1579 Background: The diagnosis and treatment of DIPG are based on typical MRI findings because of the inherent risk of biopsy. The standard treatment for this tumor is XRT. The limited ability of standard MRI to distinguish tumor from treatment effect hampers the determination of tumor response and time to progression. The objective of this study is to measure biochemical and physiologic MRI markers in DIPG after XRT that may aid in assessment of response. Methods: Fifteen pediatric patients (5 y, range, 1.8–12) with DIPG involving >50% of the pons and treated with XRT only were evaluated 12–64 days (median 38) following XRT (50.4–67.2 Gy, median 54 Gy) by MRI at 1.5 T. Standard T1, T2, and FLAIR MRI was performed in all cases. In addition, proton MR spectroscopy (MRS) was performed in 10 cases, MRS imaging (1H-MRSI) in 12, dynamic contrast enhanced MRI (DCE-MRI) in 14, and dynamic susceptibility weighted MRI (DSC-MRI) in 9. Ktrans and rCBV were measured using ROIs on enhancing portions of the tumor from the DCE- and DSC-MRI data after kinetic modeling. Results: Tumor area changed following XRT by a median of −29% (range, −61 to +37; SD, 33) and −17% (range, −65 to +101; SD, 45) on T2 and FLAIR, respectively. Enhancement was identified in 15 of 15 patients following XRT, and in only 6 of 15 prior to XRT (P = 0.0039 McNemar’s test). Following XRT, Choline: N-Acetyl Aspartate (CHO:NAA) ratio was 3.2 ± 1.9 by single voxel MRS, and the “worst voxel” CHO:NAA ratio was 3.5 ± 1.5 by 1H-MRSI. Overall, rCBV (1.98 ± 1.30) was elevated relative to normal cerebellum. However in 4 of these cases, rCBV was markedly elevated (>2), 4 were normal (1.0–1.3), and one was markedly reduced (0.6).Similarly, disruption of the blood-tumor barrier was variable across the group. Ktrans, a measure of permeability, ranged from 0.000 to 0.026 s−1, averaging 0.0086 ± 0.0085 s−1. Conclusions: Although all patients had a structurally similar tumor on MRI prior to XRT, significant variability in physiologic and metabolic response to XRT as measured by multiparametric MRI are noted. Presumably this variability represents real biologic differences resulting from differential responses to therapy. Determination of the prognostic significance is ongoing. No significant financial relationships to disclose.