være mer viktig enn tidsoppløsning. Pasienter med alvorlig AS har lavere global, basal og midtre longitudinal strain enn pasienter med mild AS, ved bruk av 3D STE. De har også høyere tvist enn mild og moderat AS. Områder som involverer apeks, har høyere spredning av data og har antagelig lavere nøyaktighet ved bruk av 3D STE.Background: 3D speckle tracking echocardiography (STE) enables measurement of multiple parameters of deformation, such as strain, rotation, twist and torsion. The main limitation of 3D STE is low temporal and spatial resolution. Increasing resolution in time will decrease resolution in space, and vice versa. In addition, other factors such as number of stitched images, sector size and depth, influence the resolution. This thesis aimed to find conditions and acquisition settings to optimize accuracy for 3D STE parameters in a controlled in vitro environment. Secondly, it aimed to evaluate regional deformation by 3D STE in a clinical study on patients with aortic valve stenosis (AS) using optimized settings. Materials and methods: Study 1 and 2 explored the accuracy of 3D STE using an in vitro setup with a left ventricle (LV) phantom. Study 1 compared 3D STE strain to strain by sonomicrometry as the gold standard. Measurements were compared in both longitudinal, circumferential and radial direction. Using a different twisting phantom in study 2, 3D STE twist was compared to twist by sonomicrometry to evaluate the accuracy of 3D STE twist. Study 3 was a cross-sectional analysis of 85 patients with variable degree of AS in a cross-sectional study. 3D echocardiography was done, and 3D STE parameters were compared between groups of patients with mild, moderate and severe AS. Results: Study 1 found 3D STE strain to have good agreement with sonomicrometry. Optimal acquisition settings were found to be volume rate 36.6 volumes per second (VPS) obtained by 6 stitched images. Study 2 found 3D STE twist to have good agreement with sonomicrometry when using both 4 and 6 stitched images with volume rates 20.3 and 17.1 VPS, respectively. Study 3 found global longitudinal strain to be lower in patients with severe AS compared to those with mild AS. Basal and mid longitudinal strains were also lower in severe AS than in mild AS. Apical basal ratio was higher for moderate than mild AS. Peak apical-basal twist was higher in patients with severe AS than in those with mild and moderate AS. Conclusion: Assessment of LV function by 3D STE is most accurate at volume rates < 40 VPS. High spatial resolution seems to be more important than temporal resolution. Patients with severe AS have lower global, as well as lower regional basal and mid longitudinal strain compared to patients with mild AS, assessed with 3D STE. They also have higher twist than mild and moderate AS. Segments involving the apex have high dispersion and probably lower accuracy in 3D STE.Doktorgradsavhandlin

    Echo Particle Image/Tracking Velocimetry: Technical Development and In Vivo Applications in Cardiovascular and Cerebrovascular Flows

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    Contrast-enhanced ultrasound (CEUS) imaging utilizes intravascular echogenic microbubbles (1-5μm in diameter) to visualize the blood flow in various organs. In this dissertation, we develop and implement techniques for analyzing the motions of microbubbles to quantify cardiovascular and cerebrovascular flows. Obtaining accurate bubble center locations from noisy CEUS images is a primary challenge. Since the bubble trace is typically modeled as a point scatter convolved with a point spread function (PSF), techniques including blind deconvolution, supervised, and self-supervised learning are introduced and calibrated for identifying the PSF and locating the bubble center. The enhanced CEUS images enable echo particle image velocimetry (echo-PIV) for characterizing 2D cardiovascular flows, and the global-optimized Kalman filter-based echo particle tracking velocimetry (echo-PTV) for determining bubble trajectories which are subsequently used for mapping the cerebral and ocular microcirculation at a spatial resolution of 20μm. These techniques are applied to two applications. First, echo-PIV is used for monitoring the aortic root flow in an adult pig undergoing veno-arterial extracorporeal membrane oxygenation (VA-ECMO), a life support technology whose parameters can be optimized based on the aortic root hemodynamics. Phase-averaged and instantaneous flow fields show that, for the pig with severe myocardial ischemia, the cardiac ejection velocity, velocity-time integral, and mean arterial pressure (MAP) reach their peak at an ECMO flow rate of 3.0L/min, indicating an optimal flow rate that provides adequate support. Second, we investigate non-invasive methods for estimating intracranial pressure (ICP), a critical parameter for hydrocephalus patients that cannot be invasively measured safely. Echo-PTV is used to map cerebral and ocular microcirculation of pediatric hydrocephalus porcine models for inferring ICP. Results show that accounting for pulse pressure, highly correlated relationships between ICP and cortical microcirculation density are obtained with correlation coefficients beyond 0.85. For cerebral ischemia, nondimensionalized cortical micro-perfusion decreases by an order of magnitude when the ICP exceeds 50% of MAP. Moreover, retinal microcirculation also shows a highly correlated relationship with ICP when accounting for pulse pressure. These findings suggest that CEUS-based microcirculation measurement is a plausible noninvasive method for evaluating the ICP and detecting brain ischemia

    Characterising Shape Variation in the Human Right Ventricle Using Statistical Shape Analysis: Preliminary Outcomes and Potential for Predicting Hypertension in a Clinical Setting

