Echocardiography examination is an important and familiar method for heart`s examination. Echocardiography is used to assess the function of the heart during to check the heart disease. In an echocardiography examination, the heart´s flow rates, contractility (pumping capacity), wall thickness, and inner diameter can be examined. All these examinations are done with the help of evolution of the ultrasonic waves that the ultrasonic transducer sends out and receives. The transducer consists of piezoelectric crystals that can both transmit and receive ultrasonic waves with frequencies exceeding 20 kHz. The purpose of the study is to compare the measurement of the left ventricular ejection fraction (LVEF) between an experienced biomedical scientist (BMA) and a student. In addition to see how the image quality affects the result. The measurement was performed by using the Simpson method. The result was analyzed by using with a static method. The results were analyzed by using a paired t-test to see if there is any significant difference between the performance of a BMA and a student. The measurement was performed on apical 4-chamber and apical 2-chamber image. The study included 30 patients, both heart -healthy and cardiac patients of the genders. The result showed that there is a significant difference in the performance of LVEF- measurements between BMA and student, with lower values measured by the student. / Ekokardiografiundersökning är en viktig och vanlig metod vid undersökning av hjärtat. Ekokardiografi används för att bedöma hjärtats funktion vid utredning av hjärtsjukdomar. Vid en ekokardiografiundersökning kan hjärtats flödeshastigheter, kontraktilitet (pumpförmåga), väggtjocklek, och innerdiameter undersökas. Alla dessa undersökningar görs med hjälp av tolkning av ultraljudsvågorna som ultraljudsgivaren skickar ut och tar emot. Givaren består av piezoelektriska kristaller som kan både sända och tar emot ultraljudsvågor med frekvens på över 20 kHz. Syftet med denna studie är att jämföra mätningen av den vänstra ventrikulära ejektionsfraktion (LVEF) mellan en erfaren biomedicinsk analytiker (BMA) och en student samt att se hur bildkvalitén påverkar resultatet. Mätningen utfördes med Simpsons- metoden. Resultatet analyserades med hjälp av en statistisk metod. Resultatet analyserades med hjälp av parat t-test för att se om det finns någon signifikant skillnad mellan utförandet av en BMA och en student. Mätningen utfördes på apikala 4-kammarbilder och apikala 2-kammarblider. Studien inkluderade 30 patienter, både hjärtfriska och hjärtsjuka patienter av både könen. Resultatet visade att det finns en signifikant skillnad i utförande av LVEF- mätningar mellan BMA och student, med lägre uppmätta värden av studenten.

Introduktion: Vänsterkammarens ejektionsfraktion (VKEF) är ett central mått på systolisk funktion i vänster kammare och är en av de mest betydelsefulla parametrar vid ekokardiografiska undersökningar. Idag är Simpson biplan metoden den mest använda metoden för bestämning av ejektionsfraktionen. Vid ekokardiografiska undersökningar sänder givaren med piezoelektriska kristaller ut ultraljudsvågor med en frekvens över 20 000 Hz. Ljudvågorna som skickas ut i kroppen reflekteras och sedan återvänder de till givaren för att skapa en bild. Denna studie jämför den tvådimensionella (2D) ultraljudsmetoden Simpsons biplan med Philips Heart Model som är en automatiserad tredimensionella (3D) funktion för bedömning av VKEF.  Material och metod: I studien inkluderades 31 hjärtfriska försökspersoner mellan åldrarna 21-64. Det samlades in bilder på apikala 4- och 2 kammarbilder från alla försökspersoner där Simpsons biplan metoden användes för att beräkna ejektionsfraktion. Apikala 4-kammarbilder samlades in för att beräkna ejektionsfraktionen med Philips Heart Model 3D funktion.  Resultat: Resultatet från denna studie visade att det inte föreligger någon signifikant skillnad mellan Simpsons biplan metoden och Philips Heart Model metoden för bestämning av ejektionsfraktion. Båda metoderna visade likvärdiga mätresultat.  Diskussion: Philips Heart Model metoden är en relativ ny funktion som använder sig av artificiell intelligens för att analysera 3D bilder. Philips Heart Model metoden är en säker funktion att använda då de flesta studier bevisar likvärdiga och säkra mätresultat i jämförelse med andra metoder.  Konklusion: Enligt denna studie ger Philips Heart Model funktionen likvärdiga mätresultat av vänsterkammarens ejektionsfraktion i jämförelse med Simpsons biplan. / Introduction: Simpson’s biplane method is the most used method for determining the left ventricular ejection fraction (LVEF) in echocardiographic examinations. Ejection fraction is a central measurement of the heart's global systolic function. The probe with piezoelectric crystals emits ultrasound waves with a frequency above 20,000 Hz. The sound waves that are sent out into the body are reflected and then return to the probe to create an image. This study compares the two-dimensional (2D) ultrasound Simpson's biplane method with the Philips Heart Model method, which is an automated three-dimensional (3D) function for assessment of LVEF.                                                                                                                          Material and method: 31 subjects with no recorded heart pathologies between the ages of 21-64 were included in the study. Apical 4- and 2-chamber images were collected from the test subjects, where the Simpson's biplane method was applied to calculate the ejection fraction. 2D apical 4-chamber images were collected to convert to 3D and used to calculate the ejection fraction with the Philips Heart Model.    Results: The results of this study showed that there is no significant difference between the Simpson’s biplane method and the Philips Heart Model method for determining ejection fraction.    Discussion: The Philips Heart Model method is a relatively new feature that uses artificial intelligence to analyze 3D images. The Philips Heart Model method is a reliable feature to use as most studies have proven similar and reliable measurements when comparing it with other methods for determining LVEF.    Conclusion: According to this study, the Philips Heart Model feature provides equivalent measurements in comparison with the manual method Simpson's biplane.

