Xiaodan Zhao

Heterogeneous growth-induced prestrain in the heart

Even when entirely unloaded, biological structures are not stress-free, as shown by Y.C. Fung׳s seminal opening angle experiment on arteries and the left ventricle. As a result of this prestrain, subject-specific geometries extracted from medical imaging do not represent an unloaded reference configuration necessary for mechanical analysis, even if the structure is externally unloaded. Here we propose a new computational method to create physiological residual stress fields in subject-specific left ventricular geometries using the continuum theory of fictitious configurations combined with a fixed-point iteration. We also reproduced the opening angle experiment on four swine models, to characterize the range of normal opening angle values. The proposed method generates residual stress fields which can reliably reproduce the range of opening angles between 8.7±1.8 and 16.6±13.7 as measured experimentally. We demonstrate that including the effects of prestrain reduces the left ventricular stiffness by up to 40%, thus facilitating the ventricular filling, which has a significant impact on cardiac function. This method can improve the fidelity of subject-specific models to improve our understanding of cardiac diseases and to optimize treatment options.

Simplified Models of Non-Invasive Fractional Flow Reserve Based on CT Images.

Invasive fractional flow reserve (FFR) is the gold standard to assess the functional coronary stenosis. The non-invasive assessment of diameter stenosis (DS) using coronary computed tomography angiography (CTA) has high false positive rate in contrast to FFR. Combining CTA with computational fluid dynamics (CFD), recent studies have shown promising predictions of FFRCT for superior assessment of lesion severity over CTA alone. The CFD models tend to be computationally expensive, however, and require several hours for completing analysis. Here, we introduce simplified models to predict noninvasive FFR at substantially less computational time. In this retrospective pilot study, 21 patients received coronary CTA. Subsequently a total of 32 vessels underwent invasive FFR measurement. For each vessel, FFR based on steady-state and analytical models (FFRSS and FFRAM, respectively) were calculated non-invasively based on CTA and compared with FFR. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value were 90.6% (87.5%), 80.0% (80.0%), 95.5% (90.9%), 88.9% (80.0%) and 91.3% (90.9%) respectively for FFRSS (and FFRAM) on a per-vessel basis, and were 75.0%, 50.0%, 86.4%, 62.5% and 79.2% respectively for DS. The area under the receiver operating characteristic curve (AUC) was 0.963, 0.954 and 0.741 for FFRSS, FFRAM and DS respectively, on a per-patient level. The results suggest that the CTA-derived FFRSS performed well in contrast to invasive FFR and they had better diagnostic performance than DS from CTA in the identification of functionally significant lesions. In contrast to FFRCT, FFRSS requires much less computational time.

Cardiac MRI based numerical modeling of left ventricular fluid dynamics with mitral valve incorporated

Recent numerical studies were focused on the modeling of flow in patient-specific left ventricle (LV); however, the mitral valve (MV) was usually excluded. In this study, both patient-specific LV and MV were modeled to achieve a more realistic intraventricular flow. Cardiac MRI images were acquired from a pulmonary arterial hypertension (PAH) patient and a healthy volunteer, and manual segmentation was conducted to reconstruct three-dimensional (3D) LV and MV geometries at each frame. Based on these 3D geometries, vortex formation time (VFT) was derived, and the values were 4.0 and 6.5 for the normal subject and the PAH patient, respectively. Based on studies in the literature, VTF in the healthy subject fell within the normal range, while that in the PAH patient exceeded the threshold for normality. The vortex structures in the LV clearly showed that the vortex ring was initiated from the tips of the MV instead of the mitral annulus. The excessive VFT during the rapid filling phase in the PAH patient resulted in a trailing flow structure behind the primary vortex ring, which was not observed in the normal subject. It can be deduced from this study that incorporating the MV into a patient-specific model is necessary to produce more reasonable VFT and intraventricular flow.

