Cardiovascular disease (CVD) is a term used to describe a variety of diseases and events that impact the heart and circulatory system. CVD is the United Kingdom's (UKs) biggest killer, causing more than 50,000 premature deaths each year. Early recognition of the potential for magnetic resonance imaging (MRI) to provide a versatile, non-ionising, non-invasive, technique for the assessment of CVD resulted in the modality becoming an area of intense interest in the research, radiology and cardiology communities. The first half of this thesis reviews some of the key developments in magnetic resonance hardware and software that have led to cardiac magnetic resonance imaging (CMRI) emerging as a reliable and reproducible tool, with a range of applications ideally suited for the evaluation of cardiac morphology, function, viability, valvular disease, perfusion, and congenital cardiomyopathies. In addition to this, the advantages and challenges of imaging at 3.0T in comparison to 1.5T are discussed. The second half of this thesis presents a number of investigations that were specifically designed to explore the capability of CMRI to accurately detect subtle age and disease related changes in the human heart. Our investigations begin with a study at 1.5T that explores the clinical and scientific significance of the less frequently used measure of right ventricular function to test the hypothesis that the inclusion of this data provides a more informative assessment of overall cardiac function. The focus then shifts to imaging at 3.0T and the challenges of optimising cardiac imaging at this field strength are discussed. Normal quantitative parameters of cardiac function are established at this field strength for the left ventricle and the left atrium of local volunteers. These values are used to investigate disease related changes in left ventricle and left atrium of distinct patient cohorts. This work concludes by investigating the impact of gadolinium-based contrast agents on the quantitative parameters of cardiac function.

Thesis (M.A.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / Cardiac Magnetic Resonance Imaging (CMRI) is an important and valuable tool in the routine management of patients with cardiovascular disease. Contrast enhanced CMRI allows detection of ischemic and scarred myocardium, including rare infiltrative processes that cause cardiomyopathies. Amyloidosis comprises a group of diseases that are characterized by the extracellular deposition of insoluble fibrillar proteins in organs. The deposition of amyloid material in the heart leads to presentations of congestive heart failure mainly of the restrictive infiltrative pattern. There may be also conduction abnormalities. Dilated cardiomyopathy is a form of cardiomyopathy that is characterized by abnormal dilatation of the heart and subsequent heart failure. One of the characteristics of the cardiomyopathies and amyloidosis is the diffuse interstitial or replacement myocardial fibrosis. Myocardial fibrosis leads to impaired cardiac diastolic and systolic function and can lead to increased cardiovascular morbidity and mortality. Cardiac Magnetic Resonance Imaging (CMRI) with contrast can be used to characterize the extent of myocardial fibrosis through T1 mapping and as such it can be used as a prognostic indicator in amyloidosis and dilated cardiomyopathy. / 2031-01-02

Since living conditions have improved and antibiotics have entered routine use, valvular heart disease (VHD) in the developed world is mostly degenerative in origin, rather than rheumatic. Our population is increasing with age, and therefore the burden of VHD is likely to increase. Despite this, the epidemiology & prognostication in VHD remain poorly understood. A better understanding of the prevalence of VHD in our population, and improved methods of predicting outcomes, are essential if we are to be better equipped to meet the challenges of this new “epidemic”. This thesis aims to improve our knowledge of the prevalence of VHD in the elderly, and the potential benefits of cardiac magnetic resonance (CMR) assessment of patients with clinically significant mitral regurgitation. The prevalence of undiagnosed valvular heart disease in those aged 65 and over is examined in Chapters 2 and 3. Chapter 2 outlines a population-based screening study for VHD in primary care in Oxfordshire, which the author played a central role in establishing. The results show that VHD is extremely common in this cohort, and is strongly associated with increasing age. In chapter 4, the level of anxiety provoked by screening for VHD is looked at; this demonstrates that only a small number of patients have significant anxiety levels, but it is more likely in those with a new diagnosis of VHD, and in women. From Chapter 5 onwards, the thesis focuses on the use of CMR in patients with significant mitral regurgitation (MR). In Chapter 5, the clinical value of quantitative assessment of MR using CMR is examined, showing that it was able to predict progression to symptoms or surgery in these patients. In conclusion, this thesis offers insights into the prevalence of VHD in the elderly population, and looks at the anxiety associated with looking for VHD in this group. The potential clinical benefits of CMR in patients with MR are examined, and quantification of MR with this modality would appear to be of prognostic utility.