Recent advances in deep learning have greatly improved the ability to generate analysis models from medical images. In particular, great attention is focused on quickly generating models of the left ventricle from cardiac magnetic resonance imaging (cMRI) to improve the diagnosis and prognosis of millions of patients. However, even state-of-the-art frameworks present challenges, such as discontinuities of the cardiac tissue and excessive jaggedness along the myocardial walls. These geometrical features are often anatomically incorrect and may lead to unrealistic results once the geometrical models are employed in computational analyses. In this research, we propose an end-to-end pipeline for a subject-specific model of the heart's left ventricle from Cine cMRI. Our novel pipeline incorporates the uncertainty originating from the segmentation methods in the estimation of cardiac indices, such as ejection fraction, myocardial volume changes, and global radial and longitudinal strain, during the cardiac cycle. First, we propose an anatomically-guided deep learning model to overcome the common segmentation challenges while preserving the advantages of state-of-the-art frameworks, such as computational efficiency, robustness, and abstraction capabilities. Our anatomically-guided neural networks include a B-spline head, which acts as a regularization layer during training. In addition, the introduction of the B-spline head contributes to achieving a robust uncertainty quantification of the left ventricle inner and outer walls. We validate our approach using human short-axis (SA) cMRI slices and later apply transfer learning to verify its generalization capabilities in swine long-axis (LA) cMRI slices. Finally, we use the SA and LA contours to build a Gaussian Process (GP) model to create inner and outer walls 3D surfaces, which are then used to compute global indices of cardiac functions. Our results show that the proposed pipeline generates anatomically consistent geometries while also providing a robust tool for quantifying uncertainty in the geometry and the derived cardiac indices.

