Noninvasive, Transient and Selective Blood-Brain Barrier Opening in Non-Human Primates In Vivo

The blood-brain barrier (BBB) is a specialized vascular system that impedes entry of all large and the vast majority of small molecules including the most potent central nervous system (CNS) disease therapeutic agents from entering from the lumen into the brain parenchyma. Microbubble-enhanced, focused ultrasound (ME-FUS) has been previously shown to disrupt noninvasively, selectively, and transiently the BBB in small animals in vivo. For the first time, the feasibility of transcranial ME-FUS BBB opening in non-human primates is demonstrated with subsequent BBB recovery. Sonications were combined with two different types of microbubbles (customized 4–5 µm and Definity®). 3T MRI was used to confirm the BBB disruption and to assess brain damage

Characterization of individual submicron perfluorocarbon gas bubbles by ultrasonic backscatter

Measurements were undertaken to determine the unknown microbubble-size distribution of a dodecafluoropentane (DDFP) emulsion consisting of 1012 droplets/ml in surfactant-stabilized water. The acoustic backscatter of 2-microsecond-duration tonebursts of 30-MHz focused ultrasound was measured from the emulsion as it moved in a coaxial flow. Calibration for the system was accomplished using 3-μm-radius polystyrene spheres, using a linear scattering model and literature values for polystyrene. Applying viscous linear scattering theory to the backscatter data from individual DDFP bubbles allowed inversion of the radius–backscatter relation. A mean microbubble radius of 130 nm was inferred for the DDFP population