Initial Condition Assessment for Reaction-Diffusion Glioma Growth Models: A Translational MRI-Histology (In)Validation Study

Abstract

Reaction-diffusion models have been proposed for decades to capture the growth of gliomas. Nevertheless, these models require an initial condition: the tumor cell density distribution over the whole brain at diagnosis time. Several works have proposed to relate this distribution to abnormalities visible on magnetic resonance imaging (MRI). In this work, we verify these hypotheses by stereotactic histological analysis of a non-operated brain with glioblastoma using a 3D-printed slicer. Cell density maps are computed from histological slides using a deep learning approach. The density maps are then registered to a postmortem MR image and related to an MR-derived geodesic distance map to the tumor core. The relation between the edema outlines visible on T2-FLAIR MRI and the distance to the core is also investigated. Our results suggest that (i) the previously proposed exponential decrease of the tumor cell density with the distance to the core is reasonable but (ii) the edema outlines would not correspond to a cell density iso-contour and (iii) the suggested tumor cell density at these outlines is likely overestimated. These findings highlight the limitations of conventional MRI to derive glioma cell density maps and the need for other initialization methods for reaction-diffusion models to be used in clinical practice.

Keywords

• cellularity
• digital pathology
• glioma
• histology
• magnetic resonance imaging
• reaction-diffusion model