Pharmacokinetic changes induced by focused ultrasound in glioma-bearing rats using dynamic contrast-enhanced MRI measurement

Abstract

It has been shown that focused ultrasound (FUS) can be effectively used for brain tumor therapy, and as a noninvasive, targeted drug delivery technique combined with microbubbles. In this study, magnetic resonance imaging (MRI) was used to measure the kinetics of Gadolinium diethylenetriamine Penta acetic acid (Gd-DTPA) in glioma-bearing rats. Ten glioma-bearing rats (9-12 weeks, 290-340 g weight) were used in the study. After the use of dynamic contrast enhancement (DCE)-MRI, the spatial permeability of FUS-induced blood-brain barrier disruption (BBB-D) was evaluated, and the kinetic parameters by the general kinetic model (GKM) were calculated. The results show that mean trans K of the contralateral tumor was significantly lower than the mean trans K of sonicated tumor. Moreover, the transfer constant trans K in ultrasound tumors was closely related to tissue extravasation (R = 0.95), suggesting that DCE-MRI can determine drug accumulation in the brain. Except for a few small red blood cell extravasations, there was no macroscopic damage according to the histologic analysis. The study showed that the DCE-MRI can be a valuable tool in quantifying BBB permeability in tumors and monitor the kinetics of FUS-induced BBB-D processes.