The anthropometric, environmental and genetic determinants of right ventricular structure and function

BACKGROUND Measures of right ventricular (RV) structure and function have significant prognostic value. The right ventricle is currently assessed by global measures, or point surrogates, which are insensitive to regional and directional changes. We aim to create a high-resolution three-dimensional RV model to improve understanding of its structural and functional determinants. These may be particularly of interest in pulmonary hypertension (PH), a condition in which RV function and outcome are strongly linked. PURPOSE To investigate the feasibility and additional benefit of applying three-dimensional phenotyping and contemporary statistical and genetic approaches to large patient populations. METHODS Healthy subjects and incident PH patients were prospectively recruited. Using a semi-automated atlas-based segmentation algorithm, 3D models characterising RV wall position and displacement were developed, validated and compared with anthropometric, physiological and genetic influences. Statistical techniques were adapted from other high-dimensional approaches to deal with the problems of multiple testing, contiguity, sparsity and computational burden. RESULTS 1527 healthy subjects successfully completed high-resolution 3D CMR and automated segmentation. Of these, 927 subjects underwent next-generation sequencing of the sarcomeric gene titin and 947 subjects completed genotyping of common variants for genome-wide association study. 405 incident PH patients were recruited, of whom 256 completed phenotyping. 3D modelling demonstrated significant reductions in sample size compared to two-dimensional approaches. 3D analysis demonstrated that RV basal-freewall function reflects global functional changes most accurately and that a similar region in PH patients provides stronger survival prediction than all anthropometric, haemodynamic and functional markers. Vascular stiffness, titin truncating variants and common variants may also contribute to changes in RV structure and function. CONCLUSIONS High-resolution phenotyping coupled with computational analysis methods can improve insights into the determinants of RV structure and function in both healthy subjects and PH patients. Large, population-based approaches offer physiological insights relevant to clinical care in selected patient groups.Open Acces

Right ventricular biomechanics in pulmonary hypertension

As outcome in pulmonary hypertension is strongly associated with progressive right ventricular dysfunction, the work in this thesis seeks to determine the regional distribution of forces on the right ventricle, its geometry, and deformations subsequent to load. This thesis contributes to the understanding of how circulating biomarkers of energy metabolism and stress-response pathways are related to adverse cardiac remodelling and functional decompensation. A numerical model of the heart was used to derive a three-dimensional representation of right ventricular morphology, function and wall stress in pulmonary hypertension patients. This approach was tested by modelling the effect of pulmonary endarterectomy in patients with chronic thromboembolic disease. The relationship between the cardiac phenotype and 10 circulating metabolites, known to be associated with all-cause mortality, was assessed using mass univariate regression. Increasing afterload (mean pulmonary artery pressure) was significantly associated with hypertrophy of the right ventricular inlet and dilatation, indicative of global eccentric remodelling, and decreased systolic excursion. Right ventricular ejection fraction was found to be negatively associated with 3-hydroxy-3-methylglutarate, N-formylmethionine, and fumarate. Wall stress was related to all-cause mortality and its decrease after pulmonary endarterectomy was associated with a fall in brain natriuretic peptide. Six metabolites were associated with elevated end-systolic wall stress: dehydroepiandrosterone sulfate, N2,N2-dimethylguanosine, N1-methylinosine, 3-hydroxy-3-methylglutarate, N-acetylmethionine, and N-formylmethionine. Metabolic profiles related to energy metabolism and stress-response are associated with elevations in right ventricular end-systolic wall stress that have prognostic significance in pulmonary hypertension patients. These results show that statistical parametric mapping can give regional information on the right ventricle and that metabolic phenotyping, as well as predicting outcomes, provides markers informative of the biomechanical status of the right ventricle in pulmonary hypertension.Open Acces

Advanced Applications of Rapid Prototyping Technology in Modern Engineering

Rapid prototyping (RP) technology has been widely known and appreciated due to its flexible and customized manufacturing capabilities. The widely studied RP techniques include stereolithography apparatus (SLA), selective laser sintering (SLS), three-dimensional printing (3DP), fused deposition modeling (FDM), 3D plotting, solid ground curing (SGC), multiphase jet solidification (MJS), laminated object manufacturing (LOM). Different techniques are associated with different materials and/or processing principles and thus are devoted to specific applications. RP technology has no longer been only for prototype building rather has been extended for real industrial manufacturing solutions. Today, the RP technology has contributed to almost all engineering areas that include mechanical, materials, industrial, aerospace, electrical and most recently biomedical engineering. This book aims to present the advanced development of RP technologies in various engineering areas as the solutions to the real world engineering problems

Image Registration Workshop Proceedings

Automatic image registration has often been considered as a preliminary step for higher-level processing, such as object recognition or data fusion. But with the unprecedented amounts of data which are being and will continue to be generated by newly developed sensors, the very topic of automatic image registration has become and important research topic. This workshop presents a collection of very high quality work which has been grouped in four main areas: (1) theoretical aspects of image registration; (2) applications to satellite imagery; (3) applications to medical imagery; and (4) image registration for computer vision research

A longitudinal study of facial growth in infants using a three-dimensional imaging technique

This study aimed to measure the facial morphology and growth of 100 infants in the West of Scotland from the age of 3 months to 2 years using a three dimensional imaging system, C3D. One of the aims of the study was to validate the use of the C3D system to measure facial morphology in infants. Further aims were to establish references values for facial dimensions in infants, to establish the normal growth of facial parameters from 3 months to 2 years, to correlate facial and body growth, to ascertain any sexual dimorphism, to establish the degree of facial asymmetry and to determine any longitudinal changes in facial asymmetry in infant’s faces. Eighty three infants at 3 months, 93 infants at 6 months, 91 infants at 1 year and 92 infants at 2 years were successfully captured with a lips apart pose. Reference values for facial dimensions in infants at these ages were established. Significant gender differences were found for most facial measurements at all ages with the males being larger than the females. These differences were greatest for face height, depths and widths with mean differences ranging from 1.7 to 4.0 mm. No gender differences were found in any of the angles measured. Several dimensions on the right side of the face were found to be significantly larger than the left. This was most marked for face depths with mean differences of 0.8 mm. The range of normal facial asymmetry scores was determined. No significant difference in asymmetry was found between the males and females. The upper face was found to be the most asymmetric region studied and the nostrils were the least asymmetric. Correlation of facial measurements with body dimensions found weak but significant correlations with the highest correlation coefficient of 0.69 between face depth and body weight. Nasal tip protrusion, nostril dimensions and lip heights were not correlated with body dimensions. Seventy one infants, 37 males and 34 females, were successfully captured at all four ages with the lips apart and were included in the longitudinal analysis. The longitudinal changes in facial parameters were established from 3 months to 2 years and mean growth curves produced. The fastest growth was found from 3 to 6 months and the slowest from 1 to 2 years. There were no correlation between growth of the face and growth in body weight, length and head circumference. Significant reductions in the overall facial asymmetry score were found from 3 months to 2 years. The clinical significance of this reduction is still to be determined