Permeability Dependence Study of the Focused Ultrasound-Induced Blood-Brain Barrier Opening at Distinct Pressures and Microbubble Diameters Using DCE-MRI

Blood-brain barrier opening using focused ultrasound and microbubbles has been experimentally established as a non-invasive and localized brain drug delivery technique. In this study, the permeability of the opening is assessed in the murine hippocampus after the application of focused ultrasound at three different acoustic pressures and microbubble sizes. Using dynamic contrast-enhanced MRI, the transfer rates were estimated, yielding permeability maps and quantitative K-trans values for a predefined region of interest. The volume of blood-brain barrier opening according to the K-trans maps was proportional to both the pressure and the microbubble diameter. A K-trans plateau of similar to 0.05 min(-1) was reached at higher pressures (0.45 and 0.60 MPa) for the larger sized bubbles (45 and 6-8 mu m), which was on the same order as the Ktrans of the epicranial muscle (no barrier). Smaller bubbles (1-2 mu m) yielded significantly lower permeability values. A small percentage (7.5%) of mice showed signs of damage under histological examination, but no correlation with permeability was established. The assessment of the blood-brain barrier permeability properties and their dependence on both the pressure and the microbubble diameter suggests that K-trans maps may constitute an in vivo tool for the quantification of the efficacy of the focused ultrasound-induced blood-brain barrier opening. Magn Reson Med 66:821-830, 2011. (C) 2011 WileyLiss, Inc.