A statistical shape modelling framework to extract 3D shape biomarkers from medical imaging data: assessing arch morphology of repaired coarctation of the aorta

Background Medical image analysis in clinical practice is commonly carried out on 2D image data, without fully exploiting the detailed 3D anatomical information that is provided by modern non-invasive medical imaging techniques. In this paper, a statistical shape analysis method is presented, which enables the extraction of 3D anatomical shape features from cardiovascular magnetic resonance (CMR) image data, with no need for manual landmarking. The method was applied to repaired aortic coarctation arches that present complex shapes, with the aim of capturing shape features as biomarkers of potential functional relevance. The method is presented from the user-perspective and is evaluated by comparing results with traditional morphometric measurements. Methods Steps required to set up the statistical shape modelling analyses, from pre-processing of the CMR images to parameter setting and strategies to account for size differences and outliers, are described in detail. The anatomical mean shape of 20 aortic arches post-aortic coarctation repair (CoA) was computed based on surface models reconstructed from CMR data. By analysing transformations that deform the mean shape towards each of the individual patient’s anatomy, shape patterns related to differences in body surface area (BSA) and ejection fraction (EF) were extracted. The resulting shape vectors, describing shape features in 3D, were compared with traditionally measured 2D and 3D morphometric parameters. Results The computed 3D mean shape was close to population mean values of geometric shape descriptors and visually integrated characteristic shape features associated with our population of CoA shapes. After removing size effects due to differences in body surface area (BSA) between patients, distinct 3D shape features of the aortic arch correlated significantly with EF (r = 0.521, p = .022) and were well in agreement with trends as shown by traditional shape descriptors. Conclusions The suggested method has the potential to discover previously unknown 3D shape biomarkers from medical imaging data. Thus, it could contribute to improving diagnosis and risk stratification in complex cardiac disease

How successful is successful?:Aortic arch shape after successful aortic coarctation repair correlates with left ventricular function

International audienceObjectives: Even after successful aortic coarctation repair, there remains a significant incidence of late systemic hypertension and other morbidities. Independently of residual obstruction, aortic arch morphology alone may affect cardiac function and outcome. We sought to uncover the relationship of arch 3-dimensional shape features with functional data obtained from cardiac magnetic resonance scans.Methods: Three-dimensional aortic arch shape models of 53 patients (mean age, 22.3 ± 5.6 years) 12 to 38 years after aortic coarctation repair were reconstructed from cardiac magnetic resonance data. A novel validated statistical shape analysis method computed a 3-dimensional mean anatomic shape of all aortic arches and calculated deformation vectors of the mean shape toward each patient's arch anatomy. From these deformations, 3-dimensional shape features most related to left ventricular ejection fraction, indexed left ventricular end-diastolic volume, indexed left ventricular mass, and resting systolic blood pressure were extracted from the deformation vectors via partial least-squares regression.Results: Distinct arch shape features correlated significantly with left ventricular ejection fraction (r = 0.42, P = .024), indexed left ventricular end-diastolic volume (r = 0.65, P < .001), and indexed left ventricular mass (r = 0.44, P = .014). Lower left ventricular ejection fraction, larger indexed left ventricular end-diastolic volume, and increased indexed left ventricular mass were identified with an aortic arch shape that has an elongated ascending aorta with a high arch height-to-width ratio, a relatively short proximal transverse arch, and a relatively dilated descending aorta. High blood pressure seemed to be linked to gothic arch shape features, but this did not achieve statistical significance.Conclusions: Independently of hemodynamically important arch obstruction or residual aortic coarctation, specific aortic arch shape features late after successful aortic coarctation repair seem to be associated with worse left ventricular function. Analyzing 3-dimensional shape information via statistical shape modeling can be an adjunct to long-term risk assessment in patients after aortic coarctation repair

