A-H LiaoH-L LiuC-H SuM-Y HuaH-W YangY-T WengP-H HsuS-M HuangS-Y WuH-El WangT-C YenP-C LiHAO-LI LIUA-H LiaoH-L LiuC-H SuM-Y HuaH-W YangY-T WengP-H HsuS-M HuangS-Y WuH-El WangT-C YenP-C LiPAI-CHI LI2020-10-072020-10-072012319155https://scholars.lib.ntu.edu.tw/handle/123456789/516655This paper presents new albumin-shelled Gd-DTPA microbubbles (MBs) that can concurrently serve as a dual-modality contrast agent for ultrasound (US) imaging and magnetic resonance (MR) imaging to assist bloodbrain barrier (BBB) opening and detect intracerebral hemorrhage (ICH) during focused ultrasound brain drug delivery. Perfluorocarbon-filled albumin-(Gd-DTPA) MBs were prepared with a mean diameter of 2320 nm and concentration of 2.903×10 9MBs ml -1using albumin-(Gd-DTPA) and by sonication with perfluorocarbon (C 3F 8) gas. The albumin-(Gd-DTPA) MBs were then centrifuged and the procedure was repeated until the free Gd 3+ions were eliminated (which were detected by the xylenol orange sodium salt solution). The albumin-(Gd-DTPA) MBs were also characterized and evaluated both in vitro and in vivo by US and MR imaging. Focused US was used with the albumin-(Gd-DTPA) MBs to induce disruption of the BBB in 18 rats. BBB disruption was confirmed with contrast-enhanced T 1-weighted turbo-spin-echo sequence MR imaging. Heavy T 2*-weighted 3D fast low-angle shot sequence MR imaging was used to detect ICH. In vitro US imaging experiments showed that albumin-(Gd-DTPA) MBs can significantly enhance the US contrast in T 1-, T 2- and T 2*-weighted MR images. The r 1and r 2relaxivities for Gd-DTPA were 7.69 and 21.35 s -1mM -1, respectively, indicating that the MBs represent a positive contrast agent in T 1-weighted images. In vivo MR imaging experiments on 18 rats showed that focused US combined with albumin-(Gd-DTPA) MBs can be used to both induce disruption of the BBB and detect ICH. To compare the signal intensity change between pure BBB opening and BBB opening accompanying ICH, albumin-(Gd-DTPA) MB imaging can provide a ratio of 5.14 with significant difference (p = 0.026), whereas Gd-DTPA imaging only provides a ratio of 2.13 and without significant difference (p = 0.108). The results indicate that albumin-(Gd-DTPA) MBs have potential as a US/MR dual-modality contrast agent for BBB opening and differentiating focused-US-induced BBB opening from ICH, and can monitor the focused ultrasound brain drug delivery process. ? 2012 Institute of Physics and Engineering in Medicine.[SDGs]SDG3Blood-brain barrier; Contrast agent; Contrast-enhanced; Drug delivery process; Dual-modality; Focused ultrasound; Gd-DTPA; Imaging experiments; In-vitro; In-vivo; Mean diameter; Microbubbles; MR images; MR imaging; Perfluorocarbons; Signal intensities; Sodium salt; Ultrasound imaging; Xylenol Orange; Drug delivery; Imaging systems; Magnetic resonance; Magnetic resonance imaging; Paramagnetism; Rats; Ultrasonic imaging; Ultrasonics; Gadolinium; albuminoid; contrast medium; diagnostic agent; fluorocarbon; gadolinium pentetate; microsphere; animal; article; blood brain barrier; chemistry; drug delivery system; echography; feasibility study; human; magnetism; male; metabolism; methodology; nuclear magnetic resonance imaging; permeability; rat; Sprague Dawley rat; Albumins; Animals; Blood-Brain Barrier; Contrast Media; Drug Delivery Systems; Feasibility Studies; Fluorocarbons; Gadolinium DTPA; Humans; Magnetic Phenomena; Magnetic Resonance Imaging; Male; Microspheres; Permeability; Rats; Rats, Sprague-Dawley; Ultrasonographyjournal article10.1088/0031-9155/57/9/27872-s2.0-84860122228