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  • 1
    Language: English
    In: PloS one, 2017, Vol.12(4), pp.e0174620
    Description: The purpose of this study was to investigate whether a voxel-wise analysis of apparent diffusion coefficient (ADC) values may differentiate between progressive disease (PD) and pseudoprogression (PsP) in patients with high-grade glioma using the parametric response map, a newly introduced postprocessing tool. Twenty-eight patients with proven PD and seven patients with PsP were identified in this retrospective feasibility study. For all patients ADC baseline and follow-up maps on four subsequent MRIs were available. ADC maps were coregistered on contrast enhanced T1-weighted follow-up images. Subsequently, enhancement in the follow-up contrast enhanced T1-weighted image was manually delineated and a reference region of interest (ROI) was drawn in the contralateral white matter. Both ROIs were transferred to the ADC images. Relative ADC (rADC) (baseline)/reference ROI values and rADC (follow up)/reference ROI values were calculated for each voxel within the ROI. The corresponding voxels of rADC (follow up) and rADC (baseline) were subtracted and the percentage of all voxels within the ROI that exceeded the threshold of 0.25 was quantified. rADC voxels showed a decrease of 59.2% (1st quartile (Q1) 36.7; 3rd quartile (Q3) 78.6) above 0.25 in patients with PD and 18.6% (Q1 3.04; Q3 26.5) in patients with PsP (p = 0.005). Receiver operating characteristic curve analysis showed the optimal decreasing rADC cut-off value for identifying PD of 〉 27.05% (area under the curve 0.844±0.065, sensitivity 0.86, specificity 0.86, p = 0.014). This feasibility study shows that the assessment of rADC using parametric response maps might be a promising approach to contribute to the differentiation between PD and PsP. Further research in larger patient cohorts is necessary to finally determine its clinical utility.
    Keywords: Brain Mapping -- Methods ; Brain Neoplasms -- Pathology ; Glioblastoma -- Pathology
    E-ISSN: 1932-6203
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  • 2
    Language: English
    In: PloS one, 2015, Vol.10(3), pp.e0121220
    Description: 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. 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. Eight of 15 patients showed a weak or moderate positive correlation of MTRasym and ADC within the T2 edema (0.16≤rSp≤0.53, p0.05, n = 4) or yielded rSp≈0 (p0.05, 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)). 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.
    Keywords: Diffusion Magnetic Resonance Imaging ; Brain Neoplasms -- Diagnosis ; Glioblastoma -- Diagnosis
    E-ISSN: 1932-6203
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  • 3
    In: Journal of Magnetic Resonance Imaging, October 2019, Vol.50(4), pp.1268-1277
    Description: Keywords: CEST-MRI; .sup.1H MRS; chemoradiotherapy response; rNOE; dns-APT; glioma Background Patients with newly diagnosed inoperable glioma receive chemoradiotherapy (CRT). Standard Response Assessment in Neuro-Oncology (RANO) takes a minimum of 4weeks after the end of treatment. Purpose/Hypothesis To investigate whether chemical exchange saturation transfer (CEST) MRI enables earlier assessment of response to CRT in glioma patients. Study Type Longitudinal prospective study. Population Twelve brain tumor patients who underwent definitive CRT were included in this study. Three longitudinal CEST MRI measurements were performed for each patient at 7T: first before, second immediately after completion of CRT, and a third measurement as a 6-week follow-up. Field Strength/Sequence Conventional MRI (contrast-enhanced, T.sub.2w and diffusion-weighted imaging) at 3T and T.sub.2w and CEST MRI at 7T was performed for all patients. Assessment The mean relaxation-compensated relayed nuclear-Overhauser-effect CEST signal (rNOE) and the mean downfield-rNOE-suppressed amide proton transfer (dns-APT) CEST signal were investigated. Additionally, choline-to-N-acetyl-aspartate ratios (Cho/NAA) were evaluated using single-voxel .sup.1H-MRS in six of these patients. Performance of obtained contrasts was analyzed in assessing treatment response as classified according to the updated RANO criteria. Statistical Test Unpaired Student's t-test. Results The rNOE signal significantly separated stable and progressive disease directly after the end of therapy (post-treatment normalized to pre-treatment mean[+ or -]SD: rNOE.sub.responder=1.090[+ or -]0.110, rNOE.sub.non-responder=0.808[+ or -]0.155, P=0.015). In contrast, no significant difference was observed between either group when assessing the normalized dns-APT (dns-APT.sub.responder = 0.953[+ or -]0.384, dns-APT.sub.non-responder=0.972[+ or -]0.477, P=0.95). In the smaller MRS subcohort, normalized Cho/NAA decreased in therapy responders (Cho/NAA.sub.responder=0.632[+ or -]0.007, Cho/NAA.sub.non-responder=0.946[+ or -]0.124, P=0.070). Data Conclusion rNOE mediated CEST imaging at 7T allowed for discrimination of responders and non-responders immediately after the end of CRT, additionally supported by .sup.1H-MRS data. This is at least 4weeks earlier than the standard clinical evaluation according to RANO. Therefore, CEST MRI may enable early response assessment in glioma patients. Level of Evidence: 1 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2019;50:1268-1277. CAPTION(S): Figure S1 Representative Z-spectra for a voxel in the tumor region (Tumor, top) and a voxel in the contralateral normal appearing white matter (CLNAWM, bottom) in the range from -10 to +10ppm. The Lorentzian fit of all data points (black line) and the 5-pool Lorentzian fits (amides, amines, rNOE, MT, water) are shown. Figure S2 rNOE contrast and T2-w images shown for four representative patients with the corresponding (ROI) segmentation. ROIs used for the quantitative evaluation are displayed in magenta. Figure S3 dns-APT contrast and T2-w images shown for four representative patients with the corresponding (ROI) segmentation. ROIs used for the quantitative evaluation are displayed in magenta. Byline: Jan-Eric Meissner, Andreas Korzowski, Sebastian Regnery, Steffen Goerke, Johannes Breitling, Ralf Omar Floca, Jurgen Debus, Heinz-Peter Schlemmer, Mark Edward Ladd, Peter Bachert, Sebastian Adeberg,Daniel Paech
    Keywords: Cest‐Mri ; 1 H Mrs ; Chemoradiotherapy Response ; Rnoe ; Dns‐Apt ; Glioma
    ISSN: 1053-1807
    E-ISSN: 1522-2586
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