Multiresolution spatiotemporal mechanical model of the heart as a prior to constrain the solution for 4D models of the heart.

In several nuclear cardiac imaging applications (SPECT and PET), images are formed by reconstructing tomographic data using an iterative reconstruction algorithm with corrections for physical factors involved in the imaging detection process and with corrections for cardiac and respiratory motion. The physical factors are modeled as coefficients in the matrix of a system of linear equations and include attenuation, scatter, and spatially varying geometric response. The solution to the tomographic problem involves solving the inverse of this system matrix. This requires the design of an iterative reconstruction algorithm with a statistical model that best fits the data acquisition. The most appropriate model is based on a Poisson distribution. Using Bayes Theorem, an iterative reconstruction algorithm is designed to determine the maximum a posteriori estimate of the reconstructed image with constraints that maximizes the Bayesian likelihood function for the Poisson statistical model. The a priori distribution is formulated as the joint entropy (JE) to measure the similarity between the gated cardiac PET image and the cardiac MRI cine image modeled as a FE mechanical model. The developed algorithm shows the potential of using a FE mechanical model of the heart derived from a cardiac MRI cine scan to constrain solutions of gated cardiac PET images

Carboxyhaemoglobin levels and their determinants in older British men

Background: Although there has been concern about the levels of carbon monoxide exposure, particularly among older people, little is known about COHb levels and their determinants in the general population. We examined these issues in a study of older British men.Methods: Cross-sectional study of 4252 men aged 60-79 years selected from one socially representative general practice in each of 24 British towns and who attended for examination between 1998 and 2000. Blood samples were measured for COHb and information on social, household and individual factors assessed by questionnaire. Analyses were based on 3603 men measured in or close to (< 10 miles) their place of residence.Results: The COHb distribution was positively skewed. Geometric mean COHb level was 0.46% and the median 0.50%; 9.2% of men had a COHb level of 2.5% or more and 0.1% of subjects had a level of 7.5% or more. Factors which were independently related to mean COHb level included season (highest in autumn and winter), region (highest in Northern England), gas cooking (slight increase) and central heating (slight decrease) and active smoking, the strongest determinant. Mean COHb levels were more than ten times greater in men smoking more than 20 cigarettes a day (3.29%) compared with non-smokers (0.32%); almost all subjects with COHb levels of 2.5% and above were smokers (93%). Pipe and cigar smoking was associated with more modest increases in COHb level. Passive cigarette smoking exposure had no independent association with COHb after adjustment for other factors. Active smoking accounted for 41% of variance in COHb level and all factors together for 47%.Conclusion: An appreciable proportion of men have COHb levels of 2.5% or more at which symptomatic effects may occur, though very high levels are uncommon. The results confirm that smoking (particularly cigarette smoking) is the dominant influence on COHb levels

Early and late systolic wall stress differentially relate to myocardial contraction and relaxation in middle-aged adults: the Asklepios study

Experimental studies implicate late systolic load as a determinant of impaired left ventricular (LV) relaxation. We aimed to assess the relationship between the myocardial loading sequence and left ventricular (LV) contraction and relaxation. Time-resolved central pressure and time-resolved LV geometry were measured with carotid tonometry and speckle-tracking echocardiography, respectively, for computation of time-resolved ejection-phase myocardial wall stress (EP-MWS) among 1,214 middle-aged adults without manifest cardiovascular disease from the general population. Early diastolic annular velocity, systolic annular velocities were measured with tissue Doppler imaging and segmentaveraged longitudinal strain was measured with speckle-tracking echocardiography. After adjustment for age, gender and potential confounders, late EP-MWS was negatively associated with early diastolic mitral annular velocity (e', standardized β=-0.25; P<0.0001) and mitral inflow propagation velocity (Vpe, standardized β=-0.13; P=0.02). In contrast, early EP-MWS was positively associated with e' (standardized β=0.18; P<0.0001) and Vpe (standardized β=0.22; P<0.0001). A higher late EP-MWS predicted a lower systolic mitral annular velocity (S', standardized β=-0.31; P<0.0001) and lesser myocardial longitudinal strain (standardized β=0.32; P<0.0001), whereas a higher early EP-MWS was associated with a higher S' (standardized β=0.16; P=0.002) and greater longitudinal strain (standardized β=-0.24; P=0.002). The loading sequence remained independently associated with e' after adjustment for S' or systolic longitudinal strain. In the context of available experimental data, our findings support the role of the myocardial loading sequence as a determinant of LV systolic and diastolic function. A loading sequence characterized by prominent late systolic wall stress was associated with lower longitudinal systolic function and diastolic relaxation

Real-world heart rate norms in the Health eHeart study.

