Myocardial Tissue Structure Research Articles

WE-E-134-11: Ultrasound Cardiac Strain Imaging of Left Ventricle Using Lagrangian Tracking

Purpose: Lagrangian description of myocardial tissue deformation is essential for accurate regional strain estimation of left ventricular wall over time. Failure to couple the estimated displacement and strain information with the correct myocardial tissue structure will lead to erroneous displacement and strain estimation. Methods: In this study, a method to obtain Lagrangian based deformation tracking is presented. Myocardial tissue is divided into a fixed number of pixels whose deformation is tracked over the cardiac cycle. An algorithm that utilizes a polar‐grid generated between the estimated endocardial and epicardial contours for the left ventricle in cardiac short axis images is proposed to ensure Lagrangian description. Displacement estimations from consecutive radiofrequency frames were then mapped onto the polar grid to obtain a distribution of the cumulated displacement that is mapped to the polar grid over time. Results: This method was validated against a finite element analysis (FEA) based canine heart model coupled to an ultrasound simulation program. Segmental analysis of the accumulated displacement and strain over cardiac cycles show excellent agreement between the ideal Results obtained directly from the FEA model and our Lagrangian approach for deformation mapping. Eulerian based estimation results on the other hand, show significant deviation from the ideal Results. A comparison of the displacement and strain estimated on parasternal short axis view on a healthy volunteer is also presented. Conclusion: Lagrangian deformation tracking using a polar grid demonstrates accurate results when validated against finite element cardiac model. In addition to the cardiac application, this approach can also be applied to transverse scans of arteries.

Modeling the Role of the Coronary Vasculature During External Field Stimulation

The exact mechanisms by which defibrillation shocks excite cardiac tissue far from both the electrodes and heart surfaces require elucidation. Bidomain theory explains this phenomena through the existence of intramural virtual electrodes (VEs), caused by discontinuities in myocardial tissue structure. In this study, we assess the modeling components essential in constructing a finite-element cardiac tissue model including blood vessels from high-resolution magnetic resonance data and investigate the specific role played by coronary vasculature in VE formation, which currently remains largely unknown. We use a novel method for assigning histologically based fiber architecture around intramural structures and include an experimentally derived vessel lumen wall conductance within the model. Shock-tissue interaction in the presence of vessels is assessed through comparison with a simplified model lacking intramural structures. Results indicate that VEs form around blood vessels for shocks > 8 V/cm. The magnitude of induced polarizations is attenuated by realistic representation of fiber negotiation around vessel cavities, as well as the insulating effects of the vessel lumen wall. Furthermore, VEs formed around large subepicardial vessels reduce epicardial polarization levels. In conclusion, we have found that coronary vasculature acts as an important substrate for VE formation, which may help interpretation of optical mapping data.

Integrated analysis of cardiac tissue structure and function for improved identification of reversible myocardial dysfunction

Myocardial deformation imaging and contrast-enhanced cardiac magnetic resonance imaging (ceMRI) have been used to define myocardial viability in ischemic left ventricular dysfunction. This study evaluated the incremental predictive value of an integrated analysis of function and tissue structure for functional improvement after revascularization therapy. In 59 patients with ischemic left ventricular dysfunction, myocardial viability was defined by pixel-tracking-derived myocardial deformation imaging and ceMRI to predict recovery of function at 9+/-2 months follow-up after revascularization. For each left ventricular segment in a 16-segment model, peak systolic radial strain was determined from parasternal two-dimensional echocardiographic views using an automatic frame-by-frame tracking system of natural acoustic echocardiographic markers, and extent of hyperenhancement using ceMRI. Five categories were generated for each parameter, allowing subsequent combination. The predictive power for segmental improvement in function was determined for each of the modalities as well as the combination of both. From 512 dysfunctional segments at baseline, 251 segments (49%) demonstrated functional recovery. The accuracy to predict functional recovery was area under curve (AUC)=0.846 for peak systolic radial strain and AUC=0.834 for extent of hyperenhancement. A combination of both parameters improved the predictive accuracy compared with hyperenhancement alone, AUC=0.861, P value of less than 0.001. In sequential Cox models, the predictive power for segmental functional recovery of extent of hyperenhancement alone (chi model 171.0, P<0.001), or peak systolic radial strain alone (chi model 205.9, P<0.001), was strengthened by a combination of both parameters (chi model 248.5, P<0.001). The advantage of image integration was particularly strong in those segments with intermediate degree of late enhancement (DeltaAUC=0.065, P<0.001). Integration of advanced information on myocardial function using deformation imaging and findings on myocardial tissue structure increases the accuracy to identify reversible myocardial dysfunction.

