Alexis N Simpkins1, Christian Dias1, Richard Leigh2. 1. From the Neuro Vascular Brain Imaging Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD. 2. From the Neuro Vascular Brain Imaging Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD. richard.leigh@nih.gov.
Abstract
BACKGROUND AND PURPOSE: Animal models of acute cerebral ischemia have demonstrated that diffuse blood-brain barrier (BBB) disruption can be reversible after early reperfusion. However, irreversible, focal BBB disruption in humans is associated with hemorrhagic transformation in patients receiving intravenous thrombolytic therapy. The goal of this study was to use a magnetic resonance imaging biomarker of BBB permeability to differentiate these 2 forms of BBB disruption. METHODS: Acute stroke patients imaged with magnetic resonance imaging before, 2 hours after, and 24 hours after treatment with intravenous tissue-type plasminogen activator were included. The average BBB permeability of the acute ischemic region before and 2 hours after treatment was calculated using a T2* perfusion-weighted source images. Change in average permeability was compared with percent reperfusion using linear regression. Focal regions of maximal BBB permeability from the pretreatment magnetic resonance imaging were compared with the occurrence of parenchymal hematoma (PH) formation on the 24-hour magnetic resonance imaging scan using logistic regression. RESULTS: Signals indicating reversible BBB permeability were detected in 18/36 patients. Change in average BBB permeability correlated inversely with percent reperfusion (P=0.006), indicating that early reperfusion is associated with decreased BBB permeability, whereas sustained ischemia is associated with increased BBB disruption. Focal regions of maximal BBB permeability were significantly associated with subsequent formation of PH (P=0.013). CONCLUSIONS: This study demonstrates that diffuse, mild BBB disruption in the acutely ischemic human brain is reversible with reperfusion. This study also confirms prior findings that focal severe BBB disruption confers an increased risk of hemorrhagic transformation in patients treated with intravenous tissue-type plasminogen activator.
BACKGROUND AND PURPOSE: Animal models of acute cerebral ischemia have demonstrated that diffuse blood-brain barrier (BBB) disruption can be reversible after early reperfusion. However, irreversible, focal BBB disruption in humans is associated with hemorrhagic transformation in patients receiving intravenous thrombolytic therapy. The goal of this study was to use a magnetic resonance imaging biomarker of BBB permeability to differentiate these 2 forms of BBB disruption. METHODS:Acute strokepatients imaged with magnetic resonance imaging before, 2 hours after, and 24 hours after treatment with intravenous tissue-type plasminogen activator were included. The average BBB permeability of the acute ischemic region before and 2 hours after treatment was calculated using a T2* perfusion-weighted source images. Change in average permeability was compared with percent reperfusion using linear regression. Focal regions of maximal BBB permeability from the pretreatment magnetic resonance imaging were compared with the occurrence of parenchymal hematoma (PH) formation on the 24-hour magnetic resonance imaging scan using logistic regression. RESULTS: Signals indicating reversible BBB permeability were detected in 18/36 patients. Change in average BBB permeability correlated inversely with percent reperfusion (P=0.006), indicating that early reperfusion is associated with decreased BBB permeability, whereas sustained ischemia is associated with increased BBB disruption. Focal regions of maximal BBB permeability were significantly associated with subsequent formation of PH (P=0.013). CONCLUSIONS: This study demonstrates that diffuse, mild BBB disruption in the acutely ischemichuman brain is reversible with reperfusion. This study also confirms prior findings that focal severe BBB disruption confers an increased risk of hemorrhagic transformation in patients treated with intravenous tissue-type plasminogen activator.
Authors: Michal Rozanski; Martin Ebinger; Wolf U Schmidt; Benjamin Hotter; Sandra Pittl; Peter U Heuschmann; Jan G Jungehuelsing; Jochen B Fiebach Journal: Eur Radiol Date: 2010-07-21 Impact factor: 5.315
Authors: Shreyansh Shah; Marie Luby; Karen Poole; Teresa Morella; Elizabeth Keller; Richard T Benson; John K Lynch; Zurab Nadareishvili; Amie W Hsia Journal: Neurology Date: 2015-05-13 Impact factor: 9.910
Authors: W Hacke; M Kaste; C Fieschi; R von Kummer; A Davalos; D Meier; V Larrue; E Bluhmki; S Davis; G Donnan; D Schneider; E Diez-Tejedor; P Trouillas Journal: Lancet Date: 1998-10-17 Impact factor: 79.321
Authors: Emi Hitomi; Alexis N Simpkins; Marie Luby; Lawrence L Latour; R John Leigh; Richard Leigh Journal: Neurology Date: 2018-02-07 Impact factor: 9.910
Authors: Francesco Arba; Richard Leigh; Domenico Inzitari; Steven J Warach; Marie Luby; Kennedy R Lees Journal: Neurology Date: 2017-10-25 Impact factor: 9.910
Authors: Xiaoyan Jiang; Anuska V Andjelkovic; Ling Zhu; Tuo Yang; Michael V L Bennett; Jun Chen; Richard F Keep; Yejie Shi Journal: Prog Neurobiol Date: 2017-10-05 Impact factor: 11.685