Hemodynamic analysis of patient‐specific coronary artery tree

Local hemodynamic parameters, such as wall shear stress (WSS), oscillatory shear index and relative resident time (RRT), have been linked to coronary plaque initiation and progression. In this study, a left coronary artery tree model was reconstructed from computed tomography angiography images of a patient with multiple stenoses. The geometry of the coronary artery tree model was virtually restored by eliminating the lesions, essentially re-creating the virtually healthy artery anatomy. Using numerical simulations, flow characteristics and hemodynamic parameter distributions in the stenosed and virtually healthy models were investigated. In the virtually healthy artery model, disturbed flows were found at four locations, prone to initialization of plaque formation. Low WSS and high RRT were exhibited in three of the four locations, and high WSS and low RRT were exhibited in the fourth. These findings suggest that coronary plaque is more likely to form in locations with disturbed flow conditions characterized by low WSS and high RRT or high WSS and low RRT. In addition, clinical index of fractional flow reserve was found to significantly correlate with blood flow rate, rather than anatomic parameters, such as diameter stenosis, which implied the importance of hemodynamic environment in stenosis formation.

Automated quantitative assessment of cardiovascular magnetic resonance-derived atrioventricular junction velocities

The assessment of atrioventricular junction (AVJ) deformation plays an important role in evaluating left ventricular systolic and diastolic function in clinical practice. This study aims to demonstrate the effectiveness and consistency of cardiovascular magnetic resonance (CMR) for quantitative assessment of AVJ velocity compared with tissue Doppler echocardiography (TDE). A group of 145 human subjects comprising 21 healthy volunteers, 8 patients with heart failure, 17 patients with hypertrophic cardiomyopathy, 52 patients with myocardial infarction, and 47 patients with repaired Tetralogy of Fallot were prospectively enrolled and underwent TDE and CMR scan. Six AVJ points were tracked with three CMR views. The peak systolic velocity (Sm1), diastolic velocity during early diastolic filling (Em), and late diastolic velocity during atrial contraction (Am) were extracted and analyzed. All CMR-derived septal and lateral AVJ velocities correlated well with TDE measurements (Sm1: r = 0.736; Em: r = 0.835; Am: r = 0.701; Em/Am: r = 0.691; all p < 0.001) and demonstrated excellent reproducibility [intrastudy: r = 0.921-0.991, intraclass correlation coefficient (ICC): 0.918-0.991; interstudy: r = 0.900-0.970, ICC: 0.887-0.957; all p < 0.001]. The evaluation of three-dimensional AVJ motion incorporating measurements from all views better differentiated normal and diseased states [area under the curve (AUC) = 0.918] and provided further insights into mechanical dyssynchrony diagnosis in HF patients (AUC = 0.987). These findings suggest that the CMR-based method is feasible, accurate, and consistent in quantifying the AVJ deformation, and subsequently in diagnosing systolic and diastolic cardiac dysfunction.

Automatic localization of the left ventricle from cardiac cine magnetic resonance imaging: a new spectrum-based computer-aided tool.

Traditionally, cardiac image analysis is done manually. Automatic image processing can help with the repetitive tasks, and also deal with huge amounts of data, a task which would be humanly tedious. This study aims to develop a spectrum-based computer-aided tool to locate the left ventricle using images obtained via cardiac magnetic resonance imaging. Discrete Fourier Transform was conducted pixelwise on the image sequence. Harmonic images of all frequencies were analyzed visually and quantitatively to determine different patterns of the left and right ventricles on spectrum. The first and fifth harmonic images were selected to perform an anisotropic weighted circle Hough detection. This tool was then tested in ten volunteers. Our tool was able to locate the left ventricle in all cases and had a significantly higher cropping ratio of 0.165 than did earlier studies. In conclusion, a new spectrum-based computer aided tool has been proposed and developed for automatic left ventricle localization. The development of this technique, which will enable the automatic location and further segmentation of the left ventricle, will have a significant impact in research and in diagnostic settings. We envisage that this automated method could be used by radiographers and cardiologists to diagnose and assess ventricular function in patients with diverse heart diseases.

