Comprehensive brain tumour characterization with VERDICT-MRI: evaluation of cellular and vascular measures validated by histology

The aim of this work is to extend the VERDICT-MRI framework for modelling brain tumours, enabling comprehensive characterization of both intra-tumoural and peri-tumoural areas with a particular focus on cellular and vascular features. Diffusion MRI data were acquired with multiple b-values (ranging from 50 to 3500 s/mm2), diffusion times and echo times, in 21 patients with brain tumours of different types and with a wide range of cellular and vascular features. We fitted a selection of diffusion models that resulted from the combination of different types of intracellular, extracellular, and vascular compartments to the signal. We compared the models using criteria for parsimony while aiming at a good characterization of all the key histological brain tumour components. Finally, we evaluated the parameters of the best-performing model in the differentiation of tumour histotypes, having ADC (apparent diffusion coefficient) as a clinical standard reference, and compared them to histopathology and relevant perfusion MRI metrics. The best-performing model for VERDICT in brain tumours was a three-compartment model accounting for anisotropically hindered and isotropically restricted diffusion and isotropic pseudo-diffusion. VERDICT metrics were compatible with the histological appearance of low-grade gliomas and metastases, and reflected differences found by histopathology between multiple biopsy samples within tumours. The comparison between histotypes showed that both the intracellular and the vascular fractions tend to be higher in tumours with high cellularity (glioblastoma and metastasis), and quantitative analysis showed a trend toward higher values of the intracellular fraction (fic) within the tumour core with increasing glioma grade. We also observed a trend towards higher free water fraction in vasogenic oedemas around metastases compared to infiltrative oedemas around glioblastomas and WHO 3 gliomas and the periphery of low-grade gliomas. In conclusion, we developed and evaluated a multi-compartment diffusion MRI model for brain tumours based on the VERDICT framework and showed agreement of non-invasive microstructural estimates with histology and encouraging trends for differentiation of tumour types and sub-regions.