Comparison of Instantaneous Wave-Free Ratio (iFR) and Fractional Flow Reserve (FFR) with respect to Their Sensitivities to Cardiovascular Factors: A Computational Model-Based Study.

While coronary revascularization strategies guided by instantaneous wave-free ratio (iFR) are, in general, noninferior to those guided by fractional flow reserve (FFR) with respect to the rate of major adverse cardiac events at one-year follow-up in patients with stable angina or an acute coronary syndrome, the overall accuracy of diagnosis with iFR in large patient cohorts is about 80% compared with the diagnosis with FFR. So far, it remains incompletely understood what factors contribute to the discordant diagnosis between iFR and FFR. In this study, a computational method was used to systemically investigate the respective effects of various cardiovascular factors on FFR and iFR. The results showed that deterioration in aortic valve disease (e.g., regurgitation or stenosis) led to a marked decrease in iFR and a mild increase in FFR given fixed severity of coronary artery stenosis and that increasing coronary microvascular resistance caused a considerable increase in both iFR and FFR, but the degree of increase in iFR was lower than that in FFR. These findings suggest that there is a high probability of discordant diagnosis between iFR and FFR in patients with severe aortic valve disease or coronary microcirculation dysfunction.

Automated personalization of biomechanical knee model.

PURPOSE: Patient-specific biomechanical models of the knee joint can effectively aid in understanding the reasons for pathologies and improve diagnostic methods and treatment procedures. For deeper research of knee diseases, the development of biomechanical models with appropriate configurations is essential. In this study, we mainly focus on the development of a personalized biomechanical model for the investigation of knee joint pathologies related to patellar motion using automated methods. METHODS: This study presents a biomechanical model created for patellar motion pathologies research and some techniques for automating the generation of the biomechanical model. To generate geometric models of bones, the U-Net neural network was adapted for 3D input datasets. The method uses the same neural network for segmentation of femur, tibia, patella and fibula. The total size of the train/validation (75/25%) dataset is 18,183 3D volumes of size 512 × 512 × 4 voxels. The configuration of the biomechanical knee model proposed in the paper includes six degrees of freedom for the tibiofemoral and patellofemoral joints, lateral and medial contact surfaces for femur and tibia, and ligaments, representing, among other things, the medial and lateral stabilizers of the knee cap. The development of the personalized biomechanical model was carried out using the OpenSim software system. The automated model generation was implemented using OpenSim Python scripting commands. RESULTS: The neural network for bones segmentation achieves mean DICE 0.9838. A biomechanical model for realistic simulation of patellar movement within the trochlear groove was proposed. Generation of personalized biomechanical models was automated. CONCLUSIONS: In this paper, we have implemented a neural network for the segmentation of 3D CT scans of the knee joint to produce a biomechanical model for the study of knee cap motion pathologies. Most stages of the generation process have been automated and can be used to generate patient-specific models.

Dynamic adaptive moving mesh finite-volume method for the blood flow and coagulation modeling.

In this work, we develop numerical methods for the solution of blood flow and coagulation on dynamic adaptive moving meshes. We consider the blood flow as a flow of incompressible Newtonian fluid governed by the Navier-Stokes equations. The blood coagulation is introduced through the additional Darcy term, with a permeability coefficient dependent on reactions. To this end, we introduce moving mesh collocated finite-volume methods for the Navier-Stokes equations, advection-diffusion equations, and a method for the stiff cascade of reactions. A monolithic nonlinear system is solved to advance the solution in time. The finite volume method for the Navier-Stokes equations features collocated arrangement of pressure and velocity unknowns and a coupled momentum and mass flux. The method is conservative and inf-sup stable despite the saddle point nature of the system. It is verified on a series of analytical problems and applied to the blood flow problem in the deforming domain of the right ventricle, reconstructed from a time series of computed tomography scans. At last, we demonstrate the ability to model the coagulation process in deforming microfluidic capillaries.

Application of compression optical coherence elastography for characterization of human pericardium: A pilot study.

The recent impressive progress in Compression Optical Coherence Elastography (C-OCE) demonstrated diverse biomedical applications, comprising ophthalmology, oncology, etc. High resolution of C-OCE enables spatially resolved characterization of elasticity of rather thin (thickness < 1 mm) samples, which previously was impossible. Besides Young's modulus, C-OCE enables obtaining of nonlinear stress-strain dependences for various tissues. Here, we report the first application of C-OCE to nondestructively characterize biomechanics of human pericardium, for which data of conventional tensile tests are very limited and controversial. C-OCE revealed pronounced differences among differently prepared pericardium samples. Ample understanding of the influence of chemo-mechanical treatment on pericardium biomechanics is very important because of rapidly growing usage of own patients' pericardium for replacement of aortic valve leaflets in cardio-surgery. The figure demonstrates differences in the tangent Young's modulus after glutaraldehyde-induced cross-linking for two pericardium samples. One sample was over-stretched during the preparation, which caused some damage to the tissue.

