Ultrasound-induced thermal elevation in clotted blood and cranial bone

Ultrasound thermal effects have been hypothesized to contribute to ultrasound-assisted thrombolysis. To explore the thermal mechanism of ultrasound-enhanced thrombolysis with recombinant tissue plasminogen activator (rt-PA) for the treatment of ischemic stroke, a detailed investigation is needed of the heating produced in skull, brain and blood clots. A theoretical model is developed to provide an estimate for the worst-case scenario of the temperature increase in blood clots and on the surface of cranial bone exposed to 0.12- to 3.5-MHz ultrasound. Thermal elevation was also assessed experimentally in human temporal bone, human clots and porcine clots exposed to 0.12 to 3.5-MHz pulsed ultrasound in vitro with a peak-to-peak pressure of 0.25 MPa and 80% duty cycle. Blood clots exposed to 0.12-MHz pulsed ultrasound exhibited a small temperature increase (0.25 degrees C) and bone exposed to 1.0-MHz pulsed ultrasound exhibited the highest temperature increase (1.0 degrees C). These experimental results were compared with the predicted temperature elevations.