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


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.


CONCLUSIONS
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.
DeLeo
Michael J
MJ
Department of Radiology, University of Massachusetts Medical School, 55 Lake Ave North, Worcester, MA 01655, USA.
Gounis
Matthew J
MJ
Hong
Bo
B
Ford
John C
JC
Wakhloo
Ajay K
AK
Bogdanov
Alexei A
AA
D000783:Aneurysm / Q000201:enzymology / Q000473:pathology*; D015901:Angiography, Digital Subtraction; D000818:Animals; D002340:Carotid Artery Diseases / Q000201:enzymology* / Q000473:pathology*; D017536:Carotid Artery, Common / Q000201:enzymology* / Q000473:pathology; D002533:Cerebral Angiography; D003287:Contrast Media / Q000737:chemistry / Q000494:pharmacology; D004195:Disease Models, Animal; D005240:Feasibility Studies; D019786:Gadolinium DTPA / Q000737:chemistry* / Q000494:pharmacology; D007089:Image Enhancement / Q000379:methods; D007249:Inflammation / Q000201:enzymology / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009195:Peroxidase / Q000378:metabolism*; D010865:Pilot Projects; D011817:Rabbits
D003287:Contrast Media; D009195:Peroxidase; D019786:Gadolinium DTPA