Characterization of Ca 2+ ‐activated K + current in human cardiac fibroblasts: its contribution to electrical coupling of cardiomyocyte‐fibroblast

Cardiac fibroblasts can maintain myocardial tissue structure. Cardiac fibroblasts can interact electrically with cardiomyocytes through gap junctions. Little was reported about ion currents in human cardiac fibroblasts. Ca2+-activated K+ currents (IK(Ca)) of cultured human cardiac fibroblasts were characterized in this study. In whole-cell configuration, depolarizing pulses evoked IK(Ca) in these cells, the amplitude of which was suppressed by paxilline (1 μM) or iberiotoxin (200 nM). Western blot analysis revealed the presence of α-subunit of BKCa channels. Dynamic Luo-Rudy model was applied to predict cell behavior during direct electrical coupling of cardiomyocyte and cardiac fibroblast. In the simulation, electrically coupled cardiac fibroblast was found to exhibit action potential. The simulation predicts that gap junction coupling conductance influences cardiac action potential and excitability. IK(Ca) can be elicited by simulated action potential waveforms of cardiac fibroblasts when they are electrically coupled to cardiomyocytes. This study demonstrates that a BKCa channel is functionally expressed in human cardiac fibroblasts. The BKCa-channel activity in human cardiac fibroblast may contribute to the functional activities of heart cells through transfer of electrical signals between these two cells.

Contribution of BKCa-Channel Activity in Human Cardiac Fibroblasts to Electrical Coupling of Cardiomyocytes-Fibroblasts

Cardiac fibroblasts are involved in the maintenance of myocardial tissue structure. However, little is known about ion currents in human cardiac fibroblasts. It has been recently reported that cardiac fibroblasts can interact electrically with cardiomyocytes through gap junctions. Ca(2+)-activated K(+) currents (I (K[Ca])) of cultured human cardiac fibroblasts were characterized in this study. In whole-cell configuration, depolarizing pulses evoked I (K(Ca)) in an outward rectification in these cells, the amplitude of which was suppressed by paxilline (1 microM: ) or iberiotoxin (200 nM: ). A large-conductance, Ca(2+)-activated K(+) (BK(Ca)) channel with single-channel conductance of 162 +/- 8 pS was also observed in human cardiac fibroblasts. Western blot analysis revealed the presence of alpha-subunit of BK(Ca) channels. The dynamic Luo-Rudy model was applied to predict cell behavior during direct electrical coupling of cardiomyocytes and cardiac fibroblasts. In the simulation, electrically coupled cardiac fibroblasts also exhibited action potential; however, they were electrically inert with no gap-junctional coupling. The simulation predicts that changes in gap junction coupling conductance can influence the configuration of cardiac action potential and cardiomyocyte excitability. I (k(Ca)) can be elicited by simulated action potential waveforms of cardiac fibroblasts when they are electrically coupled to cardiomyocytes. This study demonstrates that a BK(Ca) channel is functionally expressed in human cardiac fibroblasts. The activity of these BK(Ca) channels present in human cardiac fibroblasts may contribute to the functional activities of heart cells through transfer of electrical signals between these two cell types.

