Low-Cost Optical Mapping Systems for Panoramic Imaging of Complex Arrhythmias and Drug-Action in Translational Heart Models

Panoramic optical mapping is the primary method for imaging electrophysiological activity from the entire outer surface of Langendorff-perfused hearts. To date, it is the only method of simultaneously measuring multiple key electrophysiological parameters, such as transmembrane voltage and intracellular free calcium, at high spatial and temporal resolution. Despite the impact it has already had on the fields of cardiac arrhythmias and whole-heart computational modeling, present-day system designs precludes its adoption by the broader cardiovascular research community because of their high costs. Taking advantage of recent technological advances, we developed and validated low-cost optical mapping systems for panoramic imaging using Langendorff-perfused pig hearts, a clinically-relevant model in basic research and bioengineering. By significantly lowering financial thresholds, this powerful cardiac electrophysiology imaging modality may gain wider use in research and, even, teaching laboratories, which we substantiated using the lower-cost Langendorff-perfused rabbit heart model

Construction and validation of anisotropic and orthotropic ventricular geometries for quantitative predictive cardiac electrophysiology

Reaction–diffusion computational models of cardiac electrophysiology require both dynamic excitation models that reconstruct the action potentials of myocytes as well as datasets of cardiac geometry and architecture that provide the electrical diffusion tensor D, which determines how excitation spreads through the tissue. We illustrate an experimental pipeline we have developed in our laboratories for constructing and validating such datasets. The tensor D changes with location in the myocardium, and is determined by tissue architecture. Diffusion tensor magnetic resonance imaging (DT-MRI) provides three eigenvectors ei and eigenvalues λi at each voxel throughout the tissue that can be used to reconstruct this architecture. The primary eigenvector e1 is a histologically validated measure of myocyte orientation (responsible for anisotropic propagation). The secondary and tertiary eigenvectors (e2 and e3) specify the directions of any orthotropic structure if λ2 is significantly greater than λ3—this orthotropy has been identified with sheets or cleavage planes. For simulations, the components of D are scaled in the fibre and cross-fibre directions for anisotropic simulations (or fibre, sheet and sheet normal directions for orthotropic tissues) so that simulated conduction velocities match values from optical imaging or plunge electrode experiments. The simulated pattern of propagation of action potentials in the models is partially validated by optical recordings of spatio-temporal activity on the surfaces of hearts. We also describe several techniques that enhance components of the pipeline, or that allow the pipeline to be applied to different areas of research: Q ball imaging provides evidence for multi-modal orientation distributions within a fraction of voxels, infarcts can be identified by changes in the anisotropic structure—irregularity in myocyte orientation and a decrease in fractional anisotropy, clinical imaging provides human ventricular geometry and can identify ischaemic and infarcted regions, and simulations in human geometries examine the roles of anisotropic and orthotropic architecture in the initiation of arrhythmias

Silicon nanowires as contact between the cell membrane and CMOS circuits

We describe an innovative approach to sensing bioelectric signals at high space-time resolution with low invasiveness based on growing small Silicon Nano Wires (SiNW) at low-temperature (200 °C). The resulting SiNWs are compatible with ICs, allowing on-site amplification of bioelectric signals. We report our preliminary results showing biocompatibility and neutrality of SiNWs used as seeding substrate for cells in culture. With this technology, we aim to produce a compact device allowing on-site, synched and high signal/noise recordings of a large amounts of biological signals from networks of excitable cells (e.g. neurons) or distinct subdomains of the cell membrane, thus providing super-resolved descriptions of the propagation of electric waveforms within living cells and networks

Cardiac cell modelling: observations from the heart of the cardiac physiome project

In this manuscript we review the state of cardiac cell modelling in the context of international initiatives such as the IUPS Physiome and Virtual Physiological Human Projects, which aim to integrate computational models across scales and physics. In particular we focus on the relationship between experimental data and model parameterisation across a range of model types and cellular physiological systems. Finally, in the context of parameter identification and model reuse within the Cardiac Physiome, we suggest some future priority areas for this field