Transcranial Ultrasound Enhanced Thrombolysis

When a blood clot or thrombus is formed, strands of fibrin anchor one red blood cell to another. It is these fibrin strands that form the lattice or structural matrix of the blood clot. The formation or deposition of these clots in the arterial vessels of the brain is one of the primary causes of ischemic stroke. Intravenous thrombolytic therapy (tPA/alteplase, the only approved drug for the treatment of ischemic stroke) works by converting plasminogen in the blood stream to plasmin, the active enzyme that dissolves fibrin. Clinical studies in stroke patients have demonstrated that when transcranial ultrasound energy is directed at the occlusion during conventional intravenous tPA thrombolytic therapy, there is a dramatic improvement in the ability to dissolve blood clots and restore blood flow to the ischemic regions of the brain. Ultrasound-potentiated thrombolysis or “sonolysis” is the result of ultrasound pressure waves traveling through tissue that induce a mechanical force, which in turn causes the tissues to displace or strain.

When the tissue contains fluid compartments (such as blood), the energy of the ultrasound beam is transformed into energy of fluid motion. This is called acoustic streaming. At very low pressures this streaming inside the confined areas of complex tissues such as the brain will cause a mild streaming effect. Acoustic streaming is believed to be one of the primary means of ultrasound-potentiated thrombolysis in which additional fibrin binding sites are exposed to plasmin at the site of the clot.

Sonolysis represents a fundamentally different approach to the treatment of ischemic stroke in which externally applied ultrasound energy can significantly enhance the clot lysis potential of conventional thrombolytic therapy.