Socrates Dokos

Regional heterogeneity of function in nonischemic dilated cardiomyopathy

OBJECTIVE To quantify regional three-dimensional (3D) motion and myocardial strain using magnetic resonance (MR) tissue tagging in patients with non-ischemic dilated cardiomyopathy (DCM). METHODS MR grid tagged images were obtained in multiple short- and long-axis planes in thirteen DCM patients. Regional 3D displacements and strains were calculated with the aid of a finite element model. Five of the patients were also imaged after LV volume reduction by partial left ventriculectomy (PLV), combined with mitral and tricuspid valve repair. RESULTS DCM patients showed consistent, marked regional heterogeneity. Systolic lengthening occurred in the septum in both circumferential (%S(C) -5+/-7%) and longitudinal (%S(L) -2+/-5%) shortening components (negative values indicating lengthening). In contrast, the lateral wall showed relatively normal systolic shortening (%S(C) 12+/-6% and %S(L) 6+/-5%, P<0.001 lateral vs. septal walls). A geometric estimate of regional stress was correlated with shortening on a regional basis, but could not account for the differences in shortening between regions. In the five patients imaged post-PLV, septal function recovered (%S(C) 9+/-5%,%S(L) 6+/-5%, P<0.02 pre vs. post) with normalization of wall stress, whereas lateral wall shortening was reduced (%S(C) 7+/-6%,%S(L) 3+/-3%, P<0.02 pre vs. post) around the site of surgical resection. CONCLUSIONS A consistent pattern of regional heterogeneity of myocardial strain was seen in all patients. Reduced function may be related to increased wall stress, since recovery of septal function is possible after PLV. However, simple geometric stress determinants are not sufficient to explain the functional heterogeneity observed.

Revisiting QRS detection methodologies for portable, wearable, battery-operated, and wireless ECG systems

Cardiovascular diseases are the number one cause of death worldwide. Currently, portable battery-operated systems such as mobile phones with wireless ECG sensors have the potential to be used in continuous cardiac function assessment that can be easily integrated into daily life. These portable point-of-care diagnostic systems can therefore help unveil and treat cardiovascular diseases. The basis for ECG analysis is a robust detection of the prominent QRS complex, as well as other ECG signal characteristics. However, it is not clear from the literature which ECG analysis algorithms are suited for an implementation on a mobile device. We investigate current QRS detection algorithms based on three assessment criteria: 1) robustness to noise, 2) parameter choice, and 3) numerical efficiency, in order to target a universal fast-robust detector. Furthermore, existing QRS detection algorithms may provide an acceptable solution only on small segments of ECG signals, within a certain amplitude range, or amid particular types of arrhythmia and/or noise. These issues are discussed in the context of a comparison with the most conventional algorithms, followed by future recommendations for developing reliable QRS detection schemes suitable for implementation on battery-operated mobile devices.

A triaxial-measurement shear-test device for soft biological tissues.

A novel shear-test device for soft biological tissue, capable of applying simple shear deformations simultaneously in two orthogonal directions while measuring the resulting forces generated in three axes, is described. We validated the device using a synthetic gel, the properties of which were ascertained from independent tensile and rotational shear tests. Material parameters for the gel were fitted using neo-Hookean analytical solutions to the independent test data, and these matched the results from the device. Preliminary results obtained with rat septal myocardium are also presented to demonstrate the feasibility of the apparatus in determining the shear characteristics of living tissue.

A computational modelling study of transcranial direct current stimulation montages used in depression.

Transcranial direct current stimulation (tDCS) is a neuromodulatory technique which involves passing a mild electric current to the brain through electrodes placed on the scalp. Several clinical studies suggest that tDCS may have clinically meaningful efficacy in the treatment of depression. The objective of this study was to simulate and compare the effects of several tDCS montages either used in clinical trials or proposed, for the treatment of depression, in different high-resolution anatomically-accurate head models. Detailed segmented finite element head models of two subjects were presented, and a total of eleven tDCS electrode montages were simulated. Sensitivity analysis on the effects of changing the size of the anode, rotating both electrodes and displacing the anode was also conducted on selected montages. The F3-F8 and F3-F4 montages have been used in clinical trials reporting significant antidepressant effects and both result in relatively high electric fields in dorsolateral prefrontal cortices. Other montages using a fronto-extracephalic or fronto-occipital approach result in greater stimulation of central structures (e.g. anterior cingulate cortex) which may be advantageous in treating depression, but their efficacy has yet to be tested in randomised controlled trials. Results from sensitivity analysis suggest that electrode position and size may be adjusted slightly to accommodate other priorities, such as skin discomfort and damage.

Erratum to “Optimisation of a Generic Ionic Model of Cardiac Myocyte Electrical Activity”.

A generic cardiomyocyte ionic model, whose complexity lies between a simple phenomenological formulation and a biophysically detailed ionic membrane current description, is presented.Themodel provides a user-defined number of ionic currents, employing two-gate Hodgkin-Huxley type kinetics. Its generic nature allows accurate reconstruction of action potential waveforms recorded experimentally from a range of cardiac myocytes. Using a multiobjective optimisation approach, the generic ionic model was optimised to accurately reproduce multiple action potential waveforms recorded from central and peripheral sinoatrial nodes and right atrial and left atrial myocytes from rabbit cardiac tissue preparations, under different electrical stimulus protocols and pharmacological conditions. When fitted simultaneously to multiple datasets, the time course of several physiologically realistic ionic currents could be reconstructed. Model behaviours tend to be well identified when extra experimental information is incorporated into the optimisation.

