In vitro evaluation of dual mode ultrasonic thrombolysis method for transcranial application with an occlusive...

A recent clinical trial of transcranial low-frequency ultrasound-mediated tPA thrombolysis (LFUT) showed cerebral hemorrhages associated with high spatial peak pulse average intensity (I(SPPA)), wide beam and long pulse duration. We developed an alternative approach to LFUT wherein diagnostic power M-mode Doppler (PMD) ultrasound is combined with LFUT, with a goal of increased safety. The effectiveness of such a dual mode ultrasonic thrombolysis (DMUT) was explored in vitro. The DMUT system emitted PMD (2 MHz) and LFUT (550 kHz) beams in alternating fashion from a small 12 mm diameter probe. The LFUT had a low I(SPPA) (2 W/cm(2)) and a short pulse duration (55 micros). Occlusive clots made in plastic tips from bovine plasma and thrombin were placed in flow models pressurized to 800 mH(2)O, with 600 IU/mL monteplase injected upstream. Recanalization times were then compared among three groups: the control (monteplase alone), PMD (monteplase + PMD) and DMUT (monteplase + PMD + LFUT). The capability of the DMUT device to monitor recanalization was demonstrated by observing with Doppler the degree of flow of a blood-mimicking fluid in the vicinity of the clot. Recanalization times were 37.9 +/- 22.9, 38.9 +/- 12.4 and 18.5 +/- 8.0 min, respectively, for the control, PMD and DMUT. There were significant differences between DMUT and the control (p = 0.0004) and between DMUT and PMD (p = 0.0004). Recanalization flows were clearly detected. It is anticipated that this DMUT method presents a safer and more efficient approach than normal LFUT.