Ultrasonic transcranial brain therapy: first in vivo clinical investigation on 22 sheep using adaptive focusing

A high power prototype dedicated to trans-skull therapy has been tested in vivo on 22 sheep. An echographic array was inserted in the therapeutic array in order to perform real time monitoring of the treatment. In one set of experiments, 10 sheep were treated and sacrificed immediately after treatment. On half of these animals, a complete craniotomy was performed in order to get reference models. On the other animals, a minimally invasive surgery was performed to insert a hydrophone at the target inside the brain. A time reversal experiment was then conducted through the skull with the therapeutic array to treat the targeted point. Hyperechogeneicity was clearly visible on the sonographic system for all animals with a complete craniotomy. Without craniotomy, the ultrasonic image was distorted, but the hydrophone location was visible, allowing a rough positioning of the therapeutic device. More accurate positioning was then obtained by cross correlating the signals received by the elements in the therapeutic device. Trans-skull treatment could be achieved with phase aberration correction and electronic beam steering, not only at the geometrical focus, but also 2 cm away in all directions. In a second series of experiments, 12 animals were divided into three groups and sacrificed respectively one, two and three weeks after treatment. The evolution of the targeted region was checked each week using magnetic resonance imaging and CT scans. Finally, histological examination was performed to confirm tissue damage. These in vivo experiments highlight the strong potential of high power transcranial time reversal technology.