61 research outputs found
Neural parameters estimation for brain tumor growth modeling
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
On a Cahn--Hilliard--Darcy system for tumour growth with solution dependent source terms
We study the existence of weak solutions to a mixture model for tumour growth
that consists of a Cahn--Hilliard--Darcy system coupled with an elliptic
reaction-diffusion equation. The Darcy law gives rise to an elliptic equation
for the pressure that is coupled to the convective Cahn--Hilliard equation
through convective and source terms. Both Dirichlet and Robin boundary
conditions are considered for the pressure variable, which allows for the
source terms to be dependent on the solution variables.Comment: 18 pages, changed proof from fixed point argument to Galerkin
approximatio
On a diffuse interface model for tumour growth with non-local interactions and degenerate mobilities
We study a non-local variant of a diffuse interface model proposed by
Hawkins--Darrud et al. (2012) for tumour growth in the presence of a chemical
species acting as nutrient. The system consists of a Cahn--Hilliard equation
coupled to a reaction-diffusion equation. For non-degenerate mobilities and
smooth potentials, we derive well-posedness results, which are the non-local
analogue of those obtained in Frigeri et al. (European J. Appl. Math. 2015).
Furthermore, we establish existence of weak solutions for the case of
degenerate mobilities and singular potentials, which serves to confine the
order parameter to its physically relevant interval. Due to the non-local
nature of the equations, under additional assumptions continuous dependence on
initial data can also be shown.Comment: 28 page
Integration of Machine Learning and Mechanistic Models Accurately Predicts Variation in Cell Density of Glioblastoma Using Multiparametric MRI
Glioblastoma (GBM) is a heterogeneous and lethal brain cancer. These tumors are followed using magnetic resonance imaging (MRI), which is unable to precisely identify tumor cell invasion, impairing effective surgery and radiation planning. We present a novel hybrid model, based on multiparametric intensities, which combines machine learning (ML) with a mechanistic model of tumor growth to provide spatially resolved tumor cell density predictions. The ML component is an imaging data-driven graph-based semi-supervised learning model and we use the Proliferation-Invasion (PI) mechanistic tumor growth model. We thus refer to the hybrid model as the ML-PI model. The hybrid model was trained using 82 image-localized biopsies from 18 primary GBM patients with pre-operative MRI using a leave-one-patient-out cross validation framework. A Relief algorithm was developed to quantify relative contributions from the data sources. The ML-PI model statistically significantly outperformed (p \u3c 0.001) both individual models, ML and PI, achieving a mean absolute predicted error (MAPE) of 0.106 ± 0.125 versus 0.199 ± 0.186 (ML) and 0.227 ± 0.215 (PI), respectively. Associated Pearson correlation coefficients for ML-PI, ML, and PI were 0.838, 0.518, and 0.437, respectively. The Relief algorithm showed the PI model had the greatest contribution to the result, emphasizing the importance of the hybrid model in achieving the high accuracy
MultiCellDS : a community-developed standard for curating microenvironment-dependent multicellular data
Exchanging and understanding scientific data and their context represents a significant barrier to advancing research, especially with respect to information siloing. Maintaining information provenance and providing data curation and quality control help overcome common concerns and barriers to the effective sharing of scientific data. To address these problems in and the unique challenges of multicellular systems, we assembled a panel composed of investigators from several disciplines to create the MultiCellular Data Standard (MultiCellDS) with a use-case driven development process. The standard includes (1) digital cell lines, which are analogous to traditional biological cell lines, to record metadata, cellular microenvironment, and cellular phenotype variables of a biological cell line, (2) digital snapshots to consistently record simulation, experimental, and clinical data for multicellular systems, and (3) collections that can logically group digital cell lines and snapshots. We have created a MultiCellular DataBase (MultiCellDB) to store digital snapshots and the 200+ digital cell lines we have generated. MultiCellDS, by having a fixed standard, enables discoverability, extensibility, maintainability, searchability, and sustainability of data, creating biological applicability and clinical utility that permits us to identify upcoming challenges to uplift biology and strategies and therapies for improving human health
Identifying the spatial and temporal dynamics of molecularly-distinct glioblastoma sub-populations
Glioblastomas (GBMs) are the most aggressive primary brain tumours and have no known cure. Each individual tumour comprises multiple sub-populations of genetically-distinct cells that may respond differently to targeted therapies and may contribute to disappointing clinical trial results. Image-localized biopsy techniques allow multiple biopsies to be taken during surgery and provide information that identifies regions where particular sub-populations occur within an individual GBM, thus providing insight into their regional genetic variability. These sub-populations may also interact with one another in a competitive or cooperative manner; it is important to ascertain the nature of these interactions, as they may have implications for responses to targeted therapies
MultiCellDS: a community-developed standard for curating microenvironment-dependent multicellular data
Exchanging and understanding scientific data and their context represents a significant barrier to advancing research, especially with respect to information siloing. Maintaining information provenance and providing data curation and quality control help overcome common concerns and barriers to the effective sharing of scientific data. To address these problems in and the unique challenges of multicellular systems, we assembled a panel composed of investigators from several disciplines to create the MultiCellular Data Standard (MultiCellDS) with a use-case driven development process. The standard includes (1) digital cell lines, which are analogous to traditional biological cell lines, to record metadata, cellular microenvironment, and cellular phenotype variables of a biological cell line, (2) digital snapshots to consistently record simulation, experimental, and clinical data for multicellular systems, and (3) collections that can logically group digital cell lines and snapshots. We have created a MultiCellular DataBase (MultiCellDB) to store digital snapshots and the 200+ digital cell lines we have generated. MultiCellDS, by having a fixed standard, enables discoverability, extensibility, maintainability, searchability, and sustainability of data, creating biological applicability and clinical utility that permits us to identify upcoming challenges to uplift biology and strategies and therapies for improving human health
MultiCellDS: a standard and a community for sharing multicellular data
Cell biology is increasingly focused on cellular heterogeneity and multicellular systems. To make the fullest use of experimental, clinical, and computational efforts, we need standardized data formats, community-curated "public data libraries", and tools to combine and analyze shared data. To address these needs, our multidisciplinary community created MultiCellDS (MultiCellular Data Standard): an extensible standard, a library of digital cell lines and tissue snapshots, and support software. With the help of experimentalists, clinicians, modelers, and data and library scientists, we can grow this seed into a community-owned ecosystem of shared data and tools, to the benefit of basic science, engineering, and human health
Bayesian calibration, validation and uncertainty quantification for predictive modelling of tumour growth: a tutorial
In this work we present a pedagogical tumour growth example, in which we apply calibration and validation techniques to an uncertain, Gompertzian model of tumour spheroid growth. The key contribution of this article is the discussion and application of these methods (that are not commonly employed in the field of cancer modelling) in the context of a simple model, whose deterministic analogue is widely known within the community. In the course of the example we calibrate the model against experimental data that is subject to measurement errors, and then validate the resulting uncertain model predictions. We then analyse the sensitivity of the model predictions to the underlying measurement model. Finally, we propose an elementary learning approach for tuning a threshold parameter in the validation procedure in order to maximize predictive accuracy of our validated model
Models, measurement and inference in epithelial tissue dynamics
The majority of solid tumours arise in epithelia and therefore much research effort has gone into investigating the growth, renewal and regulation of these tissues. Here we review different mathematical and computational approaches that have been used to model epithelia. We compare different models and describe future challenges that need to be overcome in order to fully exploit new data which present, for the first time, the real possibility for detailed model validation and comparison
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