68 research outputs found
Anthropometric and genetic determinants of cardiac morphology and function
Background
Cardiac structure and function result from complex interactions between genetic and environmental factors. Population-based studies have relied on 2-dimensional cardiovascular magnetic resonance as the gold-standard for phenotyping. However, this technique provides limited global metrics and is insensitive to regional or asymmetric changes in left ventricular (LV) morphology.
High-resolution 3-dimensional cardiac magnetic resonance (3D-CMR) with computational quantitative phenotyping, might improve on traditional CMR by enabling the creation of detailed 3D statistical models of the variation in cardiac phenotypes for use in studies of genetic and/or environmental effects on cardiac form or function.
Purpose
To determine whether 3D-CMR is applicable at scale, and provides methodological and statistical advantages over conventional imaging for large-scale population studies and to apply 3D-CMR to anthropometric and genetic studies of the heart.
Methods
1530 volunteers (54.8% females, 74.7% Caucasian, mean age 41.3±13.0 years) without self-reported cardiovascular disease were recruited prospectively to the Digital Heart Project. Using a cardiac atlas-based software, these images were computationally processed and quantitatively analysed. Parameters such as myocardial shape, curvature, wall thickness, relative wall thickness, end-systolic wall stress, fractional wall thickening and ventricular volumes were extracted at over 46,000 points in the model. The relationships between these parameters and systolic blood pressure (SBP), fat mass, lean mass and genetic variationswere analysed using 3D regression models adjusted for body surface area, gender, race, age and multiple testing.
Targeted resequencing of titin (TTN), the largest human gene and the commonest genetic cause of dilated cardiomyopathy, was performed in 928 subjects while common variants (~700.000) were genotyped in 1346 subjects.
Results
Automatically segmented 3D images were more accurate than 2D images at defining cardiac surfaces, resulting in fewer subjects being required to detect a statistically significant 1 mm difference in wall thickness. 3D-CMR enabled the detection of a strong and distinct regionality of the effects of SBP, body composition and genetic variation on the heart. It shows that the precursors of the hypertensive heart phenotype can be traced to healthy normotensives and that different ratios of body composition are associated with particular gender-specific patterns of cardiac remodelling. In 17 asymptomatic subjects with genetic variations associated with dilated cardiomyopathy, early stages of ventricular impairment and wall thinning were identified, which were not apparent by 2D imaging.
Conclusions
3D-CMR combined with computational modelling provides high-resolution insight into the earliest stages of heart disease. These methods show promise for population-based studies of the anthropometric, environmental and genetic determinants of LV form and function in health and disease.Open Acces
Characterising pattern asymmetry in pigmented skin lesions
Abstract. In clinical diagnosis of pigmented skin lesions asymmetric pigmentation is often indicative of
melanoma. This paper describes a method and measures for characterizing lesion symmetry. The estimate of
mirror symmetry is computed first for a number of axes at different degrees of rotation with respect to the
lesion centre. The statistics of these estimates are the used to assess the overall symmetry. The method is
applied to three different lesion representations showing the overall pigmentation, the pigmentation pattern,
and the pattern of dermal melanin. The best measure is a 100% sensitive and 96% specific indicator of
melanoma on a test set of 33 lesions, with a separate training set consisting of 66 lesions
Clinical Use of Cardiac CT
The aim of this thesis was to investigate the optimal diagnostic strategy for patients presenting with stable angina and unstable angina and ACS.
A better diagnostic strategy, ultimately leads to a better outcome for patients with suspected CAD
Characterisation of cardiac structure and function in late adolescence and modification by adiposity and other cardiovascular risk factors
Cardiovascular disease remains one of the leading causes of death worldwide. However, a large proportion of research in the field focuses primarily on middle- to old- age, by which time much damage to the heart and vascular system has been incurred. The rationale for this research was to gain a clearer picture of cardiovascular health in late adolescence, prior to the onset of adulthood. In this thesis I characterise the cardiac structure and function of individuals from the ALSPAC cohort (average age 17.7 years) through analysing M-Mode, two dimensional and Doppler echocardiographic measures and haemodynamic, biochemical and anthropometric measures. Adiposity, sex and genetic predisposition are considered as key exposures which impact a range of cardiovascular outcomes. I consider the relationships of fat mass and lean mass with cardiovascular outcomes and the ways in which left ventricular mass indexation is affected by adiposity, lean mass, height and body surface area. I then discuss the roles which particular haemodynamic and biochemical biomarkers have in mediating associations between fat mass and left ventricular structural and functional outcomes. Finally I consider the influence which genes associated with body mass index have on key cardiovascular measures, including cardiac structural and functional measures. Adiposity has a direct and detrimental effect on cardiovascular health. My findings provide insights into the way in which adiposity affects the development of an adverse cardiometabolic phenotype from a comparatively young age and also have interesting implications for future research. Furthermore, they serve as another important reminder of the need for adiposity to be monitored throughout the life course
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