Automatic detection of attachment sites for knee ligaments and tendons on CT images.

PURPOSE: The diseases and injuries of the knee joint are the most common orthopedic disorders. Personalized knee models can be helpful in the process of early intervention and lasting treatment techniques development. Fully automatic reconstruction of knee joint anatomical structures from medical images (CT, MRI, ultrasound) remains a challenge. For this reason, most of state-of-the-art knee joint models contain simplifications such as representation of muscles and ligaments as line segments connecting two points which replace attachment areas. The paper presents algorithms for automatic detection of such points on knee CT images. METHODS: This paper presents three approaches to automatic detection of ligaments and tendons attachment sites on the patients CT images: qualitative anatomical descriptions, analysis of bones curvature, and quantitative anatomical descriptions. Combinations of these approaches result in new automatic detection algorithms. Each algorithm exploits anatomical peculiarities of each attachment site, e.g., bone curvature and number of other attachments in a neighborhood of the site. RESULTS: The experimental dataset consisted of 26 anonymized CT sequences containing right and left knee joints in different resolutions. The proposed algorithms take into account bone surface curvatures and spatial differences in locations of medial and lateral parts of both knees. The algorithms for detection of quadriceps femoris, popliteus, biceps femoris tendons, and lateral collateral and medial collateral ligaments attachment sites are provided, as well as examples of their application. Two algorithms are validated by comparison with known statistics of ligaments lengths and also using ground truth annotations for anatomical landmarks approved by clinical experts. CONCLUSIONS: The algorithms simplify generation of patient-specific knee joint models demanded in personalized biomechanical models. The algorithms in the current implementation have two important limitations. First, the correctness of the produced results depends on the bones segmentation quality. Second, the presented algorithms detect a point of the attachment site, which is not necessarily its center. Therefore, manual correction of the attachment site location may be required for attachments with relatively large area.

Comparison of algorithms for estimating blood flow velocities in cerebral arteries based on the transport information of contrast agent: An in silico study.

While many algorithms have been proposed to estimate blood flow velocities based on the transport information of contrast agent acquired by digital subtraction angiography (DSA), most relevant studies focused on a single vessel, leaving a question open as to whether the algorithms would be suitable for estimating blood flow velocities in arterial systems with complex topological structures. In this study, a one-dimensional (1-D) modeling method was developed to simulate the transport of contrast agent in cerebral arterial networks with various anatomical variations or having occlusive disease, thereby generating an in silico database for examining the accuracies of some typical algorithms (i.e., time-of-center of gravity (TCG), shifted least-squares (SLS), and cross correlation (CC) algorithms) that estimate blood flow velocity based on the concentration-time curves (CTCs) of contrast agent. The results showed that the TCG algorithm had the best performance in estimating blood flow velocities in most cerebral arteries, with the accuracy being only mildly affected by anatomical variations of the cerebral arterial network. Nevertheless, the presence of a stenosis of moderate to high severity in the internal carotid artery could considerably impair the accuracy of the TCG algorithm in estimating blood flow velocities in some cerebral arteries where the transport of contrast agent was disturbed by strong collateral flows. In summary, the study suggests that the TCG algorithm may offer a promising means for estimating blood flow velocities based on CTCs of contrast agent monitored in cerebral arteries, provided that the shapes of CTCs are not highly distorted by collateral flows.

Model-based analysis of the sensitivities and diagnostic implications of FFR and CFR under various pathological conditions.

Although fractional flow reserve (FFR) and coronary flow reserve (CFR) are both frequently used to assess the functional severity of coronary artery stenosis, discordant results of diagnosis between FFR and CFR in some patient cohorts have been reported. In the present study, a computational model was employed to quantify the impacts of various pathophysiological factors on FFR and CFR. In addition, a hyperemic myocardial ischemic index (HMIx) was proposed as a reference for comparing the diagnostic performances of FFR and CFR. Obtained results showed that CFR was more susceptible than FFR to the influence of many pathophysiological factors unrelated to coronary artery stenosis. In particular, the numerical study proved that increasing hyperemic coronary microvascular resistance significantly elevated FFR while reducing CFR despite fixed severity of coronary artery stenosis, whereas introducing aortic valve disease only caused a significant decrease in CFR with little influence on FFR. These results provided theoretical evidence for explaining some clinical observations, such as the increased risk of discordant diagnostic results between FFR and CFR in patients with increased hyperemic microvascular resistance, and significant increase in CFR after surgical relief of severe aortic valve disease. When evaluated with respect to the predictive value for hyperemic myocardial ischemia, the performance of FFR was found to be considerably compromised in the presence of severe coronary vasodilation dysfunction or aortic valve disease, whereas the relationship between CFR and HMIx remained relatively stable, suggesting that CFR may be a more reliable indicator of myocardial ischemia under complex pathophysiological conditions.