Cardiovascular diseases are responsible for approximately a third of all death worldwide, with hypertension being a major risk factor for many of those. Hypertension can lead to left ventricle hypertrophy and diastolic and systolic dysfunction. Myocardial deformation parameters have been shown to have high sensitivity at the early stage of contractile dysfunction. They can be derived from myocardial tagging, considered to be the goldstandard method, or from routinely acquired cine images using feature tracking (FT) techniques. This work aimed to validate FT as a post processing technique. Three FT software packages were used to measure strain parameters in healthy subjects and hypertensive patients in order to assess agreement. Intra- and inter-observer reproducibility was also investigated. The CVI42 software was found to have the best reproducibility. Good agreement across the three software packages and both groups was also observed for circumferential strain calculated from mid-ventricle short axis and longitudinal strain parameters. CVI42 was also compared to the reference tagging analysis by applying both techniques to a healthy and hypertensive patient cohort. Although tagging could discriminate between the two populations (longitudinal strain), no statistically significant differences were found by CVI42. The final validation step was to generate simulation models mimicking simplified cardiac views to compare the experimental results against a true gold-standard for which strain values are known. Two commercial FT software packages were used to analyze the simulated cine images with increasing complexity levels. Both showed inaccurate tracking and high errors compared to analytical values. This indicated that more realistic and complex numerical models should be investigated. Although FT is a relatively new and promising technique, the results demonstrated that it still requires going through standardization to better understand inter-vendor variability.

Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with significant cardiovascular complications, including stroke, myocardial infarction, heart failure, and premature death. The presence of subtle left ventricular (LV) dysfunction is increasingly recognised in patients with AF, raising questions regarding the underlying pathophysiology and potential treatment strategies. I used advanced and multiparametric cardiac magnetic resonance (CMR) methods to investigate potential mechanisms that could contribute to LV dysfunction in patients with AF, controlled ventricular rate and no significant cardiovascular comorbidities (i.e., with so-called 'lone' AF). Patients were evaluated before and after catheter ablation, allowing examination of the effect of restoration of sinus rhythm and reduction in AF burden on LV structure, function, energetics, tissue characteristics, and perfusion. I demonstrated for the first time that patents with lone AF before ablation have significantly impaired ventricular energetics and a subtle reduction in LV systolic function compared to control subjects in sinus rhythm. Furthermore, there was only modest improvement (but not normalisation) in LV function following successful ablation, and myocardial energetics remained impaired despite a significant and sustained reduction in AF burden. These findings imply that lone AF may actually be the consequence (rather than the cause) of an underlying cardiomyopathy. Next, to interrogate advanced ventricular tissue characteristics (such as diffuse myocardial fibrosis) in patients with tachyarrhythmia, I developed a novel CMR method involving a systolic readout T1-mapping sequence. Methodological work in volunteers and patients with tachyarrhythmia demonstrated that this method reports clinically equivalent T1 values to the conventional diastolic readout in healthy volunteers, and was feasible in tachyarrhythmia, producing excellent quality T1 maps. When applied to the investigation of patients with AF, I demonstrated that subtle LV dysfunction in lone AF occurs in the absence of CMR evidence of diffuse myocardial fibrosis, suggesting that LV dysfunction may be reversible with appropriate and targeted therapeutic strategies initiated prior to the development of structural LV remodelling. Finally, I used quantitative perfusion imaging to determine absolute myocardial blood flow and coronary reserve in patients with AF, and determine whether microvascular coronary dysfunction could underlie impaired LV function and energetics in patients with AF. I found that myocardial perfusion is significantly reduced in patients with AF in the absence of significant epicardial coronary artery disease, both at baseline and under conditions of vasodilator stress. Lower baseline blood flow was related to reduced LV performance, and there was no significant change in perfusion after successful AF ablation. These novel findings indicate that coronary microvascular dysfunction may be an important pathophysiological mechanism in lone AF, and at least partially responsible for LV dysfunction. Overall, the findings reported in this thesis have potentially far-reaching implications for the management of patients with AF. They suggest that approaches that predominantly target rhythm control (including anti-arrhythmic medications and ablation) are insufficient to normalise the systemic and cardiometabolic phenotype in patients with AF. Further studies are needed to investigate whether novel approaches that target microvascular and energetic dysfunction in patients with AF can contribute to durable restoration of sinus rhythm and improve clinical outcomes.