Cardiovascular disease varies by ethnicity in the UK. South Asians (SA) have higher coronary heart disease (CHD) and diabetes prevalence, while African-Caribbeans (AfC) have greater stroke, but intriguingly lower CHD rates despite higher blood pressures and diabetes risk than Europeans. Conventional risk factors do not fully explain such differences. This cross-sectional study tested the hypothesis that the hormones, vitamin D measured as 25(OH)D and aldosterone, would be independently associated with intermediate cardiovascular outcome markers in these ethnic groups. Community-dwelling men 40-80 years old (AfC: n=67, 55±10yr; SA: n=68, 55±10yr; European: n=63, 57±8yr) were sampled from Greater Manchester’s multi-ethnic population. The intermediate markers examined were aortic pulse wave velocity (aPWV), left ventricular (LV) mass and function, and carotid intima media thickness (CIMT), measured non-invasively by ultrasound, and hemodynamic profiling methods (the Arteriograph) in the total sample and by magnetic resonance imaging (MRI) in a subsample of 50. Adjusted for age, systolic blood pressure and diabetes, mean(SE) aPWV by the Arteriograph, was 0.5(0.2) m/s higher in SA than AfC and Europeans (p=0.01), which paralleled known cross-ethnic CHD risk differences in the UK. By MRI, aPWV along the descending aorta in SA was 0.7(0.3) and 0.8(0.3) m/s higher than that in AfC and Europeans, but aPWV along the aortic arch was not significantly different. Unlike aldosterone, 25(OH)D was independently and inversely correlated with aPWV (unstandardised B(SE)=-0.013[0.004] m/s, p<0.001), and partly explained the ethnic variation in aPWV. Similar inverse correlations were found between 25(OH)D and LV concentricity measured by echocardiography and MRI. Compared to Europeans, SA and AfC, had 21(3) and 14(3) nmol/L lower mean(SE) 25(OH)D, respectively (p<0.01). Mean(SE) of relative wall thickness, an index of LV concentricity by echocardiography, was 0.05(0.01) higher in SA and AfC than Europeans. Lower 25(OH)D levels were also associated with higher myocardial deformation rates measured by MRI myocardial tagging (n=50), supporting previous animal experimental evidence. A one standard deviation (SD) decrease in 25(OH)D was associated with a 0.38 SD increase in absolute systolic strain rate (p=0.003) and 0.22 SD rise in diastolic strain rate (p=0.04). Right and left CIMT showed different relations with 25(OH)D and aldosterone. Left-right CIMT differences varied by ethnicity and were related to SA ethnicity and aldosterone levels. Two related technical studies investigated the relatively new method of hemodynamic profiling, the Arteriograph, used here. The results suggested a standardisation method of aortic length estimation for purely central aPWV, which significantly improved aPWV agreement between the Arteriograph and MRI (reference method here), and was used for calibrating the Arteriograph aPWV in the above-mentioned results for the total sample. Future well-designed trials are necessary to investigate any cause-effect relationship between vitamin D deficiency and the unfavourable cardiovascular intermediate outcomes found here in a cross-sectional design and multi-ethnic background.

Ventricular premature beats are ectopic changes in the ECG signal. Detection of ventricular extrasystoles on 12leads ECG was created in MATLAB. At first my work involves whether the ventricular premature beats comes from the right or the left ventricle. Another algorithm evaluates the incidence outflow tract of the chamber. If the previous algorithm shows signs of indecision, another algorithm is used for detection of ventricular extrasystoles at another location in the left ventricle. The last step is to narrow the area of detection which makes it easier to find the place of origin.

Indiana University-Purdue University Indianapolis (IUPUI) / 17-β estradiol (E2) exerts protective effects in hypoxia-induced pulmonary hypertension (HPH) via endothelial cell estrogen receptor (ER)-dependent mechanisms. However, the effects of hypoxia on ER expression in the pulmonary-right ventricle (RV) axis remain unknown. Based on previous data suggesting a role of ER-β in mediating E2 protection, we hypothesized that hypoxia selectively up-regulates ER-β in the lung and pulmonary endothelial cells. In our Male Sprague-Dawley rat model, chronic hypoxia exposure (10% FiO2) resulted in a robust HPH phenotype associated with significant increases in ER- β but not ER-α protein in the lung via western blotting. More importantly, this hypoxia-induced ER-β increase was not replicated in the RV, left ventricle (LV) or in the liver. Hence, hypoxia-induced ER-β up-regulation appears to be lung-specific. Ex vivo, hypoxia exposure time-dependently up-regulated ER-β but not ER-α in cultured primary rat pulmonary artery endothelial cells (RPAECs) exposed to hypoxia (1% O2) for 4, 24 or 72h. Furthermore, the hypoxia induced ER-β protein abundance, while not accompanied by increases in its own transcript, was associated with ER-β nuclear translocation, suggesting increase in activity as well as post-transcriptional up-regulation of ER-β. Indeed, the requirement for ER-β activation was indicated in hypoxic ER-βKO mice where administration of E2 failed to inhibit hypoxia-induced pro-proliferative ERK1/2 signaling. Interestingly, HIF-1α accumulation was noted in lung tissue of hypoxic ER-βKO mice; consistent with previously reported negative feedback of ER-β on HIF-1α protein and transcriptional activation. In RAPECs, HIF-1 stabilization and overexpression did not replicate the effects of ER- β up-regulation seen in gas hypoxia; suggestive that HIF-1α is not sufficient for ER-β up- regulation. Similarly, HIF-1 inhibition with chetomin did not result in ER-β down-regulation. HIF-1α knockdown in RPAECs in hypoxic conditions is currently being investigated. Hypoxia increases ER- β, but not ER-α in the lung and lung vascular cells. Interpreted in context of beneficial effects of E2 on hypoxic PA and RV remodeling, our data suggest a protective role for ER-β in HPH. The mechanisms by which hypoxia increases ER-β appears to be post-transcriptional and HIF-1α independent. Elucidating hypoxia-related ER-β signaling pathways in PAECs may reveal novel therapeutic targets in HPH.

