Chemical exchange saturation transfer MRI serves as predictor of early progression in glioblastoma patients

Regnery, Sebastian; Adeberg, Sebastian; Dreher, Constantin; Oberhollenzer, Johanna; Meißner, Jan; Goerke, Steffen; Windschuh, Johannes; Deike-Hofmann, Katerina; Bickelhaupt, Sebastian; Zaiß, Moritz; Radbruch, Alexander; Bendszus, Martin; Wick, Wolfgang; Unterberg, Andreas; Rieken, Stefan; Debus, Jürgen; Bachert, Peter; Ladd, Mark E.; Schlemmer, Heinz–Peter; Paech, Daniel

doi:10.18632/oncotarget.25594

Cited by 64 publications

(78 citation statements)

References 52 publications

(133 reference statements)

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“…This finding is in agreement with our study results employing the dns‐APT approach at 7T. Interestingly, the pre‐treatment measurement of dns‐APT enabled a statistically significant prediction of therapy outcome, which is in accordance with two previous studies . Similar to Mehrabian et al, no significant differences between responders and non‐responders were observed for any APT contrast at the later follow‐up MRI in our study.…”

Section: Discussionsupporting

confidence: 93%

“…Interestingly, the pre-treatment measurement of dns-APT enabled a statistically significant prediction of therapy outcome, which is in accordance with two previous studies. 9,22 Similar to Mehrabian et al, 9 no significant differences between responders and non-responders were observed for any APT contrast at the later follow-up MRI in our study. This finding may be explained by the complex tumor biology, which is uncertain after the end of therapy.…”

Section: Discussionsupporting

confidence: 89%

“…The rNOE CEST signal is associated with aliphatic protons from bulk mobile proteins and lipids and has been reported to be decreased in glioma, and to correlate with histopathological grade and tumor cellularity . 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 .…”

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confidence: 99%

“…20 Recently, the potential to predict chemoradiotherapy (CRT) response has been reported. 21,22 The dns-APT contrast 15 has been shown to be increased in the tumor area of high-grade glioma and overlaps with gadolinium contrast-enhanced regions. 15,23 It also correlates with isocitrate-dehydrogenase (IDH) mutation status 23 and might be a good predictor for early progression in glioblastoma patients.…”

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confidence: 99%

“…15,23 It also correlates with isocitrate-dehydrogenase (IDH) mutation status 23 and might be a good predictor for early progression in glioblastoma patients. 22 Additional biomarkers for response assessment can be obtained by 1 H magnetic resonance spectroscopy ( 1 H MRS). 1 H MRS enables the noninvasive detection of metabolites like N-acetyl-aspartate (NAA), creatine (Cr), or choline (Cho), reflecting neuronal density, energy metabolism, and membrane metabolism, respectively.…”

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confidence: 99%

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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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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 89%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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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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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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Quantification of pulsed saturation transfer at 1.5T and 3T

Chan

Myrehaug

Stanisz

et al. 2019

Magnetic Resonance in Med

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Purpose: To compare magnetization transfer (MT) and CEST effects between 1.5T and 3T in phantom and in vivo experiments. Methods: A pulsed saturation scheme using block-shaped pulses separated by gaps was used to overcome the single RF amplifier duty cycle limitations of a clinical 1.5T scanner. Modeling was performed by incorporating the extended phase graph formalism into a Bloch-McConnell simulation. Two saturation pulse types (with long and short pulses) were used. Estimated parameters for MT (the semi-solid pool fraction, M 0 B ; the semi-solid transverse relaxation time, T 2 B) and CEST (asymmetry; areas) were compared between 1.5T and 3T in phantoms and in the healthy brain. Results: Improved fits were shown after inclusion of extended phase graphs. Semisolid pool fractions in phantom (for agar with ammonium chloride) were higher for short compared to long pulses at 3T (by 19% over all concentrations) and higher at 1.5T compared to 3T (by 5%) using short pulses. In the in vivo experiments, differentiation of white and gray matter was seen in the brain at both field strengths with improved white-gray matter contrast at 3T. In white matter, the mean semi-solid fractions were 18 ± 2% at 3T and 15 ± 2% at 1.5T. The CEST asymmetry in white matter was negative (−4.9 ± 0.4%) at 3T and zero (0.0 ± 0.3%) at 1.5T. Conclusions:The pulsed saturation method with short pulses, using the extended phase graph formalism in the Bloch McConnell simulations, led to improved model fits to the data, when compared to those without extended phase graphs. K E Y W O R D Schemical exchange saturation transfer, extended phase graphs, magnetization transfer, pulsed saturation, quantitative imaging

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Chemical exchange saturation transfer MRI serves as predictor of early progression in glioblastoma patients

Cited by 64 publications

References 52 publications

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

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

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

Quantification of pulsed saturation transfer at 1.5T and 3T

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