title: Combined non-invasive assessment of endothelial shear stress and molecular imaging of inflammation for the prediction of inflamed plaque in hyperlipidaemic rabbit aortas.
abstract: OBJECTIVE
  To evaluate the incremental value of low endothelial shear stress (ESS) combined with high-resolution magnetic resonance imaging (MRI)- and computed tomography angiography (CTA)-based imaging for the prediction of inflamed plaque.
  
  
  RESULTS
  Twelve hereditary hyperlipidaemic rabbits underwent quantitative analysis of plaque in the thoracic aorta with 256-slice CTA and USPIO-enhanced (ultra-small superparamagnetic nanoparticles, P904) 1.5-T MRI at baseline and at 6-month follow-up. Computational fluid dynamics using CTA-based 3D reconstruction of thoracic aortas identified the ESS patterns in the convex and concave curvature subsegments of interest. Subsegments with low baseline ESS exhibited significant increase in wall thickness and plaque inflammation by MRI, in non-calcified plaque burden by CTA, and developed increased plaque size, lipid and inflammatory cell accumulation (high-risk plaque features) at follow-up by histopathology. Multiple regression analysis identified baseline ESS and inflammation by MRI to be independent predictors of plaque progression, while receiver operating curve analysis revealed baseline ESS alone or in combination with inflammation by MRI as the strongest predictor for augmented plaque burden and inflammation (low ESS at baseline: AUC = 0.84, P < 0.001; low ESS and inflammation by molecular MRI at baseline: AUC = 0.89, P < 0.001).
  
  
  CONCLUSIONS
  Low ESS predicts progression of plaque burden and inflammation as assessed by non-invasive USPIO-enhanced MRI. Combined non-invasive assessment of ESS and imaging of inflammation may serve to predict plaque with high-risk features.
authors.affiliation: Department of Cardiology, University of Heidelberg, Heidelberg, Germany gitsioudis_correspondence@web.de ychatzizisis@icloud.com.
authors.forename: Gitsios
authors.initials: G
authors.lastname: Gitsioudis
authors.affiliation: Cardiovascular Division, University of Nebraska Medical Center, Omaha, Nebraska, USA gitsioudis_correspondence@web.de ychatzizisis@icloud.com.|First Department of Cardiology, AHEPA University Hospital, Aristotle University Medical School, Thessaloniki, Greece.|Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Yiannis S
authors.initials: YS
authors.lastname: Chatzizisis
authors.affiliation: Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Wolf
authors.affiliation: Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Missiou
authors.affiliation: First Department of Cardiology, AHEPA University Hospital, Aristotle University Medical School, Thessaloniki, Greece.|Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Antonios P
authors.initials: AP
authors.lastname: Antoniadis
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Mitsouras
authors.affiliation: Medical Physics in Radiology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Sönke
authors.initials: S
authors.lastname: Bartling
authors.affiliation: Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Arica
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Sciences, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Center for Biomedical Imaging, University Hospital Lausanne, Lausanne, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Stuber
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Rybicki
authors.affiliation: Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Nunninger
authors.affiliation: Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Erbel
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Libby
authors.affiliation: First Department of Cardiology, AHEPA University Hospital, Aristotle University Medical School, Thessaloniki, Greece.
authors.forename: George D
authors.initials: GD
authors.lastname: Giannoglou
authors.affiliation: Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.affiliation: Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Grigorios
authors.initials: G
authors.lastname: Korosoglou
mesh_terms: D000818:Animals; D001011:Aorta / Q000000981:diagnostic imaging / Q000473:pathology; D001707:Biopsy, Needle; D000072226:Computed Tomography Angiography / Q000379:methods*; D016001:Confidence Intervals; D004195:Disease Models, Animal; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000473:pathology*; D006949:Hyperlipidemias / Q000000981:diagnostic imaging* / Q000473:pathology; D007150:Immunohistochemistry; D007249:Inflammation / Q000000981:diagnostic imaging / Q000473:pathology; D016014:Linear Models; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D057054:Molecular Imaging / Q000379:methods; D015588:Observer Variation; D058226:Plaque, Atherosclerotic / Q000000981:diagnostic imaging* / Q000473:pathology; D011237:Predictive Value of Tests; D012372:ROC Curve; D011817:Rabbits; D011897:Random Allocation; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D033081:Shear Strength; D018084:Ultrasonography, Interventional
keywords: atherosclerosis; computed tomography angiography; endothelial shear stress; hyperlipidaemic rabbits; magnetic resonance imaging; molecular imaging