Targeted drug delivery to the brain by MRI-guided focused ultrasound

The effect of focused ultrasound on the absorption of liposome-encapsulated doxorubicin in the brain was investigated. By applying focused ultrasound in the presence of microbubble ultrasound contrast agent we achieved targeted drug delivery to the brain in vivo. Tissue drug concentrations in sonicated brain corresponded with cytotoxic levels measured in various human tumors and were significantly different from those measured in unexposed contralateral control samples (p <= 0.02). In addition, increased MR signal enhancement at the focal location on contrast-enhanced TI-weighted fast spin echo images correlated with increased penetration of doxorubicin into brain tissue (r = 0.85), indicating the potential of MRI to be used as an indicator of blood-brain barrier permeability during treatment. Further investigation is required to evaluate the efficacy of this technique and to optimize its parameters for clinical application.