In Vivo Molecular Enzyme-Specific MR Imaging of Active Inflammation in a Pilot Animal Model of Carotid Artery Aneurysm
Department of Radiology; New England Center for Stroke Research
Bogdanov, Alexei A., Jr.
Medical Subject Headings
Aneurysm; Carotid Artery Diseases; Carotid Artery, Common; Contrast Media; Gadolinium DTPA; Magnetic Resonance Imaging; Peroxidase; Models, Animal
Life Sciences | Medicine and Health Sciences | Radiology
Background: Half of all patients who suffer aneurysmal subarachnoid hemorrhage die within the first 30 days. Recent evidence implicates acute local intramural inflammation in intracranial aneurysm instability and rupture.
Objectives: The purpose of this pilot study was to demonstrate the feasibility of using a myeloperoxidase (MPO)-specific paramagnetic MR contrast agent to identify active inflammation in an animal model of carotid artery aneurysm not yet described in the literature.
Methods: All animal experiments were approved by our Institutional Animal Care and Use Committee. Elastase-induced saccular aneurysms were created at the root of the right common carotid artery in New Zealand white rabbits (n=16). Intramural and perivascular injection of E. coli lipopolysaccharide (LPS) was delivered via endovascular approach to induce aneurysm inflammation. Following intra-arterial injection of 0.1mmol/kg di-5-HT-GdDTPA, animals were subjected to 3T MRI. Intramural presence of MPO in LPS-injected aneurysms was confirmed immunohistologically. Active MPO activity was verified by measuring the spectophotometric oxidation of guaiacol.
Results: Endovascular injection of LPS resulted in inflammatory cell infiltration into the aneurysm wall and there was a difference of expression of active MPO compared to control aneurysms (20.3 ngMPO/mg tissue versus 0.12 ngMPO/mg tissue, p<0.002). 3T MR imaging of inflamed aneurysms demonstrated a difference in enhancement ratio compared to control aneurysms (1.55±0.05 for LPS versus 1.16±0.10 for control, p<0.02).
Conclusion: This pilot study establishes the feasibility of an animal model of saccular aneurysm inflammation that can be visualized with clinical field strength MRI using the enzyme-sensitive MR contrast agent di-5-hydroxytryptamide of GdDTPA, a paramagnetic MPO substrate that specifically enhances MR signal.
Rights and Permissions
This research was eventually published as follows: Michael J. DeLeo III, Matthew J. Gounis, Bo Hong, John C. Ford, Ajay K. Wakhloo, Alexei A. Bogdanov, Jr. Carotid Artery Brain Aneurysm Model: In Vivo Molecular Enzyme-specific MR Imaging of Active Inflammation in a Pilot Study. Radiology September 2009 252:696-703. Link to article on publisher's website
DeLeo, Michael J.; Gounis, Matthew J.; Hong, Bo; Ford, John C.; Wakhloo, Ajay K.; and Bogdanov, Alexei A., "In Vivo Molecular Enzyme-Specific MR Imaging of Active Inflammation in a Pilot Animal Model of Carotid Artery Aneurysm" (2009). University of Massachusetts Medical School. Senior Scholars Program. Paper 72.