Visualization of Minute Mechanical-Excitation/Relaxation Wave-front Propagation in Myocardial Tissue

Unlike the case of skeletal muscle, the direction of myocardial contraction does not coincide with the direction of work necessary to eject the intraventricular blood, contributing to great complexity of the wall deformation sequence of cardiac contraction. The advent of advanced techniques (CT^1^, MRI^2,3^, SPECT^4^, echocardiology^5-9^, electrocardiography^10^, and magnetocardiography^11,12^) has enabled to the evaluation of cardiac function and disorders by the measurement of blood flow, pressure, electrical reaction process, and other factors. However, complexity of the contraction sequence is still not fully understood because the dynamic mechanical excitation process, which directly correlates with contraction, cannot be accurately measured based on these electro-magnetic phenomena. Here, developing and using a noninvasive novel imaging modality with high temporal and spatial resolutions^13-17^, we show that the propagation of the mechanical wave-front occurs at the beginning of each cardiac contraction and relaxation sequence for the first time. The former occurs about 60 ms prior to the ordinarily accepted onset time of the contraction (R-wave of the electrocardiogram). From the apical side of the interventricular septum, close to the terminal of the Purkinje fibers (specialized to carry contraction impulses), a minute velocity component with an amplitude of several tenth micrometers is generated and propagates sequentially to the entire left ventricle, that is, it propagates from the apex to the base of the posterior wall, and then from the base to the apex of the septum, with a propagation speed of 3-9 m/s. The latter occurs at the end of the first heart sound at the apical side and propagates to the base side with a speed of 0.6 m/s. These physiological findings, unlike the widely accepted myocardial excitation process, have potential for accurate assessment of myocardial tissue damage in coronary disease and cardiomyopathy. This dynamic measurement modality is also applicable to various tissues in biology

Assessment of Left Atrial Deformation and Function by 2-Dimensional Speckle Tracking Echocardiography in Healthy Dogs and Dogs With Myxomatous Mitral Valve Disease

open7noBackground: The assessment of left atrial (LA) function by 2-dimensional speckle tracking echocardiography (STE) holds important clinical implications in human medicine. Few similar data are available in dogs. Objectives: To assess LA function by STE in dogs with and without myxomatous mitral valve disease (MMVD), analyzing LA areas, systolic function, and strain. Animals: One hundred and fifty dogs were divided according to the American College of Veterinary Internal Medicine classification of heart failure: 23 dogs in class A, 52 in class B1, 36 in class B2, and 39 in class C + D. Methods: Prospective observational study. Conventional morphologic and Doppler variables, LA areas, and STE-based LA strain analysis were performed in all dogs and results were compared among groups. Correlation analysis was carried out between LA STE variables and other echocardiographic variables. Results: Variability study showed good reproducibility for all the tested variables (coefficient of variation <16%). Left atrial areas, fractional area change, peak atrial longitudinal strain (PALS), peak atrial contraction strain, and contraction strain index (CSI) differed significantly between groups B2 and C + D and all the other groups (overall P < .001), whereas only PALS differed between groups B1 and A (P = .01). Left atrial areas increased with progression of the disease, whereas LA functional parameters decreased. Only CSI increased nonsignificantly from group A to group B1 and then progressively decreased. Thirty-one significant correlations (P < .001, r > .3) were found between conventional left heart echocardiographic variables and LA areas and strain variables. Conclusions and Clinical Importance: Left atrial STE analysis provides useful information on atrial function in the dog, highlighting a progressive decline in atrial function with worsening of MMVD.openBaron Toaldo, M; Romito, G.; Guglielmini, C.; Diana, A.; Pelle, N.G.; Contiero, B.; Cipone, M.Baron Toaldo, M; Romito, G.; Guglielmini, C.; Diana, A.; Pelle, N.G.; Contiero, B.; Cipone, M

Effects of anesthesia on conventional and speckle tracking echocardiographic parameters in a mouse model of pressure overload

