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.

Aortic valve chordae tendineae: A rare cause of aortic stenosis.

We describe a rare case of severe low-flow, low-gradient aortic stenosis due to a calcified aortic valve chordae tendineae. The chordae was captured on cardiac computed tomography (CT) using advanced 3-dimensional image reconstruction to reveal the fibrous strand tethering the non-coronary cusp to the left ventricular outflow tract, rendering it functionally immobile. This is one of the first reported cases of severe aortic stenosis from an aortic valve chordae tendineae which highlights the utility of advanced image processing techniques in cardiac CT.

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.

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.

Non-invasive characterization of complex coronary lesions.

Conventional invasive diagnostic imaging techniques do not adequately resolve complex Type B and C coronary lesions, which present unique challenges, require personalized treatment and result in worsened patient outcomes. These lesions are often excluded from large-scale non-invasive clinical trials and there does not exist a validated approach to characterize hemodynamic quantities and guide percutaneous intervention for such lesions. This work identifies key biomarkers that differentiate complex Type B and C lesions from simple Type A lesions by introducing and validating a coronary angiography-based computational fluid dynamic (CFD-CA) framework for intracoronary assessment in complex lesions at ultrahigh resolution. Among 14 patients selected in this study, 7 patients with Type B and C lesions were included in the complex lesion group including ostial, bifurcation, serial lesions and lesion where flow was supplied by collateral bed. Simple lesion group included 7 patients with lesions that were discrete, [Formula: see text] long and readily accessible. Intracoronary assessment was performed using CFD-CA framework and validated by comparing to clinically measured pressure-based index, such as FFR. Local pressure, endothelial shear stress (ESS) and velocity profiles were derived for all patients. We validates the accuracy of our CFD-CA framework and report excellent agreement with invasive measurements ([Formula: see text]). Ultra-high resolution achieved by the model enable physiological assessment in complex lesions and quantify hemodynamic metrics in all vessels up to 1mm in diameter. Importantly, we demonstrate that in contrast to traditional pressure-based metrics, there is a significant difference in the intracoronary hemodynamic forces, such as ESS, in complex lesions compared to simple lesions at both resting and hyperemic physiological states [n = 14, [Formula: see text]]. Higher ESS was observed in the complex lesion group ([Formula: see text] Pa) than in simple lesion group ([Formula: see text] Pa). Complex coronary lesions have higher ESS compared to simple lesions, such differential hemodynamic evaluation can provide much the needed insight into the increase in adverse outcomes for such patients and has incremental prognostic value over traditional pressure-based indices, such as FFR.

The importance of side branches in modeling 3D hemodynamics from angiograms for patients with coronary artery disease.

Genesis of atherosclerotic lesions in the human arterial system is critically influenced by the fluid mechanics. Applying computational fluid dynamic tools based on accurate coronary physiology derived from conventional biplane angiogram data may be useful in guiding percutaneous coronary interventions. The primary objective of this study is to build and validate a computational framework for accurate personalized 3-dimensional hemodynamic simulation across the complete coronary arterial tree and demonstrate the influence of side branches on coronary hemodynamics by comparing shear stress between coronary models with and without these included. The proposed novel computational framework based on biplane angiography enables significant arterial circulation analysis. This study shows that models that take into account flow through all side branches are required for precise computation of shear stress and pressure gradient whereas models that have only a subset of side branches are inadequate for biomechanical studies as they may overestimate volumetric outflow and shear stress. This study extends the ongoing computational efforts and demonstrates that models based on accurate coronary physiology can improve overall fidelity of biomechanical studies to compute hemodynamic risk-factors.

Cardiac C-arm computed tomography using a 3D + time ROI reconstruction method with spatial and temporal regularization.

PURPOSE: Reconstruction of the beating heart in 3D + time in the catheter laboratory using only the available C-arm system would improve diagnosis, guidance, device sizing, and outcome control for intracardiac interventions, e.g., electrophysiology, valvular disease treatment, structural or congenital heart disease. To obtain such a reconstruction, the patient's electrocardiogram (ECG) must be recorded during the acquisition and used in the reconstruction. In this paper, the authors present a 4D reconstruction method aiming to reconstruct the heart from a single sweep 10 s acquisition. METHODS: The authors introduce the 4D RecOnstructiOn using Spatial and TEmporal Regularization (short 4D ROOSTER) method, which reconstructs all cardiac phases at once, as a 3D + time volume. The algorithm alternates between a reconstruction step based on conjugate gradient and four regularization steps: enforcing positivity, averaging along time outside a motion mask that contains the heart and vessels, 3D spatial total variation minimization, and 1D temporal total variation minimization. RESULTS: 4D ROOSTER recovers the different temporal representations of a moving Shepp and Logan phantom, and outperforms both ECG-gated simultaneous algebraic reconstruction technique and prior image constrained compressed sensing on a clinical case. It generates 3D + time reconstructions with sharp edges which can be used, for example, to estimate the patient's left ventricular ejection fraction. CONCLUSIONS: 4D ROOSTER can be applied for human cardiac C-arm CT, and potentially in other dynamic tomography areas. It can easily be adapted to other problems as regularization is decoupled from projection and back projection.

The design and fabrication of two portal vein flow phantoms by different methods.

PURPOSE: This study outlines the design and fabrication techniques for two portal vein flow phantoms. METHODS: A materials study was performed as a precursor to this phantom fabrication effort and the desired material properties are restated for continuity. A three-dimensional portal vein pattern was created from the Visual Human database. The portal vein pattern was used to fabricate two flow phantoms by different methods with identical interior surface geometry using computer aided design software tools and rapid prototyping techniques. One portal flow phantom was fabricated within a solid block of clear silicone for use on a table with Ultrasound or within medical imaging systems such as MRI, CT, PET, or SPECT. The other portal flow phantom was fabricated as a thin walled tubular latex structure for use in water tanks with Ultrasound imaging. Both phantoms were evaluated for usability and durability. RESULTS: Both phantoms were fabricated successfully and passed durability criteria for flow testing in the next project phase. CONCLUSIONS: The fabrication methods and materials employed for the study yielded durable portal vein phantoms.

Coronary angiography: the need for improvement and the barriers to adoption of new technology.

Traditional coronary angiography presents a variety of limitations related to image acquisition, content, interpretation, and patient safety. These limitations were first apparent with coronary angiography used as a diagnostic tool and have been further magnified in today's world of percutaneous coronary intervention (PCI), with the frequent use of implantable coronary stents. Improvements are needed to overcome the limitations in using current two-dimensional radiographic imaging for optimizing patient selection, quantifying vessel features, guiding PCI, and assessing PCI results. Barriers to such improvements include the paucity of clinical outcomes studies related to new imaging technology, the resistance to changing long-standing practices, the need for physician and staff member training, and the costs associated with acquiring and effectively using these advances in coronary angiography.

Three-dimensional coronary visualization, Part 1: modeling.

Three-dimensional (3D) modeling techniques have been developed for clinical use to minimize the imaging limitations of two-dimensional (2D) angiography. The 3D models of the coronary arterial tree not only accurately display the complexities of coronary anatomy but also enable quantification of vessel curvature, measurement of vessel segment length, and identification of the amount of radiographic foreshortening and vessel overlap in any simulated angiographic projection. This article describes the process and applications associated with producing a 3D model of the coronary arterial tree using only a few standard 2D projection images from a routine coronary angiographic study.

The future cardiac catheterization laboratory.

This article describes the major components in the future cardiac catheterization laboratory to facilitate cardiac interventions for both coronary artery and structural heart diseases.

Quantitative assessment of the conformational change in the femoropopliteal artery with leg movement.

BACKGROUND: The unique physical forces exerted on the femoropopliteal (FP) artery during movement have been implicated in the high rates of restenosis and stent fracture in this artery. Conformational changes in the FP artery during movement are important surrogates of these forces. This study sought to quantify the conformational change in the FP artery between the straight-leg (SL) and crossed-leg (CL) positions. METHODS: Using paired angiographic images of overlapping segments of the FP artery in SL and CL positions from patients with peripheral arterial disease, 3-D models of individual segments were generated and subsequently fused to create a 3-D model of the entire FP artery in both leg positions. Based on these 3-D models, the following parameters in the SL and CL positions were quantitatively assessed for the superficial femoral artery (SFA), popliteal artery (PA), and FP artery (i.e., SFA and PA): length, curvature, torsion, twist angle, and development of new flexion angles = 15 degrees. RESULTS: In nine male patients with a mean age of 57 +/- 10.2 years, angiography was performed in 10 FP arteries, with successful generation of 3-D models for all vessels. Movement from the SL to the CL position for the SFA, PA, and FP artery was associated with (a) a mean shortening of 18.2 mm (P = 0.002), 32.2 mm (P < 0.001), and 50.3 mm (P < 0.001), respectively; (b) a mean increase in curvature of 0.04 cm(-1) (P = 0.012), 0.2 cm(-1) (P < 0.001), and 0.11 cm(-1) (P < 0.001), respectively; (c) and small absolute changes in mean torsion of 0.034 cm(-1) (P = 0.48), 0.006 cm(-1) (P < 0.001), and 0.057 cm(-1) (P < 0.001), respectively. The same leg movement was associated with a mean twist angle of 45.6 degrees +/- 27.9 degrees (range of 17.4 degrees-103.4 degrees ) and 61.1 degrees +/- 31.9 degrees (range of 20.5 degrees-101.1 degrees ) for the SFA and PA, respectively. Compared to the SL position, the CL position induced a single flexion point (FxP) =15 degrees in the SFA in two patients, and a mean of 2.4 FxPs =15 degrees (range 1-5) in the PA. CONCLUSIONS: Significant changes in length, curvature, and twist occur in the PA and significant but more modest changes in length and twist occur in the SFA during movement from the SL to the CL position. This data has important implications for endovascular therapies that are used to treat disease in the FP artery.

Application of a microstructural constitutive model of the pulmonary artery to patient-specific studies: validation and effect of orthotropy.

We applied a statistical mechanics based microstructural model of pulmonary artery mechanics, developed from our previous studies of rats with pulmonary arterial hypertension (PAH), to patient-specific clinical studies of children with PAH. Our previous animal studies provoked the hypothesis that increased cross-linking density of the molecular chains may be one biological remodeling mechanism by which the PA stiffens in PAH. This study appears to further confirm this hypothesis since varying molecular cross-linking density in the model allows us to simulate the changes in the P-D loops between normotensive and hypertensive conditions reasonably well. The model was combined with patient-specific three-dimensional vascular anatomy to obtain detailed information on the topography of stresses and strains within the proximal branches of the pulmonary vasculature. The effect of orthotropy on stressstrain within the main and branch PAs obtained from a patient was explored. This initial study also puts forward important questions that need to be considered before combining the microstructural model with complex patient-specific vascular geometries.