Transmural Direction Research Articles

Influence of Power-Weighted Center of Echo Signal Within Window Function on Local Strain Rate Distribution in Left Ventricular Wall

ObjectiveThe deviation of the power-weighted center of the echo signal from the geometric center within the velocity estimation window for calculating strain rate (SR) causes an estimation error. This study aimed to confirm whether an erroneous multilayer pattern in the SR distribution of the left ventricular wall could be corrected by considering the power-weighted center of the echo signal. MethodsThe SR distributions were measured locally in the transmural direction around the pre-ejection and early diastolic phases in healthy volunteers. The estimation error related to the power-weighted center of the echo signal was corrected using a previously proposed method, and the effectiveness of the correction was confirmed based on the accuracy of the estimated myocardial displacement. ResultsThe SR distribution in early diastole was observed as multilayers of low- and high-amplitude negative SRs. However, this multilayer pattern disappeared after correction. In the pre-ejection phase, multilayers of positive and negative SRs were observed in the SR distributions with and without correction. This correction was sufficiently effective in accurately tracking the local peak of the echo signal. ConclusionThe multilayer pattern of low- and high-amplitude positive or negative SRs is caused by estimation errors related to the power-weighted center of the echo signal. The multilayer pattern of positive and negative SRs might not be caused by these errors and might relate to the actual change in myocardial thickness because the estimation errors do not convert the negative (positive) SR to positive (negative) in a homogeneous negative (positive) SR distribution.

Patient-Specific Analysis of Ascending Thoracic Aortic Aneurysm with the Living Heart Human Model

In ascending thoracic aortic aneurysms (ATAAs), aneurysm kinematics are driven by ventricular traction occurring every heartbeat, increasing the stress level of dilated aortic wall. Aortic elongation due to heart motion and aortic length are emerging as potential indicators of adverse events in ATAAs; however, simulation of ATAA that takes into account the cardiac mechanics is technically challenging. The objective of this study was to adapt the realistic Living Heart Human Model (LHHM) to the anatomy and physiology of a patient with ATAA to assess the role of cardiac motion on aortic wall stress distribution. Patient-specific segmentation and material parameter estimation were done using preoperative computed tomography angiography (CTA) and ex vivo biaxial testing of the harvested tissue collected during surgery. The lumped-parameter model of systemic circulation implemented in the LHHM was refined using clinical and echocardiographic data. The results showed that the longitudinal stress was highest in the major curvature of the aneurysm, with specific aortic quadrants having stress levels change from tensile to compressive in a transmural direction. This study revealed the key role of heart motion that stretches the aortic root and increases ATAA wall tension. The ATAA LHHM is a realistic cardiovascular platform where patient-specific information can be easily integrated to assess the aneurysm biomechanics and potentially support the clinical management of patients with ATAAs.

Strain Rate Distribution in Layered Myocardium Measured Using Local Velocity Estimator with Multifrequency Phase Differences

Measurement of the myocardial strain rate (SR), with high spatial resolution, is useful in evaluation of the transmurality of myocardial infarction. As the SR distribution is calculated using velocities observed at multiple positions in the heart wall, it is necessary to estimate the local velocity to measure SR distribution. In the present study, our previously proposed local velocity estimator, with multifrequency phase differences, was used to measure SR distribution in the heart wall. The SR distribution measured with the proposed local velocity estimator revealed alternate layers of contraction and relaxation, which were not measured with the conventional velocity estimator with spatial averaging. The reproducibility of the SR distributions was confirmed in three consecutive heartbeats with three subjects. High-spatial-resolution SR measurement with the proposed local velocity estimator will allow myocardial layer-specific analysis in the transmural direction.

A Mathematical Model of the Wall of a Rat Cerebral Resistance Vessel

A mathematical model of the mechanical properties of the rat small cerebral artery wall is presented. It is assumed that the active component of the stress has a circumferential direction and is a function of the concentration of the activator of smooth muscle cell contractions and circumferential and radial stretch ratios; longitudinal stretching is not considered. Calculations showed a significant decrease in both the circumferential stress and circumferential stretch ratios in the vascular wall after activation; the distribution of these values in the transmural direction became more uniform. The active component has a predominant effect on the formation of the total stress. The circumferential stress component was several times higher than the radial and longitudinal ones. The modulus of the ratio of the radial stress component to the circumferential one increased as a result of activation, and a tendency to a decrease in its value with increasing circumferential stretching was observed. Numerical analysis revealed a high sensitivity of both the radius and stress to even a small change in the values of the parameters included in the functional dependence of the stress on the concentration of the smooth muscle contraction activator.

Modeling hypothermia induced effects for the heterogeneous ventricular tissue from cellular level to the impact on the ECG.

Hypothermia has a profound impact on the electrophysiological mechanisms of the heart. Experimental investigations provide a better understanding of electrophysiological alterations associated with cooling. However, there is a lack of computer models suitable for simulating the effects of hypothermia in cardio-electrophysiology. In this work, we propose a model that describes the cooling-induced electrophysiological alterations in ventricular tissue in a temperature range from 27°C to 37°C. To model the electrophysiological conditions in a 3D left ventricular tissue block it was essential to consider the following anatomical and physiological parameters in the model: the different cell types (endocardial, M, epicardial), the heterogeneous conductivities in longitudinal, transversal and transmural direction depending on the prevailing temperature, the distinct fiber orientations and the transmural repolarization sequences. Cooling-induced alterations on the morphology of the action potential (AP) of single myocardial cells thereby are described by an extension of the selected Bueno-Orovio model for human ventricular tissue using Q10 temperature coefficients. To evaluate alterations on tissue level, the corresponding pseudo electrocardiogram (pECG) was calculated. Simulations show that cooling-induced AP and pECG-related parameters, i.e. AP duration, morphology of the notch of epicardial AP, maximum AP upstroke velocity, AP rise time, QT interval, QRS duration and J wave formation are in good accordance with literature and our experimental data. The proposed model enables us to further enhance our knowledge of cooling-induced electrophysiological alterations from cellular to tissue level in the heart and may help to better understand electrophysiological mechanisms, e.g. in arrhythmias, during hypothermia.

Regional quantification of myocardial mechanics in rat using 3D cine DENSE cardiovascular magnetic resonance.

Rat models have assumed an increasingly important role in cardiac research. However, a detailed profile of regional cardiac mechanics, such as strains and torsion, is lacking for rats. We hypothesized that healthy rat left ventricles (LVs) exhibit regional differences in cardiac mechanics, which are part of normal function. In this study, images of the LV were obtained with 3D cine displacement encoding with stimulated echoes (DENSE) cardiovascular magnetic resonance in 10 healthy rats. To evaluate regional cardiac mechanics, the LV was divided into basal, mid-ventricular, and apical regions. The myocardium at the mid-LV was further partitioned into four wall segments (i.e. septal, inferior, lateral, and anterior) and three transmural layers (i.e. sub-endocardium, mid-myocardium, and sub-epicardium). The six Lagrangian strain components (i.e. Err , Ecc , Ell , Ecl , Erl , and Ecr ) were computed from the 3D displacement field and averaged within each region of interest. Torsion was quantified using the circumferential-longitudinal shear angle. While peak systolic Ecl differed between the mid-ventricle and apex, the other five components of peak systolic strain were similar across the base, mid-ventricle, and apex. In the mid-LV myocardium, Ecc decreased gradually from the sub-endocardial to the sub-epicardial layer. Ell demonstrated significant differences between the four wall segments, with the largest magnitude in the inferior segment. Err was uniform among the four wall segments. Ecl varied along the transmural direction and among wall segments, whereas Erl differed only among the wall segments. Erc was not associated with significant variations. Torsion also varied along the transmural direction and among wall segments. These results provide fundamental insights into the regional contractile function of healthy rat hearts, and form the foundation for future studies on regional changes induced by disease or treatments.

Distribution pattern of left ventricular myocardial strain by feature-tracking CMR in Chinese normal subjects

Background Myocardial strain was regarded as a sensitive parameter to quantify left ventricular function. Feature tracking CMR is emerging as a new simple and reliable technique to evaluate myocardial strain. In the present study, we were sought to investigate the distribution characteristics of left myocardial strain on the transmural direction or longitudinal direction in healthy Chinese subjects.

Ultrathin Injectable Sensors of Temperature, Thermal Conductivity, and Heat Capacity for Cardiac Ablation Monitoring.

Knowledge of the distributions of temperature in cardiac tissue during and after ablation is important in advancing a basic understanding of this process, and for improving its efficacy in treating arrhythmias. Technologies that enable real-time temperature detection and thermal characterization in the transmural direction can help to predict the depths and sizes of lesion that form. Herein, materials and designs for an injectable device platform that supports precision sensors of temperature and thermal transport properties distributed along the length of an ultrathin and flexible needle-type polymer substrate are introduced. The resulting system can insert into the myocardial tissue, in a minimally invasive manner, to monitor both radiofrequency ablation and cryoablation, in a manner that has no measurable effects on the natural mechanical motions of the heart. The measurement results exhibit excellent agreement with thermal simulations, thereby providing improved insights into lesion transmurality.

Influence of spatial resolution on the accuracy of quantitative myocardial perfusion in first pass stress perfusion CMR.

PurposeHigh-resolution myocardial perfusion analysis allows for preserving spatial information with excellent sensitivity for subendocardial ischemia detection. However, it suffers from low signal-to-noise ratio. Commonly, spatial averaging is used to increase signal-to-noise ratio. This bears the risk of losing information about the extent, localization and transmurality of ischemia. This study investigates spatial-averaging effects on perfusion-estimates accuracy.MethodsPerfusion data were obtained from patients and healthy volunteers. Spatial averaging was performed on voxel-based data in transmural and angular direction to reduce resolution to 50, 20, and 10% of its original value. Fit quality assessment method is used to measure the fraction of modeled information and remaining unmodeled information in the residuals.ResultsFraction of modeled information decreased in patients as resolution reduced. This decrease was more evident for Fermi and exponential in transmural direction. Fermi and exponential showed significant difference at 50% resolution (Fermi P < 0.001, exponential P =0.0014). No significant differences were observed for autoregressive-moving-average model (P = 0.081). At full resolution, autoregressive-moving-average model has the lowest fraction of residual information (0.3). Differences were observed comparing ischemic regions perfusion-estimates coefficient of variation at transmural and angular direction.ConclusionAngular averaging preserves more information compared to transmural averaging. Reducing resolution level below 50% at transmural and 20% at angular direction results in losing information about transmural perfusion differences. Maximum voxel size of 2 × 2 mm2 is necessary to avoid loss of physiological information due to spatial averaging. Magn Reson Med 73:1623–1631, 2015. © 2014 The Authors. Magnetic Resonance in Medicine Published by Wiley Periodicals, Inc. on behalf of International Society of Medicine in Resonance.

Effects of deformation on transmural dispersion of repolarization using in silico models of human left ventricular wedge

Mechanical deformation affects the electrical activity of the heart through multiple feedback loops. The purpose of this work is to study the effect of deformation on transmural dispersion of repolarization and on surface electrograms using an in silico human ventricular wedge. To achieve this purpose, we developed a strongly coupled electromechanical cell model by coupling a human left ventricle electrophysiology model and an active contraction model reparameterized for human cells. This model was then embedded in tissue simulations on the basis of bidomain equations and nonlinear solid mechanics. The coupled model was used to evaluate effects of mechanical deformation on important features of repolarization and electrograms. Our results indicate an increase in the T-wave amplitude of the surface electrograms in simulations that account for the effects of cardiac deformation. This increased T-wave amplitude can be explained by changes to the coupling between neighboring myocytes, also known as electrotonic effect. The thickening of the ventricular wall during repolarization contributes to the decoupling of cells in the transmural direction, enhancing action potential heterogeneity and increasing both transmural repolarization dispersion and T-wave amplitude of surface electrograms. The simulations suggest that a considerable percentage of the T-wave amplitude (15%) may be related to cardiac deformation.

Transmural and apicobasal gradients in repolarization contribute to T-wave genesis in human surface ECG

The cellular basis of the T-wave morphology of surface ECG remains controversial in clinical cardiology. We examined the effect of action potential duration (APD) distribution on T-wave morphology using a realistic model of the human ventricle and torso. We developed a finite-element model of the ventricle consisting of ∼26 million elements, including the conduction system, each implemented with the ion current model of cardiomyocytes. This model was embedded in a torso model with distinct organ structures to obtain the standard ECG leads. The APD distribution was changed in the transmural direction by locating the M cells in either the endocardial or epicardial region. We also introduced apicobasal gradients by modifying the ion channel parameters. Both the transmural gradient (with M cells on the endocardial side) and the apicobasal gradient produced positive T waves, although a very large gradient was required for the apicobasal gradient. By contrast, T waves obtained with the transmural gradient were highly symmetric and, therefore, did not represent the true physiological state. Only combination of the transmural and the moderate apicobasal gradients produced physiological T waves in surface ECG. Positive T waves in surface ECG mainly originated from the transmural distribution of APD with M cells on the endocardial side, although the apicobasal gradient was also required to attain the physiological waveform.

Imaging electrical excitation inside the myocardial wall

Cardiac arrhythmias are often triggered by ectopic membrane depolarization originating deep inside the myocardial wall. Here we propose a new method utilizing a novel near-infrared voltage-sensitive fluorescent dye DI-4-ANBDQBS to determine the three-dimensional (3D) coordinates of the sources of such depolarization. We tested the method in live preparations of pig left and right ventricular myocardium (thickness 8-18 mm) and phantoms imitating the optical properties of myocardial tissue. The method utilizes an alternating transillumination approach that involves comparing pairs of simultaneously recorded broad-field epifluorescence and transillumination images produced at two alternating directions of illumination. Recordings were taken simultaneously by two CCD cameras facing the endocardial and epicardial surfaces of the heart at a frame rate up to 3 KHz. In live preparations, we were able to localize the origin of the depolarization wave with a precision of ±1.3mm in the transmural direction and 3 mm in the image plane. The accuracy of detection was independent of the depth of the source inside ventricular wall.

Three-Dimensional Quantitative Micromorphology of Pre- and Post-Implanted Engineered Heart Valve Tissues

There is a significant gap in our knowledge of engineered heart valve tissue (EHVT) development regarding detailed three-dimensional (3D) tissue formation and remodeling from the point of in vitro culturing to full in vivo function. As a step toward understanding the complexities of EHVT formation and remodeling, a novel serial confocal microscopy technique was employed to obtain 3D microstructural information of pre-implant (PRI) and post-implant for 12weeks (POI) EHVT fabricated from PGA:PLLA scaffolds and seeded with ovine bone-marrow-derived mesenchymal stem cells. Custom scaffold fiber tracking software was developed to quantify scaffold fiber architectural features such as length, tortuosity, and minimum scaffold fiber-fiber separation distance and scaffold fiber orientation was quantified utilizing a 3D fabric tensor. In addition, collagen and cellular density of ovine pulmonary valve leaflet tissue were also analyzed for baseline comparisons. Results indicated that in the unseeded state, scaffold fibers formed a continuous, oriented network. In the PRI state, the scaffold showed some fragmentation with a scaffold volume fraction of 7.79%. In the POI specimen, the scaffold became highly fragmented, forming a randomly distributed short fibrous network (volume fraction of 2.03%) within a contiguous, dense collagenous matrix. Both PGA and PLLA scaffold fibers were observed in the PRI and POI specimens. Collagen density remained similar in both PRI and POI specimens (74.2 and 71.5%, respectively), though the distributions in the transmural direction appeared slightly more homogenous in the POI specimen. Finally, to guide future 2D histological studies for large-scale studies (since acquisition of high-resolution volumetric data is not practical for all specimens), we investigated changes in relevant collagen and scaffold metrics (collagen density and scaffold fiber orientation) with varying section spacing. It was found that a sectioning spacing up to 25μm (for scaffold morphology) and 50μm (for collagen density) in both PRI and POI tissues did not result in loss of information fidelity, and that sectioning in the circumferential or radial direction provides the greatest preservation of information. This is the first known work to investigate EHVT microstructure over a large volume with high resolution and to investigate time evolving in vivo EHVT morphology. The important scaffold fiber structural changes observed provide morphological information crucial for guiding future structurally based constitutive modeling efforts focused on better understanding EHVT tissue formation and remodeling.

Structure and torsion in the normal and situs inversus totalis cardiac left ventricle. II. Modeling cardiac adaptation to mechanical load

Mathematical models provide a suitable platform to test hypotheses on the relation between local mechanical stimuli and responses to cardiac structure and geometry. In the present model study, we tested hypothesized mechanical stimuli and responses in cardiac adaptation to mechanical load on their ability to estimate a realistic myocardial structure of the normal and situs inversus totalis (SIT) left ventricle (LV). In a cylindrical model of the LV, 1) mass was adapted in response to myofiber strain at the beginning of ejection and to global contractility (average systolic pressure), 2) cavity volume was adapted in response to fiber strain during ejection, and 3) myofiber orientations were adapted in response to myofiber strain during ejection and local misalignment between neighboring tissue parts. The model was able to generate a realistic normal LV geometry and structure. In addition, the model was also able to simulate the instigating situation in the rare SIT LV with opposite torsion and transmural courses in myofiber direction between the apex and base [Delhaas et al. (6)]. These results substantiate the importance of mechanical load in the formation and maintenance of cardiac structure and geometry. Furthermore, in the model, adapted myocardial architecture was found to be insensitive to fiber misalignment in the transmural direction, i.e., myofiber strain during ejection was sufficient to generate a realistic transmural variation in myofiber orientation. In addition, the model estimates that, despite differences in structure, global pump work and the mass of the normal and SIT LV are similar.

The heart muscle’s putative ‘secondary structure’. Functional implications of a band-like anisotropy

Opinions are divided as to whether the rope-like secondary structure, which Torrent-Guasp dissected out of the myocardial body by the blunt unwinding technique (BUT) reveals some kind of functional compartmentation of the heart muscle. The myocardial fibres are aligned parallel to the fibre disruption (cleavage) plane, along which the band has been prepared but they are not necessarily aligned parallel to the long axis of the band. Inconsistencies in the myocardial rope model arise from the obligatory zones of transmural inflection, which are obvious in the base and the apex of both ventricles. They are, however, merely discernible in the midzone of the left ventricular cone. The investigator experienced in BUT knows that the cleavage plane is not unique. We doubt the assumption that the rope structure is the predominant stress transmission pathway, because the fibre strand peel-off technique (SPOT) delivers irregular fibre disruption planes which are definitely different from those which Torrent-Guasp prepares. The rope-like fibre arrangement could be just a redundant structure, a remnant of past developmental steps without, however, any functional implication to the human heart. On the other hand, peeling-off fibre strands from the ventricular wall produces deeply perforating, i.e., oblique transmurally grooved surfaces. Putative functions of force transmission in an oblique transmural direction are (1) ventricular dilation as a function of the variable inclination angle with respect to the epicardial surface, (2) monitoring of ventricular wall stress and ventricular size and (3) segmental stiffening which could serve other dependent segments as a punctum fixum.

Coronaro-myocardial interplay determining the instantaneous mean ventricular shape (author's transl)

A working hypothesis on the mechanism of diastolic chamber expansion based on functional anatomy and physiology is developed. It should be a major determinant of the momentary average chamber width. The sum of all intramyocardial fluid-filled spaces and the myocardium itself are considered in the working hypothesis as the hydraulic medium of a process which can be summarised under the term "cavernous body mechanism". The most important factor of this hydraulic system should represent the intramural fluid volume (hydraulic medium) and the contractile-elastic tension development in the transmural direction of the chamber wall. Morphological analysis of myocardial structure shows that an endoepicardial direction of force in the myocardial net can be recognised. The "motor" of circular fibres of the middle layer is surrounded by the spiral course of the fibres of the inner and outer layers of the chamber wall (uvula mechanism). It is interwoven by very dense bifurcating myocardial fibres (structural principle of the tongue). By these means, the width of the chamber cone is influenced decisively by an active decrease in wall thickness. The coronary perfusion pressure is thought to have a chamber dilating influence in the sense of a "cavernous body mechanism". The hypothesis presented helps us to understand pathological chamber dilation secondary to transmural myocardial fibrosis. Such a narrow functional coronary-myocardial interaction gives the myocardium two functions; besides haemodynamic pumping, the cardial muscle must function as an internal antagonist to favour diastolic chamber dilation.