Catriona Baker

An integrated approach to patient-specific predictive modeling for single ventricle heart palliation

In patients with congenital heart disease and a single ventricle (SV), ventricular support of the circulation is inadequate, and staged palliative surgery (usually 3 stages) is needed for treatment. In the various palliative surgical stages individual differences in the circulation are important and patient-specific surgical planning is ideal. In this study, an integrated approach between clinicians and engineers has been developed, based on patient-specific multi-scale models, and is here applied to predict stage 2 surgical outcomes. This approach involves four distinct steps: (1) collection of pre-operative clinical data from a patient presenting for SV palliation, (2) construction of the pre-operative model, (3) creation of feasible virtual surgical options which couple a three-dimensional model of the surgical anatomy with a lumped parameter model (LPM) of the remainder of the circulation and (4) performance of post-operative simulations to aid clinical decision making. The pre-operative model is described, agreeing well with clinical flow tracings and mean pressures. Two surgical options (bi-directional Glenn and hemi-Fontan operations) are virtually performed and coupled to the pre-operative LPM, with the hemodynamics of both options reported. Results are validated against postoperative clinical data. Ultimately, this work represents the first patient-specific predictive modeling of stage 2 palliation using virtual surgery and closed-loop multi-scale modeling.

A non-invasive clinical application of wave intensity analysis based on ultrahigh temporal resolution phase-contrast cardiovascular magnetic resonance

BackgroundWave intensity analysis, traditionally derived from pressure and velocity data, can be formulated using velocity and area. Flow-velocity and area can both be derived from high-resolution phase-contrast cardiovascular magnetic resonance (PC-CMR). In this study, very high temporal resolution PC-CMR data is processed using an integrated and semi-automatic technique to derive wave intensity.MethodsWave intensity was derived in terms of area and velocity changes. These data were directly derived from PC-CMR using a breath-hold spiral sequence accelerated with sensitivity encoding (SENSE). Image processing was integrated in a plug-in for the DICOM viewer OsiriX, including calculations of wave speed and wave intensity. Ascending and descending aortic data from 15 healthy volunteers (30 ± 6 years) data were used to test the method for feasibility, and intra- and inter-observer variability. Ascending aortic data were also compared with results from 15 patients with coronary heart disease (61 ± 13 years) to assess the clinical usefulness of the method.ResultsRapid image acquisition (11 s breath-hold) and image processing was feasible in all volunteers. Wave speed was physiological (5.8 ± 1.3 m/s ascending aorta, 5.0 ± 0.7 m/s descending aorta) and the wave intensity pattern was consistent with traditionally formulated wave intensity. Wave speed, peak forward compression wave in early systole and peak forward expansion wave in late systole at both locations exhibited overall good intra- and inter-observer variability. Patients with coronary heart disease had higher wave speed (p <0.0001), and lower forward compression wave (p <0.0001) and forward expansion wave (p <0.0005) peaks. This difference is likely related to the older age of the patients’ cohort, indicating stiffer aortas, as well as compromised ventricular function due to their underlying condition.ConclusionA non-invasive, semi-automated and reproducible method for performing wave intensity analysis is presented. Its application is facilitated by the use of a very high temporal resolution spiral sequence. A formulation of wave intensity based on area change has also been proposed, involving no assumptions about the cross-sectional shape of the vessel.

Effects of pulmonary artery banding and retrograde aortic arch obstruction on the hybrid palliation of hypoplastic left heart syndrome.

OBJECTIVES The hybrid approach achieves stage 1 palliation of hypoplastic left heart syndrome with flow and physiologic characteristics that are different from those of the surgical Norwood circulations. In addition to having branch pulmonary arterial banding regulating the balance between pulmonary and systemic blood flows, coronary and cerebral perfusion are dependent on retrograde flow through the native aortic arch when aortic atresia is present. Accordingly, we used computational modeling to assess the effects of pulmonary artery banding diameter and retrograde aortic arch hypoplasia or obstruction on the hybrid stage 1 circulation, including the influence on systemic and cerebral oxygen deliveries. METHODS A computational modeling technique was used to couple a 3-dimensional geometry of the hybrid palliation with a hydraulic network of the entire circulation based on pre-stage 2 hemodynamics. This validated multiscale approach predicts clinically relevant outcomes, such as flow, pressure, ejection fraction, and oxygen delivery. Simulations with pulmonary artery banding varying between 1.5 and 3.5 mm were performed. To examine the effects of retrograde aortic arch hypoplasia and obstruction, models of differing aortic arch diameter (2-5 mm) and isthmus coarctation (2.5-5 mm) were studied. RESULTS Banding the branch pulmonary arteries to 2 mm led to pulmonary and systemic blood flows closest to 1:1 and produced the highest mixed venous saturation and systemic oxygen delivery. Both cerebral and coronary perfusion decreased markedly when the retrograde aortic arch or the coarctation was less than 3 mm in diameter. Moreover, flow reversal in the carotid arteries was observed during diastole in all models. CONCLUSIONS These computational simulations of the stage 1 hybrid palliation for hypoplastic left heart syndrome with aortic atresia suggest that small differences in the degree of branch pulmonary arterial banding can result in significant changes in the overall performance of the hybrid palliation. Furthermore, retrograde aortic arch hypoplasia or obstruction can lead to suboptimal cerebral and coronary perfusion. Precise pulmonary artery banding may be important to optimize interstage physiology in patients undergoing the hybrid approach, and pre-interventional imaging of the aortic arch and isthmus should be performed to rule out potential for post-procedural suboptimal cerebral and coronary perfusion.

