title: Optimization of 7-T chemical exchange saturation transfer parameters for validation of glycosaminoglycan and amide proton transfer of fibroglandular breast tissue.
abstract: OBJECTIVE
  To (a) implement simulation-optimized chemical exchange saturation transfer (CEST) measurements sensitive to amide proton transfer (APT) and glycosaminoglycan (GAG) hydroxyl proton transfer effects in the human breast at 7 T and (b) determine the reliability of these techniques for evaluation of fibroglandular tissue in the healthy breast as a benchmark for future studies of pathologic findings.
  
  
  METHODS
  All human studies were institutional review board approved, were HIPAA compliant, and included informed consent. The CEST parameters of saturation duration (25 msec) and amplitude (1 μT) were chosen on the basis of simulation-driven optimization for APT contrast enhancement with the CEST effect quantified by using residuals of a Lorentzian fit. Optimized parameters were implemented at 7 T in 10 healthy women in two separate examinations to evaluate the reliability of CEST magnetic resonance (MR) imaging measurements in the breast. CEST z-spectra were acquired over saturation offset frequencies ranging between ±40 ppm by using a quadrature unilateral breast coil. The imaging-repeat imaging reliability was assessed in terms of the intraclass correlation coefficient, which indicates the ratio of between-subject variation to total variation.
  
  
  RESULTS
  Simulations were performed of the Bloch equations with chemical exchange-guided selection of optimal values for pulse duration and amplitude, 25 msec and 1 μT, respectively. Reliability was evaluated by using intraclass correlation coefficients (95% confidence intervals), with acceptable results: 0.963 (95% confidence interval: 0.852, 0.991) and 0.903 (95% confidence interval: 0.609, 0.976) for APT and GAG, respectively.
  
  
  CONCLUSIONS
  Simulations were used to derive optimal CEST preparation parameters to elicit maximal CEST contrast enhancement in healthy fibroglandular breast tissue due to APT at 7 T. By using these parameters, reproducible values were obtained for both the amide and hydroxyl protons from CEST MR imaging at 7 T and are feasible in the human breast.
authors.affiliation: From the Institute of Imaging Science (A.N.D., B.E.D., L.R.A., J.M.W., D.K., T.E.Y., S.S.), Department of Radiology and Radiological Sciences (A.N.D., T.E.Y., S.S.), Program in Chemical and Physical Biology (T.E.Y., S.S.), Department of Biomedical Engineering (T.E.Y., S.S.), Department of Physics and Astronomy (T.E.Y., S.S.), Department of Cancer Biology (T.E.Y.), and Vanderbilt Ingram Cancer Center (T.E.Y.), Vanderbilt University Medical Center, AA-1105 Medical Center North, 1161 21st Ave S, Nashville, TN 37232-2310; and Department of Radiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Adrienne N
authors.initials: AN
authors.lastname: Dula
authors.forename: Blake E
authors.initials: BE
authors.lastname: Dewey
authors.forename: Lori R
authors.initials: LR
authors.lastname: Arlinghaus
authors.forename: Jason M
authors.initials: JM
authors.lastname: Williams
authors.forename: Dennis
authors.initials: D
authors.lastname: Klomp
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Yankeelov
authors.forename: Seth
authors.initials: S
authors.lastname: Smith
mesh_terms: D000328:Adult; D000577:Amides / Q000737:chemistry*; D001940:Breast / Q000737:chemistry*; D003198:Computer Simulation; D005260:Female; D006025:Glycosaminoglycans / Q000737:chemistry*; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D011522:Protons; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D000577:Amides; D006025:Glycosaminoglycans; D011522:Protons