A framework for different levels of integration of computational models into web-based virtual patients

BACKGROUND: Virtual patients are increasingly common tools used in health care education to foster learning of clinical reasoning skills. One potential way to expand their functionality is to augment virtual patients’ interactivity by enriching them with computational models of physiological and pathological processes. OBJECTIVE: The primary goal of this paper was to propose a conceptual framework for the integration of computational models within virtual patients, with particular focus on (1) characteristics to be addressed while preparing the integration, (2) the extent of the integration, (3) strategies to achieve integration, and (4) methods for evaluating the feasibility of integration. An additional goal was to pilot the first investigation of changing framework variables on altering perceptions of integration. METHODS: The framework was constructed using an iterative process informed by Soft System Methodology. The Virtual Physiological Human (VPH) initiative has been used as a source of new computational models. The technical challenges associated with development of virtual patients enhanced by computational models are discussed from the perspectives of a number of different stakeholders. Concrete design and evaluation steps are discussed in the context of an exemplar virtual patient employing the results of the VPH ARCH project, as well as improvements for future iterations. RESULTS: The proposed framework consists of four main elements. The first element is a list of feasibility features characterizing the integration process from three perspectives: the computational modelling researcher, the health care educationalist, and the virtual patient system developer. The second element included three integration levels: basic, where a single set of simulation outcomes is generated for specific nodes in the activity graph; intermediate, involving pre-generation of simulation datasets over a range of input parameters; advanced, including dynamic solution of the model. The third element is the description of four integration strategies, and the last element consisted of evaluation profiles specifying the relevant feasibility features and acceptance thresholds for specific purposes. The group of experts who evaluated the virtual patient exemplar found higher integration more interesting, but at the same time they were more concerned with the validity of the result. The observed differences were not statistically significant. CONCLUSIONS: This paper outlines a framework for the integration of computational models into virtual patients. The opportunities and challenges of model exploitation are discussed from a number of user perspectives, considering different levels of model integration. The long-term aim for future research is to isolate the most crucial factors in the framework and to determine their influence on the integration outcome

The role of venous valves in pressure shielding

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Sex differences in coronary microvascular resistance measured by a computational fluid dynamics model

BackgroundIncreased coronary microvascular resistance (CMVR) is associated with coronary microvascular dysfunction (CMD). Although CMD is more common in women, sex-specific differences in CMVR have not been demonstrated previously.AimTo compare CMVR between men and women being investigated for chest pain.Methods and resultsWe used a computational fluid dynamics (CFD) model of human coronary physiology to calculate absolute CMVR based on invasive coronary angiographic images and pressures in 203 coronary arteries from 144 individual patients. CMVR was significantly higher in women than men (860 [650–1,205] vs. 680 [520–865] WU, Z = −2.24, p = 0.025). None of the other major subgroup comparisons yielded any differences in CMVR.ConclusionCMVR was significantly higher in women compared with men. These sex-specific differences may help to explain the increased prevalence of CMD in women

Evaluation of models of sequestration flow in coronary arteries—Physiology versus anatomy?

Background: Myocardial ischaemia results from insufficient coronary blood flow. Computed virtual fractional flow reserve (vFFR) allows quantification of proportional flow loss without the need for invasive pressure-wire testing. In the current study, we describe a novel, conductivity model of side branch flow, referred to as ‘leak’. This leak model is a function of taper and local pressure, the latter of which may change radically when focal disease is present. This builds upon previous techniques, which either ignore side branch flow, or rely purely on anatomical factors. This study aimed to describe a new, conductivity model of side branch flow and compare this with established anatomical models. Methods and results: The novel technique was used to quantify vFFR, distal absolute flow (Qd) and microvascular resistance (CMVR) in 325 idealised 1D models of coronary arteries, modelled from invasive clinical data. Outputs were compared to an established anatomical model of flow. The conductivity model correlated and agreed with the reference model for vFFR (r = 0.895, p < 0.0001; ＋0.02, 95% CI 0.00 to ＋ 0.22), Qd (r = 0.959, p < 0.0001; −5.2 mL/min, 95% CI −52.2 to ＋13.0) and CMVR (r = 0.624, p < 0.0001; ＋50 Woods Units, 95% CI −325 to ＋2549). Conclusion: Agreement between the two techniques was closest for vFFR, with greater proportional differences seen for Qd and CMVR. The conductivity function assumes vessel taper was optimised for the healthy state and that CMVR was not affected by local disease. The latter may be addressed with further refinement of the technique or inferred from complementary image data.The conductivity technique may represent a refinement of current techniques for modelling coronary side-branch flow. Further work is needed to validate the technique against invasive clinical data

Measurement of in vitro cardiac deformation by means of 3D digital image correlation and ultrasound 2D speckle-tracking echocardiography

