Assessing the predictability of <i>IDH</i> mutation and <i>MGMT</i> methylation status in glioma patients using relaxation-compensated multipool CEST MRI at 7.0 T

Paech, Daniel; Windschuh, Johannes; Oberhollenzer, Johanna; Dreher, Constantin; Sahm, Felix; Meißner, Jan; Goerke, Steffen; Schuenke, Patrick; Zaiß, Moritz; Regnery, Sebastian; Bickelhaupt, Sebastian; Bäumer, Philipp; Bendszus, Martin; Wick, Wolfgang; Unterberg, Andreas; Bachert, Peter; Ladd, Mark E.; Schlemmer, Heinz–Peter; Radbruch, Alexander

doi:10.1093/neuonc/noy073

Cited by 125 publications

(128 citation statements)

References 49 publications

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“…This is consistent with lab research results, showing global downregulation of protein expression in mutant IDH1‐driven glioma cells, compared with oncogenic HRAS IDH1‐wildtype glioma cells . These early findings, together with some recent confirmatory results, are very promising. If these APTw results are validated in rigorous clinical studies, the preoperative determination of genetic biomarkers can potentially be done rapidly and noninvasively.…”

Section: Current Applicationssupporting

confidence: 91%

APT‐weighted MRI: Techniques, current neuro applications, and challenging issues

Zhou

Heo

Knutsson

et al. 2019

Magnetic Resonance Imaging

257

329

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Amide proton transfer‐weighted (APTw) imaging is a molecular MRI technique that generates image contrast based predominantly on the amide protons in mobile cellular proteins and peptides that are endogenous in tissue. This technique, the most studied type of chemical exchange saturation transfer imaging, has been used successfully for imaging of protein content and pH, the latter being possible due to the strong dependence of the amide proton exchange rate on pH. In this article we briefly review the basic principles and recent technical advances of APTw imaging, which is showing promise clinically, especially for characterizing brain tumors and distinguishing recurrent tumor from treatment effects. Early applications of this approach to stroke, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and traumatic brain injury are also illustrated. Finally, we outline the technical challenges for clinical APT‐based imaging and discuss several controversies regarding the origin of APTw imaging signals in vivo. Level of Evidence: 3 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2019;50:347–364.

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Section: Current Applicationssupporting

confidence: 91%

APT‐weighted MRI: Techniques, current neuro applications, and challenging issues

Zhou

Heo

Knutsson

et al. 2019

Magnetic Resonance Imaging

257

329

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“…However, due to the applied low‐power saturation (i.e., B 1 < 1 µT) and the evaluation at +3.5 ppm, this pool can primarily be associated with the amide proton signal, which is why it was termed APT. In addition, a compensation for underlying downfield‐rNOE signals is possible by the dnsAPT metric . Following previous findings, the ssMT was set to be asymmetric around the DS and to resonate at approximately −2.5 ppm.…”

Section: Discussionmentioning

confidence: 99%

Relaxation‐compensated APT and rNOE CEST‐MRI of human brain tumors at 3 T

Goerke

Soehngen

Deshmane

et al. 2019

Magnetic Resonance in Med

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Purpose Relaxation‐compensated CEST‐MRI (i.e., the inverse metrics magnetization transfer ratio and apparent exchange‐dependent relaxation) has already been shown to provide valuable information for brain tumor diagnosis at ultrahigh magnetic field strengths. This study aims at translating the established acquisition protocol at 7 T to a clinically relevant magnetic field strength of 3 T. Methods Protein model solutions were analyzed at multiple magnetic field strengths to assess the spectral widths of the amide proton transfer and relayed nuclear Overhauser effect (rNOE) signals at 3 T. This prior knowledge of the spectral range of CEST signals enabled a reliable and stable Lorentzian‐fitting also at 3 T where distinct peaks are no longer resolved in the Z‐spectrum. In comparison to the established acquisition protocol at 7 T, also the image readout was extended to three dimensions. Results The observed spectral range of CEST signals at 3 T was approximately ±15 ppm. Final relaxation‐compensated amide proton transfer and relayed nuclear Overhauser effect contrasts were in line with previous results at 7 T. Examination of a patient with glioblastoma demonstrated the applicability of this acquisition protocol in a clinical setting. Conclusion The presented acquisition protocol allows relaxation‐compensated CEST‐MRI at 3 T with a 3D coverage of the human brain. Translation to a clinically relevant magnetic field strength of 3 T opens the door to trials with a large number of participants, thus enabling a comprehensive assessment of the clinical relevance of relaxation compensation in CEST‐MRI.

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“…However, our study suggests that rNOE and APT effects are not equally associated with treatment response in glioma. Hence, there may be other mechanisms/factors influencing the contrast, eg, histopathological characteristics such as tumor grade and molecular features including protein conformation, pH, or genetic subtypes such as IDH mutation status . The analysis of larger study cohorts with detailed histological and molecular data would allow further investigation of this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the potential to predict chemoradiotherapy (CRT) response has been reported . The dns‐APT contrast has been shown to be increased in the tumor area of high‐grade glioma and overlaps with gadolinium contrast‐enhanced regions . It also correlates with isocitrate‐dehydrogenase (IDH) mutation status and might be a good predictor for early progression in glioblastoma patients …”

mentioning

confidence: 99%

Early response assessment of glioma patients to definitive chemoradiotherapy using chemical exchange saturation transfer imaging at 7 T

Meißner

Korzowski

Regnery

et al. 2019

Magnetic Resonance Imaging

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Background Patients with newly diagnosed inoperable glioma receive chemoradiotherapy (CRT). Standard Response Assessment in Neuro‐Oncology (RANO) takes a minimum of 4 weeks 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, T2w and diffusion‐weighted imaging) at 3T and T2w 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 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 ± SD: rNOEresponder = 1.090 ± 0.110, rNOEnon‐responder = 0.808 ± 0.155, P = 0.015). In contrast, no significant difference was observed between either group when assessing the normalized dns‐APT (dns‐APTresponder = 0.953 ± 0.384, dns‐APTnon‐responder = 0.972 ± 0.477, P = 0.95). In the smaller MRS subcohort, normalized Cho/NAA decreased in therapy responders (Cho/NAAresponder = 0.632 ± 0.007, Cho/NAAnon‐responder = 0.946 ± 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 1H‐MRS data. This is at least 4 weeks 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.

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Assessing the predictability of IDH mutation and MGMT methylation status in glioma patients using relaxation-compensated multipool CEST MRI at 7.0 T

Abstract: Relaxation-compensated multipool CEST MRI, particularly dns-APT imaging, enabled prediction of IDH mutation status and differentiation of LGG versus HGG and should therefore be considered as a non-invasive MR biomarker in the diagnostic workup.

Cited by 125 publications

References 49 publications

APT‐weighted MRI: Techniques, current neuro applications, and challenging issues

APT‐weighted MRI: Techniques, current neuro applications, and challenging issues

Relaxation‐compensated APT and rNOE CEST‐MRI of human brain tumors at 3 T

Early response assessment of glioma patients to definitive chemoradiotherapy using chemical exchange saturation transfer imaging at 7 T

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