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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.    Patients and Methods  For 15 patients with newly diagnosed glioblastoma, NOE-mediated CEST-contrast was acquired at 7 Tesla (asymmetric magnetization transfer ratio (MTR asym ) 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 MTR asym  values within both regions of interest were correlated voxelwise yielding the correlation coefficient r Spearman  (r Sp ). In three patients who underwent stereotactic biopsy, cell density of 12 specimens per patient was correlated with corresponding MTR asym  and ADC values of the biopsy site.    Results  Eight of 15 patients showed a weak or moderate positive correlation of MTR asym  and ADC within the T2 edema (0.16≤r Sp ≤0.53, p<0.05). Seven correlations were statistically insignificant (p>0.05, n = 4) or yielded r Sp ≈0 (p<0.05, n = 3). No trend towards a correlation between MTR asym  and ADC was found in CE-T1 tumor (-0.31<r Sp <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 MTR asym  values in two of the three patients (r Sp   patient3  = 0.69 and r Sp   patient15  = 0.87, p<0.05), while the correlation of ADC and cellularity was heterogeneous (r Sp   patient3  = 0.545 (p = 0.067), r Sp   patient4  = -0.021 (p = 0.948), r Sp   patient15  = -0.755 (p = 0.005)).    Discussion  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.

Nuclear Overhauser Enhancement Imaging of Glioblastoma at 7 Tesla: Region Specific Correlation with Apparent Diffusion Coefficient and Histology