Current diagnostic criteria of cardiac arrhythmias are based mostly on the electrocardiogram (ECG) recorded with body surface electrodes, which register local far-field potentials generated by all cardiac myocytes. The remote body surface placement and low number of electrodes limit the information content of ECG recordings and the details in the mechanisms of arrhythmias, the regions of electrophysiologic abnormalities, and the paths of reentry that can be identified.
Recently, high spatial resolution optical-mapping systems have been developed and used in research laboratories to investigate the mechanisms of cardiac arrhythmias in animal models under controlled conditions.1 Optical mapping uses fluorescent dyes that are sensitive to transmembrane potential or to ion concentrations as probes, optics to collect the signal-carrying fluorescence, and photon-sensing devices (eg, camera or photodiode array) to convert fluorescence to electrical signals, which are then amplified, digitized, processed, and analyzed (Fig. 10–1). The advantages of camera-based optical-mapping systems are (1) recording high spatial resolution movies of electrophysiologic activity in cardiac muscle; (2) reporting transmembrane potential, which reflects cellular electrophysiology more directly than the extracellular field potential registered by electrode-based body surface and intracardiac mapping systems; and (3) capability of recording cytosolic ion concentrations (eg, Ca2+ transient) by using ion-sensitive fluorescent dyes. The current trend in optical mapping has been moving toward dual-camera simultaneous recording of both membrane potential and Ca2+ transient within the same view field. High spatial resolution optical mapping provides details in electrophysiologic heterogeneity, focal activation, and abnormal conduction in the heart and has contributed significantly to the insight and mechanistic understanding of cardiac arrhythmias in recent years.
Optical mapping of electrical activity in cardiac muscle. Wedges of ventricular muscle are isolated and perfused via a branch of a coronary artery (left), stained with a voltage-sensitive fluorescent dye, and imaged on either a transmural or epicardial (Epi) surface with an optical-mapping system. Fluorescence movies of electrical activity are processed to obtain traces of action potentials (APs); distribution maps of activation, repolarization, and AP duration (APD); conduction sequences and velocity; and reentry pathways (right).
Most of the existing optical-mapping systems use a design that optically focuses the to-be-observed tissue surface onto the sensor array of a stationary camera, thus requiring direct view of the tissue surface. The mapping area can range from a single isolated cell to the entire heart, depending on the optics mounted in front of the camera. In this design, muscle contraction can change the relative position of tissue surface, introducing motion artifacts into the recorded electrophysiologic signal. The undesired motion artifacts are commonly eliminated by tissue immobilization with pharmacologic excitation-contraction uncoupling agents, such as cytochalasin D2,3 or blebbistatin,4 in isolated heart or tissue preparations. Alternative methods (eg, ratiometric imaging or signal processing) can also be used to extract useful data from signals containing motion artifacts obtained in beating hearts. In ...