Decoding the Heterogeneity of Malignant Gliomas by PET and MRI for Spatial Habitat Analysis of Hypoxia, Perfusion, and Diffusion Imaging: A Preliminary Study

• Published in: Frontiers in neuroscience 2022-07, Vol.16, p.885291-885291
• Main Authors: Bailo, Michele, Pecco, Nicolò, Callea, Marcella, Scifo, Paola, Gagliardi, Filippo, Presotto, Luca, Bettinardi, Valentino, Fallanca, Federico, Mapelli, Paola, Gianolli, Luigi, Doglioni, Claudio, Anzalone, Nicoletta, Picchio, Maria, Mortini, Pietro, Falini, Andrea, Castellano, Antonella
• Format: Article
• Language: English
• Subjects: Algorithms; Brain cancer; Edema; Gene expression; Habitats; high-grade glioma; Hypoxia; hypoxia imaging; Magnetic resonance imaging; Medical imaging; Metastases; MRI; Neuroimaging; Neuroscience; Patients; Perfusion; perfusion-weighted imaging; PET; Physiology; Radiomics; Software; Spatial distribution; Tumor microenvironment; Tumors; Vascularization
• ISSN: 1662-453X; 1662-4548; 1662-453X
• DOI: 10.3389/fnins.2022.885291

Background: Tumor heterogeneity poses major clinical challenges in high-grade gliomas (HGGs). Quantitative radiomic analysis with spatial tumor habitat clustering represents an innovative, noninvasive approach to represent and quantify tumor microenvironment heterogeneity. To date, habitat imaging has been applied mainly on conventional magnetic resonance imaging (MRI), although virtually extendible to any imaging modality, including advanced MRI techniques such as perfusion and diffusion MRI as well as PET imaging. Objectives: This study aims to evaluate an innovative PET and MRI approach for assessing hypoxia, perfusion, and tissue diffusion in HGGs and derive a combined map for clustering of intra-tumor heterogeneity. Methods: Seventeen patients harboring HGGs underwent a preoperative acquisition of MR perfusion (PWI), Diffusion (dMRI) and 18F-FAZA-PET imaging to evaluate tumor vascularization, cellularity, and hypoxia, respectively. Tumor volumes were segmented on FLAIR and T1 post-contrast images, and voxel-wise clustering of each quantitative imaging map identified eight combined PET and physiologic MRI habitats. Habitats’ spatial distribution, quantitative features and histopathological characteristics were analyzed. Results: A highly reproducible distribution pattern of the clusters was observed among different cases, particularly with respect to morphological landmarks as the necrotic core, contrast-enhancing vital tumor, and peritumoral infiltration and edema, providing valuable supplementary information to conventional imaging. A preliminary analysis, performed on stereotactic bioptic samples where exact intracranial coordinates were available, identified a reliable correlation between the expected microenvironment of the different spatial habitats and the actual histopathological features. A trend towards a higher representation of the most aggressive clusters in WHO grade IV compared to WHO III was observed. Conclusions: Preliminary findings demonstrated high reproducibility of the PET and MRI hypoxia, perfusion, and tissue diffusion spatial habitat maps and correlation with disease-specific histopathological features.