Review of Machine Learning Techniques in Soft Tissue Biomechanics and Biomaterials.

BACKGROUND AND OBJECTIVE: Advanced material models and material characterization of soft biological tissues play an essential role in pre-surgical planning for vascular surgeries and transcatheter interventions. Recent advances in heart valve engineering, medical device and patch design are built upon these models. Furthermore, understanding vascular growth and remodeling in native and tissue-engineered vascular biomaterials, as well as designing and testing drugs on soft tissue, are crucial aspects of predictive regenerative medicine. Traditional nonlinear optimization methods and finite element (FE) simulations have served as biomaterial characterization tools combined with soft tissue mechanics and tensile testing for decades. However, results obtained through nonlinear optimization methods are reliable only to a certain extent due to mathematical limitations, and FE simulations may require substantial computing time and resources, which might not be justified for patient-specific simulations. To a significant extent, machine learning (ML) techniques have gained increasing prominence in the field of soft tissue mechanics in recent years, offering notable advantages over conventional methods. This review article presents an in-depth examination of emerging ML algorithms utilized for estimating the mechanical characteristics of soft biological tissues and biomaterials. These algorithms are employed to analyze crucial properties such as stress-strain curves and pressure-volume loops. The focus of the review is on applications in cardiovascular engineering, and the fundamental mathematical basis of each approach is also discussed. METHODS: The review effort employed two strategies. First, the recent studies of major research groups actively engaged in cardiovascular soft tissue mechanics are compiled, and research papers utilizing ML and deep learning (DL) techniques were included in our review. The second strategy involved a standard keyword search across major databases. This approach provided 11 relevant ML articles, meticulously selected from reputable sources including ScienceDirect, Springer, PubMed, and Google Scholar. The selection process involved using specific keywords such as "machine learning" or "deep learning" in conjunction with "soft biological tissues", "cardiovascular", "patient-specific," "strain energy", "vascular" or "biomaterials". Initially, a total of 25 articles were selected. However, 14 of these articles were excluded as they did not align with the criteria of focusing on biomaterials specifically employed for soft tissue repair and regeneration. As a result, the remaining 11 articles were categorized based on the ML techniques employed and the training data utilized. RESULTS: ML techniques utilized for assessing the mechanical characteristics of soft biological tissues and biomaterials are broadly classified into two categories: standard ML algorithms and physics-informed ML algorithms. The standard ML models are then organized based on their tasks, being grouped into Regression and Classification subcategories. Within these categories, studies employ various supervised learning models, including support vector machines (SVMs), bagged decision trees (BDTs), artificial neural networks (ANNs) or deep neural networks (DNNs), and convolutional neural networks (CNNs). Additionally, the utilization of unsupervised learning approaches, such as autoencoders incorporating principal component analysis (PCA) and/or low-rank approximation (LRA), is based on the specific characteristics of the training data. The training data predominantly consists of three types: experimental mechanical data, including uniaxial or biaxial stress-strain data; synthetic mechanical data generated through non-linear fitting and/or FE simulations; and image data such as 3D second harmonic generation (SHG) images or computed tomography (CT) images. The evaluation of performance for physics-informed ML models primarily relies on the coefficient of determination R 2 . In contrast, various metrics and error measures are utilized to assess the performance of standard ML models. Furthermore, our review includes an extensive examination of prevalent biomaterial models that can serve as physical laws for physics-informed ML models. CONCLUSION: ML models offer an accurate, fast, and reliable approach for evaluating the mechanical characteristics of diseased soft tissue segments and selecting optimal biomaterials for time-critical soft tissue surgeries. Among the various ML models examined in this review, physics-informed neural network models exhibit the capability to forecast the mechanical response of soft biological tissues accurately, even with limited training samples. These models achieve high R 2 values ranging from 0.90 to 1.00. This is particularly significant considering the challenges associated with obtaining a large number of living tissue samples for experimental purposes, which can be time-consuming and impractical. Additionally, the review not only discusses the advantages identified in the current literature but also sheds light on the limitations and offers insights into future perspectives.

Effect of impeller rotational phase on the FDA blood pump velocity fields.

