Session L10: Biofluids: Physiological I

Computational modeling of multiphase transport in physiologically realistic solid tumor vasculature and intratumoral domains

Clinical diagnosis and targeted drug delivery assessments for dense tumors (e.g., in pancreatic cancer) can benefit from a quantitative framework that can project intratumoral plasma uptake from simple inputs, e.g., medical scans of the tumor. To that end, we are building a first-principles mechanics-based model that incorporates features such as the extracellular packing fraction in the tumor and the outer vasculature shapes. We have numerically modeled Eulerian multiphase blood transport in vessels reconstructed from high-resolution scans of human pancreatic tumors implanted in mice. Both red and white blood cells, along with plasma, are the different phases considered in the viscous-laminar transient simulations, which also incorporate electrohydrodynamic and pulsatile effects to capture the essential biological realism. Subsequently, we have used the plasma flow parameters at the fenestra openings to the tumor, to numerically model plasma perfusion through 2D idealized intratumoral domains that bear packing fractions similar to real tumors. Our current findings show inverse correlation between plasma percolation rates and the intratumoral diffusion distances.   

Assessment of Hemodynamic Changes During Acute Myocardial Ischemia and Infarction Using Intrinsic Frequency Method

A sudden decrease in left ventricle (LV) contractility, LV wall stiffening, and an increase in LV filling pressure are among the major hemodynamic abnormalities within seconds of a coronary artery occlusion. These changes, along with other regulatory responses, cause global hemodynamic changes in the systemic circulation. Intrinsic frequency (IF) is a systems-based approach for analyzing the hemodynamics of the cardiovascular system using a single pressure waveform. In this study, we examined the changes in cardiovascular system hemodynamics during acute myocardial ischemia and myocardial infarction (MI), utilizing a standard rat model of coronary occlusion (30 min) and reperfusion (3 hours). We used Female Sprague Dawley rats (n=45, body weight ≈200-250 g). Catheters were inserted into carotid artery for pressure waveform measurement. We computed IF parameters and their relative changes from carotid waveforms, comparing them at six distinct events before, during, or after the coronary occlusion and reperfusion. Our findings show that IF parameters can detect global hemodynamic changes during various phases of coronary occlusion and reperfusion, including ischemia and MI. This highlights the potential usage of the IF method for noninvasive detection of acute ischemia or MI.

 

Funding Acknowledgement: This study is funded by the American Heart Association (AHA) Award Number 20CDA35260167.   

Three-Dimensional Quantitative Pulsatile Flow Analysis in a Physiologically Accurate Collapsible Jugular Vein Model

The flow physics inside the cerebral veins is more complicated than in the arteries as they are prone to self-excitation. Furthermore, these veins experience unique flow dynamics as the mean flow and the first generation of the wave (generated by the right heart) are in opposite directions. Despite the extensive research on self-oscillating and collapsing tubes on steady flows, the pulsatile flow dynamics and its interaction with dominated backward pressure waves remain unexplored. To address this gap, we developed a physiologically relevant hydro-mechanical setup to investigate the three-dimensional pulsatile velocity field in the internal jugular vein (IJV). The complex three-dimensional velocity fields in collapsible tube models of IJV were obtained using volumetric 3-component Particle Image Velocimetry (PIV) system (TSI Inc., V3V-9000). We conducted quantitative 3D velocity measurements under various pulsatile flow conditions such as tube stiffness, flow rate, and heart rate (frequency of excitation). We analyzed IJV collapsing modes/motions and flow patterns by evaluating the changes in vortex formation and backflow propagation. Our results showed unique wave propagations and three-dimensional flow structures due to the excitation of the collapsible tube. This study may provide crucial insights into the flow dynamics in the cerebral venous circulation and cerebrovascular system.   

Non-Newtonian and Turbulent Perspectives in Computational Cerebral Hemodynamics

Intracranial aneurysms can cause hemorrhagic strokes, with potentially fatal consequences for the patient if they rupture. Patients exhibiting increased rupture risks may require endovascular interventions to prevent cerebral hemorrhage. Clinical imaging, from which morphological information is extracted, is critical in assessing risks and to guide interventions. In this work, we use reconstructed vessels from clinical imaging to provide additional information using computational hemodynamic analyses of the cerebral vasculature networks. It is not well understood what level of modelling is required to accurately resolve cerebral hemodynamics. In our work, we conduct full convergence analyses of several geometries with different blood rheology and turbulence models. Unresolved DNS, RANS simulations and LES are conducted. We show that overall grid convergence is difficult to achieve, but achievable in regions of interest. Our results demonstrate that in regions of increased stress, blood's viscosity may significantly decrease due to its shear thinning properties. This is exacerbated for vessels with large lateral aneurysms. Also, turbulence modelling is demonstrated to be required when feeding vessels connect to terminal aneurysms. Based on this framework, we will conduct an extensive investigation of the effects of blood rheology and turbulence modelling in 100+ patient-specific cases to provide better guidelines and inform future modelling efforts in cerebral hemodynamics.   

Mucociliary clearance in maxillary sinuses

Paranasal sinuses are hollow spaces within the bones surrounding the nose. Of these, the largest are the maxillary sinuses, that are situated near the cheek region. The sinuses are lined with a ciliated epithelium, which is the site of mucus production. The cilia constantly sweep this mucus out of the sinus into the nasal cavity, thus maintaining a clean mucus layer within the sinuses, which is essential for a healthy nasal environment. We present here an experimentally informed continuum mathematical model of this mucus clearance process: the flow of a thin fluid film produced by a wall-normal flux and swept out of the domain due to the effective action of cilia, and subject to both gravity and surface tension. Our modelling includes both one-dimensional systems and patient-specific sinus geometry. In each case, we identify physical conditions under which a steady mucus flow is possible, which allows us to highlight the competition between gravitational retention and boundary-driven drainage in the mucus dynamics.   

