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One-dimensional (1D) cardiovascular models offer a non-invasive method to answer medical questions, including predictions of wave-reflection, shear stress, functional flow reserve, vascular resistance and compliance. This model type can predict patient-specific outcomes by solving 1D fluid dynamics equations in geometric networks extracted from medical images. However, the inherent uncertainty in in vivo imaging introduces variability in network size and vessel dimensions, affecting haemodynamic predictions. Understanding the influence of variation in image-derived properties is essential to assess the fidelity of model predictions. Numerous programs exist to render three-dimensional surfaces and construct vessel centrelines. Still, there is no exact way to generate vascular trees from the centrelines while accounting for uncertainty in data. This study introduces an innovative framework employing statistical change point analysis to generate labelled trees that encode vessel dimensions and their associated uncertainty from medical images. To test this framework, we explore the impact of uncertainty in 1D haemodynamic predictions in a systemic and pulmonary arterial network. Simulations explore haemodynamic variations resulting from changes in vessel dimensions and segmentation; the latter is achieved by analysing multiple segmentations of the same images. Results demonstrate the importance of accurately defining vessel radii and lengths when generating high-fidelity patient-specific haemodynamics models. KEY POINTS: This study introduces novel algorithms for generating labelled directed trees from medical images, focusing on accurate junction node placement and radius extraction using change points to provide haemodynamic predictions with uncertainty within expected measurement error. Geometric features, such as vessel dimension (length and radius) and network size, significantly impact pressure and flow predictions in both pulmonary and aortic arterial networks. Standardizing networks to a consistent number of vessels is crucial for meaningful comparisons and decreases haemodynamic uncertainty. Change points are valuable to understanding structural transitions in vascular data, providing an automated and efficient way to detect shifts in vessel characteristics and ensure reliable extraction of representative vessel radii., (© 2024 The Author(s). The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Key Points: Inflammation in response to bacterial endotoxin challenge impacts physiological functions, including cardiovascular, thermal and pain dynamics, although the mechanisms are poorly understood. We develop an innovative mathematical model incorporating interaction pathways between inflammation and physiological processes observed in response to an endotoxin challenge. We calibrate the model to individual data from 20 subjects in an experimental study of the human inflammatory and physiological responses to endotoxin, and we validate the model against human data from an independent study. Using the model to simulate patient responses to different treatment modalities reveals that a multimodal treatment combining several therapeutic strategies gives the best recovery outcome., Abstract: Uncontrolled, excessive production of pro-inflammatory mediators from immune cells and traumatized tissues can cause systemic inflammatory conditions such as sepsis, one of the ten leading causes of death in the USA, and one of the three leading causes of death in the intensive care unit. Understanding how inflammation affects physiological processes, including cardiovascular, thermal and pain dynamics, can improve a patient's chance of recovery after an inflammatory event caused by surgery or a severe infection. Although the effects of the autonomic response on the inflammatory system are well-known, knowledge about the reverse interaction is lacking. The present study develops a mathematical model analyzing the inflammatory system's interactions with thermal, pain and cardiovascular dynamics in response to a bacterial endotoxin challenge. We calibrate the model with individual data from an experimental study of the inflammatory and physiological responses to a one-time administration of endotoxin in 20 healthy young men and validate it against data from an independent endotoxin study. We use simulation to explore how various treatments help patients exposed to a sustained pathological input. The treatments explored include bacterial endotoxin adsorption, antipyretics and vasopressors, as well as combinations of these. Our findings suggest that the most favourable recovery outcome is achieved by a multimodal strategy, combining all three interventions to simultaneously remove endotoxin from the body and alleviate symptoms caused by the immune system as it fights the infection., (© 2021 The Authors. The Journal of Physiology © 2021 The Physiological Society.)