Sonazoid®, a second-generation contrast agent, was approved in 2007. It offers in vivo stability, and contrast effects are due to resonance without destruction, allowing real-time perfusion of brain tissues. Its use also allows a new technique, the flush-replenishment (FR) method. This method breaks the contrast agent in the scan volume by high acoustic pressure, followed by observation of replenishment, which enables repeated evaluation of perfusion imaging. We could evaluate not only the main trunks of the cerebral arteries but also the microvasculature in real time, and accumulation combined with the FR method enabled us to delineate the microvasculature. Semiquantitative evaluation of brain perfusion including vasodilatory reserve capacity using acetazolamide could also be assessed by setting regions of interest and creating a time-intensity curve. This method may be useful in the evaluation of cerebrovascular reserve capacity in patients with occlusive cerebrovascular diseases, such as in the decision-making process for bypass surgery Transcranial contrast-enhanced ultrasonography is less invasive and is feasible at the bedside. This method allows real-time evaluation of the vascular anatomy following perfusion of the brain parenchyma, even though there is a limited window of observation. We hope Sonazoid® will be approved for use in the cerebrovascular region.