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

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 min diameter probe. The LFUT had a low I-SPPA (2 W/cm(2)) and a short pulse duration (55 mu s). 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.