Patient-Specific Computational Analysis of Ventricular Mechanics in Pulmonary Arterial Hypertension

Patient-specific biventricular computational models associated with a normal subject and a pulmonary arterial hypertension (PAH) patient were developed to investigate the disease effects on ventricular mechanics. These models were developed using geometry reconstructed from magnetic resonance (MR) images, and constitutive descriptors of passive and active mechanics in cardiac tissues. Model parameter values associated with ventricular mechanical properties and myofiber architecture were obtained by fitting the models with measured pressure-volume loops and circumferential strain calculated from MR images using a hyperelastic warping method. Results show that the peak right ventricle (RV) pressure was substantially higher in the PAH patient (65 mmHg versus 20 mmHg), who also has a significantly reduced ejection fraction (EF) in both ventricles (left ventricle (LV): 39% versus 66% and RV: 18% versus 64%). Peak systolic circumferential strain was comparatively lower in both the left ventricle (LV) and RV free wall (RVFW) of the PAH patient (LV: -6.8% versus -13.2% and RVFW: -2.1% versus -9.4%). Passive stiffness, contractility, and myofiber stress in the PAH patient were all found to be substantially increased in both ventricles, whereas septum wall in the PAH patient possessed a smaller curvature than that in the LV free wall. Simulations using the PAH model revealed an approximately linear relationship between the septum curvature and the transseptal pressure gradient at both early-diastole and end-systole. These findings suggest that PAH can induce LV remodeling, and septum curvature measurements may be useful in quantifying transseptal pressure gradient in PAH patients.

Coronary artery segmentation via Hessian filter and curve-skeleton extraction

Precise coronary artery segmentation is a prerequisite for quantitatively assessing the severity of coronary artery stenosis. Extracting the centre line of the 3D volumetric coronary artery tree, also named as 3D skeletonization, plays an important role in identify the variations of cross-sectional profile. Typically there are three skeletonization methods, viz. distance transformation, Voronoi method and topological thinning method. All these three skeletonization methods were applied in this study to extract the curve-skeleton of coronary arteries, after segmenting the coronary artery tree with Hessin filter. Among them, topological thinning method is recommended, as it produces reliable and accurate curve-skeleton for vessels with varying size. This will facilitate quantitative assessment of the severity of coronary artery stenosis, help clinical diagnosis and treatment planning of coronary artery disease.

Patient-specific blood flows and vortex formations in patients with hypertrophic cardiomyopathy using computational fluid dynamics

Hypertrophic cardiomyopathy (HCM) is a relatively common genetic cardiac disorder in which a portion of the myocardium becomes hypertrophied. Dynamic left ventricle outflow tract obstruction is present and associated with worsened symptom severity and disease progression. However, its mechanism is still not fully understood, and the complex interaction between the thickened ventricular wall and altered blood flow in patient-specific model has not been studied. In this study, we recruited one patient with HCM and one healthy volunteer who underwent magnetic resonance imaging scans. The patient-specific geometries were reconstructed, and both spatial and temporal interpolations were applied to increase the corresponding resolutions. The results showed that HCM patient had cirrostratus-cloud like vortex structures rather than a major vortex ring observed in healthy subject, which implies that the vortex formation from computational fluid dynamics (CFD) simulation has the potential to diagnose HCM.

Fast Marching and Runge–Kutta Based Method for Centreline Extraction of Right Coronary Artery in Human Patients

The CT angiography (CTA) is a clinically indicated test for the assessment of coronary luminal stenosis that requires centerline extractions. There is currently no centerline extraction algorithm that is automatic, real-time and very accurate. Therefore, we sought to (i) develop a hybrid approach by incorporating fast marching and Runge–Kutta based methods for the extraction of coronary artery centerlines from CTA; (ii) evaluate the accuracy of the present method compared to Van’s method by using ground truth centerline as a reference; (iii) evaluate the coronary lumen area of our centerline method in comparison with the intravascular ultrasound (IVUS) as the standard of reference. The proposed method was found to be more computationally efficient, and performed better than the Van’s method in terms of overlap measures (i.e., OV: