Measuring surface potential components necessary for transmembrane current computation using microfabricated arrays

Abstract

This study was designed to test the feasibility of using microfabricated electrodes to record surface potentials with sufficiently fine spatial resolution to measure the potential gradients necessary for improved computation of transmembrane current density. To assess that feasibility, we recorded unipolar electrograms from perfused rabbit right ventricular free wall epicardium (n = 6) using electrode arrays that included 25-microm sensors fabricated onto a flexible substrate with 75-microm interelectrode spacing. Electrode spacing was therefore on the size scale of an individual myocyte. Signal conditioning adjacent to the sensors to control lead noise was achieved by routing traces from the electrodes to the back side of the substrate where buffer amplifiers were located. For comparison, recordings were also made using arrays built from chloridized silver wire electrodes of either 50-microm (fine wire) or 250-microm (coarse wire) diameters. Electrode separations were necessarily wider than with microfabricated arrays. Comparable signal-to-noise ratios (SNRs) of 21.2 +/- 2.2, 32.5 +/- 4.1, and 22.9 +/- 0.7 for electrograms recorded using microfabricated sensors (n = 78), fine wires (n = 78), and coarse wires (n = 78), respectively, were found. High SNRs were maintained in bipolar electrograms assembled using spatial combinations of the unipolar electrograms necessary for the potential gradient measurements and in second-difference electrograms assembled using spatial combinations of the bipolar electrograms necessary for surface Laplacian (SL) measurements. Simulations incorporating a bidomain representation of tissue structure and a two-dimensional network of guinea pig myocytes prescribed following the Luo and Rudy dynamic membrane equations were completed using 12.5-microm spatial resolution to assess contributions of electrode spacing to the potential gradient and SL measurements. In those simulations, increases in electrode separation from 12.5 to 75.0, 237.5, and 875.0 microm, which were separations comparable to the finest available with our microfabricated, fine wire, and coarse wire arrays, led to 10%, 42%, and 81% reductions in maximum potential gradients and 33%, 76%, and 96% reductions in peak-to-peak SLs. Maintenance of comparable SNRs for source electrograms was therefore important because microfabrication provides a highly attractive methods to achieve spatial resolutions necessary for improved computation of transmembrane current density.

Cardiac microimpedance measurement in two-dimensional models using multisite interstitial stimulation

“…Use of selected electrodes for stimulation and recording would allow implementation of our method for microimpedance measurements. In myocardial tissue, we envision positioning of microfabricated arrays onto tissue following the approach we recently described (58). In that report, we used microfabricated sensors with spacing on the size scale of individual myocytes that were packaged in flexible assemblies that included adjacent signal conditioning to facilitate highquality interstitial potential difference recordings.…”

Design, characterization and testing of a thin-film microelectrode array and signal conditioning microchip for high spatial resolution surface laplacian measurement.

“…This may further improve the SL measurement technique, defined as the second spatial derivative of the field potential on the heart surface, which was reported to be superior to the unipolar electrogram (potential difference between the exploring electrode to the reference electrode) for the detection of local activation during ventricular fibrillation [19,20]. The in-vivo transmembrance current density (1m) calculated using the Surface Laplacian technique may be improved as suggested in previous simulation studies [21].…”

“…It has been reported that the Surface Laplacian electrogram is superior to the unipolar electrogram in detecting local activation time during VF [20,22,23]. Also, SL morphologies can determine the activation block and wavefront initiation, and improve the transmembrance current density calculation [23].…”

“…Specifically, a single Surface Laplacian electrogram requires that the electrodes be as small as possible (~25 microns in diameter), close together (~75 microns apart) [24], and recorded at a higher sampling rate than unipolar electrode recordings (16 kHz) [22]. In addition, the current conventional technology being implemented utilizes long wires to transmit the signal from the electrodes to the first stage amplifier which results in a marked decrease in the SNR.…”

“…For a configuration consisting of 5 electrodes as shown in Figure 2.6, the components of the SL can be represented by: Some investigators have suggested that the Surface Laplacian is superior to unipolar electrograms in detecting local cardiac tissue activation since the SL can accurately determine the local activation time, activation block and wavefront initiation [57]. Furthermore, because the SL is proportional to the transmembrane current density, the calculated SL allows for the quantification of transmembrane current flow [23]. In some complex ventricular activation pattern cases, as occur in VT, determination of the local activation time is often not straightforward due to the concurring repolarization waves and potential deflections of remote activity generated by atria.…”