A mathematical model to quantify the effects of platelet count, shear rate, and injury size on the initiation of blood coagulation under venous flow conditions.

Platelets upregulate the generation of thrombin and reinforce the fibrin clot which increases the incidence risk of venous thromboembolism (VTE). However, the role of platelets in the pathogenesis of venous cardiovascular diseases remains hard to quantify. An experimentally validated model of thrombin generation dynamics is formulated. The model predicts that a high platelet count increases the peak value of generated thrombin as well as the endogenous thrombin potential (ETP) as reported in experimental data. To investigate the effects of platelets density, shear rate, and wound size on the initiation of blood coagulation, we calibrate a previously developed model of venous thrombus formation and implement it in 3D using a novel cell-centered finite-volume solver. We conduct numerical simulations to reproduce in vitro experiments of blood coagulation in microfluidic capillaries. Then, we derive a reduced one-equation model of thrombin distribution from the previous model under simplifying hypotheses and we use it to determine the conditions of clotting initiation on the platelet count, the shear rate, and the plasma composition. The initiation of clotting also exhibits a threshold response to the size of the wounded region in good agreement with the reported experimental findings.

Non-invasive coronary CT angiography-derived fractional flow reserve: A benchmark study comparing the diagnostic performance of four different computational methodologies.

Non-invasive coronary computed tomography (CT) angiography-derived fractional flow reserve (cFFR) is an emergent approach to determine the functional relevance of obstructive coronary lesions. Its feasibility and diagnostic performance has been reported in several studies. It is unclear if differences in sensitivity and specificity between these studies are due to study design, population, or "computational methodology." We evaluate the diagnostic performance of four different computational workflows for the prediction of cFFR using a limited data set of 10 patients, three based on reduced-order modelling and one based on a 3D rigid-wall model. The results for three of these methodologies yield similar accuracy of 6.5% to 10.5% mean absolute difference between computed and measured FFR. The main aspects of modelling which affected cFFR estimation were choice of inlet and outlet boundary conditions and estimation of flow distribution in the coronary network. One of the reduced-order models showed the lowest overall deviation from the clinical FFR measurements, indicating that reduced-order models are capable of a similar level of accuracy to a 3D model. In addition, this reduced-order model did not include a lumped pressure-drop model for a stenosis, which implies that the additional effort of isolating a stenosis and inserting a pressure-drop element in the spatial mesh may not be required for FFR estimation. The present benchmark study is the first of this kind, in which we attempt to homogenize the data required to compute FFR using mathematical models. The clinical data utilised in the cFFR workflows are made publicly available online.

A multi-scale model of the coronary circulation applied to investigate transmural myocardial flow.

Distribution of blood flow in myocardium is a key determinant of the localization and severity of myocardial ischemia under impaired coronary perfusion conditions. Previous studies have extensively demonstrated the transmural difference of ischemic vulnerability. However, it remains incompletely understood how transmural myocardial flow is regulated under in vivo conditions. In the present study, a computational model of the coronary circulation was developed to quantitatively evaluate the sensitivity of transmural flow distribution to various cardiovascular and hemodynamic factors. The model was further incorporated with the flow autoregulatory mechanism to simulate the regulation of myocardial flow in the presence of coronary artery stenosis. Numerical tests demonstrated that heart rate (HR), intramyocardial tissue pressure (Pim ), and coronary perfusion pressure (Pper ) were the major determinant factors for transmural flow distribution (evaluated by the subendocardial-to-subepicardial (endo/epi) flow ratio) and that the flow autoregulatory mechanism played an important compensatory role in preserving subendocardial perfusion against reduced Pper . Further analysis for HR variation-induced hemodynamic changes revealed that the rise in endo/epi flow ratio accompanying HR decrease was attributable not only to the prolongation of cardiac diastole relative to systole, but more predominantly to the fall in Pim . Moreover, it was found that Pim and Pper interfered with each other with respect to their influence on transmural flow distribution. These results demonstrate the interactive effects of various cardiovascular and hemodynamic factors on transmural myocardial flow, highlighting the importance of taking into account patient-specific conditions in the explanation of clinical observations.

Could Revision of the Embryology Influence Our Cesarean Delivery Technique: Towards an Optimized Cesarean Delivery for Universal Use.

Until today, there is no standardized Cesarean Section method and many variations exist. The main variations concern the type of abdominal incision, usage of abdominal packs, suturing the uterus in one or two layers, and suturing the peritoneal layers or leaving them open. One of the questions is the optimal location of opening the uterus. Recently, omission of the bladder flap was recommended. The anatomy and histology as results from the embryological knowledge might help to solve this question. The working thesis is that the higher the incision is done, the more damage to muscle tissue can take place contrary to incision in the lower segment, where fibrous tissue prevails. In this perspective, a call for participation in a two-armed prospective study is included, which could result in an optimal, evidence-based Cesarean Section for universal use.