title: Nuclear Overhauser Enhancement imaging of glioblastoma at 7 Tesla: region specific correlation with apparent diffusion coefficient and histology.
abstract: OBJECTIVE
  To explore the correlation between Nuclear Overhauser Enhancement (NOE)-mediated signals and tumor cellularity in glioblastoma utilizing the apparent diffusion coefficient (ADC) and cell density from histologic specimens. NOE is one type of chemical exchange saturation transfer (CEST) that originates from mobile macromolecules such as proteins and might be associated with tumor cellularity via altered protein synthesis in proliferating cells.
  
  
  METHODS
  For 15 patients with newly diagnosed glioblastoma, NOE-mediated CEST-contrast was acquired at 7 Tesla (asymmetric magnetization transfer ratio (MTRasym) at 3.3ppm, B1 = 0.7 μT). Contrast enhanced T1 (CE-T1), T2 and diffusion-weighted MRI (DWI) were acquired at 3 Tesla and coregistered. The T2 edema and the CE-T1 tumor were segmented. ADC and MTRasym values within both regions of interest were correlated voxelwise yielding the correlation coefficient rSpearman (rSp). In three patients who underwent stereotactic biopsy, cell density of 12 specimens per patient was correlated with corresponding MTRasym and ADC values of the biopsy site.
  
  
  RESULTS
  Eight of 15 patients showed a weak or moderate positive correlation of MTRasym and ADC within the T2 edema (0.16≤rSp≤0.53, p<0.05). Seven correlations were statistically insignificant (p>0.05, n = 4) or yielded rSp≈0 (p<0.05, n = 3). No trend towards a correlation between MTRasym and ADC was found in CE-T1 tumor (-0.31<rSp<0.28, p<0.05, n = 9; p>0.05, n = 6). The biopsy-analysis within CE-T1 tumor revealed a strong positive correlation between tumor cellularity and MTRasym values in two of the three patients (rSppatient3 = 0.69 and rSppatient15 = 0.87, p<0.05), while the correlation of ADC and cellularity was heterogeneous (rSppatient3 = 0.545 (p = 0.067), rSppatient4 = -0.021 (p = 0.948), rSppatient15 = -0.755 (p = 0.005)).
  
  
  CONCLUSIONS
  NOE-imaging is a new contrast promising insight into pathophysiologic processes in glioblastoma regarding cell density and protein content, setting itself apart from DWI. Future studies might be based on the assumption that NOE-mediated CEST visualizes cellularity more accurately than ADC, especially in the CE-T1 tumor region.
authors: Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany; Neurooncologic Imaging, Department of Radiology, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors: Daniel
authors: D
authors: Paech
authors: Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany; Neurooncologic Imaging, Department of Radiology, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors: Sina
authors: S
authors: Burth
authors: Department of Medical Physics in Radiology, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors: Johannes
authors: J
authors: Windschuh
authors: Neurooncologic Imaging, Department of Radiology, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany; Department of Medical Physics in Radiology, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors: Jan-Eric
authors: JE
authors: Meissner
authors: Department of Medical Physics in Radiology, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors: Moritz
authors: M
authors: Zaiss
authors: Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany.
authors: Oliver
authors: O
authors: Eidel
authors: Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany.
authors: Philipp
authors: P
authors: Kickingereder
authors: Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
authors: Martha
authors: M
authors: Nowosielski
authors: Department of Neurology, University of Heidelberg Medical Center, Heidelberg, Germany.
authors: Benedikt
authors: B
authors: Wiestler
authors: Department of Neuropathology, University of Heidelberg Medical Center, Heidelberg, Germany.
authors: Felix
authors: F
authors: Sahm
authors: Department of Radiology, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors: Ralf Omar
authors: RO
authors: Floca
authors: Department of Neurosurgery, University of Heidelberg Medical Center, Heidelberg, Germany.
authors: Jan-Oliver
authors: JO
authors: Neumann
authors: Department of Neurology, University of Heidelberg Medical Center, Heidelberg, Germany.
authors: Wolfgang
authors: W
authors: Wick
authors: Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany.
authors: Sabine
authors: S
authors: Heiland
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: Department of Medical Physics in Radiology, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors: Mark Edward
authors: ME
authors: Ladd
authors: Department 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; Neurooncologic Imaging, Department of Radiology, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors: Alexander
authors: A
authors: Radbruch
mesh_terms: D001932:Brain Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000473:pathology*; D004058:Diffusion; D038524:Diffusion Magnetic Resonance Imaging; D004487:Edema / Q000150:complications; D005260:Female; D005909:Glioblastoma / Q000150:complications / Q000175:diagnosis* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013238:Stereotaxic Techniques