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For a limited range of exposure parameters, pulsed high intensity focused ultrasound (HIFU) has been shown to increase the delivery of certain systemically administered macromolecular diagnostic and therapeutic agents in mice. The mechanism for the enhanced delivery has not been demonstrated definitively and, in principle, can include thermal, cavitational, and non-cavitation mechanical effects. The sonicated tissue has no damage on histology. As a step towards clinical translation, the safety of this technique needs to be assessed in a clinically relevant manner. In this study, the safety of pulsed HIFU is evaluated with near real-time phase shift magnetic resonance (MR) thermometry and anatomic MR imaging using rabbits as subjects. MR guidance enables pulsed HIFU enhanced delivery to be implemented safely from a thermal standpoint. Although the effects of pulsed HIFU are not seen on anatomic MR images, they may be detected on MR sequences sensitive to permeability, diffusion, and elasticity. Such work that may optimize pulsed HIFU enhanced delivery is in progress. © 2007 American Institute of Physics [ABSTRACT FROM AUTHOR]

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. © 2006 American Institute of Physics [ABSTRACT FROM AUTHOR]