title: Quantifying the effect of side branches in endothelial shear stress estimates.
abstract: Low and high endothelial shear stress (ESS) is associated with coronary atherosclerosis progression and high-risk plaque features. Coronary ESS is currently assessed via computational fluid dynamic (CFD) simulation of coronary blood flow in the lumen geometry determined from invasive imaging such as intravascular ultrasound and optical coherence tomography. This process typically omits side branches of the target vessel in the CFD model as invasive imaging of those vessels is not usually clinically-indicated. The purpose of this study was to determine the extent to which this simplification affects the determination of those regions of the coronary endothelium subjected to pathologic ESS.
  
  
  
  We determined the diagnostic accuracy of ESS profiling without side branches to detect pathologic ESS in the major coronary arteries of 5 hearts imaged ex vivo with computed tomography angiography (CTA). ESS of the three major coronary arteries was calculated both without (test model), and with (reference model) inclusion of all side branches >1.5 mm in diameter, using previously-validated CFD approaches. Diagnostic test characteristics (accuracy, sensitivity, specificity and negative and positive predictive value [NPV/PPV]) with respect to the reference model were assessed for both the entire length as well as only the proximal portion of each major coronary artery, where the majority of high-risk plaques occur.
  
  
  
  Using the model without side branches overall accuracy, sensitivity, specificity, NPV and PPV were 83.4%, 54.0%, 96%, 95.9% and 55.1%, respectively to detect low ESS, and 87.0%, 67.7%, 90.7%, 93.7% and 57.5%, respectively to detect high ESS. When considering only the proximal arteries, test characteristics differed for low and high ESS, with low sensitivity (67.7%) and high specificity (90.7%) to detect low ESS, and low sensitivity (44.7%) and high specificity (95.5%) to detect high ESS.
  
  
  
  The exclusion of side branches in ESS vascular profiling studies greatly reduces the ability to detect regions of the major coronary arteries subjected to pathologic ESS. Single-conduit models can in general only be used to rule out pathologic ESS.
authors.affiliation: Applied Imaging Science Laboratory, Radiology Department, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Andreas A
authors.initials: AA
authors.lastname: Giannopoulos
authors.affiliation: Cardiovascular Division, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Yiannis S
authors.initials: YS
authors.lastname: Chatzizisis
authors.affiliation: MTA-SE Lendület Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
authors.forename: Pal
authors.initials: P
authors.lastname: Maurovich-Horvat
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA; Cardiovascular Department, Guy's and St Thomas' NHS Foundation Trust, London, UK.
authors.forename: Antonios P
authors.initials: AP
authors.lastname: Antoniadis
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Udo
authors.initials: U
authors.lastname: Hoffmann
authors.affiliation: Applied Imaging Science Laboratory, Radiology Department, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Steigner
authors.affiliation: Applied Imaging Science Laboratory, Radiology Department, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Radiology, The Ottawa Hospital, The University of Ottawa, Ontario, ON, Canada.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Rybicki
authors.affiliation: Applied Imaging Science Laboratory, Radiology Department, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: dmitsouras@partners.org.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Mitsouras
mesh_terms: D050197:Atherosclerosis / Q000473:pathology*; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000175:diagnosis; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000473:pathology; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000473:pathology*; D006321:Heart / Q000000981:diagnostic imaging; D006439:Hemodynamics; D006801:Humans; D057446:Hydrodynamics; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D058226:Plaque, Atherosclerotic / Q000473:pathology; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D033081:Shear Strength; D012984:Software; D013314:Stress, Mechanical
keywords: Computational fluid dynamics; Coronary computed tomography; Endothelial shear stress; Side branches