An ultrasound imaging system transmits a broad beam of ultrasound into tissues that are perfused with blood containing microbubbles. The ultrasound has an intensity that is sufficient to destroy the microbubbles in the tissues. A plurality of ultrasound imaging beams are then transmitted into the tissues over a sufficient period to allow the tissues to re-perfuse, and reflections from the transmitted imaging beams are processed to provide a perfusion image. The transmitted microbubble-destroying ultrasound may be in the form of a single beam or a plurality of beams that insonify a substantially larger area than the area insonified by the transmitted imaging beams. As a result, the microbubbles are all destroyed at substantially the same time, and the imaging ultrasound is transmitted only into regions of the tissues from which ultrasound reflections will be received.