4.5 Article

Combined non-invasive assessment of endothelial shear stress and molecular imaging of inflammation for the prediction of inflamed plaque in hyperlipidaemic rabbit aortas

Journal

EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING
Volume 18, Issue 1, Pages 19-30

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/ehjci/jew048

Keywords

atherosclerosis; hyperlipidaemic rabbits; endothelial shear stress; molecular imaging; magnetic resonance imaging; computed tomography angiography

Funding

  1. MSD [3909]
  2. Ernst and Berta Grimmke Foundation [1/12]
  3. Behrakis Foundation, Boston, MA, USA
  4. European Commission [249303]
  5. National Institutes of Health, National Institute of Biomedical Imaging and Bioengineering [K01-EB015868]

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Aims 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. Methods Twelve hereditary hyperlipidaemic rabbits underwent quantitative analysis of plaque in the thoracic aorta with 256-slice and results 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, white receiver operating curve analysis revealed baseline ESS atone or in combination with inflammation by MRI as the strongest predictor for augmented plaque burden and inflammation (tow ESS at baseline: AUC = 0.84, P < 0.001; tow ESS and inflammation by molecular MRI at baseline: AUC = 0.89, P < 0.001). Conclusion 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.

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