@article{oai:repo.qst.go.jp:00048312,
 author = {Shiraishi, Kouichi and Wang, Zuojun and Kokuryo, Daisuke and Aoki, Ichio and Yokoyama, Masayuki and 國領 大介 and 青木 伊知男},
 journal = {Journal of Controlled Release},
 month = {May},
 note = {Blood–brain barrier (BBB) opening is a key phenomenon for understanding ischemia-reperfusion injuries that are directly linked to hemorrhagic transformation. The recombinant human tissue-type plasminogen activator (rtPA) increases the risk of symptomatic intracranial hemorrhages. Recent imaging technologies have advanced our understanding of pathological BBB disorders; however, an ongoing challenge in the pre-“rtPA treatment” stage is the task of developing a rigorous method for hemorrhage-risk assessments. Therefore, we examined a novel method for assessment of rtPA-extravasation through a hyper-permeable BBB. To examine the image diagnosis of rtPA-extravasation for a rat transient occlusion-reperfusion model, in this study we used a polymeric micelle MRI contrast-agent (Gd-micelles). Specifically, we used two MRI contrast agents at 1 h after reperfusion. Gd-micelles provided very clear contrast images in 15.5 ± 10.3% of the ischemic hemisphere at 30 min after i.v. injection, whereas a classic gadolinium chelate MRI contrast agent provided no satisfactorily clear images. The obtained images indicate both the hyper-permeable BBB area for macromolecules and the distribution area of macromolecules in the ischemic hemisphere. Owing to their large molecular weight, Gd-micelles remained in the ischemic hemisphere through the hyper-permeable BBB. Our results indicate the feasibility of a novel clinical diagnosis for evaluating rtPA-related hemorrhage risks.},
 pages = {165--171},
 title = {A polymeric micelle magnetic resonance imaging (MRI) contrast agent reveals blood-brain barrier (BBB) permeability for macromolecules in cerebral ischemia-reperfusion injury.},
 volume = {253},
 year = {2017}
}