Uncertainty quantification in virtual surgery hemodynamics predictions for single ventricle palliation.

The adoption of simulation tools to predict surgical outcomes is increasingly leading to questions about the variability of these predictions in the presence of uncertainty associated with the input clinical data. In the present study, we propose a methodology for full propagation of uncertainty from clinical data to model results that, unlike deterministic simulation, enables estimation of the confidence associated with model predictions. We illustrate this problem in a virtual stage II single ventricle palliation surgery example. First, probability density functions (PDFs) of right pulmonary artery (PA) flow split ratio and average pulmonary pressure are determined from clinical measurements, complemented by literature data. Starting from a zero-dimensional semi-empirical approximation, Bayesian parameter estimation is used to find the distributions of boundary conditions that produce the expected PA flow split and average pressure PDFs as pre-operative model results. To reduce computational cost, this inverse problem is solved using a Kriging approximant. Second, uncertainties in the boundary conditions are propagated to simulation predictions. Sparse grid stochastic collocation is employed to statistically characterize model predictions of post-operative hemodynamics in models with and without PA stenosis. The results quantify the statistical variability in virtual surgery predictions, allowing for placement of confidence intervals on simulation outputs.

Hemodynamic effects of left pulmonary artery stenosis after superior cavopulmonary connection: a patient-specific multiscale modeling study.

OBJECTIVE Currently, no quantitative guidelines have been established for treatment of left pulmonary artery (LPA) stenosis. This study aims to quantify the effects of LPA stenosis on postoperative hemodynamics for single-ventricle patients undergoing stage II superior cavopulmonary connection (SCPC) surgery, using a multiscale computational approach. METHODS Image data from 6 patients were segmented to produce 3-dimensional models of the pulmonary arteries before stage II surgery. Pressure and flow measurements were used to tune a 0-dimensional model of the entire circulation. Postoperative geometries were generated through stage II virtual surgery; varying degrees of LPA stenosis were applied using mesh morphing and hemodynamics assessed through coupled 0-3-dimensional simulations. To relate metrics of stenosis to clinical classifications, pediatric cardiologists and surgeons ranked the degrees of stenosis in the models. The effects of LPA stenosis were assessed based on left-to-right pulmonary artery flow split ratios, mean pressure drop across the stenosis, cardiac pressure-volume loops, and other clinically relevant parameters. RESULTS Stenosis of >65% of the vessel diameter was required to produce a right pulmonary artery:LPA flow split <30%, and/or a mean pressure drop of >3.0 mm Hg, defined as clinically significant changes. CONCLUSIONS The effects of <65% stenosis on SCPC hemodynamics and physiology were minor and may not justify the increased complexity of adding LPA arterioplasty to the SCPC operation. However, in the longer term, pulmonary augmentation may affect outcomes of the Fontan completion surgery, as pulmonary artery distortion is a risk factor that may influence stage III physiology.

In vitro study of the norwood palliation: A patient-specific mock circulatory system

The aim of this study was to build a mock circulatory system replicating in vitro the hemodynamics following the Norwood procedure and testing patient-specific anatomies focusing on the effect of aortic coarctation. Three anatomies were reconstructed from magnetic resonance images and rapid prototyped with transparent rigid resin. The models presented varying degrees of coarctation (none, moderate, and severe). A Blalock-Taussing (BT) shunt was modeled in all phantoms, which were inserted into a mock circulation. The single ventricle was simulated using a Berlin Heart driven with a PC-controlled piston. Resistive and compliant elements were implemented, creating a lumped parameter network. Pressure was measured at three locations: the transverse aortic arch, just after the aortic isthmus, and further downstream in the thoracic aorta. Volume distribution was derived from the instantaneous flow measurements at three outlets: upper body, lower body, and BT shunt. The combination of three-dimensional (3D) detailed anatomy and lumped parameter network effectively renders the circuit a multiscale in vitro model that successfully reproduces physiologic pressure signals. The pressure results highlight the larger pressure drop caused by coarctation and show the effect of pressure recovery. Results also suggest a reduction of flow to the lower body with increasing severity of coarctation, to the advantage of upper body and pulmonary circulation.

