Absence of biological damage from prolonged exposure to intravascular ultrasound: A swine model

Ultrasound (US) has been used in IMS II (intravascular US) and CLOTBUST (transcranial US) clinical trials for thrombolysis. During the treatment, in addition to the targeted thrombus, other biological components, such as blood and vessel walls are subjected to long durations of US exposure. In this study we explored evidence of biological damage due to mechanical forces or thermal effects of US exposure at the frequency, intensity and duration employed for thrombolysis treatment. Biological effects were investigated by exposing swine ilio-femoral arteries bilaterally to an intravascular US generating catheter and a conventional catheter. A total of 12 animals each underwent 8 h of exposure to intravascular pulsed US with a frequency of 2.2 MHz and spatial peak time average intensity (ISPTA) of 6 W/cm2 per transducer (a total of six transducers per catheter) while the ultrasonic device surface temperature was maintained at ⩽43 °C. The animals were euthanized either 24 ± 3 h or 28 ± 3 days post treatment. A range of physiological and hematological parameters were evaluated pre-, post-, and during US exposure. The vascular diameter was determined pre- and post-US exposure using angiograms. Following euthanasia, each animal underwent a gross pathological examination, and the treated vessels and an unexposed vessel were excised for comparative histopathological evaluation. No evidence of biological damage was found at the end of 8 h exposure to intravascular US.