BACKGROUND: The Food and Drug Administration (FDA) blood pump is an open-source benchmark cardiovascular device introduced for validating computational and experimental performance analysis tools. The time-resolved velocity field for the whole impeller has not been established, as is undertaken in this particle image velocimetry (PIV) study. The level of instantaneous velocity fluctuations is important, to assess the flow-induced rotor vibrations which may contribute to the total blood damage. METHODS: To document these factors, time-resolved two-dimensional PIV experiments were performed that were precisely phase-locked with the impeller rotation angle. The velocity fields in the impeller and in the volute conformed with the previous single blade passage experiments of literature. RESULTS: Depending on the impeller orientation, present experiments showed that volute outlet nozzle flow can fluctuate up to 34% during impeller rotation, with a maximum standard experimental uncertainty of 2.2%. Likewise, the flow fields in each impeller passage also altered in average 33.5%. Considerably different vortex patterns were observed for different blade passages, with the largest vortical structures reaching an average core radii of 7 mm. The constant volute area employed in the FDA pump design contributes to the observed velocity imbalance, as illustrated in our velocity measurements. CONCLUSIONS: By introducing the impeller orientation parameter for the nozzle flow, this study considers the possible uncertainties influencing pump flow. Expanding the available literature data, analysis of inter-blade relative velocity fields is provided here for the first-time to the best of our knowledge. Consequently, our research fills a critical knowledge gap in the understanding of the flow dynamics of an important benchmark cardiovascular device. This study prompts the need for improved hydrodynamic designs and optimized devices to be used as benchmark test devices, to build more confidence and safety in future ventricular assist device performance assessment studies.

Evaluation of the total hydrodynamic energy loss using 4D flow MRI in a case with Fontan failure.

Fontan Failure (FF) is a common problem for single-ventricle patients as they reach adulthood. Although several mechanisms may cause FF, an optimized blood flow stream through the surgical conduits is essential to avoid excessive energy loss (EL). Recent clinical studies showed EL is related to the quality of life, exercise capacity, and hepatic function since the single-ventricle feeds pulmonary and systemic circulation serially. 4D flow MRI effectively estimates EL in Fontan circulation and allows clinicians to compare the effectiveness of the treatment strategy concerning pre-intervention. Here, we present 26-year-old women with FF who had normal cardiac catheterization findings and were treated according to high EL definitions that are measured through 4D flow MRI.

Mechanical characterization and torsional buckling of pediatric cardiovascular materials.

In complex cardiovascular surgical reconstructions, conduit materials that avoid possible large-scale structural deformations should be considered. A fundamental mode of mechanical complication is torsional buckling which occurs at the anastomosis site due to the mechanical instability, leading surgical conduit/patch surface deformation. The objective of this study is to investigate the torsional buckling behavior of commonly used materials and to develop a practical method for estimating the critical buckling rotation angle under physiological intramural vessel pressures. For this task, mechanical tests of four clinically approved materials, expanded polytetrafluoroethylene (ePTFE), Dacron, porcine and bovine pericardia, commonly used in pediatric cardiovascular surgeries, are conducted (n = 6). Torsional buckling initiation tests with n = 4 for the baseline case (L = 7.5 cm) and n = 3 for the validation of ePTFE (L = 15 cm) and Dacron (L = 15 cm and L = 25 cm) for each are also conducted at low venous pressures. A practical predictive formulation for the buckling potential is proposed using experimental observations and available theory. The relationship between the critical buckling rotation angle and the lumen pressure is determined by balancing the circumferential component of the compressive principal stress with the shear stress generated by the modified critical buckling torque, where the modified critical buckling torque depends linearly on the lumen pressure. While the proposed technique successfully predicted the critical rotation angle values lying within two standard deviations of the mean in the baseline case for all four materials at all lumen pressures, it could reliably predict the critical buckling rotation angles for ePTFE and Dacron samples of length 15 cm with maximum relative errors of 31% and 38%, respectively, in the validation phase. However, the validation of the performance of the technique demonstrated lower accuracy for Dacron samples of length 25 cm at higher pressure levels of 12 mmHg and 15 mmHg. Applicable to all surgical materials, this formulation enables surgeons to assess the torsional buckling potential of vascular conduits noninvasively. Bovine pericardium has been found to exhibit the highest stability, while Dacron (the lowest) and porcine pericardium have been identified as the least stable with the (unitless) torsional buckling resistance constants, 43,800, 12,300 and 14,000, respectively. There was no significant difference between ePTFE and Dacron, and between porcine and bovine pericardia. However, both porcine and bovine pericardia were found to be statistically different from ePTFE and Dacron individually (p < 0.0001). ePTFE exhibited highly nonlinear behavior across the entire strain range [0, 0.1] (or 10% elongation). The significant differences among the surgical materials reported here require special care in conduit construction and anastomosis design.

Interstitial flow, pressure and residual stress in the aging carotid artery model in FEBio.

Vascular smooth muscle cells (VSMCs) are subject to interstitial flow-induced shear stress, which is a critical parameter in cardiovascular disease progression. Transmural pressure loading and residual stresses alter the hydraulic conductivity of the arterial layers and modulate the interstitial fluid flux through the arterial wall. In this paper, a biphasic multilayer model of a common carotid artery (CCA) with anisotropic fiber-reinforced soft tissue and strain-dependent permeability is developed in FEBio software. After the verification of the numerical predictions, age-related arterial thickening and stiffening effects on arterial deformation and interstitial flow are computed under physiological geometry and physical parameters. We found that circumferential residual stress shifts outward in each layer and its gradient increases up to 6 times with aging. Internally pressurized CCA displays nonlinear deformation. In the aged artery, the circumferential stress becomes greater on the media layer (82-158 kPa) and lower on the intima and adventitia (19-23 kPa and 25-28 kPa, respectively). The radial compression of the intima reduces the total hydraulic conductivity by 48% in the young and 16% in the aged arterial walls. Consequently, the average radial interstitial flux increases with pressure by 14% in the young and 91% in the aged arteries. Accordingly, the flow shear stress experienced by the VSMCs becomes more significant for aged arteries, which may accelerate cardiovascular disease progression compared to young arteries.

Switching the Left and the Right Hearts: A Novel Bi-ventricle Mechanical Support Strategy with Spared Native Single-Ventricle.

End-stage Fontan patients with single-ventricle (SV) circulation are often bridged-to-heart transplantation via mechanical circulatory support (MCS). Donor shortage and complexity of the SV physiology demand innovative MCS. In this paper, an out-of-the-box circulation concept, in which the left and right ventricles are switched with each other is introduced as a novel bi-ventricle MCS configuration for the "failing" Fontan patients. In the proposed configuration, the systemic circulation is maintained through a conventional mechanical ventricle assist device (VAD) while the venous circulation is delegated to the native SV. This approach spares the SV and puts it to a new use at the right-side providing the most-needed venous flow pulsatility to the failed Fontan circulation. To analyze its feasibility and performance, eight SV failure modes have been studied via an established multi-compartmental lumped parameter cardiovascular model (LPM). Here the LPM model is experimentally validated against the corresponding pulsatile mock-up flow loop measurements of a representative 15-year-old Fontan patient employing a clinically-approved VAD (Medtronic-HeartWare). The proposed surgical configuration maintained the healthy cardiac index (3-3.5 l/min/m2) and the normal mean systemic arterial pressure levels. For a failed SV with low ejection fraction (EF = 26%), representing a typical systemic Fontan failure, the proposed configuration enabled a ~ 28 mmHg amplitude in the venous/pulmonary waveforms and a 2 mmHg decrease in the central venous pressure (CVP) together with acceptable mean pulmonary artery pressures (17.5 mmHg). The pulmonary vascular resistance (PVR)-SV failure case provided a ~ 5 mmHg drop in the CVP, with venous/pulmonary pulsatility reaching to ~ 22 mmHg. For the high PVR failure case with a healthy SV (EF = 44%) pulmonary hypertension is likely to occur as expected. While this condition is routinely encountered during the heart transplantation and managed through pulmonary vasodilators a need for precise functional assessment of the spared failed-ventricle is recommended if utilized in the PVR failure mode. Comprehensive in vitro and in silico results encourage this novel concept as a low-cost, more physiological alternative to the conventional bi-ventricle MCS pending animal experiments.

Left Atrial Ligation in the Avian Embryo as a Model for Altered Hemodynamic Loading During Early Vascular Development.

