title: Retrospectively gated MRI for in vivo assessment of endothelium-dependent vasodilatation and endothelial permeability in murine models of endothelial dysfunction.
abstract: Endothelial dysfunction is linked to impaired endothelial-dependent vasodilatation and permeability changes. Here, we quantify both of these phenomena associated with endothelial dysfunction by MRI in vivo in mice. Endothelial function was evaluated in the brachiocephalic artery (BCA) and left carotid artery (LCA) in ApoE/LDLR(-/-) and high-fat diet (HFD)-fed mice as compared with control mice (C57BL/6J). The 3D IntraGate® FLASH sequence was used for evaluation of changes in vessels' cross-sectional area (CSA) and volume following acetylcholine (Ach) administration. Evaluation of endothelial permeability after administration of contrast agent (Galbumin, BioPAL) was based on the variable flip angle method for the assessment of parameters based on the relaxation time (T1 ) value. In order to confirm the involvement of nitric oxide (NO) in response to Ach, L-NAME-treated mice were also analyzed. To confirm that endothelial permeability changes accompany the impairment of Ach-dependent vasodilatation, permeability changes were analyzed in isolated, perfused carotid artery. In C57BL/6J mice, Ach-induced vasodilatation led to an approximately 25% increase in CSA in both vessels, which was temporarily dissociated from the effect of Ach on heart rate. In ApoE/LDLR(-/-) or HFD-fed mice Ach induced a paradoxical vasoconstriction that amounted to approximately 30% and 50% decreases in CSA of BCA and LCA respectively. In ApoE/LDLR(-/-) and HFD-fed mice endothelial permeability in BCA was also increased (fall in T1 by about 25%). In L-NAME-treated mice Ach-induced vasodilatation in BCA was lost. In isolated, perfused artery from ApoE/LDLR(-/-) mice endothelial permeability was increased. MRI-based assessment of endothelium-dependent vasodilatation induced by Ach and endothelial permeability using a retrospectively self-gated 3D gradient-echo sequence (IntraGate® FLASH) enables the reliable detection of systemic endothelial dysfunction in mice and provides an important tool for the experimental pharmacology of the endothelium in murine models of diseases in vivo. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Kraków, Poland.|Chair of Pharmacology, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Bar
authors.affiliation: Department of Magnetic Resonance Imaging, Institute of Nuclear Physics, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Skórka
authors.affiliation: Department of Magnetic Resonance Imaging, Institute of Nuclear Physics, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Jasiński
authors.affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Kraków, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Sternak
authors.affiliation: Department of Magnetic Resonance Imaging, Institute of Nuclear Physics, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Żaneta
authors.initials: Ż
authors.lastname: Bartel
authors.affiliation: Department of Magnetic Resonance Imaging, Institute of Nuclear Physics, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Tyrankiewicz
authors.affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Kraków, Poland.|Chair of Pharmacology, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Chlopicki
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D002199:Capillary Permeability; D055424:Cardiac-Gated Imaging Techniques / Q000379:methods*; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D021621:Imaging, Three-Dimensional / Q000379:methods*; D018810:Magnetic Resonance Angiography / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012815:Signal Processing, Computer-Assisted; D014664:Vasodilation
keywords: 3D IntraGate® FLASH; MRI; atherosclerosis; endothelium