Three-dimensional anatomic structure as substrate for ventricular tachycardia/ventricular fibrillation

size. In fact, cell size has a significantly larger effect on conduction than does the gap junction pattern. The increase in conduction velocity with cell size implies that conduction is faster in cells in hypertrophy and heart failure. Increased conduction velocity has been observed, but contradictory results have been reported for failing hearts. Increased conduction velocity is potentially antiarrhythmogenic. However, this effect might be counteracted in the failing hypertrophic heart by the increase in myocardial mass and alterations in other electrophysiologic parameters. Anisotropic structure and fiber rotation Fiber anatomy of the myocardium has a profound effect on the electrical properties of both normal and diseased hearts. The anisotropic structure of myocardial tissue plays a major role in cardiac conduction, which is faster longitudinally than perpendicular to the fiber direction. The role of fiber orientation in conduction is further complicated because myocardial fibers rotate from epicardium to endocardium. Rotation of the fiber direction from epicardial to endocardial is high and has been reported to be as large as 120°. Fiber rotation has been shown to maintain twist in scroll waves, thereby promoting filament bending and scroll breakup. In addition, fiber rotation induces curvature in scroll waves and weakens conduction that further facilitates wave break. 2 Other studies have shown that ventricular fibrillation (VF) activation patterns vary in structurally different ventricular tissues and that most complex activation during VF occurs in the interventricular septum, a structurally complex region of the ventricle.

Microstructured Cocultures of Cardiac Myocytes and Fibroblasts: A Two-DimensionalIn VitroModel of Cardiac Tissue

Cardiac myocytes and fibroblasts are essential elements of myocardial tissue structure and function. In vivo, myocytes constitute the majority of cardiac tissue volume, whereas fibroblasts dominate in numbers. In vitro, cardiac cell cultures are usually designed to exclude fibroblasts, which, because of their maintained proliferative potential, tend to overgrow the myocytes. Recent advances in microstructuring of cultures and cell growth on elastic membranes have greatly enhanced in vitro preservation of tissue properties and offer a novel platform technology for producing more in vivo-like models of myocardium. We used microfluidic techniques to grow two-dimensional structured cardiac tissue models, containing both myocytes and fibroblasts, and characterized cell morphology, distribution, and coupling using immunohistochemical techniques. In vitro findings were compared with in vivo ventricular cyto-architecture. Cardiac myocytes and fibroblasts, cultured on intersecting 30-microm-wide collagen tracks, acquire an in vivo-like phenotype. Their spatial arrangement closely resembles that observed in native tissue: Strands of highly aligned myocytes are surrounded by parallel threads of fibroblasts. In this in vitro system, fibroblasts form contacts with other fibroblasts and myocytes, which can support homogeneous and heterogeneous gap junctional coupling, as observed in vivo. We conclude that structured cocultures of cardiomyocytes and fibroblasts mimic in vivo ventricular tissue organization and provide a novel tool for in vitro research into cardiac electromechanical function.

Multiscale computational modelling of the heart

A computational framework is presented for integrating the electrical, mechanical and biochemical functions of the heart. Finite element techniques are used to solve the large-deformation soft tissue mechanics using orthotropic constitutive laws based in the measured fibre-sheet structure of myocardial (heart muscle) tissue. The reaction-diffusion equations governing electrical current flow in the heart are solved on a grid of deforming material points which access systems of ODEs representing the cellular processes underlying the cardiac action potential. Navier-Stokes equations are solved for coronary blood flow in a system of branching blood vessels embedded in the deforming myocardium and the delivery of oxygen and metabolites is coupled to the energy-dependent cellular processes. The framework presented here for modelling coupled physical conservation laws at the tissue and organ levels is also appropriate for other organ systems in the body and we briefly discuss applications to the lungs and the musculo-skeletal system. The computational framework is also designed to reach down to subcellular processes, including signal transduction cascades and metabolic pathways as well as ion channel electrophysiology, and we discuss the development of ontologies and markup language standards that will help link the tissue and organ level models to the vast array of gene and protein data that are now available in web-accessible databases.

Modeling total heart function.

Computational models of the electrical and mechanical function of the heart are reviewed. These models attempt to explain the integrated function of the heart in terms of ventricular anatomy, the structure and material properties of myocardial tissue, the membrane ion channels, and calcium handling and myofilament mechanics of cardiac myocytes. The models have established the computational framework for linking the structure and function of cardiac cells and tissue to the integrated behavior of the intact heart, but many more aspects of physiological function, including metabolic and signal transduction pathways, need to be included before significant progress can be made in understanding many disease processes.

