Carotid artery brain aneurysm model: in vivo molecular enzyme-specific MR imaging of active inflammation in a pilot study
Authors
DeLeo, Michael J. 3rdGounis, Matthew J.
Hong, Bo
Ford, John C.
Wakhloo, Ajay K.
Bogdanov, Alexei A. Jr.
Faculty Advisor
Bogdanov, Alexei A., Jr.UMass Chan Affiliations
Department of RadiologyDocument Type
Journal ArticlePublication Date
2009-09-01Keywords
AneurysmCarotid Artery Diseases
Carotid Artery, Common
Contrast Media
Gadolinium DTPA
Magnetic Resonance Imaging
Peroxidase
Models, Animal
Radiology
Metadata
Show full item recordAbstract
PURPOSE: To demonstrate the feasibility of using a myeloperoxidase (MPO)-specific paramagnetic magnetic resonance (MR) contrast agent to identify active inflammation in an animal model of common carotid artery (CCA) aneurysm. MATERIALS AND METHODS: All animal experiments were approved by the institutional animal care and use committee. Elastase-induced saccular aneurysms were created at the root of the right CCA in 16 New Zealand white rabbits. Intramural and perivascular injection of Escherichia coli lipopolysaccharide (LPS) was performed with an endovascular approach to induce aneurysm inflammation. After intraarterial injection of an MPO-specific (di-5-hydroxytryptamide of gadopentetate dimeglumine, 0.1 mmol per kilogram of bodyweight) or a non-MPO-specific (di-tyrosine of gadopentetate dimeglumine, 0.1 mmol/kg) contrast agent, animals underwent 3-T MR imaging. Intramural presence of MPO in aneurysms in which LPS had been injected was confirmed at immunohistologic analysis. Active MPO activity was verified by measuring the spectrophotometric oxidation of guaiacol. RESULTS: Endovascular injection of LPS resulted in inflammatory cell infiltration into the aneurysm wall, and there was a difference in active MPO expression between aneurysms in which LPS had been injected and control aneurysms (20.3 ng of MPO per milligram of tissue vs 0.12 ng of MPO per milligram of tissue, respectively; P < .002). MR imaging with di-5-hydroxytryptamide of gadopentetate dimeglumine revealed a difference in enhancement ratio between inflamed aneurysms in which LPS had been injected and control aneurysms (1.55 +/- 0.05 vs 1.16 +/- 0.10, respectively; P < .02). In inflamed aneurysms, di-5-hydroxytryptamide of gadopentetate dimeglumine exhibited delayed washout kinetics compared with the kinetics of di-tyrosine of gadopentetate dimeglumine. This finding enabled the verification of MPO specificity. CONCLUSION: The findings of this pilot study established the feasibility of an animal model of saccular aneurysm inflammation that can be seen with clinical-field-strength MR imaging and use of the enzyme-sensitive MR contrast agent di-5-hydroxytryptamide of gadopentetate dimeglumine, which is a paramagnetic MPO substrate that specifically enhances MR signal.Source
Radiology. 2009 Sep;252(3):696-703. doi: 10.1148/radiol.2523081426. Epub 2009 Jun 22. Link to article on publisher's websiteDOI
10.1148/radiol.2523081426Permanent Link to this Item
http://hdl.handle.net/20.500.14038/49414PubMed ID
19546428Notes
Michael J. DeLeo participated in this study as a medical student as part of the Senior Scholars research program at the University of Massachusetts Medical School.
Poster presented about this research on Senior Scholars Program Presentation Day at the University of Massachusetts Medical School, Worcester, MA, on May 4, 2009, was entitled: In Vivo Molecular Enzyme-Specific MR Imaging of Active Inflammation in a Pilot Animal Model of Carotid Artery Aneurysm. Poster abstract is available as an additional file.
Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1148/radiol.2523081426