Genetically‑modified mice are widely applied in cardiovascular studies as model organisms. Echocardiography is a key tool for evaluating cardiac and hemodynamic functions in mice. The present study aimed to examine the effects of isoflurane (ISF) on conventional and speckle tracking echocardiography (STE) parameters under healthy and pathological conditions using a murine model of pressure overload. In addition, the optimal dose of ISF in the process of echocardiographic measurement, with minimum cardiac contraction depression, was investigated. Conventional echocardiographic and STE examinations were performed on 38 adult C57BL/6 male mice. The mice were divided into the following three groups: The sham (n=15); mild thoracic aortic banding (TAB; n=15); and severe TAB (n=8) groups. ISF was administered under deep anesthesia (DA; 1‑2% ISF), light anesthesia (LA; 0.5‑1% ISF) and immediately prior to the mice waking up (awake; 0‑0.5% ISF). Conventional echocardiographic parameters were preserved within the sham and mild TAB groups (P>0.05 for each parameter) under LA and awake conditions. However, under DA conditions, the majority of these parameters were reduced compared with the LA and awake conditions (P<0.05). In the severe TAB group, conventional echocardiographic parameters remained constant under LA, DA and awake conditions. STE parameters in the groups remained similar between the LA and awake conditions, but were significantly reduced under DA conditions. Therefore, conventional echocardiography and STE may be performed using LA induced with low doses of ISF, under various pathological conditions without affecting cardiac function

Three-dimensional structure of the flow inside the left ventricle of the human heart

The laboratory models of the human heart left ventricle developed in the last decades gave a valuable contribution to the comprehension of the role of the fluid dynamics in the cardiac function and to support the interpretation of the data obtained in vivo. Nevertheless, some questions are still open and new ones stem from the continuous improvements in the diagnostic imaging techniques. Many of these unresolved issues are related to the three-dimensional structure of the left-ventricular flow during the cardiac cycle. In this paper we investigated in detail this aspect using a laboratory model. The ventricle was simulated by a flexible sack varying its volume in time according to a physiologically shaped law. Velocities measured during several cycles on series of parallel planes, taken from two orthogonal points of view, were combined together in order to reconstruct the phase averaged, three-dimensional velocity field. During the diastole, three main steps are recognized in the evolution of the vortical structures: i) straight propagation in the direction of the long axis of a vortex-ring originated from the mitral orifice; ii) asymmetric development of the vortex-ring on an inclined plane; iii) single vortex formation. The analysis of three-dimensional data gives the experimental evidence of the reorganization of the flow in a single vortex persisting until the end of the diastole. This flow pattern seems to optimize the cardiac function since it directs velocity towards the aortic valve just before the systole and minimizes the fraction of blood residing within the ventricle for more cycles

Moving Domain Computational Fluid Dynamics to Interface with an Embryonic Model of Cardiac Morphogenesis

Peristaltic contraction of the embryonic heart tube produces time- and spatial-varying wall shear stress (WSS) and pressure gradients (∇P) across the atrioventricular (AV) canal. Zebrafish (Danio rerio) are a genetically tractable system to investigate cardiac morphogenesis. The use of Tg(fli1a:EGFP)y1 transgenic embryos allowed for delineation and two-dimensional reconstruction of the endocardium. This time-varying wall motion was then prescribed in a two-dimensional moving domain computational fluid dynamics (CFD) model, providing new insights into spatial and temporal variations in WSS and ∇P during cardiac development. The CFD simulations were validated with particle image velocimetry (PIV) across the atrioventricular (AV) canal, revealing an increase in both velocities and heart rates, but a decrease in the duration of atrial systole from early to later stages. At 20-30 hours post fertilization (hpf), simulation results revealed bidirectional WSS across the AV canal in the heart tube in response to peristaltic motion of the wall. At 40-50 hpf, the tube structure undergoes cardiac looping, accompanied by a nearly 3-fold increase in WSS magnitude. At 110-120 hpf, distinct AV valve, atrium, ventricle, and bulbus arteriosus form, accompanied by incremental increases in both WSS magnitude and ∇P, but a decrease in bi-directional flow. Laminar flow develops across the AV canal at 20-30 hpf, and persists at 110-120 hpf. Reynolds numbers at the AV canal increase from 0.07±0.03 at 20-30 hpf to 0.23±0.07 at 110-120 hpf (p< 0.05, n=6), whereas Womersley numbers remain relatively unchanged from 0.11 to 0.13. Our moving domain simulations highlights hemodynamic changes in relation to cardiac morphogenesis; thereby, providing a 2-D quantitative approach to complement imaging analysis. © 2013 Lee et al

Three-dimensional echocardiography and 2D-3D speckle tracking imaging in chronic pulmonary hypertension. diagnostic accuracy in detecting hemodynamic signs of RV failure

Background and objective. Our aim was to compare three-dimensional (3D) and 2D and 3D speckle tracking (2D-STE, 3D-STE) echocardiographic parameters with conventional right ventricular (RV) indexes in patients with chronic pulmonary hypertension (PH), and investigate whether these techniques could result in better correlation with hemodynamic variables indicative of heart failure. Methods. Seventy-three adult patients (mean age, 53±13 years; 44% male) with chronic PH of different etiologies were studied by echocardiography and cardiac catheterization (25 precapillary PH from pulmonary arterial hypertension, 23 obstructive pulmonary heart disease, and 23 postcapillary PH from mitral regurgitation). Thirty healthy subjects (mean age, 54±15 years; 43% male) served as controls. Standard 2D measurements (RV-FAC -fractional area change-, TAPSE -tricuspid annular plane systolic excursion-) and mitral and tricuspid tissue Doppler annular velocities were obtained. RV 3D volumes, and global and regional ejection fraction (3D-RVEF) were determined. RV strains were calculated by 2D-STE and 3D-STE. Results. RV 3D global-free-wall longitudinal strain (3DGFW-RVLS), 2D global-free-wall longitudinal strain (GFW-RVLS), apical-free-wall longitudinal strain (AFW-RVLS), basal-free-wall longitudinal strain (BFW-RVLS), and 3D-RVEF were lower in patients with pre-capillary PH (p<0.0001) and post-capillary PH (p<0.01) compared to controls. 3DGFW-RVLS (HR 4.6, 95% CI 2.79-8.38, p=0.004) and 3D-RVEF (HR 5.3, 95% CI 2.85-9.89, p=0.002) were independent predictors of mortality. ROC curves showed that the thresholds offering an adequate compromise between sensitivity and specificity for detecting hemodynamic signs of RV failure were 39% for 3D-RVEF (AUC 0.89), -17% for 3DGFW-RVLS (AUC 0.88), -18% for GFW-RVLS (AUC 0.88), -16% for AFW-RVLS (AUC 0.85), 16mm for TAPSE (AUC 0.67), and 38% for RV-FAC (AUC 0.62). Conclusions. In chronic PH, 3D, 2D-STE and 3D-STE parameters indicate global and regional RV dysfunction that is associated with RV failure hemodynamics better than conventional echo indices

Retrospective study of the association between neutering status and changes secondary to degenerative mitral valve disease

Dissertação de Mestrado Integrado em Medicina VeterináriaMyxomatous mitral valve disease is the most common cardiovascular disease reported in dogs. Although many patients may remain asymptomatic, some of them progress to left-sided congestive heart failure and develop clinical signs. Little has yet been published regarding the possible influence of the neutering status on changes secondary to myxomatous mitral valve disease. This study aims to assess a possible correlation between neutering status and myxomatous mitral valve disease. A retrospective study was conducted and included all the cases diagnosed with myxomatous mitral valve disease, consulted at the Cardiology service of the University of Liverpool. To help assess the association between neutering status and cardiac remodelling, dogs were categorized into four groups: FE (female entire), FN (female neutered), ME (male entire) and MN (male neutered). Retrospective review of echocardiographic data, signalment, and underlying diseases were performed. Echocardiographic measurements were made through offline analysis. Echocardiographic measurements were then compared between groups. Five hundred and eighty-two dogs (n = 582) were included: female entire (n = 24), female neutered (n = 235), male entire (n = 115) and male neutered (n = 208). Left ventricular internal diameter at end diastole (LVIDd), left atrial dimension to the aortic root diameter (LA:Ao) and left atrium maximal dimension to the aortic root dimension (LAmax:Ao) were significantly different between ME and MN, with ME dogs presenting higher mean values for LVIDd and higher median LA:Ao and LAmax:Ao measurements. Left ventricular internal diameter at end systole (LVIDs) was not significantly different between ME and MN. There were no significant differences between FE and FN groups. This study shows that neutering status may influence the development of myxomatous mitral valve disease in male dogs and that entire male dogs could be at higher risk of developing cardiac remodelling secondary to myxomatous mitral valve disease. On the other hand, neutering status doesn’t seem to have an influence on disease progression in female dogs.RESUMO - Estudo retrospetivo da associação entre a esterilização e alterações secundárias à doença mixomatosa da válvula mitral - A doença mixomatosa da válvula mitral é a doença cardiovascular mais prevalente em cães. Apesar da maior parte dos pacientes permanecerem assintomáticos, alguns podem progredir para insuficiência cardíaca esquerda e desenvolver sinais clínicos. Até hoje, existem poucas publicações sobre o possível efeito que a esterilização possa ter no desenvolvimento da doença mixomatosa da válvula mitral. O objetivo deste estudo é avaliar se existe de facto uma relação entre a esterilização e a doença mixomatosa da válvula mitral. Foi realizado um estudo retrospetivo que incluiu todos os casos diagnosticados com doença mixomatosa da válvula mitral consultados no serviço de Cardiologia da Universidade de Liverpool. Para avaliar a relação entre a esterilização e a presença de remodelação cardíaca, os cães foram categorizados em quatro grupos: FE (fêmeas inteiras), FN (fêmeas esterilizadas), ME (machos inteiros) e MN (machos castrados). A história pregressa e os dados ecocardiográficos dos animais foram revistos retrospetivamente e as medidas ecocardiográficas foram obtidas por medição offline. Estas medições foram depois comparadas entre os diferentes grupos. Quinhentos e oitenta e dois cães (n = 582) foram incluídos: fêmeas inteiras (n = 24), fêmeas esterilizadas (n = 235), machos inteiros (n = 115) e machos castrados (n = 208). Nos resultados obtidos, o diâmetro interno do ventrículo esquerdo no final da diástole (LVIDd), o rácio átrio esquerdo-aorta (LA:Ao) e o rácio diâmetro máximo do átrio esquerdo-aorta (LAmax:Ao) foram estatisticamente significativos entre machos inteiros e machos castrados. Os machos inteiros apresentaram não só um LVIDd médio superior, como também uma mediana de LA:Ao e LAmax:Ao superior aos machos castrados. Ao mesmo tempo, o diâmetro interno do ventrículo esquerdo no final da sístole (LVIDs) não mostrou ser estatisticamente significativo entre machos inteiros e machos castrados e nenhum dos parâmetros ecocardiográficos anteriormente referidos revelou ser estatisticamente significativo entre fêmeas inteiras e fêmeas esterilizadas. Este estudo demonstra que a esterilização poderá influenciar o desenvolvimento da doença mixomatosa da válvula mitral e que os cães machos inteiros poderão apresentar um maior risco de desenvolver remodelação cardíaca secundária a esta doença. No entanto, a esterilização não aparenta influenciar a progressão desta doença em cadelas.N/

The Relationship between Brachycephalic Head Features in Modern Persian Cats and Dysmorphologies of the Skull and Internal Hydrocephalus

Background: Cat breeders observed a frequent occurrence of internal hydrocephalus in Persian cats with extreme brachycephalic head morphology. Objective: To investigate a possible relationship among the grade of brachycephaly, ventricular dilatation, and skull dysmorphologies in Persian cats. Animals: 92 Persian-, 10 Domestic shorthair cats. Methods: The grade of brachycephaly was determined on skull models based on CT datasets. Cranial measurements were examined with regard to a possible correlation with relative ventricular volume, and cranial capacity. Persians with high (peke-face Persians) and lower grades of brachycephaly (doll-face Persians) were investigated for the presence of skull dysmorphologies. Results: The mean cranial index of the peke-face Persians (0.97 ± 0.14) was significantly higher than the mean cranial index of doll-face Persians (0.66 ± 0.04; P < 0.001). Peke-face Persians had a lower relative nasal bone length (0.15 ± 0.04) compared to doll-face (0.29 ± 0.08; P < 0.001). The endocranial volume was significantly lower in doll-face than peke-face Persians (89.6 ± 1.27% versus 91.76 ± 2.07%; P < 0.001). The cranial index was significantly correlated with this variable (Spearman´s r: 0.7; P < 0.0001). Mean ventricle: Brain ratio of the peke-face group (0.159 ± 0.14) was significantly higher compared to doll-face Persians (0.015 ± 0.01; P < 0.001). Conclusion and Clinical Relevance: High grades of brachycephaly are also associated with malformations of the calvarial and facial bones as well as dental malformations. As these dysmorphologies can affect animal welfare, the selection for extreme forms of brachycephaly in Persian cats should be reconsidered

Timely-automatic procedure for estimating the endocardial limits of the left ventricle assessed echocardiographically in clinical practice

In this paper, we propose an analytical rapid method to estimate the endocardial borders of the left ventricular walls on echocardiographic images for prospective clinical integration. The procedure was created as a diagnostic support tool for the clinician and it is based on the use of the anisotropic generalized Hough transform. Its application is guided by a Gabor-like filtering for the approximate delimitation of the region of interest without the need for computing further anatomical characteristics. The algorithm is applying directly a deformable template on the predetermined filtered region and therefore it is responsive and straightforward implementable. For accuracy considerations, we have employed a support vector machine classifier to determine the confidence level of the automated marking. The clinical tests were performed at the Cardiology Clinic of the County Emergency Hospital Timisoara and they improved the physicians perception in more than 50% of the cases. The report is concluded with medical discussions.European Union (UE)Ministerio de Economía y Competitividad (MINECO). Españ

Doctor of Philosophy

dissertationImage-based biomechanics, particularly numerical modeling using subject-specific data obtained via imaging, has proven useful for elucidating several biomechanical processes, such as prediction of deformation due to external loads, applicable to both normal function and pathophysiology of various organs. As the field evolves towards applications that stretch the limits of imaging hardware and acquisition time, the information traditionally expected as input for numerical routines often becomes incomplete or ambiguous, and requires specific acquisition and processing strategies to ensure physical accuracy and compatibility with predictive mathematical modeling. These strategies, often derivatives or specializations of traditional mechanics, effectively extend the nominal capability of medical imaging hardware providing subject-specific information coupled with the option of using the results for predictive numerical simulations. This research deals with the development of tools for extracting mechanical measurements from a finite set of imaging data and finite element analysis in the context of constructing structural atlases of the heart, understanding the biomechanics of the venous vasculature, and right ventricular failure. The tools include: (1) application of Hyperelastic Warping image registration to displacement-encoded MRI for reconstructing absolute displacement fields, (2) combination of imaging and a material parameter identification approach to measure morphology, deformation, and mechanical properties of vascular tissue, and (3) extrapolation of diffusion tensor MRI acquired at a single time point for the prediction the structural changes across the cardiac cycle with mechanical simulations. Selected tools were then applied to evaluate structural changes in a reversible animal model for right ventricular failure due to pressure overload