title: Pharmacokinetic changes induced by focused ultrasound in glioma-bearing rats as measured by dynamic contrast-enhanced MRI.
abstract: 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 Ktrans 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 Ktrans 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.
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan; Biophotonics and Molecular Imaging Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Feng-Yi
authors.initials: FY
authors.lastname: Yang
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chia-En
authors.initials: CE
authors.lastname: Ko
authors.affiliation: Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Sheng-Yao
authors.initials: SY
authors.lastname: Huang
authors.affiliation: Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan.
authors.forename: I-Fang
authors.initials: IF
authors.lastname: Chung
authors.affiliation: Division of Medical Engineering Research, National Health Research Institutes, Miaoli County, Taiwan.
authors.forename: Gin-Shin
authors.initials: GS
authors.lastname: Chen
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging / Q000473:pathology; D001932:Brain Neoplasms / Q000000981:diagnostic imaging*; D003287:Contrast Media / Q000493:pharmacokinetics*; D005070:Evans Blue / Q000378:metabolism; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000000981:diagnostic imaging; D019786:Gadolinium DTPA / Q000493:pharmacokinetics; D005910:Glioma / Q000000981:diagnostic imaging* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D011916:Rats, Inbred F344; D013010:Sonication; D014465:Ultrasonics; D014463:Ultrasonography
chemical_list: D003287:Contrast Media; D005070:Evans Blue; D019786:Gadolinium DTPA