Emerging technology allows patients to measure and record their heart rate (HR) remotely by photoplethysmography (PPG) using smart devices like smartphones. However, the validity and expected distribution of such measurements are unclear, making it difficult for physicians to help patients interpret real-world, remote and on-demand HR measurements. Our goal was to validate HR-PPG, measured using a smartphone app, against HR-electrocardiogram (ECG) measurements and describe out-of-clinic, real-world, HR-PPG values according to age, demographics, body mass index, physical activity level, and disease. To validate the measurements, we obtained simultaneous HR-PPG and HR-ECG in 50 consecutive patients at our cardiology clinic. We then used data from participants enrolled in the Health eHeart cohort between 1 April 2014 and 30 April 2018 to derive real-world norms of HR-PPG according to demographics and medical conditions. HR-PPG and HR-ECG were highly correlated (Intraclass correlation = 0.90). A total of 66,788 Health eHeart Study participants contributed 3,144,332 HR-PPG measurements. The mean real-world HR was 79.1 bpm ± 14.5. The 95th percentile of real-world HR was ≤110 in individuals aged 18-45, ≤100 in those aged 45-60 and ≤95 bpm in individuals older than 60 years old. In multivariable linear regression, the number of medical conditions, female gender, increasing body mass index, and being Hispanic was associated with an increased HR, whereas increasing age was associated with a reduced HR. Our study provides the largest real-world norms for remotely obtained, real-world HR according to various strata and they may help physicians interpret and engage with patients presenting such data

Compensated right ventricular function of the onset of pulmonary hypertension in a rat model depends on chamber remodeling and contractile augmentation.

Right-ventricular function is a good indicator of pulmonary arterial hypertension (PAH) prognosis; however, how the right ventricle (RV) adapts to the pressure overload is not well understood. Here, we aimed at characterizing the time course of RV early remodeling and discriminate the contribution of ventricular geometric remodeling and intrinsic changes in myocardial mechanical properties in a monocrotaline (MCT) animal model. In a longitudinal study of PAH, ventricular morphology and function were assessed weekly during the first four weeks after MCT exposure. Using invasive measurements of RV pressure and volume, heart performance was evaluated at end of systole and diastole to quantify contractility (end-systolic elastance) and chamber stiffness (end-diastolic elastance). To distinguish between morphological and intrinsic mechanisms, a computational model of the RV was developed and used to determine the level of prediction when accounting for wall masses and unloaded volume measurements changes. By four weeks, mean pulmonary arterial pressure and elastance rose significantly. RV pressures rose significantly after the second week accompanied by significant RV hypertrophy, but RV stroke volume and cardiac output were maintained. The model analysis suggested that, after two weeks, this compensation was only possible due to a significant increase in the intrinsic inotropy of RV myocardium. We conclude that this MCT-PAH rat is a model of RV compensation during the first month after treatment, where geometric remodeling on EDPVR and increased myocardial contractility on ESPVR are the major mechanisms by which stroke volume is preserved in the setting of elevated pulmonary arterial pressure. The mediators of this compensation might themselves promote longer-term adverse remodeling and decompensation in this animal model

Doctor of Philosophy

dissertationComputational simulation has become an indispensable tool in the study of both basic mechanisms and pathophysiology of all forms of cardiac electrical activity. Because the heart is comprised of approximately 4 billion electrically active cells, it is not possible to geometrically model or computationally simulate each individual cell. As a result computational models of the heart are, of necessity, abstractions that approximate electrical behavior at the cell, tissue, and whole body level. The goal of this PhD dissertation was to evaluate several aspects of these abstractions by exploring a set of modeling approaches in the field of cardiac electrophysiology and to develop means to evaluate both the amplitude of these errors from a purely technical perspective as well as the impacts of those errors in terms of physiological parameters. The first project used subject specific models and experiments with acute myocardial ischemia to show that one common simplification used to model myocardial ischemia-the simplest form of the border zone between healthy and ischemic tissue-was not supported by the experimental results. We propose a alternative approximation of the border zone that better simulates the experimental results. The second study examined the impact of simplifications in geometric models on simulations of cardiac electrophysiology. Such models consist of a connected mesh of polygonal elements and must often capture complex external and internal boundaries. A conforming mesh contains elements that follow closely the shapes of boundaries; nonconforming meshes fit the boundaries only approximately and are easier to construct but their impact on simulation accuracy has, to our knowledge, remained unknown. We evaluated the impact of this simplification on a set of three different forms of bioelectric field simulations. The third project evaluated the impact of an additional geometric modeling error; positional uncertainty of the heart in simulations of the ECG. We applied a relatively novel and highly efficient statistical approach, the generalized Polynomial Chaos-Stochastic Collocation method (gPC-SC), to a boundary element formulation of the electrocardiographic forward problem to carry out the necessary comprehensive sensitivity analysis. We found variations large enough to mask or to mimic signs of ischemia in the ECG

