Characterization of Pulsed High Intensity Focused Ultrasound for Enhanced Drug and Gene Delivery

Within a certain range of parameters, pulsed high intensity focused ultrasound (HIFU) has been shown to increase the delivery of systemically administered drugs and plasmid DNA in tumors in mice. The sonicated tissue is not damaged by light microscopy. The mechanism for the enhanced delivery has not been shown conclusively and can include thermal, cavitational, and non-cavitation mechanical effects. In order to assess the effects of pulsed HIFU in a manner that allows for clinical translation, pulsed HIFU is performed within a magnetic resonance (MR) scanner. In this work, the thermal effect is evaluated with phase-shift MR thermometry in ex vivo chicken muscle. The thermal effect is small at the most common exposure parameters. In the future, non-thermal effects like permeability, diffusion, and elasticity changes will be evaluated with dynamic contrast enhanced MRI, diffusion-weighted MRI, and MR elastography. If changes in permeability, diffusion, and shear modulus are associated with pulsed HIFU enhanced delivery, then these parameters can be used as markers for optimization of pulsed HIFU enhanced delivery.