van de Fn Frans Vosse

A pulse wave propagation model to support decision-making in vascular access planning in the clinic

The preferred vascular access for hemodialysis is an autologous arteriovenous fistula (AVF) in the arm: a surgically created connection between an artery and vein. The surgeon selects the AVF location based on experience and preoperative diagnostics. However, 20-50% of all lower arm AVFs are hampered by a too low access flow, whereas complications associated with too high flows are observed in 20% of all upper arm AVFs. We hypothesize that a pulse wave propagation model fed by patient-specific data has the ability to assist the surgeon in selecting the optimal AVF configuration by predicting direct postoperative flow. Previously, a 1D wave propagation model (spectral elements) was developed in which an approximated velocity profile was assumed based on boundary layer theory. In this study, we derived a distributed lumped parameter implementation of the pulse wave propagation model. The elements of the electrical analog for a segment are based on the approximated velocity profiles and dependent on the Womersley number. We present the application of the lumped parameter pulse wave propagation model to vascular access surgery and show how a patient-specific model is able to predict the hemodynamical impact of AVF creation and might assist in vascular access planning. The lumped parameter pulse wave propagation model was able to select the same AVF configuration as an experienced surgeon in nine out of ten patients. In addition, in six out of ten patients predicted postoperative flows were in the same order of magnitude as measured postoperative flows. Future research should quantify uncertainty in model predictions and measurements.

Experimental validation of a pulse wave propagation model for predicting hemodynamics after vascular access surgery

Hemodialysis patients require a vascular access that is, preferably, surgically created by connecting an artery and vein in the arm, i.e. an arteriovenous fistula (AVF). The site for AVF creation is chosen by the surgeon based on preoperative diagnostics, but AVFs are still compromised by flow-associated complications. Previously, it was shown that a computational 1D-model is able to describe pressure and flow after AVF surgery. However, predicted flows differed from measurements in 4/10 patients. Differences can be attributed to inaccuracies in Doppler measurements and input data, to neglecting physiological mechanisms or to an incomplete physical description of the pulse wave propagation after AVF surgery. The physical description can be checked by validating against an experimental setup consisting of silicone tubes mimicking the aorta and arm vasculature both before and after AVF surgery, which is the aim of the current study. In such an analysis, the output uncertainty resulting from measurement uncertainty in model input should be quantified. The computational model was fed by geometrical and mechanical properties collected from the setup. Pressure and flow waveforms were simulated and compared with experimental waveforms. The precision of the simulations was determined by performing a Monte Carlo study. It was concluded that the computational model was able to simulate mean pressures and flows accurately, whereas simulated waveforms were less attenuated than experimental ones, likely resulting from neglecting viscoelasticity. Furthermore, it was found that in the analysis output uncertainties, resulting from input uncertainties, cannot be neglected and should thus be considered.

A sensitivity analysis of a personalized pulse wave propagation model for arteriovenous fistula surgery. Part A: Identification of most influential model parameters

Previously, a pulse wave propagation model was developed that has potential in supporting decision-making in arteriovenous fistula (AVF) surgery for hemodialysis. To adapt the wave propagation model to personalized conditions, patient-specific input parameters should be available. In clinics, the number of measurable input parameters is limited which results in sparse datasets. In addition, patient data are compromised with uncertainty. These uncertain and incomplete input datasets will result in model output uncertainties. By means of a sensitivity analysis the propagation of input uncertainties into output uncertainty can be studied which can give directions for input measurement improvement. In this study, a computational framework has been developed to perform such a sensitivity analysis with a variance-based method and Monte Carlo simulations. The framework was used to determine the influential parameters of our pulse wave propagation model applied to AVF surgery, with respect to parameter prioritization and parameter fixing. With this we were able to determine the model parameters that have the largest influence on the predicted mean brachial flow and systolic radial artery pressure after AVF surgery. Of all 73 parameters 51 could be fixed within their measurement uncertainty interval without significantly influencing the output, while 16 parameters importantly influence the output uncertainty. Measurement accuracy improvement should thus focus on these 16 influential parameters. The most rewarding are measurement improvements of the following parameters: the mean aortic flow, the aortic windkessel resistance, the parameters associated with the smallest arterial or venous diameters of the AVF in- and outflow tract and the radial artery windkessel compliance.

Personalization of models with many model parameters: an efficient sensitivity analysis approach

Uncertainty quantification and global sensitivity analysis are indispensable for patient-specific applications of models that enhance diagnosis or aid decision-making. Variance-based sensitivity analysis methods, which apportion each fraction of the output uncertainty (variance) to the effects of individual input parameters or their interactions, are considered the gold standard. The variance portions are called the Sobol sensitivity indices and can be estimated by a Monte Carlo (MC) approach (e.g., Saltellis method [1]) or by employing a metamodel (e.g., the (generalized) polynomial chaos expansion (gPCE) [2, 3]). All these methods require a large number of model evaluations when estimating the Sobol sensitivity indices for models with many parameters [4]. To reduce the computational cost, we introduce a two-step approach. In the first step, a subset of important parameters is identified for each output of interest using the screening method of Morris [5]. In the second step, a quantitative variance-based sensitivity analysis is performed using gPCE. Efficient sampling strategies are introduced to minimize the number of model runs required to obtain the sensitivity indices for models considering multiple outputs. The approach is tested using a model that was developed for predicting post-operative flows after creation of a vascular access for renal failure patients. We compare the sensitivity indices obtained with the novel two-step approach with those obtained from a reference analysis that applies Saltellis MC method. The two-step approach was found to yield accurate estimates of the sensitivity indices at two orders of magnitude lower computational cost.