title: Sample size calculation for clinical trials using magnetic resonance imaging for the quantitative assessment of carotid atherosclerosis.
abstract: OBJECTIVE
  To provide sample size calculation for the quantitative assessment of carotid atherosclerotic plaque using non-invasive magnetic resonance imaging in multi-center clinical trials. METHODS. As part of a broader double-blind randomized trial of an experimental pharmaceutical agent, 20 asymptomatic placebo-control subjects were recruited from 5 clinical sites for a multi-center study. Subjects had 4 scans in 13 weeks on GE 1.5 T scanners, using TOF, T1-/PD-/T2- and contrast-enhanced Tl-weighted images. Measurement variability was assessed by comparing quantitative data from the index carotid artery over the four time points. The wall/outer wall (W/OW) ratio was calculated as wall volume divided by outer wall volume. The percent lipid-rich/necrotic core (%LR/NC) and calcification (%Ca) were measured as a proportion of the vessel wall. For %LR/NC and %Ca, only those subjects that exhibited LR/NC or Ca components were used in the analysis.
  
  
  RESULTS
  Measurement error was 5.8% for wall volume, 3.2% for W/OW ratio, 11.1% for %LR/NC volume and 18.6% for %Ca volume. Power analysis based on these values shows that a study with 14 participants in each group could detect a 5% change in W/OW ratio, 10% change in wall volume, and 20% change in %LR/NC volume (power = 80%, p < .05). The calculated measurement errors presume any true biological changes were negligible over the 3 months that subjects received placebo.
  
  
  CONCLUSIONS
  In vivo MRI is capable of quantifying plaque volume and plaque composition, such as %lipid-rich/necrotic core and %calcification, in the clinical setting of a multi-center trial with low inter-scan variability. This study provides the basis for sample size calculation of future MRI trials.
authors.affiliation: Department of Radiology, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Tobias
authors.initials: T
authors.lastname: Saam
authors.forename: William S
authors.initials: WS
authors.lastname: Kerwin
authors.forename: Baocheng
authors.initials: B
authors.lastname: Chu
authors.forename: Jianming
authors.initials: J
authors.lastname: Cai
authors.forename: Annette
authors.initials: A
authors.lastname: Kampschulte
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Hatsukami
authors.forename: Xue-Qiao
authors.initials: XQ
authors.lastname: Zhao
authors.forename: Nayak L
authors.initials: NL
authors.lastname: Polissar
authors.forename: Blazej
authors.initials: B
authors.lastname: Neradilek
authors.forename: Vasily L
authors.initials: VL
authors.lastname: Yarnykh
authors.forename: Kelly
authors.initials: K
authors.lastname: Flemming
authors.forename: John
authors.initials: J
authors.lastname: Huston
authors.forename: William
authors.initials: W
authors.lastname: Insull
authors.forename: Joel D
authors.initials: JD
authors.lastname: Morrisett
authors.forename: Scott D
authors.initials: SD
authors.lastname: Rand
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: DeMarco
authors.forename: Chun
authors.initials: C
authors.lastname: Yuan
mesh_terms: D000368:Aged; D019412:Anatomy, Cross-Sectional; D002340:Carotid Artery Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000473:pathology*; D017536:Carotid Artery, Common / Q000033:anatomy & histology / Q000473:pathology*; D015986:Confounding Factors, Epidemiologic; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007089:Image Enhancement; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D018401:Sample Size