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

Abstract

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.

Adaptive denoising for chemical exchange saturation transfer MR imaging

“…21,22 Several CEST applications involve the fitting of spectrally selective CEST effects related to proteins, including isolation of amide, amine and relayed nuclear Overhauser effects (rNOE), as well as smaller peaks potentially related to creatine and choline-containing phospholipids. 10,11,23,24 Due to recent reports of spatial correlations between isolated amide CEST and gadolinium ring enhancement, 5,6 changes in rNOE with correlation to histology, [25][26][27][28] and the ability of these contrasts to measure and predict brain tumor therapy response, [29][30][31][32] spatial correlations of spectrally selective protein CEST effects are also garnering increased clinical interest. Furthermore, novel experiments that target CEST signals specifically originating from bulk mobile proteins 33 are being investigated to identify altered states of proteins under conditions of disease.…”

Whole‐brain chemical exchange saturation transfer imaging with optimized turbo spin echo readout

“…CEST MRI has been shown to be highly promising in multiple clinical applications, especially neurological applications. For example, amide proton transfer (APT) imaging, a subtype of the CEST technique that detects proteins and peptides at 3.5 ppm upfield from the water frequency, has been used to grade brain tumors, differentiate true progression from treatment effects in brain tumors after completion of chemoradiotherapy, detect early therapeutic response during chemoradiation, predict oncogenic markers, and identify ischemic penumbra in strokes . Glutamate CEST imaging, which detects the glutamate pool at 3 ppm upfield from water, has been used to lateralize epileptic foci and diagnose patients with psychosis .…”

Are We Heading to the Future of Musculoskeletal Tumor Imaging with Ultra-High Field 7T MRI?

“…Subtle metabolites changes have been detected during chemotherapy using 31-phosphorus (31P) MRI at UHF so that non responders could be distinguished from partial and complete responders. In brain, CEST imaging performed at 7T was able to distinguish stable and progressive disease under chemo-radiotherapy [57,58]. Particular attention should however be paid to specific tumour characteristics.…”