Contrast imaging has significantly improved clinical diagnosis by increasing the contrast-to-tissue ratio after microbubble injection. Pulse inversion imaging is the most commonly used contrast imaging technique because it greatly increases the contrast-to-tissue ratio by extracting microbubble nonlinearities. The main purpose of our study was to propose an automatic technique providing the best contrast- to-tissue ratio throughout the experiment. For reasons of simplicity, we proposed maximizing the contrast-to-tissue ratio with an appropriate choice of the transmit frequency. The contrast-to-tissue ratio was maximized by a closed-loop system including the pulse inversion technique. An algorithm based on gradient descent provided iterative determination of the optimal transmit frequency. The optimization method converged quickly after six iterations. This optimal control method is easy to implement and it optimizes the contrast-to-tissue ratio by adaptively selecting the transmit frequency.