title: Quantitative Contrast-Enhanced Ultrasound Parameters in Crohn Disease: Their Role in Disease Activity Determination With Ultrasound.
abstract: OBJECTIVE
  The primary objective of our study was to examine the association between contrast-enhanced ultrasound (CEUS) parameters and established gray-scale ultrasound with color Doppler imaging (CDI) for the determination of disease activity in patients with Crohn disease. Our secondary objective was to develop quantitative time-signal intensity curve thresholds for disease activity.
  
  
  METHODS
  One hundred twenty-seven patients with Crohn disease underwent ultrasound with CDI and CEUS. Reviewers graded wall thickness, inflammatory fat, and mural blood flow as showing remission or inflammation (mild, moderate, or severe). If both gray-scale ultrasound and CDI predicted equal levels of disease activity, the studies were considered concordant. If ultrasound images suggested active disease not supported by CDI findings, the ultrasound results for disease activity were indeterminate. Time-signal intensity curves from CEUS were acquired with calculation of peak enhancement (PE), and AUCs. Interobserver variation and associations between PE and ultrasound parameters were examined. Multiclass ROC analysis was used to develop CEUS thresholds for activity.
  
  
  RESULTS
  Ninety-six (76%) studies were concordant, 19 of which showed severe disease, and 31 (24%) studies were indeterminate. Kappa analyses revealed good interobserver agreement on grades for CDI (κ = 0.76) and ultrasound (κ = 0.80) assessments. PE values on CEUS and wall thickness showed good association with the Spearman rank correlation coefficient for the entire population (ρ = 0.62, p < 0.01) and for the concordant group (ρ = 0.70, p < 0.01). Multiclass ROC analyses of the concordant group using wall thickness alone as the reference standard showed cutoff points of 18.2 dB for differentiating mild versus moderate activity (sensitivity, 89.0% and specificity, 87.0%) and 23.0 dB for differentiating moderate versus severe (sensitivity, 90% and specificity, 86.8%). Almost identical cutoff points were observed when using ultrasound global assessment as the reference standard: using 18.2 dB to differentiate mild versus moderate activity yielded sensitivity of 89.2% and specificity of 90.9% and using 22.9 dB to differentiate moderate versus severe activity yielded sensitivity of 89.5% and specificity of 83.1%.
  
  
  CONCLUSIONS
  Quantitative CEUS parameters integrated into inflammatory assessments with ultrasound reduce indeterminate results and improve disease activity level determinations.
authors.affiliation: 1 Department of Radiology, University of Calgary, Foothills Medical Centre, 1403 29 St, NW, Calgary, AB T2N 2T9, Canada.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Medellin-Kowalewski
authors.affiliation: 1 Department of Radiology, University of Calgary, Foothills Medical Centre, 1403 29 St, NW, Calgary, AB T2N 2T9, Canada.|2 Department of Medicine, Division of Gastroenterology, University of Calgary, Calgary, AB, Canada.|3 Present address: Diagnostic Centre, University Research Clinic for Innovative Patient Pathways, Silkeborg Regional Hospital, Silkeborg, Denmark.|4 Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Rune
authors.initials: R
authors.lastname: Wilkens
authors.affiliation: 5 Cumming School of Medicine, University of Calgary, Health Sciences Centre Foothills Campus, Calgary, AB, Canada.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Wilson
authors.affiliation: 6 Department of Mathematics and Statistics, University of Calgary, Calgary, AB, Canada.
authors.forename: Ji
authors.initials: J
authors.lastname: Ruan
authors.affiliation: 1 Department of Radiology, University of Calgary, Foothills Medical Centre, 1403 29 St, NW, Calgary, AB T2N 2T9, Canada.|2 Department of Medicine, Division of Gastroenterology, University of Calgary, Calgary, AB, Canada.
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Wilson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003287:Contrast Media; D003424:Crohn Disease / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D018615:Ultrasonography, Doppler, Color / Q000379:methods*
chemical_list: D003287:Contrast Media
keywords: Crohn disease; color Doppler imaging; quantitative contrast-enhanced ultrasound; thresholds for disease activity; ultrasound