Assessment of multimodal CEST, perfusion and diffusion MRI for predicting clinical outcome of patients with diffuse glioma following surgery at baseline before radiotherapy

To assess the predictive value of different chemical exchange saturation transfer (CEST) contrasts, i.e. of the amide proton transfer (APT), relayed nuclear Overhauser effect (rNOE), and semi-solid magnetization transfer (ssMT), as well as of clinical routine perfusion- and diffusion-weighted MRI, in terms of treatment outcome in patients with glioma following surgery at baseline before radiotherapy at 3 T. From September 2018 to December 2022, 78 study participants (median age 62 years, 27/78 female) prospectively underwent CEST, diffusion, and perfusion imaging. CEST contrasts were reconstructed for the APT-weighted magnetization transfer ratio asymmetry (APTwasym), relaxation-compensated CEST metrics (MTRRexAPT, MTRRexNOE, MTRRexMT), and MTconst. Contrast-enhancing and whole tumor volumes were segmented on T2w-FLAIR and T1w images. Associations of mean contrast values with therapy response were tested using ROC analyses, while relationships with progression-free survival (PFS, median 6.04 months) and overall survival (OS, median 11.58 months), as well as added benefit compared to nCBV and ADC maps, were assessed using dichotomized Cox regression models. MTRRexAPT, MTRRexNOE, and MTRRexMT were associated with therapy response (AUC = 0.82, 0.81, 0.68; all p ≤ 0.03), PFS (HR = 2.92, 0.37, 3.40; all p ≤ 0.02), and OS (HR = 2.76, 0.63, 8.09; all p ≤ 0.05). MTconst was correlated with OS (HR = 5.52, p < 0.01), while APTwasym was linked to therapy response (AUC = 0.71, p = 0.02). MTRRexMT (χ² = 13.71, p < 0.01) and MTconst (χ² = 5.62, p = 0.018) provided each additional value to nCBV for OS prediction. Relaxation-compensated CEST imaging of the APT, rNOE, and ssMT, as well as conventional APTwasym showed ability to predict treatment outcome, whilst ssMT-weighted imaging provided added benefit for OS prediction in patients with diffuse glioma following surgery at baseline before radiotherapy at 3 T.