title: In vivo characterization of a new abdominal aortic aneurysm mouse model with conventional and molecular magnetic resonance imaging.
abstract: OBJECTIVE
  The goal of this study was to use noninvasive conventional and molecular magnetic resonance imaging (MRI) to detect and characterize abdominal aortic aneurysms (AAAs) in vivo.
  
  
  BACKGROUND
  Collagen is an essential constituent of aneurysms. Noninvasive MRI of collagen may represent an opportunity to help detect and better characterize AAAs and initiate intervention.
  
  
  METHODS
  We used an AAA C57BL/6 mouse model in which a combination of angiotensin II infusion and transforming growth factor-β neutralization results in AAA formation with incidence of aortic rupture. High-resolution, multisequence MRI was performed to characterize the temporal progression of an AAA. To allow molecular MRI of collagen, paramagnetic/fluorescent micellar nanoparticles functionalized with a collagen-binding protein (CNA-35) were intravenously administered. In vivo imaging results were corroborated with immunohistochemistry and confocal fluorescence microscopy.
  
  
  RESULTS
  High-resolution, multisequence MRI allowed the visualization of the primary fibrotic response in the aortic wall. As the aneurysm progressed, the formation of a secondary channel or dissection was detected. Further analysis revealed a dramatic increase of the aortic diameter. Injection of CNA-35 micelles resulted in a significantly higher magnetic resonance signal enhancement in the aneurysmal wall compared with nonspecific micelles. Histological studies revealed the presence of collagen in regions of magnetic resonance signal enhancement, and confocal microscopy proved the precise co-localization of CNA-35 micelles with type I collagen. In addition, in a proof-of-concept experiment, we reported the potential of CNA-35 micelles to discriminate between stable AAA lesions and aneurysms that were likely to rapidly progress or rupture.
  
  
  CONCLUSIONS
  High-resolution, multisequence MRI allowed longitudinal monitoring of AAA progression while the presence of collagen was visualized by nanoparticle-enhanced MRI.
authors: Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, 1428 Madison Avenue, New York, NY 10029, USA.
authors: Ahmed
authors: A
authors: Klink
authors: Joeri
authors: J
authors: Heynens
authors: Beatriz
authors: B
authors: Herranz
authors: Mark E
authors: ME
authors: Lobatto
authors: Teresa
authors: T
authors: Arias
authors: Honorius M H F
authors: HM
authors: Sanders
authors: Gustav J
authors: GJ
authors: Strijkers
authors: Maarten
authors: M
authors: Merkx
authors: Klaas
authors: K
authors: Nicolay
authors: Valentin
authors: V
authors: Fuster
authors: Alain
authors: A
authors: Tedgui
authors: Ziad
authors: Z
authors: Mallat
authors: Willem J M
authors: WJ
authors: Mulder
authors: Zahi A
authors: ZA
authors: Fayad
mesh_terms: D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000032:analysis; D003287:Contrast Media; D004195:Disease Models, Animal; D018450:Disease Progression; D007089:Image Enhancement; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors
chemical_list: D003287:Contrast Media; D016212:Transforming Growth Factor beta; D003094:Collagen