Open AccessPharmacokinetic Changes Induced by Focused Ultrasound in Glioma-Bearing Rats as Measured by Dynamic Contrast-Enhanced MRI
Author(s) -
Feng-Yi Yang,
Chia-En Ko,
Sheng-Yao Huang,
IFang Chung,
Gin-Shin Chen
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0092910
Subject(s) - glioma , extravasation , magnetic resonance imaging , microbubbles , ultrasound , dynamic contrast enhanced mri , gadolinium , sonication , permeability (electromagnetism) , pharmacokinetics , vascular permeability , blood–brain barrier , contrast enhanced ultrasound , medicine , chemistry , nuclear magnetic resonance , pathology , nuclear medicine , cancer research , pharmacology , radiology , central nervous system , biochemistry , physics , organic chemistry , membrane
Focused ultrasound (FUS) combined with microbubbles has been shown to be a noninvasive and targeted drug delivery technique for brain tumor treatment. The purpose of this study was to measure the kinetics of Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) in glioma-bearing rats in the presence of FUS-induced blood-brain barrier disruption (BBB-D) by magnetic resonance imaging (MRI). A total of ten glioma-bearing rats (9–12 weeks, 290–340 g) were used in this study. Using dynamic contrast-enhanced (DCE)-MRI, the spatial permeability of FUS-induced BBB-D was evaluated and the kinetic parameters were calculated by a general kinetic model (GKM). The results demonstrate that the mean K trans of the sonicated tumor (0.128±0.019 at 20 min and 0.103±0.023 at 24 h after sonication, respectively) was significantly higher than (2.46-fold at 20 min and 1.78-fold at 24 h) that of the contralateral (non-sonicated) tumor (0.052±0.019 at 20 min and 0.058±0.012 at 24 h after sonication, respectively). In addition, the transfer constant K trans in the sonicated tumor correlated strongly with tissue EB extravasation (R = 0.95), which suggests that DCE-MRI may reflect drug accumulation in the brain. Histological observations showed no macroscopic damage except for a few small erythrocyte extravasations. The current study demonstrates that DCE-MRI can monitor the dynamics of the FUS-induced BBB-D process and constitutes a useful tool for quantifying BBB permeability in tumors.