RESUMEN
A key parameter of interest recovered from hyperpolarized (HP) MRI measurements is the apparent pyruvate-to-lactate exchange rate, [Formula: see text], for measuring tumor metabolism. This manuscript presents an information-theory-based optimal experimental design approach that minimizes the uncertainty in the rate parameter, [Formula: see text], recovered from HP-MRI measurements. Mutual information is employed to measure the information content of the HP measurements with respect to the first-order exchange kinetics of the pyruvate conversion to lactate. Flip angles of the pulse sequence acquisition are optimized with respect to the mutual information. A time-varying flip angle scheme leads to a higher parameter optimization that can further improve the quantitative value of mutual information over a constant flip angle scheme. However, the constant flip angle scheme, 35 and 28 degrees for pyruvate and lactate measurements, leads to an accuracy and precision comparable to the variable flip angle schemes obtained from our method. Combining the comparable performance and practical implementation, optimized pyruvate and lactate flip angles of 35 and 28 degrees, respectively, are recommended.
RESUMEN
Tumor-associated vasculature is responsible for the delivery of nutrients, removal of waste, and allowing growth beyond 2-3 mm3. Additionally, the vascular network, which is changing in both space and time, fundamentally influences tumor response to both systemic and radiation therapy. Thus, a robust understanding of vascular dynamics is necessary to accurately predict tumor growth, as well as establish optimal treatment protocols to achieve optimal tumor control. Such a goal requires the intimate integration of both theory and experiment. Quantitative and time-resolved imaging methods have emerged as technologies able to visualize and characterize tumor vascular properties before and during therapy at the tissue and cell scale. Parallel to, but separate from those developments, mathematical modeling techniques have been developed to enable in silico investigations into theoretical tumor and vascular dynamics. In particular, recent efforts have sought to integrate both theory and experiment to enable data-driven mathematical modeling. Such mathematical models are calibrated by data obtained from individual tumor-vascular systems to predict future vascular growth, delivery of systemic agents, and response to radiotherapy. In this review, we discuss experimental techniques for visualizing and quantifying vascular dynamics including magnetic resonance imaging, microfluidic devices, and confocal microscopy. We then focus on the integration of these experimental measures with biologically based mathematical models to generate testable predictions.
RESUMEN
We consider a mixture-theoretic continuum model of the spread of COVID-19 in Texas. The model consists of multiple coupled partial differential reaction-diffusion equations governing the evolution of susceptible, exposed, infectious, recovered, and deceased fractions of the total population in a given region. We consider the problem of model calibration, validation, and prediction following a Bayesian learning approach implemented in OPAL (the Occam Plausibility Algorithm). Our goal is to incorporate COVID-19 data to calibrate the model in real-time and make meaningful predictions and specify the confidence level in the prediction by quantifying the uncertainty in key quantities of interests. Our results show smaller mortality rates in Texas than what is reported in the literature. We predict 7003 deceased cases by September 1, 2020 in Texas with 95 % CI 6802-7204. The model is validated for the total deceased cases, however, is found to be invalid for the total infected cases. We discuss possible improvements of the model.
