Towards a Framework for Predictive Mathematical Modeling of the Biomechanical Forces Causing Brain Tumor Mass-Effect

GBMs present with different growth phenotypes, ranging from invasive lesions without notable mass-effect to strongly displacing lesions that induce mechanical stresses and result in healthy-tissue deformation, midline shift or herniation. Biomechanical forces, such as those resulting from displacive tumor growth, are recognized to shape the tumor environment and to contribute to tumor progression. We therefore expect that biomechanical forces exerted by lesions on the brain parenchyma have implications on the biophysical level, and that they may affect treatment response and outcome. To better understand the role of biomechanics in the formation of different GBM phenotypes we started developing a framework for the predictive mathematical modeling of mechanical tumor-healthy tissue interaction on the macroscopic level. The tumor’s mass-effect is represented by a solid-mechanics model of brain tissue that computes tumor-induced strain based on local tumor cell concentration. The framework allows to seed tumors at multiple locations in a human brain atlas. It simulates tumor evolution over time and across different brain regions using literature-based parameter estimates for tumor cell proliferation, as well as isotropic motility, and mechanical tissue properties. Despite its simplicity, the mathematical model yielded realistic estimates of the mechanical impact of a growing tumor on intra-cranial pressure. However, comparison to publicly available GBM imaging data showed that asymmetric shapes could not be reproduced by isotropic growth assumptions. Here we present and evaluate an extended version of this mechanically-coupled reaction-diffusion model that takes into account tissue anisotropies based on MRI diffusion tensor imaging (MR-DTI). Structural anisotropies in brain tissue have been found to affect the directionality of tumor cell migration and are critical to mechanical behavior. This makes them likely to play a role also in the development of GBM phenotypes

A Comparative Study of Biomechanical Simulators in Deformable Registration of Brain Tumor Images

Simulating the brain tissue deformation caused by tumor growth has been found to aid the deformable registration of brain tumor images. In this paper, we evaluate the impact that different biomechanical simulators have on the accuracy of deformable registration. We use two alternative frameworks for biomechanical simulations of mass effect in 3-D magnetic resonance (MR) brain images. The first one is based on a finite-element model of nonlinear elasticity and unstructured meshes using the commercial software package ABAQUS. The second one employs incremental linear elasticity and regular grids in a fictitious domain method. In practice, biomechanical simulations via the second approach may be at least ten times faster. Landmarks error and visual examination of the coregistered images indicate that the two alternative frameworks for biomechanical simulations lead to comparable results of deformable registration. Thus, the computationally less expensive biomechanical simulator offers a practical alternative for registration purposes

Registration of brain tumor images using hyper-elastic regularization

In this paper, we present a method to estimate a deformation field between two instances of a brain volume having tumor. The novelties include the assessment of the disease progress by observing the healthy tissue deformation and usage of the Neo-Hookean strain energy density model as a regularizer in deformable registration framework. Implementations on synthetic and patient data provide promising results, which might have relevant use in clinical problems

Coupling solid and fluid stresses with brain tumour growth and white matter tract deformations in a neuroimaging-informed model

Brain tumours are among the deadliest types of cancer, since they display a strong ability to invade the surrounding tissues and an extensive resistance to common therapeutic treatments. It is therefore important to reproduce the heterogeneity of brain microstructure through mathematical and computational models, that can provide powerful instruments to investigate cancer progression. However, only a few models include a proper mechanical and constitutive description of brain tissue, which instead may be relevant to predict the progression of the pathology and to analyse the reorganization of healthy tissues occurring during tumour growth and, possibly, after surgical resection. Motivated by the need to enrich the description of brain cancer growth through mechanics, in this paper we present a mathematical multiphase model that explicitly includes brain hyperelasticity. We find that our mechanical description allows to evaluate the impact of the growing tumour mass on the surrounding healthy tissue, quantifying the displacements, deformations, and stresses induced by its proliferation. At the same time, the knowledge of the mechanical variables may be used to model the stress-induced inhibition of growth, as well as to properly modify the preferential directions of white matter tracts as a consequence of deformations caused by the tumour. Finally, the simulations of our model are implemented in a personalized framework, which allows to incorporate the realistic brain geometry, the patient-specific diffusion and permeability tensors reconstructed from imaging data and to modify them as a consequence of the mechanical deformation due to cancer growth

Simulation of brain tumors in MR images for evaluation of segmentation efficacy

Obtaining validation data and comparison metrics for segmentation of magnetic resonance images (MRI) are difficult tasks due to the lack of reliable ground truth. This problem is even more evident for images presenting pathology, which can both alter tissue appearance through infiltration and cause geometric distortions. Systems for generating synthetic images with user-defined degradation by noise and intensity inhomogeneity offer the possibility for testing and comparison of segmentation methods. Such systems do not yet offer simulation of sufficiently realistic looking pathology. This paper presents a system that combines physical and statistical modeling to generate synthetic multi-modal 3D brain MRI with tumor and edema, along with the underlying anatomical ground truth, Main emphasis is placed on simulation of the major effects known for tumor MRI, such as contrast enhancement, local distortion of healthy tissue, infiltrating edema adjacent to tumors, destruction and deformation of fiber tracts, and multi-modal MRI contrast of healthy tissue and pathology. The new method synthesizes pathology in multi-modal MRI and diffusion tensor imaging (DTI) by simulating mass effect, warping and destruction of white matter fibers, and infiltration of brain tissues by tumor cells. We generate synthetic contrast enhanced MR images by simulating the accumulation of contrast agent within the brain. The appearance of the the brain tissue and tumor in MRI is simulated by synthesizing texture images from real MR images. The proposed method is able to generate synthetic ground truth and synthesized MR images with tumor and edema that exhibit comparable segmentation challenges to real tumor MRI. Such image data sets will find use in segmentation reliability studies, comparison and validation of different segmentation methods, training and teaching, or even in evaluating standards for tumor size like the RECIST (Response Evaluation Criteria in Solid Tumors) criteria

Computer generative method on brain tumor segmentation in MRI images

Computer generative method has been used for a long time in brain tumor segmentation tasks on magnetic resonance images. The popularity of machine learning also prompts people to explore the use of generative methods to better train their segmentation models. At the early stage, brain tumor segmentation competitions like BraTS 2012 used computer synthetic MR images with tumor to solve the lack of enough data in the training set, and now, with the rise of computer generative models in deep learning, more researchers have started to work on this track to find a better solution for the task. This thesis addresses the implementation and analysis of some existing methods, specifically a tumor synthetic tool called TumorSim and a competition winning deep learning model that incorporates variational auto-encoder as a generative model. This thesis also reports on an experiment that uses imperfect segmented tumors from simple models as the input to a generative adversarial network to generate a better result.Ope