Unequal anisotropy ratios has even an even greater impact during electrical stimulation of the heart. Again using the finite element model, Wikswo, Roth and Sepulveda predicted the transmembrane potential distribution around a unipolar electrode passing current into a passive, two-dimensional sheet of cardiac tissue. They found that the region of depolarization under a cathode extends farther in the direction perpendicular to the fibers than parallel to the fibers, a shape that Wikswo named the dog-bone. This prediction immediately explained the virtual cathode effect found experimentally in the dog heart; they were observing the dog-bone shaped virtual cathode. Later simulations using an active, time-dependent bidomain model confirmed this conclusion. The calculation of the transmembrane potential by a unipolar electrode resulted in another prediction: regions of hyperpolarization adjacent to the cathode in the direction parallel to the myocardial fibers. Reversal of the stimulus polarization provided a mechanism for anodal stimulation of cardiac tissue. In order to test this prediction experimentally, Wikswo mastered the technique of optical mapping using voltage sensitive dyes, allowing the measurement of transmembrane potential using optical methods. With Marc Lin, Wikswo made high resolution measurements of excitation following stimulation through a unipolar electrode in a rabbit heart, and confirmed four mechanisms of electrical stimulation—cathode make, cathode break, anode make, and anode break—that had been predicted by bidomain calculations. (Cathode and anode refer to the polarity of the stimulus, and make and break indicate if the excitation occurred following the start or end of the stimulus pulse.) Later experiments using this technique led to the prediction of a new type of cardiac arrhythmia, which Wikswo named quatrefoil reentry. In the 1990s, Wikswo began developing high spatial resolution SQUID magnetometers for mapping the magnetic field, to use in both biomagnetic studies and in non-destructive testing. As is characteristic of Wikswo's work, he simultaneously developed theoretical methods to image a two-dimensional current density distribution from magnetic field measurements. In the first two decades of the 21st century, Wikswo's research has emphasized the development and application of micro- and nano-scale devices for instrumenting and controlling single cells. In 2001 he founded the Vanderbilt Institute for Integrative Biosystems Research and Education (VIIBRE) to foster and enhance interdisciplinary research in the biophysical sciences and bioengineering at Vanderbilt.