The present invention provides imaging devices, systems, and methods of operation for acoustic-enhanced optical coherence tomography. The systems coordinate imaging devices, optical coherence tomography (OCT), and pulsed ultrasound (FUS) and or pulsed ultrasound (PUS) to enhance the contrast of images. Moreover, the systems improve in vivo diagnosis and drug release through the utilization of sonographic enhancers such as microbubbles (MBs).