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Modeling of brain tumor dynamics has the potential to advance therapeutic planning. Current modeling approaches resort to numerical solvers that simulate the tumor progression according to a given differential equation. Using highly-efficient numerical solvers, a single forward simulation takes up to a few minutes of compute. At the same time, clinical applications of tumor modeling often imply solving an inverse problem, requiring up to tens of thousands forward model evaluations when used for a Bayesian model personalization via sampling. This results in a total inference time prohibitively expensive for clinical translation. While recent data-driven approaches become capable of emulating physics simulation, they tend to fail in generalizing over the variability of the boundary conditions imposed by the patient-specific anatomy. In this paper, we propose a learnable surrogate for simulating tumor growth which maps the biophysical model parameters directly to simulation outputs, i.e. the local tumor cell densities, whilst respecting patient geometry. We test the neural solver on Bayesian tumor model personalization for a cohort of glioma patients. Bayesian inference using the proposed surrogate yields estimates analogous to those obtained by solving the forward model with a regular numerical solver. The near-real-time computation cost renders the proposed method suitable for clinical settings. The code is available at https://github.com/IvanEz/tumor-surrogate.
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Glioblastoma is a highly invasive brain tumor, whose cells infiltrate surrounding normal brain tissue beyond the lesion outlines visible in the current medical scans. These infiltrative cells are treated mainly by radiotherapy. Existing radiotherapy plans for brain tumors derive from population studies and scarcely account for patient-specific conditions. Here we provide a Bayesian machine learning framework for the rational design of improved, personalized radiotherapy plans using mathematical modeling and patient multimodal medical scans. Our method, for the first time, integrates complementary information from high resolution MRI scans and highly specific FET-PET metabolic maps to infer tumor cell density in glioblastoma patients. The Bayesian framework quantifies imaging and modeling uncertainties and predicts patient-specific tumor cell density with confidence intervals. The proposed methodology relies only on data acquired at a single time point and thus is applicable to standard clinical settings. An initial clinical population study shows that the radiotherapy plans generated from the inferred tumor cell infiltration maps spare more healthy tissue thereby reducing radiation toxicity while yielding comparable accuracy with standard radiotherapy protocols. Moreover, the inferred regions of high tumor cell densities coincide with the tumor radioresistant areas, providing guidance for personalized dose-escalation. The proposed integration of multimodal scans and mathematical modeling provides a robust, non-invasive tool to assist personalized radiotherapy design.
We present a 3D fully-automatic method for the calibration of partial differential equation (PDE) models of glioblastoma (GBM) growth with mass effect, the deformation of brain tissue due to the tumor. We quantify the mass effect, tumor proliferation, tumor migration, and the localized tumor initial condition from a single multiparameteric Magnetic Resonance Imaging (mpMRI) patient scan. The PDE is a reaction-advection-diffusion partial differential equation coupled with linear elasticity equations to capture mass effect. The single-scan calibration model is notoriously difficult because the precancerous (healthy) brain anatomy is unknown. To solve this inherently ill-posed and ill-conditioned optimization problem, we introduce a novel inversion scheme that uses multiple brain atlases as proxies for the healthy precancer patient brain resulting in robust and reliable parameter estimation. We apply our method on both synthetic and clinical datasets representative of the heterogeneous spatial landscape typically observed in glioblastomas to demonstrate the validity and performance of our methods. In the synthetic data, we report calibration errors (due to the ill-posedness and our solution scheme) in the 10%-20% range. In the clinical data, we report good quantitative agreement with the observed tumor and qualitative agreement with the mass effect (for which we do not have a ground truth). Our method uses a minimal set of parameters and provides both global and local quantitative measures of tumor infiltration and mass effect.
Understanding the dynamics of brain tumor progression is essential for optimal treatment planning. Cast in a mathematical formulation, it is typically viewed as evaluation of a system of partial differential equations, wherein the physiological processes that govern the growth of the tumor are considered. To personalize the model, i.e. find a relevant set of parameters, with respect to the tumor dynamics of a particular patient, the model is informed from empirical data, e.g., medical images obtained from diagnostic modalities, such as magnetic-resonance imaging. Existing model-observation coupling schemes require a large number of forward integrations of the biophysical model and rely on simplifying assumption on the functional form, linking the output of the model with the image information. In this work, we propose a learning-based technique for the estimation of tumor growth model parameters from medical scans. The technique allows for explicit evaluation of the posterior distribution of the parameters by sequentially training a mixture-density network, relaxing the constraint on the functional form and reducing the number of samples necessary to propagate through the forward model for the estimation. We test the method on synthetic and real scans of rats injected with brain tumors to calibrate the model and to predict tumor progression.
Glioma constitutes 80% of malignant primary brain tumors and is usually classified as HGG and LGG. The LGG tumors are less aggressive, with slower growth rate as compared to HGG, and are responsive to therapy. Tumor biopsy being challenging for brain tumor patients, noninvasive imaging techniques like Magnetic Resonance Imaging (MRI) have been extensively employed in diagnosing brain tumors. Therefore automated systems for the detection and prediction of the grade of tumors based on MRI data becomes necessary for assisting doctors in the framework of augmented intelligence. In this paper, we thoroughly investigate the power of Deep ConvNets for classification of brain tumors using multi-sequence MR images. We propose novel ConvNet models, which are trained from scratch, on MRI patches, slices, and multi-planar volumetric slices. The suitability of transfer learning for the task is next studied by applying two existing ConvNets models (VGGNet and ResNet) trained on ImageNet dataset, through fine-tuning of the last few layers. LOPO testing, and testing on the holdout dataset are used to evaluate the performance of the ConvNets. Results demonstrate that the proposed ConvNets achieve better accuracy in all cases where the model is trained on the multi-planar volumetric dataset. Unlike conventional models, it obtains a testing accuracy of 95% for the low/high grade glioma classification problem. A score of 97% is generated for classification of LGG with/without 1p/19q codeletion, without any additional effort towards extraction and selection of features. We study the properties of self-learned kernels/ filters in different layers, through visualization of the intermediate layer outputs. We also compare the results with that of state-of-the-art methods, demonstrating a maximum improvement of 7% on the grading performance of ConvNets and 9% on the prediction of 1p/19q codeletion status.
In medical applications, the same anatomical structures may be observed in multiple modalities despite the different image characteristics. Currently, most deep models for multimodal segmentation rely on paired registered images. However, multimodal paired registered images are difficult to obtain in many cases. Therefore, developing a model that can segment the target objects from different modalities with unpaired images is significant for many clinical applications. In this work, we propose a novel two-stream translation and segmentation unified attentional generative adversarial network (UAGAN), which can perform any-to-any image modality translation and segment the target objects simultaneously in the case where two or more modalities are available. The translation stream is used to capture modality-invariant features of the target anatomical structures. In addition, to focus on segmentation-related features, we add attentional blocks to extract valuable features from the translation stream. Experiments on three-modality brain tumor segmentation indicate that UAGAN outperforms the existing methods in most cases.
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