Thermal threshold for localized Blood-Brain-Barrier disruption

Abstract

Abstract The Blood-Brain Barrier is the gatekeeper of the CNS. It effectively shields the brain from blood-borne harm but simultaneously represents a significant challenge for treating neurological diseases. Altering its permeability enables increasing the local drug concentration and thereby improving the therapeutic effect. Although permeability increase is achieved by raised tissue temperature, the determination of the thermal dosage suffers from imprecise thermometry during hyperthermia application. Knowledge of the thermal dosage is crucial for improving hyperthermia related interventions of the CNS. Here we show an approach to determine the thermal threshold for localized Blood-Brain Barrier disruption estimated by MR thermometry. Using an IR laser (λ = 1470nm) we showed that highly localized Blood-Brain-Barrier opening can be achieved with mild to moderate hyperthermia. Non-invasive MR thermometry has been used to determine the temperature at the heating site. Blood-Brain Barrier opening has been monitored by DCE-MRI in vivo and post mortem via Evan’s Blue extravasation. The Blood-Brain-Barrier permeability can be altered locally with minimal thermal dosages. Thus mild hyperthermia represents a promising approach to making the brain accessible for therapeutic interventions.