Neurological disorders leading to mechanical dysfunction of organs: emergent behavior of a neuromechanical dynamical system

An understanding of how neurological disorders lead to mechanical dysfunction of organs remains an open problem. For example, opioid-induced gastrointestinal (GI) motility disorder is known to be of neurological origin but with scarce understanding of how mechanical dysfunction emerges. Organ-scale neuromechanical models are needed to answer such questions. Using esophagus as a model problem, we demonstrate how emergent behavior of a neuromechanical dynamical system can help resolve longstanding questions. Specifically, we focus on repetitive antegrade contractions (RACs) pattern in the esophagus that emerges in response to sustained volumetric distension. Any deviations from the baseline RACs pattern indicates esophageal motility disorder. In this study, we seek to settle an ongoing debate on the emergence of RACs by developing a new empirically guided neuromechanical model. The neural circuitry is constructed as a chain of unidirectionally coupled relaxation oscillators, receiving excitatory signals from stretch receptors along the esophageal body. We successfully reproduce normal and abnormal esophageal response to distension. This work potentially provides a template to interrogate neurologically driven mechanophysiological pathologies of organs.   

Bleb mechanics during subcutaneous injection into ex vivo pork bellies

During large volume subcutaneous injections, liquid can accumulate and create a bleb around the injection site. Predicting the size of this bleb is important because it affects the rate the fluid absorbs into the body and because it may be linked to patient discomfort. In vivo pig tests have documented how the bleb height, area, and pressure vary over a range of infused liquid viscosities, flow rates, and injection volumes. However, there are inconsistencies between the various experiments and prevailing models based on poromechanics. Here we carry out systematic experiments with ex vivo tissue that replicate and extend the previous in vivo studies. Our results demonstrate that in vivo and ex vivo tissue exhibit comparable bleb dynamics over the injection timescales and highlight that certain assumptions in the current theoretical models are questionable.   

Computational modeling of solid food digestion inside the stomach

The stomach plays a vital role in the physical and chemical breakdown of ingested meals. Solid components of the meals are processed differently from liquids because only particles smaller than 2 mm are allowed to pass through to the intestines. Solid particles settle at the bottom of the stomach upon arrival and peristaltic contractions subject them to vigorous fluid motion leading to the grinding of the larger particles into smaller sizes, a phenomenon known as trituration. While previous studies have extensively modeled liquid meals, limited attention has been given to the physical breakdown of solids. Here we present a model that incorporates the trituration phenomenon and the subsequent emptying of solid meals into the duodenum. Imaging data is used to specify the wall motion and the properties of ingested food are derived from experimental studies on chewing. Lagrangian point-particle method is used to model the multiphase flow and a particle fracturing model is also included. We investigate the impact of food and motility parameters on particle trajectories and sizes. The model yields valuable insights into the gastric digestion of solid meals and the influence of wall motion in this process.   

Unseen Branch model based on physiologic principles for perfusion simulation of coronary arteries

Epicardial coronary arteries bifurcate to small vessels and transport blood to the heart tissue. As some of these vessel sizes are below the image resolution of typical imaging modalities, they are often missed when segmenting coronary arteries. These vessels, however, transport blood to the myocardium and pressure loss can be overestimated when they are not modeled in the coronary arteries as they generally taper after vessels bifurcate. We developed methods to model vessels below image resolution using the assumption that healthy epicardial coronary arteries transport blood while minimizing pressure loss. Ideal pressure loss was computed using the Poiseuille pressure loss when the vessel has no tapering while maintaining an input flow rate along the vessel path. Pressure loss of an actual vessel without diseases is computed and continually updated as unseen branches are added until the same pressure loss as in the ideal vessel is obtained. Flow to the added unseen branches is computed using scaling laws. The unseen branch model was validated using ideal cylinder models with various tapering ratios and image-based patient-specific coronary artery models. Further, perfusion simulation was performed by incorporating the unseen branch models and blood pressure and perfusion territories were compared against the ones without them.   

Mechano-pathogenesis of esophageal hypertrophy and atrophy

Esophageal hypertrophy and atrophy are chronic conditions associated with abnormal inner pressures during swallowing. Clinical data indicates that disease pathogenesis proceeds via remodeling of the esophageal tissue causing hypertrophy and/or atrophy and eventually leading to end-stage esophageal dilatation. However, it has remained unclear how different mechanical triggers lead to different pathways of disease progression. In this study, using a 1D anisotropic finite growth tissue remodeling model we uncover the fundamental mechanisms of esophageal wall remodeling. The model incorporates the progression of esophageal pressure during swallowing (short time scale peristalsis) on the long-time scale remodeling of the esophageal wall. We explore how different mechanical conditions lead to the emergence of different pathologies by plotting disease trajectories on a regime map (virtual disease landscape). The results reveal that while the esophageal muscle is sensitive to both radial and circumferential strains, the primary differentiator between different disease types is the circumferential stress. This work potentially provides a roadmap to investigate hypertrophies in other organ systems, for example, the mechano-pathogenesis of different types of hypertrophies of the heart.