Carmustine wafers (Gliadel Wafer) are implanted at resection in some patients with high-grade gliomas. Studies suggest that proton magnetic resonance spectroscopic imaging ((1)H MRSI) demonstrates early changes predictive of future failure or response to systemic chemotherapy. This study explores (1)H MRSI as a means to assess peri-tumoral tissue response post-resection and Gliadel((R)) implantation in patients with high-grade gliomas. Pilot (1)H MRSI data are presented that demonstrate noninvasive, serial monitoring of metabolic changes at the tumor site following Gliadel implantation. Three patients with newly diagnosed glioblastoma multiforme (GBM) underwent MRI and (1)H MRSI at 3.0 Tesla prior to resection and at 3-5 and > or =12 weeks post-operatively. Baseline MRS spectra of tumor tissue from all patients were characterized by marked increases of choline (CHO) and lactate (LAC), and a decrease of N-acetylaspartate (NAA), typical of GBM compared with normal contra-lateral brain tissue. Post-operatively, spectra were analyzed from the resection cavity and peri-tumoral regions and compared with normal tissue from the contra-lateral brain at baseline. In 2 of 3 patients, peri-tumoral NAA/CRE increased and CHO/NAA decreased compared to contra-lateral brain at 3-5 weeks compared with baseline following Gliadel therapy and surgery but prior to radiotherapy. This study indicates that (1)H MRSI has the ability to localize regions of heterogeneous response following Gliadel treatment. Although data are limited, these results suggest that metabolic indicators of outcome can be successfully monitored pre- and post-surgical resection and Gliadel implantation with (1)H MRSI. Additional study of patients receiving Gliadel Wafers using (1)H MRSI may serve to aid clinicians in assessing tumor regression and gauging efficacy of this chemotherapy treatment.