Electric crosstalk impairs spatial resolution of multi-electrode arrays in retinal implants

Active multi-electrode arrays are used in vision prostheses, including optic nerve cuffs and cortical and retinal implants for stimulation of neural tissue. For retinal implants, arrays with up to 1500 electrodes are used in clinical trials. The ability to convey information with high spatial resolution is critical for these applications. To assess the extent to which spatial resolution is impaired by electric crosstalk, finite-element simulation of electric field distribution in a simplified passive tissue model of the retina is performed. The effects of electrode size, electrode spacing, distance to target cells, and electrode return configuration (monopolar, tripolar, hexagonal) on spatial resolution is investigated in the form of a mathematical model of electric field distribution. Results show that spatial resolution is impaired with increased distance from the electrode array to the target cells. This effect can be partly compensated by non-monopolar electrode configurations and larger electrode diameters, albeit at the expense of lower pixel densities due to larger covering areas by each stimulation electrode. In applications where multi-electrode arrays can be brought into close proximity to target cells, as presumably with epiretinal implants, smaller electrodes in monopolar configuration can provide the highest spatial resolution. However, if the implantation site is further from the target cells, as is the case in suprachoroidal approaches, hexagonally guarded electrode return configurations can convey higher spatial resolution.

Parameter-Optimized Model of Cardiovascular–Rotary Blood Pump Interactions

A lumped parameter model of human cardiovascular-implantable rotary blood pump (iRBP) interaction has been developed based on experimental data recorded in two healthy pigs with the iRBP in situ. The model includes descriptions of the left and right heart, direct ventricular interaction through the septum and pericardium, the systemic and pulmonary circulations, as well as the iRBP. A subset of parameters was optimized in a least squares sense to faithfully reproduce the experimental measurements (pressures, flows and pump variables). Our fitted model compares favorably with our experimental measurements at a range of pump operating points. Furthermore, we have also suggested the importance of various model features, such as the curvilinearity of the end systolic pressure-volume relationship, the Starling resistance, the suction resistance, the effect of respiration, as well as the influence of the pump inflow and outflow cannulae. Alterations of model parameters were done to investigate the circulatory response to rotary blood pump assistance under heart failure conditions. The present model provides a valuable tool for experiment designs, as well as a platform to aid in the development and evaluation of robust physiological pump control algorithms.

A bidomain model of epiretinal stimulation

A computational bidomain model of epiretinal stimulation is presented, consisting of a continuum description of active retinal tissue in contact with bulk vitreous fluid. Results from two-electrode and four-electrode bipolar stimulation suggest that a biphasic cathodic-anodic stimulus sequence is effective in providing targeted focal activation of retinal tissue. Undesired secondary activations beneath each electrode return may be eliminated by using multiple returns for each stimulus electrode.

Current Steering in Retinal Stimulation via a Quasimonopolar Stimulation Paradigm

PURPOSE Research to restore some degree of vision to patients suffering from retinal degeneration is becoming increasingly more promising. Several groups have chosen electrical stimulation of the remaining network of a degenerate retina as a means to generate discrete light percepts (phosphenes). Approaches vary significantly, with the greatest difference being the location of the stimulating electrode itself. METHODS Suprachoroidal positioning offers excellent mechanical stability and surgical simplicity; however, at the cost of activation thresholds and focused stimulation due to the distance from the electrodes to the target neurons. Past studies proposed a hexapolar electrode configuration to focus the cortical activation and minimize cross-talk between electrodes during concurrent stimulation. The high impedance nature of the choroid and pigment epithelium, however, cause current to shunt between the stimulating and return electrodes, resulting in even higher activation thresholds. In our study, we analyzed the effect of stimulating the feline retina using a quasimonopolar stimulation by simultaneously stimulating a hexapolar and distant monopolar return configurations. RESULTS Results of in vivo studies showed that quasimonopolar stimulation can be used to maintain the activation containment properties of hexapolar stimulation, while lowering the activation threshold to values almost equivalent to those of monopolar stimulation. CONCLUSIONS The optimal stimulus was found to be composed of a subthreshold monopolar stimulus combined with a suprathreshold hexapolar stimulation. This resulted in a decrease of activation threshold of 60% with respect to hexapolar alone, but with no discernible deleterious effect on the charge containment of a pure hexapolar stimulation.

A computational model of direct brain excitation induced by electroconvulsive therapy: Comparison among three conventional electrode placements

BACKGROUND Electroconvulsive therapy (ECT) is a highly effective treatment for severe depressive disorder. Efficacy and cognitive outcomes have been shown to depend on variations in electrode placement and other stimulus parameters, presumably because of differences in the pattern of neuronal activation. This latter effect, however, is poorly understood. OBJECTIVE In this study, we present an anatomically accurate human head computational model to stimulate neuronal excitation during ECT, to better understand the effects of varying electrode placement and stimulus parameters. METHODS Electric field and current density throughout the head, as well as direct neural activation within the brain, were computed using the finite element method. Regions representing passive volume conductors (skin, skull, cerebrospinal fluid) were extracellularly coupled to an excitable neural continuum region representing the brain. The skull was modeled with anistropic electrical conductivity. RESULTS Simulation results indicated that direct activation of the brain occurred immediately beneath the electrodes on the scalp, consistent with existing imaging studies. In addition, we found that the brainstem was also activated using a right unilateral electrode configuration. Simulation also demonstrated that a reduction in stimulus amplitude or pulse width led to a reduction in the spatial extent of brain activation. CONCLUSIONS The novel model described in this study was able to simulate direct excitation of the brain during ECT, was useful in characterizing differences in neuronal activation as electrode placement, pulse width, and amplitude were altered, and is proposed as a tool for further exploring the effects of variations in ECT stimulation approaches. Results from the simulations assist in understanding recently described clinical phenomena, in particular, the reduction in cognitive side effects with ultrabrief pulse width stimulation, and greater effects of the ECT stimulus on cardiovascular function with unilateral electrode placement.