title: Downfield-NOE-suppressed amide-CEST-MRI at 7 Tesla provides a unique contrast in human glioblastoma.
abstract: The chemical exchange saturation transfer (CEST) effect observed in brain tissue in vivo at the frequency offset 3.5 ppm downfield of water was assigned to amide protons of the protein backbone. Obeying a base-catalyzed exchange process such an amide-CEST effect would correlate with intracellular pH and protein concentration, correlations that are highly interesting for cancer diagnosis. However, recent experiments suggested that, besides the known aliphatic relayed-nuclear Overhauser effect (rNOE) upfield of water, an additional downfield rNOE is apparent in vivo resonating as well around +3.5 ppm. In this study, we present further evidence for the underlying downfield-rNOE signal, and we propose a first method that suppresses the downfield-rNOE contribution to the amide-CEST contrast. Thus, an isolated amide-CEST effect depending mainly on amide proton concentration and pH is generated.
  
  
  
  The isolation of the exchange mediated amide proton effect was investigated in protein model-solutions and tissue lysates and successfully applied to in vivo CEST images of 11 glioblastoma patients.
  
  
  
  Comparison with gadolinium contrast enhancing longitudinal relaxation time-weighted images revealed that the downfield-rNOE-suppressed amide-CEST contrast forms a unique contrast that delineates tumor regions and show remarkable overlap with the gadolinium contrast enhancement.
  
  
  
  Thus, suppression of the downfield rNOE contribution might be the important step to yield the amide proton CEST contrast originally aimed at. Magn Reson Med 77:196-208, 2017. © 2016 Wiley Periodicals, Inc.
authors: Division of Medical Physics in Radiology, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors: Moritz
authors: M
authors: Zaiss
authors: Division of Medical Physics in Radiology, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors: Johannes
authors: J
authors: Windschuh
authors: Division of Medical Physics in Radiology, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors: Steffen
authors: S
authors: Goerke
authors: Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany.|Department of Radiology, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors: Daniel
authors: D
authors: Paech
authors: Division of Medical Physics in Radiology, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.|Department of Radiology, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors: Jan-Eric
authors: JE
authors: Meissner
authors: Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany.|Department of Radiology, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors: Sina
authors: S
authors: Burth
authors: Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany.
authors: Philipp
authors: P
authors: Kickingereder
authors: University of Heidelberg Neurology Clinic, Heidelberg, Germany.|Clinical Cooperation Unit Neuro-oncology, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg.
authors: Wolfgang
authors: W
authors: Wick
authors: Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany.
authors: Martin
authors: M
authors: Bendszus
authors: Department of Radiology, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors: Heinz-Peter
authors: HP
authors: Schlemmer
authors: Division of Medical Physics in Radiology, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors: Mark E
authors: ME
authors: Ladd
authors: Division of Medical Physics in Radiology, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors: Peter
authors: P
authors: Bachert
authors: Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany.|Department of Radiology, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors: Alexander
authors: A
authors: Radbruch
mesh_terms: D000465:Algorithms; D001921:Brain / Q000000981:diagnostic imaging; D001932:Brain Neoplasms / Q000000981:diagnostic imaging*; D005909:Glioblastoma / Q000000981:diagnostic imaging*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D019047:Phantoms, Imaging
keywords: 7T; AREX; CEST; aliphatic rNOE; aromatic rNOE; brain tumor; glioblastoma; relaxation compensation; relaxation-compensated CEST; spillover correction; ultra-high field