Giovanni Biglino

Rapid prototyping compliant arterial phantoms for in-vitro studies and device testing

BackgroundCompliant vascular phantoms are desirable for in-vitro patient-specific experiments and device testing. TangoPlus FullCure 930® is a commercially available rubber-like material that can be used for PolyJet rapid prototyping. This work aims to gather preliminary data on the distensibility of this material, in order to assess the feasibility of its use in the context of experimental cardiovascular modelling.MethodsThe descending aorta anatomy of a volunteer was modelled in 3D from cardiovascular magnetic resonance (CMR) images and rapid prototyped using TangoPlus. The model was printed with a range of increasing wall thicknesses (0.6, 0.7, 0.8, 1.0 and 1.5 mm), keeping the lumen of the vessel constant. Models were also printed in both vertical and horizontal orientations, thus resulting in a total of ten specimens. Compliance tests were performed by monitoring pressure variations while gradually increasing and decreasing internal volume. Knowledge of distensibility was thus derived and then implemented with CMR data to test two applications. Firstly, a patient-specific compliant model of hypoplastic aorta suitable for connection in a mock circulatory loop for in-vitro tests was manufactured. Secondly, the right ventricular outflow tract (RVOT) of a patient necessitating pulmonary valve replacement was printed in order to physically test device insertion and assess patient’s suitability for percutaneous pulmonary valve intervention.ResultsThe distensibility of the material was identified in a range from 6.5 × 10-3 mmHg-1 for the 0.6 mm case, to 3.0 × 10-3 mmHg-1 for the 1.5 mm case. The models printed in the vertical orientation were always more compliant than their horizontal counterpart. Rapid prototyping of a compliant hypoplastic aorta and of a RVOT anatomical model were both feasible. Device insertion in the RVOT model was successful.ConclusionValues of distensibility, compared with literature data, show that TangoPlus is suitable for manufacturing arterial phantoms, with the added benefit of being compatible with PolyJet printing, thus guaranteeing representative anatomical finishing, and quick and inexpensive fabrication. The appealing possibility of printing models of non-uniform wall thickness, resembling more closely certain physiological scenarios, can also be explored. However, this material appears to be too stiff for modelling the more compliant systemic venous system.

3D-manufactured patient-specific models of congenital heart defects for communication in clinical practice: feasibility and acceptability

Objectives To assess the communication potential of three-dimensional (3D) patient-specific models of congenital heart defects and their acceptability in clinical practice for cardiology consultations. Design This was a questionnaire-based study in which participants were randomised into two groups: the ‘model group’ received a 3D model of the cardiac lesion(s) being discussed during their appointment, while the ‘control group’ had a routine visit. Setting Outpatient clinic, cardiology follow-up visits. Participants 103 parents of children with congenital heart disease were recruited (parental age: 43±8 years; patient age: 12±6 years). In order to have a 3D model made, patients needed to have a recent cardiac MRI examination; this was the crucial inclusion criterion. Interventions Questionnaires were administered to the participants before and after the visits and an additional questionnaire was administered to the attending cardiologist. Main outcome measures Rating (1–10) for the liking of the 3D model, its usefulness and the clarity of the explanation received were recorded, as well as rating (1–10) of the parental understanding and their engagement according to the cardiologist. Furthermore, parental knowledge was assessed by asking them to mark diagrams, tick keywords and provide free text answers. The duration of consultations was recorded and parent feedback collected. Results Parents and cardiologists both found the models to be very useful and helpful in engaging the parents in discussing congenital heart defects. Parental knowledge was not associated with their level of education (p=0.2) and did not improve following their visit. Consultations involving 3D models lasted on average 5 min longer (p=0.02). Conclusions Patient-specific models can enhance engagement with parents and improve communication between cardiologists and parents, potentially impacting on parent and patient psychological adjustment following treatment. However, in the short-term, parental understanding of their childs condition did not improve.

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.

Computational modelling for congenital heart disease: how far are we from clinical translation?

Computational models of congenital heart disease (CHD) have become increasingly sophisticated over the last 20 years. They can provide an insight into complex flow phenomena, allow for testing devices into patient-specific anatomies (pre-CHD or post-CHD repair) and generate predictive data. This has been applied to different CHD scenarios, including patients with single ventricle, tetralogy of Fallot, aortic coarctation and transposition of the great arteries. Patient-specific simulations have been shown to be informative for preprocedural planning in complex cases, allowing for virtual stent deployment. Novel techniques such as statistical shape modelling can further aid in the morphological assessment of CHD, risk stratification of patients and possible identification of new ‘shape biomarkers’. Cardiovascular statistical shape models can provide valuable insights into phenomena such as ventricular growth in tetralogy of Fallot, or morphological aortic arch differences in repaired coarctation. In a constant move towards more realistic simulations, models can also account for multiscale phenomena (eg, thrombus formation) and importantly include measures of uncertainty (ie, CIs around simulation results). While their potential to aid understanding of CHD, surgical/procedural decision-making and personalisation of treatments is undeniable, important elements are still lacking prior to clinical translation of computational models in the field of CHD, that is, large validation studies, cost-effectiveness evaluation and establishing possible improvements in patient outcomes.

