In Vivo Molecular Characterization of Abdominal Aortic Aneurysms Using Fibrin-Specific Magnetic Resonance Imaging

TY - JOUR

T1 - In Vivo Molecular Characterization of Abdominal Aortic Aneurysms Using Fibrin-Specific Magnetic Resonance Imaging

AU - Botnar, René M

AU - Brangsch, Julia

AU - Reimann, Carolin

AU - Janssen, Christian H P

AU - Razavi, Reza

AU - Hamm, Bernd

AU - Makowski, Marcus R

N1 - © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

PY - 2018/6/5

Y1 - 2018/6/5

N2 - BACKGROUND: The incidence of abdominal aortic aneurysms (AAAs) will significantly increase during the next decade. Novel biomarkers, besides diameter, are needed for a better characterization of aneurysms and the estimation of the risk of rupture. Fibrin is a key protein in the formation of focal hematoma associated with the dissection of the aortic wall and the development of larger thrombi during the progression of AAAs. This study evaluated the potential of a fibrin-specific magnetic resonance (MR) probe for the in vivo characterization of the different stages of AAAs.METHODS AND RESULTS: AAAs spontaneously developed in ApoE-/- mice following the infusion of angiotensin-II (Ang-II, 1 μg/kg-1·per minute). An established fibrin-specific molecular MR probe (EP2104R, 10 μmol/kg-1) was administered after 1 to 4 weeks following Ang-II infusion (n=8 per group). All imaging experiments were performed on a clinical 3T Achieva MR system with a microscopy coil (Philips Healthcare, Netherlands). The development of AAA-associated fibrin-rich hematoma and thrombi was assessed. The high signal generated by the fibrin probe enabled high-resolution MR imaging for an accurate assessment and quantification of the relative fibrin composition of focal hematoma and thrombi. Contrast-to-noise-ratios (CNRs) and R1-relaxation rates following the administration of the fibrin probe were in good agreement with ex vivo immunohistomorphometry (R2=0.83 and 0.85) and gadolinium concentrations determined by inductively coupled plasma mass spectroscopy (R2=0.78 and 0.72).CONCLUSIONS: The fibrin-specific molecular MR probe allowed the delineation and quantification of changes in fibrin content in early and advanced AAAs. Fibrin MRI could provide a novel in vivo biomarker to improve the risk stratification of patients with aortic aneurysms.

AB - BACKGROUND: The incidence of abdominal aortic aneurysms (AAAs) will significantly increase during the next decade. Novel biomarkers, besides diameter, are needed for a better characterization of aneurysms and the estimation of the risk of rupture. Fibrin is a key protein in the formation of focal hematoma associated with the dissection of the aortic wall and the development of larger thrombi during the progression of AAAs. This study evaluated the potential of a fibrin-specific magnetic resonance (MR) probe for the in vivo characterization of the different stages of AAAs.METHODS AND RESULTS: AAAs spontaneously developed in ApoE-/- mice following the infusion of angiotensin-II (Ang-II, 1 μg/kg-1·per minute). An established fibrin-specific molecular MR probe (EP2104R, 10 μmol/kg-1) was administered after 1 to 4 weeks following Ang-II infusion (n=8 per group). All imaging experiments were performed on a clinical 3T Achieva MR system with a microscopy coil (Philips Healthcare, Netherlands). The development of AAA-associated fibrin-rich hematoma and thrombi was assessed. The high signal generated by the fibrin probe enabled high-resolution MR imaging for an accurate assessment and quantification of the relative fibrin composition of focal hematoma and thrombi. Contrast-to-noise-ratios (CNRs) and R1-relaxation rates following the administration of the fibrin probe were in good agreement with ex vivo immunohistomorphometry (R2=0.83 and 0.85) and gadolinium concentrations determined by inductively coupled plasma mass spectroscopy (R2=0.78 and 0.72).CONCLUSIONS: The fibrin-specific molecular MR probe allowed the delineation and quantification of changes in fibrin content in early and advanced AAAs. Fibrin MRI could provide a novel in vivo biomarker to improve the risk stratification of patients with aortic aneurysms.

U2 - 10.1161/JAHA.117.007909

DO - 10.1161/JAHA.117.007909

M3 - Article

C2 - 29848500

SN - 2047-9980

VL - 7

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

IS - 11

ER -