title: A new micro-computed tomography-based high-resolution blood-brain barrier imaging technique to study ischemic stroke.
abstract: OBJECTIVE
  Micro-computed tomography (mCT) offers high-resolution images, but it suffers from low contrast sensitivity and poor soft tissue contrast. We introduce a new mCT imaging technique with improved sensitivity for the dynamic spatial and temporal characterization of poststroke blood-brain barrier (BBB) dysfunction in small animals in vivo.
  
  
  METHODS
  Transient middle cerebral artery occlusion was induced for 1 hour in 10- to 12-week-old C57BL/6 mice (n=35). At 4, 24, and 48 hours after ischemic stroke, serial in vivo mCT imaging was performed 5 minutes after intravenous infusion (n=3) or intracarotid infusion of iopromide (240 μL) for 5 minutes (n=32). After intravenous injection of 2% Evans blue, we performed ex vivo near-infrared fluorescent imaging of parenchymal Evans blue leakage, visual assessment of poststroke parenchymal hematoma, triphenyltetrazolium chloride staining of the brain tissue, and quantitative mapping of stroke-related brain lesions.
  
  
  RESULTS
  Infarct-related BBB dysfunction could be demonstrated with intra-arterial but not with intravenous infusion of iopromide. Iopromide leakage across the dysfunctional BBB showed a monophasic (not biphasic) course for 48 hours after ischemic insult in both the parenchymal hematoma (n=5) and the non-parenchymal hematoma (n=24) groups, with relatively severe leakiness and greater hemispheric midline shift in animals with hemorrhage. Parenchymal staining on in vivo mCT overlapped with ex vivo fluorescent staining because of Evans blue. Multivariable analyses showed that midline shift and the amount of iopromide leakage at each of the 3 time points predicted the final infarct size at 48 hours.
  
  
  CONCLUSIONS
  The new mCT BBB imaging technique, based on the intra-arterial infusion of clinically available iopromide, allows serial quantitative visualization of poststroke BBB dysfunction in mice, with high resolution and in a sensitive manner.
authors.affiliation: From the Molecular Imaging and Neurovascular Research (MINER) Laboratory, Department of Neurology, Dongguk University Ilsan Hospital, Goyang, Korea (J.-Y.P., S.-K.L., J.-Y.K., K.-H.J., D.-E.K.); and Departments of Radiology and Experimental Diagnostic Imaging, University of Texas MD Anderson Cancer Center, Houston (D.S.).
authors.forename: Jin-Yong
authors.initials: JY
authors.lastname: Park
authors.affiliation: From the Molecular Imaging and Neurovascular Research (MINER) Laboratory, Department of Neurology, Dongguk University Ilsan Hospital, Goyang, Korea (J.-Y.P., S.-K.L., J.-Y.K., K.-H.J., D.-E.K.); and Departments of Radiology and Experimental Diagnostic Imaging, University of Texas MD Anderson Cancer Center, Houston (D.S.).
authors.forename: Su-Kyoung
authors.initials: SK
authors.lastname: Lee
authors.affiliation: From the Molecular Imaging and Neurovascular Research (MINER) Laboratory, Department of Neurology, Dongguk University Ilsan Hospital, Goyang, Korea (J.-Y.P., S.-K.L., J.-Y.K., K.-H.J., D.-E.K.); and Departments of Radiology and Experimental Diagnostic Imaging, University of Texas MD Anderson Cancer Center, Houston (D.S.).
authors.forename: Jeong-Yeon
authors.initials: JY
authors.lastname: Kim
authors.affiliation: From the Molecular Imaging and Neurovascular Research (MINER) Laboratory, Department of Neurology, Dongguk University Ilsan Hospital, Goyang, Korea (J.-Y.P., S.-K.L., J.-Y.K., K.-H.J., D.-E.K.); and Departments of Radiology and Experimental Diagnostic Imaging, University of Texas MD Anderson Cancer Center, Houston (D.S.).
authors.forename: Kang-Hoon
authors.initials: KH
authors.lastname: Je
authors.affiliation: From the Molecular Imaging and Neurovascular Research (MINER) Laboratory, Department of Neurology, Dongguk University Ilsan Hospital, Goyang, Korea (J.-Y.P., S.-K.L., J.-Y.K., K.-H.J., D.-E.K.); and Departments of Radiology and Experimental Diagnostic Imaging, University of Texas MD Anderson Cancer Center, Houston (D.S.).
authors.forename: Dawid
authors.initials: D
authors.lastname: Schellingerhout
authors.affiliation: From the Molecular Imaging and Neurovascular Research (MINER) Laboratory, Department of Neurology, Dongguk University Ilsan Hospital, Goyang, Korea (J.-Y.P., S.-K.L., J.-Y.K., K.-H.J., D.-E.K.); and Departments of Radiology and Experimental Diagnostic Imaging, University of Texas MD Anderson Cancer Center, Houston (D.S.). kdongeog@duih.org.
authors.forename: Dong-Eog
authors.initials: DE
authors.lastname: Kim
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging*; D001921:Brain / Q000000981:diagnostic imaging; D002545:Brain Ischemia / Q000000981:diagnostic imaging*; D020244:Infarction, Middle Cerebral Artery / Q000000981:diagnostic imaging*; D051379:Mice; D020521:Stroke / Q000000981:diagnostic imaging*; D055114:X-Ray Microtomography / Q000379:methods*
keywords: blood-brain barrier; infusion, intra-arterial; iopromide; ischemic stroke; micro–CT