No description available.

Quantitative cardiac magnetic resonance imaging (CMR) has gained traction within both the clinical and research field due to high prevalence of cardiovascular diseases. Cardiac magnetic resonance fingerprinting (cMRF) is a novel approach introduced to address the limitation associated with evaluation of multiparametric quantitative CMR. cMRF enables simultaneous and co-registered estimation of tissue relaxation times, T1 and T2, in a single acquisition, making it a more time-efficient approach to multiparametric quantitative CMR. Nevertheless, cMRF has not gained widespread adaption due to insufficient evidence regarding its performance in accurately quantifying tissue characteristics. This study aims to evaluate the accuracy and reproducibility of a single cMRF sequence described by Hamilton et. al. using self-constructed phantoms to validate the sequence performance for cardiac imaging. The objective was to construct in-vitro phantoms with physiological combinations of T1 and T2 markers. The phantoms were then imaged using gold standard and conventional mapping sequences to establish reference values for comparison. The measurements obtained from the two distinct cMRF reconstruction approaches were then compared to these reference values and to each other to evaluate the accuracy. The statistical assessments did not find a statistically significant difference between neither the cMRF sequence and conventional mapping techniques, nor cMRF and the gold-standard method, when compared in in-vitro phantoms with physiological combinations of T1 and T2. / Kvantitativ kardiovaskulär magnetresonans (CMR) har fått ökad uppmärksamhet inom både den kliniska- och forskningsfältet på grund av hög förekomst av hjärt- och kärlsjukdomar. För att åtgärda begränsningarna vid utvärdering av multiparametrisk kvantitativ CMR, introducerades cardiac magnetic resonance fingerprinting (cMRF) som en ny metod. cMRF möjliggör simultan och samregistrerad uppskattning av vävnadens relaxationstider, T1 och T2, i samma insamling, vilket gör det till en mer tidseffektiv metod för multiparametrisk kvantitativ CMR. Trots detta är kliniska implementeringen av cMRF inte utbredd på grund av otillräckligt bevis för dess utförande vid exakt kvantifiering av vävnadsegenskaper. Syftet med denna studie är att bedöma noggrannheten hos en cMRF-sekvens som utvecklats av Hamilton et al. genom att använda egentillverkade fantomer för att verifiera hur effektiv sekvensen är för avbildning av hjärtat. Målet är att konstruera in vitro-fantom med fysiologiska kombinationer av  T1- och T2-markörer. Dessa fantomer avbildades med hjälp av referensmetoder och konventionell karaktärisering för att etablera jämförelsevärden. Mätningarna som erhölls från de två distinkta cMRF-rekonstruktionsmetoderna jämfördes sedan statistiskt med jämförelsevärdena och med varandra för att utvärdera mätnoggrannheten. De statistiska bedömningarna kunde inte påvisa en skillnad mellan varken cMRF-sekvensen och konventionella metoder, eller referensmetod, vid jämförelse i in vitro-fantom med fysiologiska kombinationer av T1- och T2-värden.

