Pulsed ultrasound, when used as an adjuvant to recombinant tissue plasminogen activator (rt-PA), has been shown to enhance thrombolysis in the laboratory as well as in clinical trials for the treatment of ischemic stroke. The exact mechanism of this enhancement has not yet been elucidated. In this work, stable and inertial cavitation (SC and IC) are investigated as possible mechanisms for this enhancement. A passive cavitation detection scheme was utilized to measure cavitation thresholds at 120 kHz (80% duty cycle, 1667 Hz pulse repetition frequency) for four host fluid and sample combinations: plasma, plasma with rt-PA, plasma with clot and plasma with clot and rt-PA. Following cavitation threshold determination, clots were exposed to pulsed ultrasound for 30 min in vitro using three separate ultrasound treatment regimes: (1) no cavitation (0.15 MPa), (2) SC alone (0.24 MPa) or (3) SC + IC combined (0.36 MPa) in the presence of rt-PA. Percent clot mass loss after each treatment was used to determine thrombolysis efficacy. The highest percent mass loss was observed in the stable cavitation regime (26%), followed by the combined stable and inertial cavitation regime (20.7%). Interestingly, the percent mass loss in clots exposed to ultrasound without cavitation (13.7%) was not statistically significantly different from rt-PA alone (13%) [p > 0.05]. Significant enhancement of thrombolysis correlates with presence of cavitation and stable cavitation appears to play a more important role in the enhancement of thrombolysis.

Ultrasound has been previously shown to act synergistically with a thrombolytic agent, such as recombinant tissue plasminogen activator (rt-PA) to accelerate thrombolysis. In this in vitro study, a commercial contrast agent, Definity ® , was used to promote and sustain the nucleation of cavitation during pulsed ultrasound exposure at 120 kHz. Ultraharmonic signals, broadband emissions, and harmonics of the fundamental were measured acoustically by using a focused hydrophone as a passive cavitation detector and utilized to quantify the level of cavitation activity. Human whole blood clots suspended in human plasma were exposed to a combination of rt-PA, Definity ® , and ultrasound at a range of ultrasound peak-to-peak pressure amplitudes, which were selected to expose clots to various degrees of cavitation activity. Thrombolytic efficacy was determined by measuring clot mass loss before and after the treatment and correlated with the degree of cavitation activity. The penetration depth of rt-PA and plasminogen was also evaluated in the presence of cavitating microbubbles using a dual antibody fluorescence imaging technique. The largest mass loss (26.2%) was observed for clots treated with 120 kHz ultrasound (0.32 MPa peak-to-peak pressure amplitude), rt-PA and stable cavitation nucleated by Definity ® . A significant correlation was observed between mass loss and ultraharmonic signals (r=0.8549, p<0.0001, n=24). The largest mean penetration depth of rt-PA (222 µm) and plasminogen (241 µm) was observed in the presence of stable cavitation activity. Stable cavitation activity plays an important role in enhancement of thrombolysis and can be monitored to evaluate the efficacy of thrombolytic treatment.

A method is presented for passive imaging of cavitational acoustic emissions using an ultrasound array, with potential application in real-time monitoring of ultrasound ablation. To create such images, microbubble emissions were passively sensed by an imaging array and dynamically focused at multiple depths. In this paper, an analytic expression for a passive image is obtained by solving the Rayleigh-Sommerfield integral, under the Fresnel approximation, and passive images were simulated. A 192-element array was used to create passive images, in real time, from 520-kHz ultrasound scattered by a 1-mm steel wire. Azimuthal positions of this target were accurately estimated from the passive images. Next, stable and inertial cavitation was passively imaged in saline solution sonicated at 520 kHz. Bubble clusters formed in the saline samples were consistently located on both passive images and B-scans. Passive images were also created using broadband emissions from bovine liver sonicated at 2.2 MHz. Agreement was found between the images and source beam shape, indicating an ability to map therapeutic ultrasound beams in situ. The relation between these broadband emissions, sonication amplitude, and exposure conditions are discussed.

Since their first deployment in November 1978, the Total Ozone Mapping Spectrometer (TOMS) instruments have provided a robust and near-continuous record of sulphur dioxide (SO2) and ash emissions from active volcanoes worldwide. Data from the four TOMS satellites that have flown to date have been analysed with the latest SO2/ash algorithms and incorporated into a TOMS volcanic emissions database that presently covers 22 years of SO2 and ash emissions. The 1978-2001 record comprises 102 eruptions from 61 volcanoes, resulting in 784 days of volcanic cloud observations. Regular eruptions of Nyamuragira (DR Congo) since 1978, accompanied by copious SO2 production, have contributed material on approximately 30% of the days on which clouds were observed. The latest SO2 retrieval results from Earth Probe (EP) TOMS document a period (1996)(1997)(1998)(1999)(2000)(2001) lacking large explosive eruptions, and also dominated by SO2 emission from four eruptions of Nyamuragira. EP TOMS has detected the SO2 and ash produced during 23 eruptions from 15 volcanoes to date, with volcanic clouds observed on 158 days. The EP TOMS instrument began to degrade in 2001, but has now stabilized, although its planned successor (QuikTOMS) recently failed to achieve orbit. New SO2 algorithms are currently being developed for the Ozone Monitoring Instrument, which will continue the TOMS record of UV remote sensing of volcanic emissions from 2004 onwards.Volcanic eruptions vary greatly in style, duration and vigour, but all sub-aerial eruptions involve the emplacement of material, typically including water vapour and other gases, silicate ash, and aerosols, into the atmosphere above the eruption vent. The detection, analysis and tracking of the ensuing volcanic clouds and plumes is crucial for effective mitigation of volcanic hazards such as airborne ash (e.g. Casadevall 1994), understanding of magmatic degassing processes (e.g. Scaillet et al. 1998;Wallace 2001) and quantify-