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

Corentin Martens,Thierry Metens,Antonin Rovai,Isabelle Salmon,Christine Decaestecker,Thomas Vandamme,Yves-Rémi Van Eycke,Serge Goldman,Laetitia Lebrun,Gaetan Van Simaeys,Olivier Debeir

doi:10.3390/tomography7040055

Corentin Martens, Thierry Metens + Show 9 more

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https://doi.org/10.3390/tomography7040055

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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.

Highlights

Gliomas are the most common primary brain tumors
An over-cellularity front is visible in Figure 3c, progressing from the frontal necrotic tumor core but rapidly decreasing to reach an apparently normal cellularity of around 1450 cell/mm2 beyond a geodesic distance of 20 mm (Figure 3d)
Through a translational radiological/histological analysis performed on a case of non-operated glioblastoma, we invalidated two commonly made assumptions relating the outlines of the visible abnormalities in magnetic resonance images to the tumor cell density function in the context of reaction-diffusion glioma growth modeling

Summary

Introduction

Gliomas are the most common primary brain tumors. Diffuse gliomas, which include their most aggressive form glioblastoma (GBM), are known to be highly infiltrative [1], with the presence of tumor cells reported as far as 4 cm from the gross tumor [2]. Tumor-induced alterations of the microenvironment are seen on MR images, such as peritumor vasogenic edema visible on T2/T2-FLAIR sequences and the enhancing tumor core visible on T1weighted sequences with injection of gadolinium-based contrast agent (T1Gd). Peritumor vasogenic edema originates from an increase in the blood–brain barrier (BBB) permeability induced by the release of vascular endothelial growth factor (VEGF) by tissues under hypoxic stress [3,4] combined with changes in the brain hydrodynamic pressure [5]. The formation of an enhancing tumor core results from a breakdown of the BBB subsequent to neo-vascularization induced by VEGF, allowing gadolinium-based contrast agents to diffuse freely into brain tissues [3]

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