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...

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Background: Clinical glioblastoma treatment mostly focuses on the contrast-enhancing tumor mass. Amino acid positron emission tomography (PET) can detect additional, nonenhancing glioblastoma-infiltrated brain regions that are difficult to distinguish on conventional magnetic resonance imaging (MRI). We combined MRI with perfusion imaging and amino acid PET to evaluate such nonenhancing glioblastoma regions. Methods: Structural MRI, relative cerebral blood volume (rCBV) maps from perfusion MRI, and α-[11C]-methyl-l-tryptophan (AMT)-PET images were analyzed in 20 patients with glioblastoma. The AMT uptake and rCBV (expressed as tumor to normal [T/N] ratios) were compared in nonenhancing tumor portions showing increased signal on T2/fluid-attenuated inversion recovery (T2/FLAIR) images. Results: Thirteen (65%) tumors showed robust heterogeneity in nonenhancing T2/FLAIR hyperintense areas on AMT-PET, whereas the nonenhancing regions in the remaining 7 cases had homogeneous AMT uptake (low in 6, high in 1). AMT and rCBV T/N ratios showed only a moderate correlation in the nonenhancing regions ( r = 0.41, P = .017), but regions with very low rCBV (<0.79 T/N ratio) had invariably low AMT uptake. Conclusions: The findings demonstrate the metabolic and perfusion heterogeneity of nonenhancing T2/FLAIR hyperintense glioblastoma regions. Amino acid PET imaging of such regions can detect glioma-infiltrated brain for treatment targeting; however, very low rCBV values outside the contrast-enhancing tumor mass make increased AMT uptake in nonenhancing glioblastoma regions unlikely.

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