Simultaneous Mapping of Vasculature, Hypoxia, and Proliferation Using Dynamic Susceptibility Contrast MRI, 18F-FMISO PET, and 18F-FLT PET in Relation to Contrast Enhancement in Newly Diagnosed Glioblastoma

Conventional MRI plays a key role in the management of patients with high-grade glioma, but multiparametric MRI and PET tracers could pro-vide further information to better characterize tumor metabolism and heterogeneity by identifying regions having a high risk of recurrence. In this study, we focused on proliferation, hypervascularization, and hypoxia, all factors considered indicative of poor prognosis. They were assessed by measuring uptake of F-18-3'-deoxy-3'-F-18-fluorothy-midine (F-18-FLT), relative cerebral blood volume (rCBV) maps, and uptake of F-18-fluoromisonidazole (F-18-FMISO), respectively. For each modality, the volumes and high-uptake subvolumes (hot spots) were semiautomatically segmented and compared with the contrast enhancement (CE) volume on T1-weighted gadolinium-enhanced (T1w-Gd) images, commonly used in the management of patients with glioblastoma. Methods: Dynamic susceptibility contrast-enhanced MRI (31 patients), F-18-FLT PET (20 patients), or F-18-FMISO PET (20 patients), for a total of 31 patients, was performed on preoper-ative glioblastoma patients. Volumes and hot spots were segmented on SUV maps for F-18-FLT PET (using the fuzzy locally adaptive bayesian algorithm) and F-18-FMISO PET (using a mean contralateral image + 3.3 SDs) and on rCBV maps (using a mean contralateral image + 1.96 SDs) for dynamic susceptibility contrast-enhanced MRI and overlaid on T1w-Gd images. For each modality, the percentages of the periph-eral volumes and the peripheral hot spots outside the CE volume were calculated. Results: All tumors showed highly proliferated, hypervascu-larized, and hypoxic regions. The images also showed pronounced het-erogeneity of both tracers regarding their uptake and rCBV maps, within each individual patient. Overlaid volumes on T1w-Gd images showed that some proliferative, hypervascularized, and hypoxic regions extended beyond the CE volume but with marked differences between patients. The ranges of peripheral volume outside the CE volume were 1.6%-155.5%, 1.5%-89.5%, and 3.1%-78.0% for F-18-FLT, rCBV, and F-18-FMISO, respectively. All patients had hyperproliferative hot spots outside the CE volume, whereas hypervascularized and hypoxic hot spots were detected mainly within the enhancing region. Conclu-sion: Spatial analysis of multiparametric maps with segmented volumes and hot spots provides valuable information to optimize the manage-ment and treatment of patients with glioblastoma.

Automated summary

Conventional MRI plays a crucial role in managing high-grade glioma patients, but multiparametric MRI and PET tracers provide additional information to characterize tumor metabolism and heterogeneity. This study focused on evaluating proliferation, hypervascularization, and hypoxia in glioblastoma patients, finding marked differences in tracer uptake and rCBV maps between individuals, with certain tumor regions extending beyond the contrast enhancement volume.