Assessment of extracranial carotid artery disease using digital twins - A pilot study.

To improve risk stratification in extracranial internal carotid artery disease (CAD), patients who would benefit maximally from revascularization must be identified. In cardiology, the fractional flow reserve (FFR) has become a reference standard for evaluating the functional severity of coronary artery stenosis, and noninvasive surrogates thereof relying on computational fluid dynamics (CFD) have been developed. Here, we present a CFD-based workflow using digital twins of patients' carotid bifurcations derived from computed tomography angiography for the noninvasive functional assessment of CAD. We reconstructed patient-specific digital twins of 37 carotid bifurcations. We implemented a CFD model using common carotid artery peak systolic velocity (PSV) acquired with Doppler ultrasound (DUS) as inlet boundary condition and a two-element Windkessel model as oulet boundary condition. The agreement between CFD and DUS on the PSV in the internal carotid artery (ICA) was then compared. The relative error for the agreement between DUS and CFD was 9% ± 20% and the intraclass correlation coefficient was 0.88. Furthermore, hyperemic simulations in a physiological range were feasible and unmasked markedly different pressure drops along two ICA stenoses with similar degree of narrowing under comparable ICA blood flow. Hereby, we lay the foundation for prospective studies on noninvasive CFD-based derivation of metrics similar to the FFR for the assessment of CAD.

Are standing osmotic gradients the main driver of cerebrospinal fluid production? A computational analysis.

BACKGROUND: The mechanisms of cerebrospinal fluid (CSF) production by the ventricular choroid plexus (ChP) have not been fully deciphered. One prominent hypothesized mechanism is trans-epithelial water transport mediated by accumulation of solutes at the luminal ChP membrane that produces local osmotic gradients. However, this standing osmotic gradient hypothesis has not been systematically tested. METHODS: To assess the plausibility of the standing gradient mechanism serving as the main driver of CSF production by the ChP, we developed a three-dimensional (3D) and a one-dimensional (1D) computational model to quantitatively describe the associated processes in the rat ChP inter-microvillar spaces and in CSF pools between macroscopic ChP folds (1D only). The computationally expensive 3D model was used to examine the applicability of the 1D model for hypothesis testing. The 1D model was employed to predict the rate of CSF produced by the standing gradient mechanism for 200,000 parameter permutations. Model parameter values for each permutation were chosen by random sampling from distributions derived from published experimental data. RESULTS: Both models predict that the CSF production rate by the standing osmotic gradient mechanism is below 10% of experimentally measured values that reflect the contribution of all actual production mechanisms. The 1D model indicates that increasing the size of CSF pools between ChP folds, where diffusion dominates solute transport, would increase the contribution of the standing gradient mechanism to CSF production. CONCLUSIONS: The models suggest that the effect of standing osmotic gradients is too small to contribute substantially to CSF production. ChP motion and movement of CSF in the ventricles, which are not accounted for in the models, would further reduce this effect, making it unlikely that standing osmotic gradients are the main drivers of CSF production.

Influence of Surface Roughness on Droplet Evaporation and Absorption: Insights into Experiments from Lubrication-Theory-Based Models.

While solid substrates are often idealized as being perfectly smooth, all real surfaces possess some level of topographical and chemical heterogeneity. This heterogeneity can greatly influence droplet dynamics. Mathematical models based on lubrication theory that account for surface roughness reveal how topographical defects induce contact-line pinning and affect the deposition patterns of colloidal particles suspended in the droplet. Contact-line pinning profoundly changes the behavior of droplet evaporation on horizontal and inclined impermeable substrates and droplet absorption on horizontal permeable substrates. Models accounting for surface roughness yield predictions that are qualitatively consistent with experimental observations and also provide insight into the underlying physical mechanisms. These models are a foundation for the exploration of a rich array of problems concerning droplet dynamics which are of both fundamental and practical interest.

Droplet evaporation on soft solid substrates.

Droplet evaporation on soft solid substrates is relevant to applications such as fabrication of microlenses and controlled particle deposition. Here, we develop a lubrication-theory-based model to advance fundamental understanding of the important limiting case of a planar droplet evaporating on a linear viscoelastic solid. A set of partial differential equations describing the time evolution of the liquid-air and liquid-solid interfaces is derived and solved with a finite-difference method. A disjoining-pressure/precursor-film approach is used to describe contact-line motion, and the one sided model is used to describe solvent evaporation. Parametric studies are conducted to investigate the effect of solid properties (thickness, viscosity, shear modulus, wettability) and evaporation rate on droplet dynamics. Our results indicate that softer substrates speed up droplet evaporation due to prolonged pinning of the contact line. Results from our model are able to qualitatively reproduce some key trends observed in experiments. Due to its systematic formulation, our model can readily be extended to more complex situations of interest such as evaporation of particle-laden droplets on soft solid substrates.

A thin-film model for droplet spreading on soft solid substrates.

The spreading of droplets on soft solid substrates is relevant to applications such as tumor biophysics and controlled droplet condensation and evaporation. In this paper, we apply lubrication theory to advance fundamental understanding of the important limiting case of spreading of a planar droplet on a linear viscoelastic solid. The contact-line region is described by a disjoining-pressure/precursor-film approach, and nonlinear evolution equations describing how the liquid-air and liquid-solid interfaces evolve in space and time are derived and solved numerically. Parametric studies are conducted to investigate the effects of solid thickness, viscosity, shear modulus, and wettability on droplet spreading. Softer substrates are found to speed up spreading for perfectly wetting droplets but slow down spreading for partially wetting droplets. For perfectly wetting droplets, faster spreading is a result of more liquid being pumped toward the contact line due to a larger liquid-film thickness there arising from the repulsive component of the disjoining pressure. In contrast, slower spreading of partially wetting droplets is a result of less liquid being pumped toward the contact line due to a smaller liquid-film thickness there arising from the attractive component of the disjoining pressure. The model predictions for partially wetting droplets are qualitatively consistent with experimental observations, and allow us to disentangle the effects of substrate deformability and wettability on droplet spreading. Due to its systematic formulation, our model can readily be extended to more complex situations involving multiple droplets, substrate inclination, and droplet phase changes.