title: An assessment of intra-patient variability on observed relationships between wall shear stress and plaque progression in coronary arteries.
abstract: BACKGROUND
  Wall shear stress (WSS) has been associated with sites of plaque localization and with changes in plaque composition in human coronary arteries. Different values have been suggested for categorizing WSS as low, physiologic or high; however, uncertainties in flow rates, both across subjects and within a given individual, can affect the classification of WSS and thus influence the observed relationships between local hemodynamics and plaque changes over time. This study examines the effects of uncertainties in flow rate boundary conditions upon WSS values and investigates the influence of this variability on the observed associations of WSS with changes in VH-IVUS derived plaque components.
  
  
  METHODS
  Three patients with coronary artery disease underwent baseline and 12 month follow-up angiography and virtual histology-intravascular ultrasound (VH-IVUS) measurements. Coronary artery models were reconstructed from the data and models with and without side-branches were created. Patient-specific Doppler ultrasound (DUS) data were employed as inflow boundary conditions and computational fluid dynamics was used to calculate the WSS in each model. Further, the influence of representative coronary artery flow waveforms upon WSS values was investigated and the concept of treating WSS using relative, rather than actual, values was explored.
  
  
  RESULTS
  Models that included side-branch outflows and subject-specific DUS velocities were considered to be the reference cases. Hemodynamic differences were caused by the exclusion of side-branches and by imposing alternative velocity waveforms. One patient with fewer side-branches and a scaled generic waveform had little deviation from the reference case, while another patient with several side-branches excluded showed much larger departures from the reference situation. Differences between models and the respective reference cases were reduced when data were analyzed using relative, rather than actual, WSS.
  
  
  CONCLUSIONS
  When considering individual subjects, large variations in patient-specific flow rates and exclusion of multiple side-branches in computational models can cause significant differences in observed associations between plaque evolution and ranges of computed WSS. These differences may contribute to the large variability typically found among subjects in pooled populations. Relative WSS may be more useful than actual WSS as a correlative variable when there is a large degree of uncertainty in flow rate data.
authors.forename: David S
authors.initials: DS
authors.lastname: Molony
authors.forename: Lucas H
authors.initials: LH
authors.lastname: Timmins
authors.forename: Olivia Y
authors.initials: OY
authors.lastname: Hung
authors.forename: Emad
authors.initials: E
authors.lastname: Rasoul-Arzrumly
authors.forename: Habib
authors.initials: H
authors.lastname: Samady
authors.forename: Don P
authors.initials: DP
authors.lastname: Giddens
mesh_terms: D003331:Coronary Vessels / Q000473:pathology* / Q000503:physiopathology*; D018450:Disease Progression; D006439:Hemodynamics; D006801:Humans; D066230:Patient-Specific Modeling; D058226:Plaque, Atherosclerotic / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D013314:Stress, Mechanical; D014463:Ultrasonography