title: Quantitative assessment of amide proton transfer (APT) and nuclear overhauser enhancement (NOE) imaging with extrapolated semi-solid magnetization transfer reference (EMR) signals: Application to a rat glioma model at 4.7 Tesla.
abstract: OBJECTIVE
  To quantify amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) contributions to in vivo chemical exchange saturation transfer MRI signals in tumors.
  
  
  METHODS
  Two-pool (free water and semi-solid protons) and four-pool (free water, semi-solid, amide, and upfield NOE-related protons) tissue models combined with the super-Lorentzian lineshape for semi-solid protons were used to fit wide and narrow frequency-offset magnetization-transfer (MT) data, respectively. Extrapolated semi-solid MT signals at 3.5 and -3.5 ppm from water were used as reference signals to quantify APT and NOE, respectively. Six glioma-bearing rats were scanned at 4.7 Tesla. Quantitative APT and NOE signals were compared at three saturation power levels.
  
  
  RESULTS
  The observed APT signals were significantly higher in the tumor (center and rim) than in the contralateral normal brain tissue at all saturation powers, and were the major contributor to the APT-weighted image contrast (based on MT asymmetry analysis) between the tumor and the normal brain tissue. The NOE (a positive confounding factor) enhanced this APT-weighted image contrast. The fitted amide pool sizes were significantly larger, while the NOE-related pool sizes were significantly smaller in the tumor than in the normal brain tissue.
  
  
  CONCLUSIONS
  The extrapolated semi-solid magnetization transfer reference provides a relatively accurate approach for quantitatively measuring pure APT and NOE signals.
authors.affiliation: Divison of MR Research, Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Heo
authors.affiliation: Divison of MR Research, Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Divison of MR Research, Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Dong-Hoon
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Divison of MR Research, Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Hong
authors.affiliation: Divison of MR Research, Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, USA.
authors.forename: Jinyuan
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000465:Algorithms; D000577:Amides / Q000378:metabolism*; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D045744:Cell Line, Tumor; D005910:Glioma / Q000175:diagnosis* / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D011522:Protons; D051381:Rats; D011916:Rats, Inbred F344; D012680:Sensitivity and Specificity
chemical_list: D000577:Amides; D014408:Biomarkers, Tumor; D011522:Protons
keywords: APT; CEST; MT; NOE; brain tumor