Chemical exchange saturation transfer (CEST) imaging reveals tumor-specific molecular changes in adult gliomas after radiotherapy

PURPOSE: Response assessment after radiotherapy (RT) of gliomas remains challenging due to radiation-induced reactions that mimic tumor growth (pseudoprogression, PsPD). Unlike standard anatomical MRI, Chemical Exchange Saturation Transfer (CEST) MRI offers molecular image contrasts that could differentiate tumor growth from PsPD. Our aim was to quantify the influence of radiation dose on CEST contrasts in both healthy-appearing brain tissues and tumor tissues. METHODS: This prospective study enrolled 33 glioma patients (26 glioblastoma, 7 IDH-mutant glioma). In total, 81 longitudinal CEST MRI scans were performed before RT until seven months thereafter. CEST MRI included asymmetry analysis of the amide proton transfer-weighted (APTw) signal, and a multipool Lorentzian fitting approach was used to quantify the amide signal, ssMT signal and rNOE signal. CEST contrast changes were analyzed in normal-appearing brain tissues and tumor by cumulative histograms and based on Bayesian linear multilevel models. RESULTS: Normal-appearing brain tissues did not exhibit significant changes in any CEST contrasts after high-dose radiation. Conversely, the CEST contrasts changed in the tumor region of glioma patients according to their response to treatment. Particularly the APTw-signal demonstrated moderate opposing trends for tumor growth versus PsPD as early as four weeks after RT (stable disease: -0.08/month [-0.15 to -0.01], progressive disease: +0.18/month [0.07 - 0.29], PsPD: -0.53/month [-0.65 to 0.42]). CONCLUSIONS: Our findings indicate that CEST contrasts reveal tumor-specific molecular changes in gliomas following RT. These early changes support the potential of CEST MRI to differentiate PsPD from tumor growth at later time points.