Indiana University-Purdue University Indianapolis (IUPUI) / Recent advancements in the management of systemic glucose regulation in obesity/T2DM include drug therapies designed to utilize components of the incretin system specifically related to glucagon-like peptide 1 (GLP-1). More recently, GLP-1 has been investigated for potential cardioprotective effects. Several investigations have revealed that acute/sub-acute intravenous administration of GLP-1 significantly reduces myocardial infarct size following ischemia/reperfusion injury and improves cardiac contractile function in the settings of coronary artery disease, myocardial ischemia/reperfusion injury, and heart failure. Despite an abundance of data indicating that intravenous infusion of GLP-1 is cardioprotective, information has been lacking on the cardiac effects of iv GLP-1 in the MetS or T2DM population. Some important questions this study aimed to address are 1) what are the direct, dose-dependent cardiac effects of GLP-1 in-vivo 2) are the cardiac effects influenced by cardiac demand (MVO2) and/or ischemia, 3) does GLP-1 effect myocardial blood flow, glucose uptake or total oxidative metabolism in human subjects, and 4) are the cardiac effects of GLP-1 treatment impaired in the settings of obesity/MetS and T2DM. Initial studies conducted in canines demonstrated that GLP-1 had no direct effect on coronary blood flow in-vivo or vasomotor tone in-vitro, but preferentially increased myocardial glucose uptake in ischemic myocardium independent of effects on cardiac contractile function or coronary blood flow. Parallel translational studies conducted in the humans and Ossabaw swine demonstrate that iv GLP-1 significantly increases myocardial glucose uptake at rest and in response to increases in cardiac demand (MVO2) in lean subjects, but not in the settings of obesity/MetS and T2DM. Further investigation in isolated cardiac tissue from lean and obese/MetS swine indicate that this impairment in GLP-1 responsiveness is related to attenuated activation of p38-MAPK, independent of alterations in GLP-1 receptor expression or PKA-dependent signaling. Our results indicate that the affects of GLP-1 to reduce cardiac damage and increase left ventricular performance may be impaired by obesity/MetS and T2DM.

This biomedical engineering thesis explores the opportunities and challenges of 2D+t contrast echocardiography for left ventricle functional analysis, both clinically and within a computer vision atlas-based deformable template model framework. A database was created for the experiments in this thesis, with 21 studies of contrast Dobutamine Stress Echo, in all 4 principal planes. The database includes clinical variables, human expert hand-traced myocardial contours and visual scoring. First the problem is studied from a clinical perspective. Quantification of endocardial global and local function using standard measures shows expected values and agreement with human expert visual scoring, but the results are less reliable for myocardial thickening. Next, the problem of segmenting the endocardium with a computer is posed in a standard landmark and atlas-based deformable template model framework. The underlying assumption is that these models can emulate human experts in terms of integrating previous knowledge about the anatomy and physiology with three sources of information from the image: texture, geometry and kinetics. Probabilistic atlases of contrast echocardiography are computed, while noting from histograms at selected anatomical locations that modelling texture with just mean intensity values may be too naive. Intensity analysis together with the clinical results above suggest that lack of external boundary definition may preclude this imaging technique for appropriate measuring of myocardial thickening, while endocardial boundary definition is appropriate for evaluation of wall motion. Geometry is presented in a Principal Component Analysis (PCA) context, highlighting issues about Gaussianity, the correlation and covariance matrices with respect to physiology, and analysing different measures of dimensionality. A popular extension of deformable models ---Active Appearance Models (AAMs)--- is then studied in depth. Contrary to common wisdom, it is contended that using a PCA texture space instead of a fixed atlas is detrimental to segmentation, and that PCA models are not convenient for texture modelling. To integrate kinetics, a novel spatio-temporal model of cardiac contours is proposed. The new explicit model does not require frame interpolation, and it is compared to previous implicit models in terms of approximation error when the shape vector changes from frame to frame or remains constant throughout the cardiac cycle. Finally, the 2D+t atlas-based deformable model segmentation problem is formulated and solved with a gradient descent approach. Experiments using the similarity transformation suggest that segmentation of the whole cardiac volume outperforms segmentation of individual frames. A relatively new approach ---the inverse compositional algorithm--- is shown to decrease running times of the classic Lucas-Kanade algorithm by a factor of 20 to 25, to values that are within real-time processing reach.