Link of nonhemodynamic factors to hemodynamic determinants of left ventricular hypertrophy.

Despite current evidence suggesting that hemodynamic load is the fundamental stimulus to begin the sequence of biological events leading to the development of left ventricular hypertrophy, genotype, gender, body size, and less easily recognizable environmental factors may contribute to generate the cascade of molecular changes that eventually yield the increase in protein synthesis needed to increase left ventricular mass. However, even nonhemodynamic factors such as gender and body size eventually regulate the growth of left ventricular mass by at least in part influencing loading conditions. Consideration of measurable factors, such as gender, body size, and hemodynamic load, allows evaluation of individual echocardiographic left ventricular mass as the deviation from the level that would be required to face a gender-specific hemodynamic load at a given body size. Values of left ventricular mass that are inappropriately high for individual gender, body size, and hemodynamic load are associated with a high cardiovascular risk phenotype, even independent of the presence of arterial hypertension. Thus, the condition of inappropriately high left ventricular mass may be recognized as a more advanced stage of pathological structural changes initially induced by overload, going beyond the compensatory needs. The biological process that yields inappropriate left ventricular mass is probably linked to the protracted activity over time of biological mediators of left ventricular hypertrophy, such as proto-oncogenes and other growth factors, neurohormones, and cytokines, inducing structural modifications that initially compensate imposed overload but eventually change the structure of myocardial tissue and the composition of motor units.

Efficient cardiac diffusion tensor MRI by three-dimensional reconstruction of solenoidal tensor fields

Tensor tomography is being investigated as a technique for reconstruction of in vivo diffusion tensor fields that can potentially be used to reduce the number of magnetic resonance imaging (MRI) measurements. Specifically, assessments are being made of the reconstruction of cardiac diffusion tensor fields from 3D Radon planar projections using a filtered backprojection algorithm in order to specify the helical fiber structure of myocardial tissue. Helmholtz type decomposition is proposed for 3D second order tensor fields. Using this decomposition a Fourier projection theorem is formulated in terms of the solenoidal and irrotational components of the tensor field. From the Fourier projection theorem, two sets of Radon directional measurements, one that reconstructs the solenoidal component and one that reconstructs the irrotational component of the tensor field, are prescribed. Based on these observations filtered backprojection reconstruction formulae are given for the reconstruction of a 3D second order tensor field and its solenoidal and irrotational components from Radon projection measurements. Computer simulations demonstrate the validity of the mathematical formulations and demonstrate that a realistic model of the helical fiber structure of the myocardial tissue specifies a diffusion tensor field for which the first principal vector (the vector associated with the maximum eigenvalue) of the solenoidal component accurately approximates the first principal vector of the diffusion tensor. A priori knowledge of this allows the orientation of the myocardial fiber structure to be specified utilizing one half of the number of MRI measurements of a normal diffusion tensor field study.

A model of ultrasound backscatter for the assessment of myocardial tissue structure and architecture.

A statistical parametric model of returning echoes from myocardium is theorized in order to investigate the relationship between normal myocardium structure and spectral signatures with the use of ultrasonic tissue characterization. It is hypothesized, that in a clinical setting the normal myofiber architecture in the left ventricular wall is structured as a matrix of cylinder scatterers whose orientation and spatial distribution vary according to two different statistical distribution laws: 1) a Gaussian law to approximate parametric angular myofiber variability at each site within the myocardial wall; 2) a gamma distribution law to describe parametric regularity in scatterer interdistance. In the model, the effect of the angle of insonification with respect to the alignment of myofibers on ultrasound backscatter was considered. The slope of the power spectral density (PSD) evaluated within the echocardiographic transducer bandwidth has been used as a ultrasonic tissue characterization parameter. The model has been tested by computer simulation and in vitro measurements on myocardial pig tissue specimens. The concordance between experimental and simulated results confirms that the model accounts for the process underlying the echo formation from normal myocardium. Moreover, it provides a simple method of simulation which can be easily implemented and used for the assessment of pathologic alterations.

Hypertensive heart disease: cardioreparation by reversal of interstitial collagen in patients.

