Differentiation between Radiation Necrosis and Tumor Progression Using Chemical Exchange Saturation Transfer

Purpose: Stereotactic radiosurgery (SRS) is a common treatment used in patients with brain metastases and is associated with high rates of local control, however, at the risk of radiation necrosis. It is difficult to differentiate radiation necrosis from tumor progression using conventional MRI, making it a major diagnostic dilemma for practitioners. This prospective study investigated whether chemical exchange saturation transfer (CEST) was able to differentiate these two conditions.Experimental Design: Sixteen patients with brain metastases who had been previously treated with SRS were included. Average time between SRS and evaluation was 12.6 months. Lesion type was determined by pathology in 9 patients and the other 7 were clinically followed. CEST imaging was performed on a 3T Philips scanner and the following CEST metrics were measured: amide proton transfer (APT), magnetization transfer (MT), magnetization transfer ratio (MTR), and area under the curve for CEST peaks corresponding to amide and nuclear Overhauser effect (NOE).Results: Five lesions were classified as progressing tumor and 11 were classified as radiation necrosis (using histopathologic confirmation and radiographic follow-up). The best separation was obtained by NOE_MTR (NOE_MTR,necrosis = 8.9 ± 0.9%, NOE_{MTR,progression} = 12.6 ± 1.6%, P < 0.0001) and Amide_MTR (Amide_MTR,necrosis = 8.2 ± 1.0%, Amide_{MTR,progression} = 12.0 ± 1.9%, P < 0.0001). MT (MT_necrosis = 4.7 ± 1.0%, MT_progression = 6.7 ± 1.7%, P = 0.009) and NOE_AUC (NOE_AUC,necrosis = 4.3 ± 2.0% Hz, NOE_{AUC,progression} = 7.2 ± 1.9% Hz, P = 0.019) provided statistically significant separation but with higher P values.Conclusions: CEST was capable of differentiating radiation necrosis from tumor progression in brain metastases. Both NOE_MTR and Amide_MTR provided statistically significant separation of the two cohorts. However, APT was unable to differentiate the two groups. Clin Cancer Res; 23(14); 3667-75. ©2017 AACR.