Chemical Exchange Saturation Transfer MRI for Differentiating Radiation Necrosis From Tumor Progression in Brain Metastasis-Application in a Clinical Setting

Background High radiation doses of stereotactic radiosurgery (SRS) for brain metastases (BM) can increase the likelihood of radiation necrosis (RN). Advanced MRI sequences can improve the differentiation between RN and tumor progression (TP). Purpose To use saturation transfer MRI methods including chemical exchange saturation transfer (CEST) and magnetization transfer (MT) to distinguish RN from TP. Study Type Prospective cohort study. Subjects Seventy patients (median age 60; 73% females) with BM (75 lesions) post-SRS. Field Strength/Sequence 3-T, CEST imaging using low/high-power (saturation B-1 = 0.52 and 2.0 mu T), quantitative MT imaging using B-1 = 1.5, 3.0, and 5.0 mu T, WAter Saturation Shift Referencing (WASSR), WAter Shift And B-1 (WASABI), T-1, and T-2 mapping. All used gradient echoes except T-2 mapping (gradient and spin echo). Assessment Voxel-wise metrics included: magnetization transfer ratio (MTR); apparent exchange-dependent relaxation (AREX); MTR asymmetry; normalized MT exchange rate and pool size product; direct water saturation peak width; and the observed T-1 and T-2. Regions of interests (ROIs) were manually contoured on the post-Gd T(1)w. The mean (of median ROI values) was compared between groups. Clinical outcomes were determined by clinical and radiologic follow-up or histopathology. Statistical Tests t-Test, univariable and multivariable logistic regression, receiver operating characteristic, and area under the curve (AUC) with sensitivity/specificity values with the optimal cut point using the Youden index, Akaike information criterion (AIC), Cohen's d. P < 0.05 with Bonferroni correction was considered significant. Results Seven metrics showed significant differences between RN and TP. The high-power MTR showed the highest AUC of 0.88, followed by low-power MTR (AUC = 0.87). The combination of low-power CEST scans improved the separation compared to individual parameters (with an AIC of 70.3 for low-power MTR/AREX). Cohen's d effect size showed that the MTR provided the largest effect sizes among all metrics. Data Conclusion Significant differences between RN and TP were observed based on saturation transfer MRI. Evidence Level: 3 Technical Efficacy: Stage 2