Therapeutic TCD for Patients with Acute Cerebral Ischemia

Ultrasound in frequencies commonly used in routine clinical practice potentiates thrombolytic medications through improved drug delivery, modification of fibrin structure and enhanced drug binding. A study of thrombolysis monitoring – the continuous monitoring of MCA waveforms representing residual flow with 2 MHz pulsed wave transcranial Doppler (TCD) during provision of tPA in the setting of acute cerebral ischemia – demonstrated a rate of dramatic and early recovery much higher than those seen in the pivotal trial that established thrombolysis for acute ischemic stroke as the worldwide standard of care for stroke. This led to a phase II trial of Ultrasound Enhanced Thrombolysis – or sonothrombolysis – which established patients undergoing continuous 2 MHz pulsed wave TCD during tPA infusion were more likely to completely recanalize or show dramatic improvement within 2 hours of tPA infusion as compared to controls and a non-significant trend toward better chance of recovery to mRS of 0–1 at 3 months. Additional phase II data suggest sonothrombolysis can be enhanced with adjunctive microbubble injection. While the role of sonothrombolysis in the era of effective mechanical thrombectomy for recanalization of large vessel occlusion is being actively researched in a drip-and-ship paradigm, monitoring of reperfusion treatments remains useful in patients with persisting occlusions, re-occlusions or hyperemic reperfusion. The technique for sonothrombolysis and thrombolysis monitoring is safe, noninvasive and described in detail in this chapter.