Magnetic resonance imaging analysis predicts nanoparticle concentration delivered to the brain parenchyma

Abstract

Ultrasound in combination with the introduction of microbubbles into the vasculature effectively opens the blood brain barrier (BBB) to allow the passage of therapeutic agents. Increased permeability of the BBB is typically demonstrated with small-molecule agents (e.g., 1-nm gadolinium salts). Permeability to small-molecule agents, however, cannot reliably predict the transfer of remarkably larger molecules (e.g., monoclonal antibodies) required by numerous therapies. To overcome this issue, we developed a magnetic resonance imaging analysis based on the ΔR₂* physical parameter that can be measured intraoperatively for efficient real-time treatment management. We demonstrate successful correlations between ΔR₂* values and parenchymal concentrations of 3 differently sized (18 nm–44 nm) populations of liposomes in a rat model. Reaching an appropriate ΔR₂* value during treatment can reflect the effective delivery of large therapeutic agents. This prediction power enables the achievement of desirable parenchymal drug concentrations, which is paramount to obtaining effective therapeutic outcomes.

ΔR₂* values from MRI analysis correlate with concentrations of liposomes in the size range of 18–44 nm in a rat model.