Abstract
BACKGROUND: Amide proton transfer (APT) imaging has been proposed as a technique to assess tumor metabolic activity. We have previously (11)C-methionine positron emission tomography ((11)C-Met-PET) can evaluate the metabolic activity of peritumoral area including infiltrating tumor cells in glioblastoma (GBM). To resolve disadvantages of (11)C-Met-PET, in the present study, we aimed to evaluate whether three-dimensional fast spin echo-based APT (3D FSE-APT) imaging is usable for not only presenting the metabolic activity of brain tumors, but also detecting areas where infiltrating tumor cells including glioma stem cells (GSCs) could exist, by applying an image-guided navigation system incorporating 3D FSE-APT to glioblastoma surgery. METHODS: Twenty-six consecutive patients with GBMs were enrolled in this study. Among these 26 cases, 10 patients underwent (11)C-Met-PET examination. All 26 patients underwent two-dimensional single shot fast spine echo-based APT acquisition with a chemical exchange saturation transfer sequence (2D SSFSE-APT). The most recent 14 cases underwent 3D FSE-APT to examine whether 3D APT imaging was applicable to the navigation system. We investigated the clinical applicability of 3D FSE-APT by comparison with 2D SSFSE-APT and evaluated the utility of 3D FSE-APT as a metabolic imaging guide in the intraoperative navigation system. We also analyzed whether 3D FSE-APT can depict the extent of infiltrating tumor cells including GSCs in the peritumoral area in GBM. RESULTS: The most recent 14 cases underwent 3D FSE-APT. The 3D FSE-APT was visually almost equivalent to 2D SSFSE-APT and mean APT intensity (APT(mean)) in GBM obtained by 3D FSE-APT was almost equal to that from 2D SSFSE-APT. Mean APT(mean) on 2D SSFSE-APT at the site showing a tumor-to-contralateral normal brain tissue ratio (TNR) of 1.4 on (11)C-Met-PET was 1.52 ± 0.16%. In contrast, mean APT(mean) on 3D FSE-APT at the same site was 1.30 ± 0.06%. The optimal cut-off value for APT(mean) on 3D FSE-APT was evaluated as 1.28%, offering 100% sensitivity and 100% specificity. Incorporating 3D FSE-APT into the navigation system allowed tumor resection including infiltrating tumor cells under image-guided navigation. Mean Ki-67 staining index in the area with a mean APT(mean) of 1.28% was 11.8% (range, 5.0-20.0%). CONCLUSIONS: The area of tumor invasion could be evaluated by 3D FSE-APT in a similar way to (11)C-Met-PET, and the cut-off value for deciding the borderline between the area including infiltrating tumor cells and that with almost no tumor cells was 12.8%. In addition, 3D FSE-APT could be applied to navigation systems and may have great potential as an imaging modality replacing (11)C-Met-PET in GBM surgery.