Bayesian inference and model selection for physiologically-based pharmacokinetic modeling of superparamagnetic iron oxide nanoparticles

Lynn Bi; Javad Sovizi; Kelsey Mathieu; Wolfgang Stefan; Sara Thrower; John Hazle; David Fuentes

doi:10.1117/12.2293953

12 March 2018 Bayesian inference and model selection for physiologically-based pharmacokinetic modeling of superparamagnetic iron oxide nanoparticles

Lynn Bi, Javad Sovizi, Kelsey Mathieu, Wolfgang Stefan, Sara Thrower, John Hazle , David Fuentes

Author Affiliations +

Proceedings Volume 10578, Medical Imaging 2018: Biomedical Applications in Molecular, Structural, and Functional Imaging; 105782G (2018) https://doi.org/10.1117/12.2293953
Event: SPIE Medical Imaging, 2018, Houston, Texas, United States

Abstract

The growing use of superparamagnetic iron oxide nanoparticles (SPIONs) in early cancer detection technologies has created a demand for physiologically-based pharmacokinetic (PBPK) models that accurately model and predict the biodistribution of SPIONs in the mouse and human model. The objective of this work is to use a Bayesian approach built upon nested-sampling to select a model based on qualitative criteria of the fit of the model and the likelihood function landscape, as well as quantitative criteria of the evidence and maximum likelihood values. Four first-order PBPK compartmental models of ranging complexity are considered. Compartments included in the models comprise of a combination of the plasma, liver, spleen, tumor, and “other” (the remaining body tissue), with parameters including the volume, blood flow rate, and plasma:tissue distribution ratios. The model parameters for each model are evaluated using Bayesian inference, in addition to the respective evidence integrals, maximum log-likelihoods, and Bayes factors. The model containing all compartments and the model containing the plasma, liver, tumor and “other” had the highest log-likelihood and evidence values, indicating both a high goodness-of-fit and a high likelihood of the model given the data. This is similarly reflected in a faithful quality-of-fit and non-flat log-likelihood landscapes. Overall, these findings illustrate the strength of the Bayesian model selection framework in ranking different models to determine the best model that accurately represents the experimental data.

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Lynn Bi, Javad Sovizi, Kelsey Mathieu, Wolfgang Stefan, Sara Thrower, John Hazle , and David Fuentes "Bayesian inference and model selection for physiologically-based pharmacokinetic modeling of superparamagnetic iron oxide nanoparticles", Proc. SPIE 10578, Medical Imaging 2018: Biomedical Applications in Molecular, Structural, and Functional Imaging, 105782G (12 March 2018); https://doi.org/10.1117/12.2293953

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