Cardiovascular disease remains a leading a cause of mortality and morbidity. Primary prevention is known to reduce the incidence of cardiovascular disease. The use of medication is currently targeted at those at increased predicted risk of cardiovascular disease using risk prediction tools developed from large epidemiological studies. However these have poor external validity particularly for those at low or intermediate risk: a significant number of cardiovascular events still occurs in these groups. We hypothesised that screening for asymptomatic pre-clinical cardiovascular disease using B-type natriuretic peptide (BNP) and whole body contrast enhanced magnetic resonance imaging (MRI) could identify those at low/intermediate risk or disease whowill develop clinical disease and thus facilitate improved targeting of primary prevention at those most likely to benefit. The Tayside Screening for Cardiac Events (TASCFORCE) study is a prospective normal volunteer cohort study. Men and women aged 40 years or older free from cardiovascular disease and with a predicted 10-year coronary heart disease risk less than 20% were recruited. All had comprehensive baseline cardiovascular risk information and a BNP level measured. If the BNP level was greater than the median for their gender participants were invited to attend for a whole body contrast enhancedMRI scan comprising cardiac imaging and whole body angiography. The images were analysed to measure left ventricular mass (LVM), left ventricular volumes and left ventricular function. These were indexed for body size using height, height1.7, height2.7 and body surface area. Angiogram images were analysed for the presence and degree of intraluminal stenosis. All participants are being followed up using anonymised electronic data linkage for incident cardiovascular disease and death. 4423 participants (39.3% male) were recruited between November 2007 and February 2013. Median age was 51.2 years. The median 10-year coronary heart disease (CHD) 23 risk was 2% and 13.6% had a CHD risk of 10-19.9% (intermediate risk). The medianBNP results for men and women were 7.5 and 15.3 pg/ml respectively. Age, female sex and high density lipoprotein were independently associated with BNP level. Heart rate, total cholesterol and ex-smoking status were independently inversely associated with BNP level. 1528 (74.8% of those invited) underwent an MRI scan. Mean left ventricular mass was 129.2g and 87.0g for men and women respectively. LVM and left ventricular mass index (LVMI) were significantly higher in men than women. The vast majority (94.6%) of arterial segments analysed were normal and 50.6% of individuals had no evidence of luminal stenosis. From follow up data obtained 2 years after the end of recruitment 18,364 person years at risk were analysed. 17 cardiovascularevents and no deaths occurred in those not invited for an MRI scan based on their BNP result and 16 events and 1 death occurred in those invited for an MRI scan. There was no significant difference in event rates between those with above and below median BNP levels, between those with higher or lower LVM or LVMI or between those with and without the presence of stenosis on angiography. As expected we have not demonstrated the ability of LVM, LVMI or stenosis burden determined using magnetic resonance imaging to predict cardiovascular disease in a population at low or intermediate risk of CHD. We have also not demonstrated the ability of BNP to identify those at low orintermediate risk of CHD who will develop clinical CV disease. However it is the pre-planned longer-term follow up where difference might be expected. The low number of events at this early stage in follow up mean that it is difficult to draw firm conclusions. As follow up continues and further events accumulate we hope to determine if these measures will be shown to predict cardiovascular events in future analyses. We have characterised the normal values and distribution of a range of left ventricular structural and functional parameters derived using a steady state free precision sequence MRI in a population at low or intermediate risk of CHD which will provide a useful reference for normal values that are different to other imaging modalities including chocardiography and other protocols of MRI scanning.