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    Variations in the shape of the human right ventricle (RV) have previously been shown to be predictive of heart function and long term prognosis in Pulmonary Hypertension (PH), a deadly disease characterised by high blood pressure in the pulmonary arteries. The extent to which ventricular shape is also affected by non-pathological features such as sex, body mass index (BMI) and age is explored in this thesis. If fundamental differences in the shape of a structurally normal RV exist, these might also impact the success of a predictive model. This thesis evaluates the extent to which non-pathological features affect the shape of the RV and determines the best ways, in terms of procedure and analysis, to adapt the model to consistently predict PH. It also identifies areas where the statistical shape analysis procedure is robust, and considers the extent to which specific, non-pathological, characteristics impact the diagnostic potential of the statistical shape model. Finally, recommendations are made on next steps in the development of a classification procedure for PH. The dataset was composed of clinically-obtained, cardiovascular magnetic resonance images (CMR) from two independent sources; The University of Pittsburgh Medical Center and Newcastle University. Shape change is assessed using a 3D statistical shape analysis technique, which topologically maps heart meshes through an harmonic mapping approach to create a unique shape function for each shape. Proper Orthogonal Decomposition (POD) was applied to the complete set of shape functions in order to determine and rank a set of shape features (i.e. modes and corresponding coefficients from the decomposition). MRI scanning protocol produced the most significant difference in shape; a shape mode associated with detail at the RV apex and ventricular length from apex to base strongly correlated with the MRI sequence used to record each subject. Qualitatively, a protocol which skipped slices produced a shorter RV with less detail at the apex. Decomposition of sex, age and BMI also derives unique RV shape descriptors which correspond to anatomically meaningful features. The shape features are shown to be able to predict presence of PH. The predictive model can be improved by including BMI as a factor, but these improvements are mainly concentrated in identification of healthy subjects

    Investigating cardiac metabolism and the effect of novel metabolic modulation therapy on cardiac physiology and exercise capacity in aortic stenosis: a multi-parametric cardiac magnetic resonance study

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    Aortic stenosis is a major cause of morbidity and mortality in the western world. Whilst symptomatic patients with severe AS are treated with valve replacement surgery, there remains uncertainty about the best treatment for asymptomatic severe AS. Current guidelines recommend wait and watch strategy and offer surgery on occurrence of symptoms or evidence of systolic dysfunction. The annual rate of sudden cardiac death in asymptomatic severe AS remains close to 1%. Aortic disease is both a disease of the valve and myocardium. The valve mechanisms and structural LV changes secondary to pressure overload have been extensively studied before, but no medical therapy directed at the valve processes has so far shown beneficial effect on cardiac physiology or disease progression. Changes in cardiac metabolism in pressure overload hypertrophy seem to play an important role in pathophysiology of AS and transition to decompensation. The healthy human heart uses fatty acids as the main energy source ~70% of adenosine triphosphate (ATP) requirements. In AS, there is substrate shift with downregulation of fatty acid oxidation (FAO) and increased reliance on glycolysis, with evidence of myocardial lipid accumulation and impairment of myocardial energetics. Peroxisome proliferator activated receptor-alpha (PPAR-a) plays a central role in FAO signalling and controlling lipid homeostasis in the heart. Downregulation of this transcriptional factor is associated with the metabolic alterations and subsequent lipotoxicity in AS, which ultimately causes reduced ATP production and heart failure. However, it is unclear whether these metabolic changes have a cause or effect relationship with the two main pathological features of AS, left ventricular (LV) pressure loading and LV hypertrophy, and their relationship with myocardial fibrosis (which is commonly seen in AS), is unclear. Furthermore, it is yet unknown whether modulating cardiac metabolism would have any beneficial effect on disease progression or outcomes in AS. This thesis set out to establish the relationship between metabolic remodelling and cardiac structure and physiology in AS. It then evaluates the role of novel metabolic modulator therapy in asymptomatic moderate-severe AS. In Chapter 3 and 4, patients across the spectrum of AS were studied with advanced CMR imaging and phosphorus-31 magnetic resonance spectroscopy (31P-MRS) and cardiopulmonary exercise testing (CPET) respectively. It is demonstrated that metabolic changes, specifically myocardial lipid accumulation (steatosis) and impaired cardiac energetics appear to occur early in the disease process. In addition, whilst impairment in cardiac energetics is related to degree of LV hypertrophy, steatosis appears to be more related to the degree of LV pressure loading from valve obstruction. Furthermore, these patients despite being asymptomatic with normal LVEF have evidence of subclinical LV dysfunction which occurs early in the disease process. Moreover, these patients though able to exercise to volitional exhaustion without developing symptoms have reduced average peak VO2 and VE/VCO2, both of which are predictors of outcome in cardiac disease. In Chapter 4 and 5, the effect of the PPARa agonist Fenofibrate was evaluated on cardiac metabolism and physiology in a randomised double-blind placebo-controlled study. Fenofibrate reduced myocardial triglyceride content significantly after 6 months’ treatment with evidence of in vivo fatty acid oxidation upregulation. It also caused a modest improvement in cardiac energetics. However, this modulation did not show any measurable improvement in cardiac physiology or exercise capacity. Together, these data show that myocardial metabolic remodelling plays an important role in pathophysiology and progression of AS. The novel finding from this research is that metabolic changes occur early in the AS disease process and are associated with early subclinical systolic and diastolic dysfunction. This highlights that metabolic remodelling may play a causal role in disease progression. This research has also shown, for the first time, that metabolic alterations in AS are amenable to modulation with a PPARa agonist, with some improvement in cardiac physiology but the benefit of such modulation in advanced disease remains questionable. Whether targeting earlier disease would yield different results remains unanswered

    Hemodynamic Quantifications By Contrast-Enhanced Ultrasound:From In-Vitro Modelling To Clinical Validation

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