Ultrasound-based 2D speckle-tracking echocardiography (US-2D-STE) is increasingly used to assess the functionality of the heart. In particular, the analysis of cardiac strain plays an important role in the identification of several cardiovascular diseases. However, this imaging technique presents some limitations associated with its operating principle that result in low accuracy and reproducibility of the measurement. In this study, an experimental framework for multimodal strain imaging in an in vitro porcine heart was developed. Specifically, the aim of this work was to analyse displacement and strain in the heart by means of 3D digital image correlation (3D-DIC) and US-2D-STE. Over a single cardiac cycle, displacement values obtained from the two techniques were in strong correlation, although systematically larger displacements were observed with 3D-DIC. Notwithstanding an absolute comparison of the strain measurements was not possible to achieve between the two methods, maximum principal strain directions computed with 3D-DIC were consistent with the longitudinal and circumferential strain distribution measured with US-2D-STE. 3D-DIC confirmed its high repeatability in quantifying displacement and strain over multiple cardiac cycles, unlike US-2D-STE which is affected by accumulated errors over time (i.e. drift). To conclude, this study demonstrates the potential of 3D-DIC to perform dynamic measurement of displacement and strain during heart deformations and supports future applications of this method in ex vivo beating heart platforms, which replicate more fully the complex contraction of the heart

The Accuracy of 3D Optical Reconstruction and Additive Manufacturing Processes in Reproducing Detailed Subject-Specific Anatomy

3D reconstruction and 3D printing of subject-specific anatomy is a promising technology for supporting clinicians in the visualisation of disease progression and planning for surgical intervention. In this context, the 3D model is typically obtained from segmentation of magnetic resonance imaging (MRI), computed tomography (CT) or echocardiography images. Although these modalities allow imaging of the tissues in vivo, assessment of quality of the reconstruction is limited by the lack of a reference geometry as the subject-specific anatomy is unknown prior to image acquisition. In this work, an optical method based on 3D digital image correlation (3D-DIC) techniques is used to reconstruct the shape of the surface of an ex vivo porcine heart. This technique requires two digital charge-coupled device (CCD) cameras to provide full-field shape measurements and to generate a standard tessellation language (STL) file of the sample surface. The aim of this work was to quantify the error of 3D-DIC shape measurements using the additive manufacturing process. The limitations of 3D printed object resolution, the discrepancy in reconstruction of the surface of cardiac soft tissue and a 3D printed model of the same surface were evaluated. The results obtained demonstrated the ability of the 3D-DIC technique to reconstruct localised and detailed features on the cardiac surface with sub-millimeter accuracy

Contribution of Mechanical and Fluid Stresses to the Magnitude of In-stent Restenosis at the Level of Individual Stent Struts

Structural and fluid stresses acting on the artery wall are proposed as mechanical mediators of in-stent restenosis (ISR). This study reports an investigation of the correlation between stresses obtained from computational simulations with the magnitude of ISR at the level of individual stent struts observed in an in vivo model of restenosis. Structural and fluid dynamic analyses were undertaken in a model based on volumetric micro-CT data from an in vivo stent deployment in a porcine right coronary artery. Structural and fluid mechanics were compared with histological data from the same stented vessel sample. Interpretation of the combined data at the level of individual stent struts was possible by identifying the location of each 2-D histological section within the 3-D micro-CT volume. Linear correlation between structural and fluid stimuli and neointimal thickness at the level of individual struts is less clear when individual stimuli are considered [compressive force (CF), R 2 = 0.19, wall shear stress (WSS), R 2 = 0.25, oscillatory shear index (OSI), R 2 = 0.28]. Closer correlation is observed if combined structural and fluid stimuli are assumed to stimulate ISR (CF/WSS, R 2 = 0.64). The use of micro-CT to characterise stent geometry after deployment enhances the clinical relevance of computational simulations, allowing direct comparison with histology. The results support the combined role of both structural and fluid mechanics to determine the magnitude of ISR at the level of individual struts. This finding is consistent with other studies which consider these stimuli averaged over a transverse section of the vessel

Influence of intermittent compression cuff design on interface pressure and calf deformation: experimental results

The intermittent compression of the calf with an external pressure cuff for the prevention of deep vein thrombosis (DVT) is a well established treatment for surgical patients. The exact mechanisms by which DVT is prevented are poorly understood. This study presents a finite element model of calf cross section, based on MR images of calf geometry, to examine the variation in calf deformation during compression with four different cuff types. Cuff pressure distribution is modelled using interface pressures obtained in a volunteer study. The model has been validated against gross calf deformation obtained from MR images of the compressed calf. This validation has illustrated the importance of out-of-plane boundary conditions, material properties and the variation in cuff loading in the axial direction. In the future this model may have merit in determining optimum pressure loading regimes for Intermittent Pneumatic Compression (IPC) cuff design

Influence of intermittent compression cuff design on calf deformation: computational results

The intermittent compression of the calf with an external pressure cuff for the prevention of deep vein thrombosis (DVT) is a well established treatment for surgical patients. The exact mechanisms by which DVT is prevented are poorly understood. This study presents a finite element model of calf cross section, based on MR images of calf geometry, to examine the variation in calf deformation during compression with four different cuff types. Cuff pressure distribution is modelled using interface pressures obtained in a volunteer study. The model has been validated against gross calf deformation obtained from MR images of the compressed calf. This validation has illustrated the importance of out-of-plane boundary conditions, material properties and the variation in cuff loading in the axial direction. In the future this model may have merit in determining optimum pressure loading regimes for Intermittent Pneumatic Compression (IPC) cuff design