Practical Use of Regularization in Individualizing a Mathematical Model of Cardiovascular Hemodynamics Using Scarce...

Individualizing physiological models to a patient can enable patient-specific monitoring and treatment in critical care environments. However, this task often presents a unique "practical identifiability" challenge due to the conflict between model complexity and data scarcity. Regularization provides an established framework to cope with this conflict by compensating for data scarcity with prior knowledge. However, regularization has not been widely pursued in individualizing physiological models to facilitate patient-specific critical care. Thus, the goal of this work is to garner potentially generalizable insight into the practical use of regularization in individualizing a complex physiological model using scarce data by investigating its effect in a clinically significant critical care case study of blood volume kinetics and cardiovascular hemodynamics in hemorrhage and circulatory resuscitation. We construct a population-average model as prior knowledge and individualize the physiological model via regularization to illustrate that regularization can be effective in individualizing a physiological model to learn salient individual-specific characteristics (resulting in the goodness of fit to individual-specific data) while restricting unnecessary deviations from the population-average model (achieving practical identifiability). We also illustrate that regularization yields parsimonious individualization of only sensitive parameters as well as adequate physiological plausibility and relevance in predicting internal physiological states.