Conclusions And Future Directions

Ultrasound-enhanced thrombolysis can be further amplified by adding gaseous microbubbles (106-110 ) . Microbubbles, safe ultrasound contrast agents, are about micron-sized galactose or lipid shells that, when exposed to ultrasound, expand and produce stable cavitation with stronger reflected echoes, which are used to generate ultrasound images with better resolution. At the same time, microbubbles agitate fluid where they are released by ultrasound, thereby providing a method for drug delivery and mechanical "grinding" of a thrombus. In fact, microbubbles have their own ability to lyse thrombi without a lytic drug (109).

Several studies have been reported with different types of commercially available micro-bubbles (110). The largest study to date compared the CLOTBUST Target arm to the CLOTBUST Target insonation protocol combined with Levovist air microbubbles (Schering AG) (108 ) . Investigators demonstrated that, at 2 hours after rtPA bolus, the rtPA + TCD+Levovist group achieved a 55% sustained recanalization rate, compared to 38% in the rtPA+TCD group of the CLOTBUST trial. An international, multicentered study of a new and more stable C3F8 micro-bubble (MRX 815 platform, ImaRx, Tucson, Arizona, USA) is under way (111).

Microbubbles offer a mechanical method to amplify stroke therapies and can be developed as a new kind of device to augment brain perfusion and drug and nutrient delivery within the existing (and at an extended) time window. Development of ultrasound- and microbubble-assisted stroke therapies requires experienced sonographers to find intracranial thrombi and expose their surfaces to residual flow in order to lodge more rtPA and agitate stagnant flow. In that most emergency centers have few personnel with these skills, future studies will focus on the development of an operator-independent ultrasound device that can be used by existing medical personnel regardless of their experience in diagnostic ultrasound (111).

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