Impairment of coronary flow reserve in arterial hypertension and hypertrophy is caused by multiple mechanisms. Medial wall thickening of the small intramural arteries and rarification of capillarization are the major structural alterations in hypertensive hypertrophy. Since the small intramural resistance arteries contribute more to coronary resistance than capillaries, medial wall thickening of the intramyocardial arterioles has to be considered the most relevant mechanism for causing impaired coronary flow reserve in arterial hypertension. Additionally, qualitative changes in myocardial tissue composition and structure, such as reactive interstitial fibrosis, rather than the mere augmentation of the myocardial muscle mass, impair flow reserve extravascularly. Except for the structural vascular and myocardial changes, in some hypertensive patients an impaired endothelium-mediated vasodilation of the microvessels occurs. Preliminary clinical data indicate that myocardial interstitial collagen content can be regressed in some hypertensive patients by clinical antihypertensive therapy over a period of 9-12 months.

Evaluation of Cardiac Damage in Hypertension

Functional and structural alterations of the coronary microcirculation and left ventricular hypertrophy represent the two key cardiac manifestations of arterial hypertension. In addition, qualitative changes in myocardial tissue composition and structure, such as reactive interstitial fibrosis, are frequently present. The extent of the impairment of coronary flow reserve can be measured using Doppler, argon gas chromatography or thermodilution techniques. Impaired flow reserve can be detected non-invasively using positron emission tomography. The combination of both a normal coronary angiogram and a positive exercise tolerance test (electrocardiogram or thallium) strongly indicates the presence of a hypertension-related disorder of the coronary microcirculation. Left ventricular hypertrophy can easily be quantified using echocardiography (Penn formula). Diastolic function can be assessed by measuring mitral inflow using pulsed-wave Doppler echocardiography (E/A ratio). Non-invasive assessment of myocardial structural alternations may be possible in the future using backscatter echocardiography.

Ultrasonic Tissue Characterization in Cardiology

The standard clinical applications of echocardiography involve display of the smooth surfaces of the heart, such as the endocardium, epicardium and valve leaflets. A relatively new area of endeavor in cardiac ultrasound is the attempt to evaluate myocardial tissue composition and/or structure based on the acoustic properties of the heart. The rationale for this area of study - termed ultrasound tissue characterization - is that ultrasound interacts (is absorbed or reflected) differently with abnormal myocardium than with normal myocardium. This rationale stems from the common clinical observation that certain abnormalities of the heart (calcification, amyloidosis, and others) affect the appearance of échocardiographie images. Several approaches to the evaluation of tissue composition with ultrasound include the display of acoustically abnormal tissue using gray scale or color encoding, the measurement of classical acoustic variables, and computer-based analysis of ultrasound signals and images. Promising results have been obtained through the use of ultrasound tissue characterization methods to identify acute ischemia, acute and chronic myocardial infarction, cardiomyopathies, myocardial contusion, and intracardiac masses. Although many technical problems remain to be solved, ultrasound tissue characterization may soon be added to the routine diagnostic armamentarium of the cardiologist.

Pluricausal Pathogenesis and Preventability of Ischemic Heart Disease

SUMMARY The traditional concept of coronary atherosclerosis as being the one and only pathogenic factor, responsible for the origin of degenerative (so-calledcoronary) heart disease, is no longer tenable. Additional myocardial vulnerability-augmenting neurogenic and hormonal interferences in the heart muscle's oxygen and electrolyte metabolism have to be taken into account, in keeping with today's state of knowledge. Attempts at the preventive protection of the myocardial tissue's function and structure are to be aimed specifically (a) at retardation of predisposing atherogenesis, chiefly by means of dietary and anti-hypertensive measures, and (b) at reduction of potentially myocardial hypoxia-producing and potassium-depleting adreno-sympathetic and adrenocortical overactivity by means of environmental-emotional relaxation, abstinence from smoking, and regular physical exercise. Administration of potassium and magnesium ions in appropriate polarizing combinations, especially in the form of aspartates, is theoretically justified as a prophylactic measure, the merits of which are at present being subjected to prospective epidemiologic investigation.