A statistical shape modelling framework to extract 3D shape biomarkers from medical imaging data: assessing arch morphology of repaired coarctation of the aorta

BackgroundMedical image analysis in clinical practice is commonly carried out on 2D image data, without fully exploiting the detailed 3D anatomical information that is provided by modern non-invasive medical imaging techniques. In this paper, a statistical shape analysis method is presented, which enables the extraction of 3D anatomical shape features from cardiovascular magnetic resonance (CMR) image data, with no need for manual landmarking. The method was applied to repaired aortic coarctation arches that present complex shapes, with the aim of capturing shape features as biomarkers of potential functional relevance. The method is presented from the user-perspective and is evaluated by comparing results with traditional morphometric measurements.MethodsSteps required to set up the statistical shape modelling analyses, from pre-processing of the CMR images to parameter setting and strategies to account for size differences and outliers, are described in detail. The anatomical mean shape of 20 aortic arches post-aortic coarctation repair (CoA) was computed based on surface models reconstructed from CMR data. By analysing transformations that deform the mean shape towards each of the individual patient’s anatomy, shape patterns related to differences in body surface area (BSA) and ejection fraction (EF) were extracted. The resulting shape vectors, describing shape features in 3D, were compared with traditionally measured 2D and 3D morphometric parameters.ResultsThe computed 3D mean shape was close to population mean values of geometric shape descriptors and visually integrated characteristic shape features associated with our population of CoA shapes. After removing size effects due to differences in body surface area (BSA) between patients, distinct 3D shape features of the aortic arch correlated significantly with EF (r = 0.521, p = .022) and were well in agreement with trends as shown by traditional shape descriptors.ConclusionsThe suggested method has the potential to discover previously unknown 3D shape biomarkers from medical imaging data. Thus, it could contribute to improving diagnosis and risk stratification in complex cardiac disease.

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.

Pressure and Flow‐Volume Distribution Associated With Intra‐aortic Balloon Inflation: An In Vitro Study

The intra-aortic balloon pump (IABP) is the most widely used cardiac assist device, whose main benefits are augmentation of coronary flow and reduction of left-ventricular afterload. The aim of this study is to investigate the pressure and flow-volume distribution associated with balloon inflation. We hypothesize that in order to displace fluid on both sides of the balloon, a pressure locus must be present along the balloon during inflation. In vitro experiments were performed in two positions, horizontal and angled, using four balloon sizes: 25, 34, 40, and 50 cc. Along and on both sides of each balloon, we measured pressure, flow rate, and calculated flow velocity, volume displacement, wave intensity and energy. A pressure locus was found at the center of each balloon and the average flow volume displaced toward the tip at the horizontal position was about 57% of the balloon volume. In the angled position, the location of the pressure locus was less obvious and average volume displacement toward the top end of the balloon was reduced to 45%. These results confirm the existence of a pressure locus at the center of each of the balloons we tested. Because a clear reduction in flow volume was observed at the angled position, these results may have clinical implications as most patients using IABP in the intensive care units are nursed in semirecumbent position.

Virtual and real bench testing of a new percutaneous valve device: a case study.

AIMS To validate patient-specific computational testing of a second-generation device for percutaneous pulmonary valve implantation (PPVI), against realistic in vitro data. METHODS AND RESULTS Tests were initially carried out in a simple loading mode, performing a compliance test on a rapid prototyped cylinder. This model was reproduced computationally and validated against the experimental data. A second-generation PPVI stent-graft, with no valve mounted, was then deployed in a simplified cylindrical geometry, measuring its displacement when subjected to a pressure pulse. Experimental and computational measurements were in good agreement. Finally, having selected a patient regarded as unsuitable for first-generation PPVI, but potentially suitable for a second-generation device, the stent-graft was studied in the rapidly prototyped patient-specific right ventricular outflow tract (RVOT). Stent positioning and radial displacements with pulsatile flow were observed in a mock circuit using fluoroscopy imaging. Stent deformation and anchoring were measured both in vitro and computationally. Both tests indicated that the stent was well anchored in the RVOT, especially in the distal position, and its central region was rounded, ensuring, were a valve present, optimal valve function. CONCLUSION We suggest that an experimentally validated computational model can be used for preclinical device characterisation and patient selection.

Finite Element Strategies to Satisfy Clinical and Engineering Requirements in the Field of Percutaneous Valves

Finite element (FE) modelling can be a very resourceful tool in the field of cardiovascular devices. To ensure result reliability, FE models must be validated experimentally against physical data. Their clinical application (e.g., patients’ suitability, morphological evaluation) also requires fast simulation process and access to results, while engineering applications need highly accurate results. This study shows how FE models with different mesh discretisations can suit clinical and engineering requirements for studying a novel device designed for percutaneous valve implantation. Following sensitivity analysis and experimental characterisation of the materials, the stent-graft was first studied in a simplified geometry (i.e., compliant cylinder) and validated against in vitro data, and then in a patient-specific implantation site (i.e., distensible right ventricular outflow tract). Different meshing strategies using solid, beam and shell elements were tested. Results showed excellent agreement between computational and experimental data in the simplified implantation site. Beam elements were found to be convenient for clinical applications, providing reliable results in less than one hour in a patient-specific anatomical model. Solid elements remain the FE choice for engineering applications, albeit more computationally expensive (>100 times). This work also showed how information on device mechanical behaviour differs when acquired in a simplified model as opposed to a patient-specific model.