Modulation of luciferase activity using high intensity focused ultrasound in combination with bioluminescence imaging, magnetic resonance imaging and histological analysis in muscle tissue.

Abstract This study investigates the effect of high intensity focused ultrasound (HIFU) to muscle tissue transfected with a luciferase reporter gene under the control of a CMV-promoter. HIFU was applied to the transfected muscle tissue using a dual HIFU system. In a first group four different intensities (802 W/cm 2 , 1401 W/cm 2 , 2117 W/cm 2 , 3067 W/cm 2 ) of continuous HIFU were applied 20 s every other week for four times. In a second group two different intensities (802 W/cm 2 , 1401 W/cm 2 ) were applied 20 s every fourth day for 20 times. The luciferase activity was determined by bioluminescence imaging. The effect of HIFU to the muscle tissue was assessed by T1-weighted ± Gd-DTPA, T2-weighted and a diffusion-weighted STEAM sequence obtained on a 1.5-T GE-MRI scanner. Histology of the treated tissue was done at the end. In the first group the photon emission was at 3067.6 W/cm 2 1.28 × 10 7  ± 3.1 × 10 6  photon/s (5.5 ± 1.2-fold), of 2157.9 W/cm 2 8.1 ± 2.7 × 10 6  photon/s (3.2 ± 1.1-fold), of 1401.9 W/cm 2 9.3 ± 1.3 × 10 6  photon/s (4.9 ± 0.4-fold) and of 802.0 W/cm 2 8.6x ± 1.2 × 10 6  photon/s (4.5 ± 0.6-fold) compared to baseline. In the second group the photon emission was at 1401.9 W/cm 2 and 802.0 W/cm 2 14.1 ± 3.6 × 10 6  photon/s (6.1 ± 1.5-fold), respectively, 5.1 ± 4.7 × 10 6  photon/s (6.5 ± 2.0-fold). HIFU can enhance the luciferase activity controlled by a CMV-promoter.