Molecular Magnetic Resonance Imaging of Aneurysmal Inflammation Using a Redox Active Iron Complex

Area of Science:

• Biomedical Imaging
• Vascular Biology
• Inflammation Research

Background:

• Inflammation is a critical factor in brain aneurysm instability and rupture.
• Current clinical tools lack noninvasive methods to differentiate between inflamed and stable aneurysms.
• Oxidative changes in the aneurysm microenvironment may serve as a biomarker for rupture risk.

Purpose of the Study:

• To evaluate Fe-PyC3A, an oxidatively activated probe, as a tool for magnetic resonance imaging (MRI) of inflammation in a rabbit saccular aneurysm model.
• To assess Fe-PyC3A's potential as a noninvasive biomarker for evaluating brain aneurysm rupture risk.

Main Methods:

• Developed a rabbit saccular aneurysm model via endovascular intervention.
• Performed dynamic and delayed MRI scans using Fe-PyC3A and gadobutrol (control) at 4 and 12 weeks post-induction.
• Quantified aneurysmal enhancement ratios (ERs) and correlated with myeloperoxidase activity and calprotectin immunostaining.

Main Results:

• Fe-PyC3A demonstrated a 15-fold increase in relaxivity upon oxidation in vitro.
• Aneurysmal ER with Fe-PyC3A was significantly higher in 4-week (inflamed) versus 12-week (stable) aneurysms (1.6 vs 1.2, P < 0.05).
• Fe-PyC3A showed higher ER compared to gadobutrol in delayed imaging of 12-week aneurysms (1.25 vs 1.03, P < 0.05).
• Immunohistochemistry confirmed higher leukocyte infiltration in 4-week aneurysms.

Conclusions:

• MRI with Fe-PyC3A generates higher signal enhancement in inflamed aneurysms.
• Fe-PyC3A shows promise as a noninvasive MRI biomarker for assessing aneurysmal inflammation and potentially rupture risk.