Background. Although glioblastomas are heterogeneous brain-infiltrating tumors, their treatment is mostly focused on the contrast-enhancing tumor mass. In this study, we combined conventional MRI, diffusion-weighted imaging (DWI), and amino acid PET to explore imaging-defined glioblastoma subregions and evaluate their potential prognostic value. Methods. Contrast-enhanced T1, T2/fluid attenuated inversion recovery (FLAIR) MR images, apparent diffusion coefficient (ADC) maps from DWI, and alpha-[ 11 C]-methyl-L-tryptophan (AMT)-PET images were analyzed in 30 patients with newly diagnosed glioblastoma. Five tumor subregions were identified based on a combination of MRI contrast enhancement, T2/FLAIR signal abnormalities, and AMT uptake on PET. ADC and AMT uptake tumor/contralateral normal cortex (T/N) ratios in these tumor subregions were correlated, and their prognostic value was determined. Results. A total of 115 MRI/PET-defined subregions were analyzed. Most tumors showed not only a high-AMT uptake (T/N ratio > 1.65, N = 27) but also a low-uptake subregion (N = 21) within the contrast-enhancing tumor mass. High AMT uptake extending beyond contrast enhancement was also common (N = 25) and was associated with low ADC (r = −0.40, P = 0.05). Higher AMT uptake in the contrast-enhancing tumor subregions was strongly prognostic for overall survival (hazard ratio: 7.83; 95% CI: 1.98-31.02, P = 0.003), independent of clinical and molecular genetic prognostic variables. Nonresected high-AMT uptake subregions predicted the sites of tumor progression on posttreatment PET performed in 10 patients. Conclusions. Glioblastomas show heterogeneous amino acid uptake with high-uptake regions often extending into non-enhancing brain with high cellularity; nonresection of these predict the site of posttreatment progression. High tryptophan uptake values in MRI contrast-enhancing tumor subregions are a strong, independent imaging marker for longer overall survival. Key Points1. Regions with high tryptophan uptake in peritumoral brain show high cellularity on diffusion MRI.2. Nonresection of such regions predicts the site of posttreatment tumor progression.3. High tryptophan uptake in contrast-enhancing tumor regions is prognostic for longer survival. 265John et al. Multimodal imaging-defined glioblastoma subregions Neuro-OncologyDespite aggressive multimodal treatment with surgery and chemoradiation therapy, glioblastomas continue to have extremely poor prognosis, with a median overall survival of 15 months. 1,2 Clinical prognostic factors for glioblastoma include age, performance status, tumor radiologic features, and extent of initial tumor resection. 3,4 Among molecular features, high Ki-67 nuclear labeling index carries unfavorable prognosis, 5 whereas isocitrate dehydrogenase 1 (IDH1) mutation is associated with prolonged survival. 6,7 O 6methylguanine-DNA methyltransferase (MGMT) promoter methylation is associated with a favorable response to the alkylating chemotherapeutic agent temozolomide. 8,9 In clinical practice, conventi...

Children with epilepsy and normal structural MRI pose a particular challenge in localization of epileptic foci for surgical resection. Many of these patients have subtle structural lesions such as mild cortical dysplasia that can be missed by conventional MRI but may become detectable by optimized and advanced MRI acquisitions and post-processing. Specificity of objective analytic techniques such as voxel-based morphometry remains an issue. Combination of MRI with functional imaging approaches can improve the accuracy of detecting epileptogenic brain regions. Analysis of glucose positron emission tomography (PET) combined with high-resolution MRI can optimize detection of hypometabolic cortex associated with subtle cortical malformations and can also enhance presurgical evaluation in children with epileptic spasms. Additional PET tracers may detect subtle epileptogenic lesions and cortex with enhanced specificity in carefully selected subgroups with various etiologies; e.g., increased tryptophan uptake can identify epileptogenic cortical dysplasia in the interictal state. Subtraction ictal SPECT can be also useful to delineate ictal foci in those with non-localizing PET or after failed surgical resection. Presurgical delineation of language and motor cortex and the corresponding white matter tracts is increasingly reliable by functional MRI and DTI techniques; with careful preparation, these can be useful even in young and sedated children. While evidence-based pediatric guidelines are still lacking, the data accumulated in the last decade strongly indicate that multimodal imaging with combined analysis of MRI, PET, and/or ictal SPECT data can optimize the detection of subtle epileptogenic lesions and facilitate seizure-free outcome while minimizing the postsurgical functional deficit in children with normal conventional MRI.