Noninvasive mapping of endothelial dysfunction in myocardial ischemia by magnetic resonance imaging using an albumin-based contrast agent.
Noninvasive preclinical methods for the characterization of myocardial vascular function are crucial to an understanding of the dynamics of ischemic cardiac disease. Ischemic heart disease is associated with myocardial endothelial dysfunction, resulting in leakage of plasma albumin into the extravascular space. These features can be harnessed in a novel noninvasive three-dimensional magnetic resonance imaging method to measure fractional blood volume (fBV) and vascular permeability (permeability-surface area product, PS) using labeled albumin as a blood pool contrast agent. C57BL/6 mice were imaged before and 3 days after myocardial infarction (MI). Following the quantification of endogenous myocardial R1, the dynamics of intravenously injected albumin-based contrast agent, extravasating from permeable myocardial blood vessels, were tracked on short-axis magnetic resonance images of the entire heart. This study successfully discriminated between infarcted and remote regions at 3 days post-infarct, based on a reduced fBV and increased PS in the infarcted region. These findings were confirmed using ex vivo fluorescence imaging and histology. We have demonstrated a novel method to quantify blood volume and permeability in the infarcted myocardium, providing an imaging biomarker for the assessment of endothelial dysfunction. This method has the potential to three-dimensionally visualize subtle changes in myocardial permeability and to track endothelial function for longitudinal cardiac studies determining pathophysiological processes during infarct healing.
Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands. k.vandoorne@tue.nl.
Katrien
K
Vandoorne
Department of Physiology, University of Kentucky, Lexington, KY, USA.
Moriel H
0000-0003-4052-205X
MH
Vandsburger
Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
I
I
Jacobs
Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
Y
Y
Han
Department of Veterinary Resources, Weizmann Institute of Science, Rehovot, Israel.
Hagit
H
Dafni
Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
Klaas
K
Nicolay
Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.|Biomedical Engineering and Physics, Academic Medical Center (AMC), Amsterdam, the Netherlands.
Gustav J
GJ
Strijkers
D000818:Animals; D057791:Cardiac Imaging Techniques / Q000379:methods*; D003287:Contrast Media; D007089:Image Enhancement / Q000379:methods*; D019028:Magnetic Resonance Imaging, Cine / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017202:Myocardial Ischemia / Q000150:complications / Q000000981:diagnostic imaging* / Q000473:pathology; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012710:Serum Albumin, Bovine; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging* / Q000209:etiology / Q000473:pathology
D003287:Contrast Media; D012710:Serum Albumin, Bovine
albumin; magnetic resonance imaging; mice; myocardial infarction; permeability