Schneider F et al. (2006) Brain edema and intracerebral necrosis caused by transcranial low-frequency 20-kHz ultrasound: a safety study in rats. Stroke 37: 1301–1306

The effectiveness of thrombolysis in acute stroke treatment can be enhanced by transcranial ultrasound, which has been shown to improve recanalization rates. Ultrasound in the low-frequency (kHz) range may be more effective than high-frequency ultrasound, because low-frequency sound penetrates bone and tissue more effectively. Concerns have, however, been raised about the safety of low-frequency transcranial ultrasound; insonation at 300 kHz was associated with increased rates of cerebral hemorrhage in a recent trial.

Researchers in Germany have assessed the safety of 20 kHz transcranial ultrasound in rats, at power outputs ranging from 0 W/cm2 to 2.6 W/cm2. Treatment at an output ≥0.5 W/cm2 was associated with cytotoxic and vasogenic edema, as measured by MRI. Ultrasound at 2.6 W/cm2 caused intracerebral necrosis and loss of neurons. Tympanic temperature measurements and the histological necrosis pattern suggest that the damage was not caused by thermal effects, although the possibility of such effects cannot be completely excluded. No damage was detected after treatment at an output of 0.2 W/cm2, an intensity that has been shown to be effective in in vitro thrombolysis experiments.

The study shows that low-frequency ultrasound can be harmful to healthy brain tissue, and the authors caution that damaged tissue might be more vulnerable to adverse effects of treatment. Neurological damage cased by the treatment was dose-dependent, however, and the authors state that low-intensity treatment (0.2 W/cm2) should be further evaluated in animal models.