Marielle Bosboom

Clinical study protocol for the ARCH project - Computational modeling for improvement of outcome after vascular access creation

Despite clinical guidelines and the possibility of diagnostic vascular imaging, creation and maintenance of a vascular access (VA) remains problematic: avoiding short- and long-term VA dysfunction is challenging. Although prognostic factors for VA dysfunction have been identified in previous studies, their potential interplay at a systemic level is disregarded. Consideration of multiple prognostic patient specific factors and their complex interaction using dedicated computational modeling tools might improve outcome after VA creation by enabling a better selection of VA configuration. These computational modeling tools are developed and validated in the ARCH project: a joint initiative of four medical centers and three industrial partners (FP7-ICT-224390). This paper reports the rationale behind computational modeling and presents the clinical study protocol designed for calibrating and validating these modeling tools. The clinical study is based on the pre-operative collection of structural and functional data at a vascular level, as well as a VA functional evaluation during the follow-up period. The strategy adopted to perform the study and for data collection is also described here.

A numerical method of reduced complexity for simulating vascular hemodynamics using coupled 0D lumped and 1D wave propagation models.

A computational method of reduced complexity is developed for simulating vascular hemodynamics by combination of one-dimensional (1D) wave propagation models for the blood vessels with zero-dimensional (0D) lumped models for the microcirculation. Despite the reduced dimension, current algorithms used to solve the model equations and simulate pressure and flow are rather complex, thereby limiting acceptance in the medical field. This complexity mainly arises from the methods used to combine the 1D and the 0D model equations. In this paper a numerical method is presented that no longer requires additional coupling methods and enables random combinations of 1D and 0D models using pressure as only state variable. The method is applied to a vascular tree consisting of 60 major arteries in the body and the head. Simulated results are realistic. The numerical method is stable and shows good convergence.

Computational model for estimating the short- and long-term cardiac response to arteriovenous fistula creation for hemodialysis

Creation of an arteriovenous fistula (AVF) for hemodialysis may result in cardiac failure due to dramatic increases in cardiac output. To investigate the quantitative relations between AVF flow, changes in cardiac output, myocardial stress and strain and resulting left ventricular adaptation, a computational model is developed. The model combines a one-dimensional pulse wave propagation model of the arterial network with a zero-dimensional one-fiber model of cardiac mechanics and includes adaptation rules to capture the effect of the baro-reflex and long-term structural remodelling of the left ventricle. Using generic vascular and cardiac parameters based on literature, simulations are done that illustrate the model’s ability to quantitatively reproduce the clinically observed increase in brachial flow and cardiac output as well as occurence of eccentric hypertrophy. Patient-specific clinical data is needed to investigate the value of the computational model for personalized predictions.

Biomechanical analysis of abdominal aortic aneurysms

The aorta is the largest artery in the human body, transporting oxygenized blood directly from the left ventricle of the heart to the rest of the body. An aortic aneurysm is a local dilation in the aorta of more than 1.5 times the original diameter [27]. Although aneurysms can be present in every part of the aorta, the majority of the aortic aneurysms are situated in the abdominal aorta (AAA, Fig. 6.1), below the level of the renal arteries and above the aortic bifurcation to the common iliac arteries [7]. A diameter of 3 cm or more is generally used as indication for an AAA (abdominal aortic aneurysm). In most AAAs, thrombus is found between the perfused flow lumen and the aortic wall. Thrombus is a fibrin structure with mainly blood cells, platelets, and blood proteins, which is deposited onto the vessel wall [21].

MODELING THE EFFECTS OF AN ARTERIOVENOUS FISTULA ON CARDIAC FUNCTION

Introduction A surgically created vascular access like an arteriovenous fistula (AVF) is of vital importance in end-stage renal disease (ESRD) patients receiving hemodialysis. However, an AVF causes an increase in cardiac output which is a risk factor for the development of left ventricular hypertrophy [Ori, 2002, Iwashima, 2002]. Because cardiac disease is the most import cause of death in ESRD patients [Dhingra, 2001], it is important to gain insight into the hemodynamics and the effect of AVF creation on cardiac function. As differences in vascular anatomy and cardiac condition are large, the patient-specific situation should be considered. Therefore, in this study a patient-specific model is developed to study the effect of an AVF on cardiac function. Ultimately, such a model could be used in surgical planning to choose between different alternatives for an AVF.

IMPROVING PERSONALIZATION OF A 1D WAVE PROPAGATION MODEL APPLIED FOR AVF SURGERY

An arteriovenous fistula (AVF) is used as vascular access in hemodialysis. A previously developed patient-specific pulse wave propagation model [Huberts, 2011] might be useful to improve selection of the optimal AVF location (upper or lower arm) by predicting postoperative flow. However, personalizing the model parameters is difficult due to the limitations of measurement modalities, the large uncertainties in clinical measurements and the burden on the patient that should be minimized, resulting in sparse datasets. Therefore, it would be beneficial to identify the model parameters that are essential in the flow prediction and should thus be measured for each patient. Hence, the aim of this study was to identify the (non-) influential model parameters of the pulse wave propagation model applied to AVF surgery.

EXPERIMENTAL VALIDATION OF A 1D WAVE PROPAGATION MODEL FOR HEMODYNAMICS AFTER AVF SURGERY

An arteriovenous fistula (AVF) is a surgically created connection between an artery and vein in the arm, made for connecting hemodialysis patients to an artificial kidney [Tordoir, 2003]. Previously, a pulse wave propagation model was developed [Huberts, 2011] that has potential in supporting decision-making in AVF surgery by predicting mean postoperative flow. The model was able to select the same AVF configuration as an experienced vascular surgeon (> 1000 AVFs created) in 9/10 patients. Although the model might already be of clinical use, model improvements can be made since the predicted flow differed in 4/10 patients with flow measured after surgery. Differences can result either from inaccurate postoperative flow measurements, inaccurate model input, neglecting adaptation and/or an incomplete physical description of the pulse wave propagation after AVF surgery. To examine if the physical description is complete the model should be validated with an experimental setup. Moreover, the experimental setup gives the possibility to validate the pressure and flow waveforms which are required when adaptation laws will be incorporated in the model. Therefore, the aim of this study was to validate the pulse wave propagation model with an experimental setup mimicking AVF surgery.

SELECTING THE OPTIMAL LOCATION FOR AVF CREATION: THE LIFELINE FOR HEMODIALYSIS PATIENTS

A vascular access facilitates the high blood flow needed for hemodialysis and is therefore crucial for successful treatment of patients suffering from endstage renal disease. Preferably, a vascular access is created by surgically connecting an artery and vein in the arm (arteriovenous fistula, AVF). The optimal location (upper or lower arm) is selected by the vascular surgeon based on extensive preoperative diagnostics. Nevertheless, flow-related complications still occur in up to 30% of all cases [Allon, 2003]. Previously, a pulse wave propagation model was developed that has potential to support decision-making in AVF surgery. In this study, the model’s feasibility for personalized AVF surgery planning is examined.