NIMG-77. MULTIMODAL IMAGING OF GLIOBLASTOMA SUBREGIONS: IMPACT ON OVERALL SURVIVAL

Glioblastomas are heterogeneous brain-infiltrating tumors with diverse histopathological and molecular genetic features. Although treatment is mostly focused on the contrast-enhancing tumor mass, combination of advanced structural and molecular imaging can enhance more accurate tumor delineation and capture glioblastoma heterogeneity. Here we combined conventional MRI with diffusion-weighted imaging (DWI) and amino acid PET characteristics to explore imaging-defined glioblastoma subregions and evaluate their potential prognostic value. Contrast-enhanced T1, T2/FLAIR MR images, apparent diffusion coefficient (ADC) maps from DWI, and alpha-[11C]-methyl-L-tryptophan (AMT)-PET images were analyzed in 30 patients (mean age: 59 years) with newly-diagnosed glioblastoma. 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 measured, and their prognostic value for overall survival was determined. A total of 115 MRI/PET-defined subregions were analyzed in the 30 glioblastomas. 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 extended beyond contrast enhancement in 25 cases and correlated with low ADC (r=-0.40, p=0.05), consistent with high cellularity in tumor-infiltrated brain. Non-enhancing T2/FLAIR abnormal subregions had low AMT uptake and high ADC, consistent with vasogenic edema (N=24) or central necrosis (N=18). Cox regression analysis showed that high AMT uptake in the contrast-enhancing tumor subregions was prognostic for overall survival (HR: 7.83 [95%CI: 1.98–31.02], p=0.003), independent of several clinical and molecular genetic prognostic variables. CONCLUSIONS: Amino acid uptake by PET can differentiate metabolically active glioblastoma subregions, often showing dense cellularity, vs. necrotic/edematous areas, both in enhancing and non-enhancing tumor portions. High tryptophan uptake in MRI contrast-enhancing tumor subregions is a strong, independent imaging marker for longer survival in patients with newly-diagnosed glioblastomas.