Diagnostic Performance of Coronary Angiography Derived Computational Fractional Flow Reserve.

BACKGROUND: Computational fluid dynamics can compute fractional flow reserve (FFR) accurately. However, existing models are limited by either the intravascular hemodynamic phenomarkers that can be captured or the fidelity of geometries that can be modeled. METHODS AND RESULTS: This study aimed to validate a new coronary angiography-based FFR framework, FFRHARVEY, and examine intravascular hemodynamics to identify new biomarkers that could augment FFR in discerning unrevascularized patients requiring intervention. A 2-center cohort was used to examine diagnostic performance of FFRHARVEY compared with reference wire-based FFR (FFRINVASIVE). Additional biomarkers, longitudinal vorticity, velocity, and wall shear stress, were evaluated for their ability to augment FFR and indicate major adverse cardiac events. A total of 160 patients with 166 lesions were investigated. FFRHARVEY was compared with FFRINVASIVE by investigators blinded to the invasive FFR results with a per-stenosis area under the curve of 0.91, positive predictive value of 90.2%, negative predictive value of 89.6%, sensitivity of 79.3%, and specificity of 95.4%. The percentage ofdiscrepancy for continuous values of FFR was 6.63%. We identified a hemodynamic phenomarker, longitudinal vorticity, as a metric indicative of major adverse cardiac events in unrevascularized gray-zone cases. CONCLUSIONS: FFRHARVEY had high performance (area under the curve: 0.91, positive predictive value: 90.2%, negative predictive value: 89.6%) compared with FFRINVASIVE. The proposed framework provides a robust and accurate way to compute a complete set of intravascular phenomarkers, in which longitudinal vorticity was specifically shown to differentiate vessels predisposed to major adverse cardiac events.

Cloud Computing to Enable Wearable-Driven Longitudinal Hemodynamic Maps.

Tracking hemodynamic responses to treatment and stimuli over long periods remains a grand challenge. Moving from established single-heartbeat technology to longitudinal profiles would require continuous data describing how the patient's state evolves, new methods to extend the temporal domain over which flow is sampled, and high-throughput computing resources. While personalized digital twins can accurately measure 3D hemodynamics over several heartbeats, state-of-the-art methods would require hundreds of years of wallclock time on leadership scale systems to simulate one day of activity. To address these challenges, we propose a cloud-based, parallel-in-time framework leveraging continuous data from wearable devices to capture the first 3D patient-specific, longitudinal hemodynamic maps. We demonstrate the validity of our method by establishing ground truth data for 750 beats and comparing the results. Our cloud-based framework is based on an initial fixed set of simulations to enable the wearable-informed creation of personalized longitudinal hemodynamic maps.

Analysis identifying minimal governing parameters for clinically accurate in silico fractional flow reserve.

Background: Personalized hemodynamic models can accurately compute fractional flow reserve (FFR) from coronary angiograms and clinical measurements (FFR baseline ), but obtaining patient-specific data could be challenging and sometimes not feasible. Understanding which measurements need to be patient-tuned vs. patient-generalized would inform models with minimal inputs that could expedite data collection and simulation pipelines. Aims: To determine the minimum set of patient-specific inputs to compute FFR using invasive measurement of FFR (FFR invasive ) as gold standard. Materials and Methods: Personalized coronary geometries ( N = 50 ) were derived from patient coronary angiograms. A computational fluid dynamics framework, FFR baseline , was parameterized with patient-specific inputs: coronary geometry, stenosis geometry, mean arterial pressure, cardiac output, heart rate, hematocrit, and distal pressure location. FFR baseline was validated against FFR invasive and used as the baseline to elucidate the impact of uncertainty on personalized inputs through global uncertainty analysis. FFR streamlined was created by only incorporating the most sensitive inputs and FFR semi-streamlined additionally included patient-specific distal location. Results: FFR baseline was validated against FFR invasive via correlation ( r = 0.714 , p < 0.001 ), agreement (mean difference: 0.01 ± 0.09 ), and diagnostic performance (sensitivity: 89.5%, specificity: 93.6%, PPV: 89.5%, NPV: 93.6%, AUC: 0.95). FFR semi-streamlined provided identical diagnostic performance with FFR baseline . Compared to FFR baseline vs. FFR invasive , FFR streamlined vs. FFR invasive had decreased correlation ( r = 0.64 , p < 0.001 ), improved agreement (mean difference: 0.01 ± 0.08 ), and comparable diagnostic performance (sensitivity: 79.0%, specificity: 90.3%, PPV: 83.3%, NPV: 87.5%, AUC: 0.90). Conclusion: Streamlined models could match the diagnostic performance of the baseline with a full gamut of patient-specific measurements. Capturing coronary hemodynamics depended most on accurate geometry reconstruction and cardiac output measurement.

A Computational Framework for Pre-Interventional Planning of Peripheral Arteriovenous Malformations.

PURPOSE: Peripheral arteriovenous malformations (pAVMs) are congenital lesions characterised by abnormal high-flow, low-resistance vascular connections-the so-called nidus-between arteries and veins. The mainstay treatment typically involves the embolisation of the nidus, however the complexity of pAVMs often leads to uncertain outcomes. This study aims at developing a simple, yet effective computational framework to aid the clinical decision making around the treatment of pAVMs using routinely acquired clinical data. METHODS: A computational model was developed to simulate the pre-, intra-, and post-intervention haemodynamics of a patient-specific pAVM. A porous medium of varying permeability was employed to simulate the sclerosant effect on the nidus haemodynamics. Results were compared against clinical data (digital subtraction angiography, DSA, images) and experimental flow-visualization results in a 3D-printed phantom of the same pAVM. RESULTS: The computational model allowed the simulation of the pAVM haemodynamics and the sclerotherapy-induced changes at different interventional stages. The predicted inlet flow rates closely matched the DSA-derived data, although the post-intervention one was overestimated, probably due to vascular system adaptations not accounted for numerically. The nidus embolization was successfully captured by varying the nidus permeability and increasing its hydraulic resistance from 0.330 to 3970 mmHg s ml-1. The nidus flow rate decreased from 71% of the inlet flow rate pre-intervention to 1%: the flow completely bypassed the nidus post-intervention confirming the success of the procedure. CONCLUSION: The study demonstrates that the haemodynamic effects of the embolisation procedure can be simulated from routinely acquired clinical data via a porous medium with varying permeability as evidenced by the good qualitative agreement between numerical predictions and both in vivo and in vitro data. It provides a fundamental building block towards a computational treatment-planning framework for AVM embolisation.

Global Sensitivity Analysis For Clinically Validated 1D Models of Fractional Flow Reserve.

Computation of Fractional Flow Reserve (FFR) through computational fluid dynamics (CFD) is used to guide intervention and often uses a number of clinically-derived metrics, but these patient-specific data could be costly and difficult to obtain. Understanding which parameters can be approximated from population averages and which parameters need to be patient-specific is important and remains largely unexplored. In this study, we performed a global sensitivity study on two 1D models of FFR to identify the most influential patient parameters. Our results indicated that vessel compliance, cardiac cycle period, flow rate, density, viscosity, and elastic modulus contributed minimally to the variance in FFR and may be approximated from population averages. On the other hand, outlet resistance (i.e., microvascular resistance), stenosis degree, and percent stenosis length contributed the most to FFR computation and needed to be tuned to the patient of interest. Selective measuring of patient-specific parameters may significantly reduce costs and streamline the simulation pipeline without reducing accuracy.

Hybrid Modeling of Ebola Propagation.

The Ebola virus disease (EVD) epidemic that occurred in West Africa between 2014-16 resulted in over 28,000 cases and 11,000 deaths - one of the deadliest to date. A generalized model of the spatiotemporal progression of EVD for Liberia, Guinea, and Sierra Leone in 2014-16 remains elusive. There is also a disconnect in the literature on which interventions are most effective in curbing disease progression. To solve these two key issues, we designed a hybrid agent-based and compartmental model that switches from one paradigm to the other on a stochastic threshold. We modeled disease progression with promising accuracy using WHO datasets.