Today, invasive coronary angiography is still the gold standard to perform the diagnosis of coronary artery disease. But it is an invasive procedure that carries non negligible morbidity (1.5%) and mortality (0.15%), and results in high costs. Less invasive and more cost-effective techniques are highly desirable. Over the past 15 years, substantial advances have been made in non-invasive cardiac imaging. In the first part of this work, we prospectively evaluated the diagnostic accuracy of 40-slice multidetector CT (MDCT) to detect coronary artery disease prior to cardiac valve surgery in 82 patients. On a per-patient basis, MDCT correctly identified 14/15 patients with (sensitivity 93%) and 60/67 patients without coronary disease (specificity 90%). Performing invasive angiography only in case of abnormal CT might have avoided invasive angiography in 60/82 (73%) patients without coronary disease. Thus, MDCT could be potentially useful in the preoperative evaluation of such patients, allowing to avoid systematic cardiac catheterization in a large number of patients. Magnetic resonance coronary angiography (MRCA) has also emerged as a promising alternative due to the lack of ionizing radiation and absence of iodinated contrast injection. Therefore, we compared diagnostic accuracy of whole-heart MRCA and MDCT, against QCA, to identify >50% stenosis basis in 77 patients. WH-MRCA acquisition failed in a high number of patients. This was caused by an unstable breathing pattern or drift of the diaphragm position. Because of higher success rate, MDCT had higher diagnostic accuracy than WH-MRCA to detect coronary stenosis. Thus MDCT is superior to WH-MRCA, however WH-MRCA can perform as well as CT in interpretable segments with adequate image quality. In the second part of this work, to evaluate whether MDCT and cardiac magnetic resonance (cMR) might allow simultaneous assessment of aortic valve area (AVA), we compared measurements of AVA by MDCT to cMR, transesophageal and transthoracic echocardiography. AVA by MDCT and cMR correlated highly with AVA by other techniques. In our study, we compared 3 planimetric approaches to AVA calculated by the continuity equation using TTE. We did observe excellent correlations between planimetric and continuity equation-derived AVA, but all 3 planimetric measures were found to overestimate continuity equation AVA. A potential explanation for this observation could be that we measure different aortic valve orifices. Indeed planimetric techniques measure the true dimensions of the anatomical orifice, whereas the continuity equation measures the "effective" orifice area. The ability of MDCT and cMR to accurately assess aortic valve area at the time of non-invasive coronary imaging, places these techniques in a strong position for the comprehensive assessment of such patients. However, despite these good results, it must nonetheless be emphasized that to be acceptable in daily clinical practice, a strategy in which invasive coronary angiography would not be performed systematically but rather selectively in only a subset of patients, requires a perfect sensitivity for disease detection in individual patients. Unfortunately, the present work shows that MDCT and WH-MRCA have not yet reached such a level of accuracy. Finally, these tests are not a substitute for other imaging techniques in all cardiovascular conditions. Unlike an echocardiogram machine, the MRI and MDCT scanners cannot be brought to the bedside of an acutely ill patient.

Techniques described to date for the reproducible and noninvasive quantification of regional cardiac function have been largely relegated to research settings due to time-consuming and cumbersome image acquisition and analysis. In this thesis, feature tracking algorithms are developed for 2-D+Time cardiac magnetic resonance (CMR) and 3-D+Time cardiac computed tomography (CCT) image sequences that are easily acquired clinically, while emphasising reproducibility and automation in their design. First, a commercially-implemented CMR feature tracking algorithm for the analysis of steady state free precession (SSFP) cine series is evaluated in patients with hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC), which primarily affect the left ventricle (LV) and right ventricle (RV), respectively, and functional impairment compared with control populations is found in both cases. The limitations of this implementation are then used to guide development of an automated algorithm for the same purpose, making use of fully convolutional neural networks (CNN) for segmentation and spline registration across all frames simultaneously for tracking. This study is performed in the subjects with HCM, and functional impairment is again identified in disease subjects. Finally, as myocardial contraction is inherently a 3-D phenomenon, a technique is developed for quantification of regional function from 3-D+Time functional CCT studies using simultaneous registration of automatically generated Loop subdivision surface models for tracking. This study is performed in canine mongrels, and compared with the current state of the art technique for CCT functional analysis. This work demonstrates the feasibility of automated, reproducible cardiac functional analysis from CMR and CCT image sequences. While work remains to be done in extending the principles demonstrated and modular components described to fully automated whole-heart analysis, it is hoped that this thesis will accelerate the clinical adoption of regional functional analysis.