Interface Investigations on Titanium Nitride Bilayer Systems

Nanocomposite coatings composed of two phases with atomically sharp phase boundaries, show interesting mechanical properties. These properties are often originating from their high interface to volume ratio. Composites of nanocrystalline titanium nitride (TiN) grains surrounded by a one to two monolayer thick interlayer of silicon nitride (Si3N4) show an enhanced nanohardness. The central theme of this thesis is concernedwith the interfacial properties of two-dimensional bilayer systems, which are used as model systems to describe the interfaces occurring in nanocomposite coatings. The systems under investigation are TiN interfaces in contact with silicon (Si), silicon nitride (Si3N4) and aluminum nitride (AlN). The primary tool used to analyze the interfaces of bilayer systems is X-ray Photoelectron Spectroscopy (XPS) with emphasis put on the shake-up feature of the Ti 2p photoelectron line. Shake-ups in TiN are observed as an additional peak on the lower binding energy side of the energy lines of the Ti 2p orbitals. Shake-ups are strongly influenced by valence electrons and electron density distributions. This makes them a powerful tool to probe the chemical and electronic structure of TiN interfaces. The aim of this study is to utilize the shake-up energy and its intensity to gain insight into interfacial structures and correlate their changes to interfacial polarization and macroscopic mechanical properties. Single crystalline (sc-) and oxygen-free TiN as well as oxygen-free bilayer systems were deposited by unbalanced magnetron sputtering and analyzed by Angle Resolved (AR-)XPS. Bilayer samples were deposited and their quality was controlled using X-ray diffraction (crystallinity), Rutherford back scattering (elemental composition), and atomic force microscopy (roughness). All XPS samples were fabricated, transfered and analyzed whilst maintaining ultra high vacuum. A precise and self-consistent XPS data processing method was developed to evaluate Ti 2p spectra. This method accounts for the correct photoelectron line shape, background subtraction and photoelectron peak area intensity. Binding energy, shake-up energy and intensity ratios of shake-ups taken frompristine TiN surfaces are precisely determined, and the influence of oxygen on the information content in peak positions and intensities was investigated. The shake-up energy and intensity of bulk sc-TiN and its origin of the shake-up are discussed. An analytical description for the XPS signal ratio of bilayer systems is derived to separate the interfacial signals from the bulk information. The results obtained by this analytical description are strongly influenced by the interface thickness that has been found to be proportional to the overlayer thickness. The revealed interface properties show a correlation between the shake-up intensity and the interface morphology, oxygen content, overlayer material and overlayer thickness. AR-XPS and X-ray Photoelectron Diffraction (XPD) results were used to interpret the crystalline structure of the different TiN/AlN and TiN/Si3N4 bilayer systems. AlN shows XPD patterns indicating a crystalline growth of AlN on sc-TiN. The electrically insulating AlN overlayer creates a charge accumulation at the TiN interface, which results in an enhanced shake-up intensity. XPD patterns of Si3N4 systems revealed a crystalline growth of Si3N4 in the first 0.6nm. The intensity of the diffraction patterns reduces with increasing Si3N4 overlayer thickness due to a change in the growth behavior from crystalline to amorphous structures. Si3N4 films show, in comparison to AlN, reduced interface charging and hence a lower shakeup intensity. The crystalline growth of Si3N4 in the initial stages is hindered in systems where a bias voltage is applied to the substrate during the deposition process. In contrast to the unbiased systems, which have crystalline interfacial structures, the biased systems no longer show XPD patterns due to a loss of crystallinity. Additionally the shake-up intensity of biased systems is thickness-independent, which is in contrast to unbiased systems. The difference in the shake-up intensity of biased and unbiased Si3N4 is explained by a different band gap of the Si3N4 structure in the first two monolayers. This thesis shows that the increase in the shake-up intensity is correlated to intrinsic and extrinsic interface charging. The obtained results, in combination with theoretical structure models from literature, show that in one to two monolayer thick interlayers a build-up of interface polarization is unlikely. The observed nanohardness enhancement in TiN/Si3N4 systems is explained with already known hardness effects

Quantifying the effect of corrective surgery for trigonocephaly: A non-invasive, non-ionizing method using three-dimensional handheld scanning and statistical shape modelling

Trigonocephaly in patients with metopic synostosis is corrected by fronto-orbital remodelling (FOR). The aim of this study was to quantitatively assess aesthetic outcomes of FOR by capturing 3D forehead scans of metopic patients pre- and post-operatively and comparing them with controls. Ten single-suture metopic patients undergoing FOR and 15 age-matched non-craniosynostotic controls were recruited at Great Ormond Street Hospital for Children (UK). Scans were acquired with a three-dimensional (3D) handheld camera and post-processed combining 3D imaging software. 3D scans were first used for cephalometric measurements. Statistical shape modelling was then used to compute the 3D mean head shapes of the three groups (FOR pre-op, post-op and controls). Head shape variations were described via principal component analysis (PCA). Cephalometric measurements showed that FOR significantly increased the forehead volume and improved trigonocephaly. This improvement was supported visually by pre- and post-operative computed mean 3D shapes and numerically by PCA (p < 0.001). Compared with controls, post-operative scans showed flatter foreheads (p < 0.001). In conclusion, 3D scanning followed by 3D statistical shape modelling enabled the 3D comparison of forehead shapes of metopic patients and non-craniosynostotic controls, and demonstrated that the adopted FOR technique was successful in correcting bitemporal narrowing but overcorrected the rounding of the forehead

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways