Activation of transgene expression in skeletal muscle by focused ultrasound

To correlate thermal dose from focused ultrasound (FUS) with gene expression and tissue injury, a temperature plateau strategy was employed. Plasmids encoding luciferase gene under the control of hsp70B promoter were transfected into the right gastrocnemius muscle in a rat via electroporation. One day after transfection, hind limbs were treated with 3.3-MHz focused ultrasound, using one of four different temperature plateaus with spatial-peak time-average focal temperatures (T(SPTA)) of 46 degrees C, 48 degrees C, 51 degrees C and 62 degrees C. The treatment duration at the plateau temperature was varied from 0 to 30s. Gene expression was analyzed in vivo one day following FUS treatment, and HE staining was employed to assess tissue injury. Gene activation and tissue damage correlated closely with thermal dose. The highest level of gene activation was induced by FUS at T(SPTA)=51 degrees C for 20s, which was found to be statistically equivalent to that produced by water-bath hyperthermia.