title: Determining carotid plaque vulnerability using ultrasound center frequency shifts.
abstract: BACKGROUND
  The leading cause of morbidity and mortality worldwide is atherosclerotic cardiovascular disease, most commonly caused by rupture of a high-risk plaque and subsequent thrombosis resulting in stroke, myocardial infarction or sudden death depending on the affected arterial territory. Accurate, non-invasive methods to identify such lesions known as vulnerable or high-risk plaques are currently sub-optimal. Our aim was to validate a new non-invasive ultrasound method to identify high-risk carotid plaques.
  
  
  METHODS
  We evaluated a new method based on the center frequency shift (CFS) of the ultrasound radio frequency data obtained from carotid plaques compared to a reference phantom. We evaluated the method both ex vivo, on 157 sections from 18 plaques, and in vivo, in 39 patients 1-day prior to carotid plaque removal, and correlated the data with histology.
  
  
  RESULTS
  The CFS correlated with a plaque vulnerability index based on histological areas stained for lipids, macrophages, hemorrhage, smooth muscle cells and collagen (r = -0.726, P = 1.7 × 10(-8)). Plaques with CFS below median had larger cores, more macrophages and were less rich in collagen in agreement with the definition of rupture-prone plaques. The accuracy to detect plaques with high vulnerability index was 78% (confidence interval (CI) 61-89%), with sensitivity 77% (CI 61-89%) and specificity 78% (CI 62-89%).
  
  
  CONCLUSIONS
  Our method is the first to characterize atherosclerotic plaque components that affect plaque vulnerability using CFS.
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, Lund University, Sweden. Electronic address: tobias.erlov@bme.lth.se.
authors.forename: Tobias
authors.initials: T
authors.lastname: Erlöv
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, Lund University, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Cinthio
authors.affiliation: Experimental Cardiovascular Research Group, Department of Clinical Sciences Malmö, Lund University, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Edsfeldt
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, Lund University, Sweden.
authors.forename: Simon
authors.initials: S
authors.lastname: Segstedt
authors.affiliation: Vascular Center, Skåne University Hospital, Sweden.
authors.forename: Nuno
authors.initials: N
authors.lastname: Dias
authors.affiliation: Experimental Cardiovascular Research Group, Department of Clinical Sciences Malmö, Lund University, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Nilsson
authors.affiliation: Experimental Cardiovascular Research Group, Department of Clinical Sciences Malmö, Lund University, Sweden; Department of Cardiology, Skåne University Hospital, Sweden.
authors.forename: Isabel
authors.initials: I
authors.lastname: Gonçalves
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002339:Carotid Arteries / Q000737:chemistry / Q000000981:diagnostic imaging* / Q000473:pathology; D016893:Carotid Stenosis / Q000150:complications / Q000000981:diagnostic imaging* / Q000378:metabolism; D003094:Collagen / Q000032:analysis; D005355:Fibrosis; D006801:Humans; D007091:Image Processing, Computer-Assisted; D002546:Ischemic Attack, Transient / Q000209:etiology; D008055:Lipids / Q000032:analysis; D008297:Male; D008875:Middle Aged; D019047:Phantoms, Imaging; D058226:Plaque, Atherosclerotic; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012307:Risk Factors; D012422:Rupture, Spontaneous; D012720:Severity of Illness Index; D020521:Stroke / Q000209:etiology; D014463:Ultrasonography / Q000295:instrumentation / Q000379:methods*
chemical_list: D008055:Lipids; D003094:Collagen
keywords: Atherosclerosis; Imaging; Ultrasound; Vulnerable plaque