Decoding malignant glioma heterogeneity by PET-MRI habitat analysis of HYpoxia, PERfusion and DIffusion imaging: preliminary results of the HYPERDIrect study
Antonella Castellano, Milan / Italy
Author Block: G. Nocera, N. Pecco, M. Bailo, M. Callea, P. V. Scifo, P. Della Rosa, F. Gagliardi, A. Falini, A. Castellano; Milan/ITPurpose: Malignant gliomas are characterised by considerable intratumour heterogeneity, directly related to treatment failure. A novel method for cancer detection involves identifying regions or habitats within tumours by assessing shared imaging characteristics. This approach utilises quantitative analysis of conventional and advanced imaging data through mathematical models, which effectively partition the tumour into voxel-based subregions exhibiting similar radiological features. The integration of multiple images further refines the creation of distinct tumour habitats. In this study, habitat analysis has been applied on hybrid PET/MR images to map hypoxia, neoangiogenesis, cellularity, and tumour metabolism.Methods or Background: Twenty patients with suspected malignant glioma candidate for surgical resection or biopsy underwent preoperative hybrid 3T PET/MRI acquisitions for assessing HYpoxia (using quantitative blood oxygenation level-dependent – q-BOLD imaging), PErfusion (using Dynamic Contrast-Enhanced DCE-MRI), DIffusion (usng DTI), and methionine-PET for tumour metabolism. Data obtained were processed to generate HYPERDIrect habitat maps. In FLAIR-derived tumour volumes, an automatic clustering algorithm classified voxels of each quantitative map into two clusters (high and low intensity) . The combination of the clusters from all maps identified eight distinct habitats. Maps were imported into the neuronavigational system to perform imaging-guided sampling for histopathological correlation.Results or Findings: Preliminary findings demonstrated high habitat imaging reproducibility and a reliable correlation between the expected microenvironment of the different habitats and the actual histopathological characteristics: samples from more aggressive habitats (with reduced diffusivity, high perfusion, and low hypoxia) histologically coincide with regions displaying elevated cell density and increased microvascular proliferation. Samples from less aggressive habitats (high diffusivity, low perfusion, and low hypoxia) correspond to glioma infiltrative areas.Conclusion: Habitat imaging using the HYPERDIrect map approach might serve as a potential biomarker for non-invasively characterizing tumour heterogeneity in vivo.Limitations: No limitations were identified.Funding for this study: Funding was received from the Italian Ministry of Health, grant number GR-2018-Has your study been approved by an ethics committee? YesEthics committee - additional information: This study was approved by the Ethics Committee of Ospedale San Raffaele on March 9th, 2022 (code 19/INT/2022).