title: Salicylic acid analogues as chemical exchange saturation transfer MRI contrast agents for the assessment of brain perfusion territory and blood-brain barrier opening after intra-arterial infusion.
abstract: The blood-brain barrier (BBB) is a major obstacle for drug delivery to the brain. Predicted, focal opening of the BBB through intra-arterial infusion of hyperosmolar mannitol is feasible, but there is a need to facilitate imaging techniques (e.g. MRI) to guide interventional procedures and assess the outcomes. Here, we show that salicylic acid analogues (SAA) can depict the brain territory supplied by the catheter and detect the BBB opening, through chemical exchange saturation transfer (CEST) MRI. Hyperosmolar SAA solutions themselves are also capable of opening the BBB, and, when multiple SAA agents were co-injected, their locoregional perfusion could be differentiated.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltmore, MD, USA F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Song
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltmore, MD, USA F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA Department of Radiology, Faculty of Medical Sciences, University of Warmia and Mazury, Olsztyn, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Walczak
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltmore, MD, USA School of Information Sciences and Technology, Northwest University, Xi'an, P. R. China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: He
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltmore, MD, USA.
authors.forename: Xing
authors.initials: X
authors.lastname: Yang
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltmore, MD, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Pearl
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltmore, MD, USA F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Jeff W M
authors.initials: JWM
authors.lastname: Bulte
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltmore, MD, USA.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltmore, MD, USA F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: McMahon
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltmore, MD, USA Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA NeuroRepair Department, MMRC, PAS, Warsaw, Poland Department of Neurosurgery, MMRC, PAS, Warsaw, Poland mjanows1@jhmi.edu mcmahon@mri.jhu.edu.
authors.forename: Mirosław
authors.initials: M
authors.lastname: Janowski
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging* / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging; D003287:Contrast Media / Q000008:administration & dosage / Q000737:chemistry*; D062385:Hydroxybenzoates / Q000008:administration & dosage / Q000737:chemistry; D007261:Infusions, Intra-Arterial; D053783:Magnetic Resonance Imaging, Interventional / Q000379:methods*; D009994:Osmolar Concentration; D010477:Perfusion; D055420:Perfusion Imaging / Q000379:methods*; D010795:Phthalic Acids / Q000008:administration & dosage / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D020156:Salicylic Acid / Q000008:administration & dosage / Q000737:chemistry*; D012980:Sodium Salicylate / Q000008:administration & dosage / Q000737:chemistry; D012996:Solutions
chemical_list: C000599921:2,5-dihydroxyterephthalic acid; D003287:Contrast Media; D062385:Hydroxybenzoates; D010795:Phthalic Acids; D012996:Solutions; C017704:beta-resorcylic acid; D020156:Salicylic Acid; D012980:Sodium Salicylate
keywords: BBB opening; CEST MRI; Salicylic acid analogues; perfusion territory