Data assimilation and modelling of patient-specific single-ventricle physiology with and without valve regurgitation

A closed-loop lumped parameter model of blood circulation is considered for single-ventricle shunt physiology. Its parameters are estimated by an inverse problem based on patient-specific haemodynamics measurements. As opposed to a black-box approach, maximizing the number of parameters that are related to physically measurable quantities motivates the present model. Heart chambers are described by a single-fibre mechanics model, and valve function is modelled with smooth opening and closure. A model for valve prolapse leading to valve regurgitation is proposed. The method of data assimilation, in particular the unscented Kalman filter, is used to estimate the model parameters from time-varying clinical measurements. This method takes into account both the uncertainty in prior knowledge related to the parameters and the uncertainty associated with the clinical measurements. Two patient-specific cases - one without regurgitation and one with atrioventricular valve regurgitation - are presented. Pulmonary and systemic circulation parameters are successfully estimated, without assumptions on their relationships. Parameters governing the behaviour of heart chambers and valves are either fixed based on biomechanics, or estimated. Results of the inverse problem are validated qualitatively through clinical measurements or clinical estimates that were not included in the parameter estimation procedure. The model and the estimation method are shown to successfully capture patient-specific clinical observations, even with regurgitation, such as the double peaked nature of valvular flows and anomalies in electrocardiogram readings. Lastly, biomechanical implications of the results are discussed.

Implementing the Sano Modification in an Experimental Model of First-stage Palliation of Hypoplastic Left Heart Syndrome

This study describes the implementation of an experimental model of the “Sano” variant (right-ventricle to pulmonary-artery shunt) of the Norwood operation used to treat hypoplastic left-heart syndrome (HLHS). The Sano operation is an alternative to the modified Blalock-Taussig shunt (innominate to pulmonary artery shunt). In the experimental setup, the single ventricle is simulated using a Berlin Heart Excor ventricular assist device and the Sano shunt is constructed by attaching a Tygon tube (6 mm internal diameter, 40 mm long) to the perforated de-airing valve of the Berlin Heart at one end, and to a pulmonary compliance chamber at the other end. The feasibility of the setup was verified by testing two rapid-prototyped patient-specific anatomical models (one without and one with aortic coarctation) under pulsatile flow conditions typical of Norwood patients. Results showed physiological and repeatable pressure and flow signals, as well as physiological values for pulmonary and aortic flow. Shunt flow was regulated by shunt size, and diastolic runoff through the shunt was also observed, both being features of Sano physiology. This system allows for comparing variations of first stage palliation of HLHS in vitro, and it also represents a source of data for validation of computational models.

Inverse problems in reduced order models of cardiovascular haemodynamics: Aspects of data assimilation and heart rate variability

Inverse problems in cardiovascular modelling have become increasingly important to assess each patient individually. These problems entail estimation of patient-specific model parameters from uncertain measurements acquired in the clinic. In recent years, the method of data assimilation, especially the unscented Kalman filter, has gained popularity to address computational efficiency and uncertainty consideration in such problems. This work highlights and presents solutions to several challenges of this method pertinent to models of cardiovascular haemodynamics. These include methods to (i) avoid ill-conditioning of the covariance matrix, (ii) handle a variety of measurement types, (iii) include a variety of prior knowledge in the method, and (iv) incorporate measurements acquired at different heart rates, a common situation in the clinic where the patient state differs according to the clinical situation. Results are presented for two patient-specific cases of congenital heart disease. To illustrate and validate data assimilation with measurements at different heart rates, the results are presented on a synthetic dataset and on a patient-specific case with heart valve regurgitation. It is shown that the new method significantly improves the agreement between model predictions and measurements. The developed methods can be readily applied to other pathophysiologies and extended to dynamical systems which exhibit different responses under different sets of known parameters or different sets of inputs (such as forcing/excitation frequencies).

Does TCPC power loss really affect exercise capacity

To the Editor, We read with interest the article by Khiabani et al ,1 where the authors examine the relationship between power loss in the total cavopulmonary connection (TCPC) and clinical exercise testing. Using an indexed power loss, ‘iPL’, they report that higher iPL correlates with worse minute oxygen consumption and exercise work at anaerobic threshold. Based on this, the authors suggest that power loss in the TCPC could affect exercise performance in a patient with Fontan circulation. In the manuscript, the authors attempt to discover a correlation of the hydraulics of the Fontan circulation with exercise performance. In doing so, they use the unique parameter, iPL, instead of the unadjusted power loss. We believe that this approach is misleading and leads to the wrong conclusion. The term iPL was defined as:![Formula][1] where PL, ρ, Q … [1]: /embed/graphic-1.gif