Association of N-terminal pro-brain natriuretic peptide with cognitive function and depression in elderly people with type 2 diabetes

&lt;p&gt;Background: Type 2 diabetes mellitus is associated with risk of congestive heart failure (CHF), cognitive dysfunction and depression. CHF itself is linked both to poor cognition and depression. The ventricular N-terminal pro-brain natriuretic peptide (NT-proBNP) is a marker of CHF, suggesting potential as a marker for cognitive impairment and/or depression. This was tested in the Edinburgh Type 2 Diabetes Study (ET2DS).&lt;/p&gt; &lt;p&gt;Methodology and Principal Findings: Cross-sectional analysis of 1066 men and women aged 60–75 with type 2 diabetes. Results from seven neuropsychological tests were combined in a standardised general cognitive ability factor, ‘g’. A vocabulary-based test estimated pre-morbid cognitive ability. The Hospital Anxiety and Depression Scale (HADS) assessed possible depression. After adjustment for age and sex, raised plasma NT-proBNP was weakly associated with lower ‘g’ and higher depression scores (ß −0.09, 95% CI −0.13 to −0.03, p = 0.004 and ß 0.08, 95% CI 0.04 to 0.12, p&#60;0.001, respectively). Comparing extreme quintiles of NT-proBNP, subjects in the highest quintile were more likely to have reduced cognitive ability (within the lowest tertile of ‘g’) and ‘possible’ depression (HADS depression &#8805;8) (OR 1.80; 95% CI: 1.20, 2.70; p = 0.005 and OR 2.18; 95% CI: 1.28, 3.71; p = 0.004, respectively). Associations persisted when pre-morbid ability was adjusted for, but as expected were no longer statistically significant following the adjustment for diabetes-related and vascular co-variates (β −0.02, 95% CI −0.07 to 0.03, p&#62;0.05 for ‘g’; β 0.03, 95% CI −0.02 to 0.07, p&#62;0.05 for depression scores).&lt;/p&gt; &lt;p&gt;Conclusion: Raised plasma NT-proBNP was weakly but statistically significantly associated with poorer cognitive function and depression. The prospective phases of the ET2DS will help determine whether or not NT-proBNP can be considered a risk marker for subsequent cognitive impairment and incident depression and whether it provides additional information over and above traditional risk factors for these conditions.&lt;/p&gt

An Angiosperm species dataset reveals relationships between seed size and two-dimensional shape

Datasets containing information on seed size have been published and are currently available. Nevertheless, there is a lack in the literature of a dataset dedicated to seed shape. We present a preliminary version for a dataset on seed morphology based on a comparison of seed shape with geometric figures. Similarity of the outline of seed images with geometric models is considered as a basis to classify seeds according to the geometric figures they resemble (e.g., ellipse, oval, cardioid). This allows, first, the classification of plant species according to their geometric type of seed, and second, seed shape quantification. For each seed image, the percent of similarity of their outline with a geometric figure can be calculated as a J index. Similarity in absolute terms is considered only when the J index >90. This criterion is important to avoid ambiguity and increase discrimination. The dataset opens the possibility of studying the relationship between seed shape and other variables such as seed size, genome complexity, life form or adaptive responses

Image-based Quantification of 3D Morphology for Bifurcations in the Left Coronary Artery: Application to Stent Design

Background Improved strategies for stent‐based treatment of coronary artery disease at bifurcations require a greater understanding of artery morphology. Objective We developed a workflow to quantify morphology in the left main coronary (LMCA), left anterior descending (LAD), and left circumflex (LCX) artery bifurcations. Methods Computational models of each bifurcation were created for 55 patients using computed tomography images in 3D segmentation software. Metrics including cross‐sectional area, length, eccentricity, taper, curvature, planarity, branching law parameters, and bifurcation angles were assessed using open‐sources software and custom applications. Geometric characterization was performed by comparison of means, correlation, and linear discriminant analysis (LDA). Results Differences between metrics suggest dedicated or multistent approaches should be tailored for each bifurcation. For example, the side branch of the LCX (i.e., obtuse marginal; OM) was longer than that of the LMCA (i.e., LCXprox) and LAD (i.e., first diagonal; D1). Bifurcation metrics for some locations (e.g., LMCA Finet ratio) provide results and confidence intervals agreeing with prior findings, while revised metric values are presented for others (e.g., LAD and LCX). LDA revealed several metrics that differentiate between artery locations (e.g., LMCA vs. D1, LMCA vs. OM, LADprox vs. D1, and LCXprox vs. D1). Conclusions These results provide a foundation for elucidating common parameters from healthy coronary arteries and could be leveraged in the future for treating diseased arteries. Collectively the current results may ultimately be used for design iterations that improve outcomes following implantation of future dedicated bifurcation stents