Optimization of the contrast-to-noise ratio (CNR) is described for microcirculation magnetic resonance (MR) imaging techniques based on flow-compensated/flow-dephased sequences, both with and without even-echo rephasing. The authors present the most advantageous manner of applying flow-dephased gradients, such that dephasing is maximal while diffusion losses are minimal. The theoretical considerations include phase, diffusion, echo time, and bandwidth in the determination of the optimal parameters for microcirculation imaging. Studies in phantoms consisting of stationary and flowing copper sulfate in Sephadex columns demonstrate the validity of the calculations. Optimized in vivo images of a rat stroke model demonstrate the potential of the flow-compensated/flow-dephased technique and the importance of optimizing CNR.