Senior Scholars Program

Title

Carotid artery brain aneurysm model: in vivo molecular enzyme-specific MR imaging of active inflammation in a pilot study

UMMS Affiliation

Department of Radiology

Faculty Advisor

Bogdanov, Alexei A., Jr.

Date

9-2009

Document Type

Article

Medical Subject Headings

Aneurysm; Carotid Artery Diseases; Carotid Artery, Common; Contrast Media; Gadolinium DTPA; Magnetic Resonance Imaging; Peroxidase; Models, Animal

Disciplines

Radiology

Abstract

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.

Rights and Permissions

Citation: Radiology. 2009 Sep;252(3):696-703. doi: 10.1148/radiol.2523081426. Epub 2009 Jun 22. Link to article on publisher's website

Related Resources

Link to article in PubMed

Comments

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.

PubMed ID

19546428

DeLeo_Michael.pdf (107 kB)
Poster abstract