Due to its four-chambered mature ventricular configuration, ease of culture, imaging access, and efficiency, the avian embryo is a preferred vertebrate animal model for studying cardiovascular development. Studies aiming to understand the normal development and congenital heart defect prognosis widely adopt this model. Microscopic surgical techniques are introduced to alter the normal mechanical loading patterns at a specific embryonic time point and track the downstream molecular and genetic cascade. The most common mechanical interventions are left vitelline vein ligation, conotruncal banding, and left atrial ligation (LAL), modulating the intramural vascular pressure and wall shear stress due to blood flow. LAL, particularly if performed in ovo, is the most challenging intervention, with very small sample yields due to the extremely fine sequential microsurgical operations. Despite its high risk, in ovo LAL is very valuable scientifically as it mimics hypoplastic left heart syndrome (HLHS) pathogenesis. HLHS is a clinically relevant, complex congenital heart disease observed in human newborns. A detailed protocol for in ovo LAL is documented in this paper. Briefly, fertilized avian embryos were incubated at 37.5 °C and 60% constant humidity typically until they reached Hamburger-Hamilton (HH) stages 20 to 21. The egg shells were cracked open, and the outer and inner membranes were removed. The embryo was gently rotated to expose the left atrial bulb of the common atrium. Pre-assembled micro-knots from 10-0 nylon sutures were gently positioned and tied around the left atrial bud. Finally, the embryo was returned to its original position, and LAL was completed. Normal and LAL-instrumented ventricles demonstrated statistically significant differences in tissue compaction. An efficient LAL model generation pipeline would contribute to studies focusing on synchronized mechanical and genetic manipulation during the embryonic development of cardiovascular components. Likewise, this model will provide a perturbed cell source for tissue culture research and vascular biology.

Tension controlled hollow-fiber winding machine for blood oxygenator prototypes.

Blood oxygenators involve a complex network of hollow fibers for efficient gas exchange with blood. The optimal microstructural arrangement of these fibers is an ongoing research interest. While the fiber systems of commercial oxygenators are manufactured to address mass production, the research oxygenator prototypes demand more flexibility so that different design parameters can be tested. Here a hollow-fiber assembly system is designed and built for winding research grade extracorporeal blood oxygenator mandrels at different layout dimensions so that these different configurations can be evaluated for mass transfer capacity and blood damage. The hardware design and manufacturing details of this system presented together with its impact on the prototype oxygenator device assembly process. This in-house built system can wind thin fibers, having outer diameters ranging from 100 µm to 1 mm, at any specified winding angle continuously. A control system for fiber stress is also incorporated to eliminate fiber damage. Our system consists of three main units: (1) unwinding, (2) accumulator, and (3) winding systems, integrated together via the control software. The unwinding unit has a PID controller to maintain the position of the accumulator motor on the reference point by tuning the velocity of feeding fibers to the accumulator unit. Another PID controller preserves the desired tension value of the fibers by adjusting the position of the accumulator motor. Desired tension value is defined by the user and typically obtained through uniaxial testing of fibers. The control unit employs a "cascaded" PID controller since the PID controller in the accumulator unit maintains the tension and the PID controller in the unwinding unit controls the position of the accumulator motor. Finally, the winding unit utilizes two motors to wind the fibers over the outer diameter of a mandrel at the desired winding angle. The first motor drives the translational movement, and the second one provides mandrel rotation. The desired angles are achieved by tuning the synchronous movement of the winding motors. While the system is designed to produce assembled blood oxygenator mandrel prototypes, this concept is also applicable for producing cylindrical fiber-reinforced composite materials with specified fiber angles and stents winded on jigs.

Surgical and transcatheter pulmonary valve replacement in patients with repaired tetralogy of Fallot: cardiac magnetic resonance imaging characteristics and morphology of right ventricular outflow tract.

BACKGROUND: Pulmonary valve replacement is recommended in patients with repaired tetralogy of Fallot based on cardiac magnetic resonance imaging (MRI) criteria. This procedure is performed by surgical or transcatheter approaches. OBJECTIVE: We aimed to investigate the differences in preprocedural MRI characteristics (volume, function, strain) and morphology of the right ventricular outflow tract and branch pulmonary arteries in patients for whom surgical or transcatheter pulmonary valve replacement was planned. MATERIALS AND METHODS: Cardiac MRI of 166 patients with tetralogy of Fallot were analyzed. Of these, 36 patients for whom pulmonary valve replacement was planned were included. Magnetic resonance imaging characteristics, right ventricular outflow tract morphology, branch pulmonary artery flow distribution and diameter were compared between surgical and transcatheter groups. Spearman correlation and Kruskal-Wallis tests were performed. RESULTS: Circumferential and radial MRI strain for the right ventricle were lower in the surgical group (P=0.045 and P=0.046, respectively). The diameter of the left pulmonary artery was significantly lower (P=0.021) and branch pulmonary artery flow and diameter ratio were higher (P=0.044 and P = 0.002, respectively) in the transcatheter group. There was a significant correlation between right ventricular outflow tract morphology and right ventricular end-diastolic volume index and global circumferential and radial MRI strain (P=0.046, P=0.046 and P= 0.049, respectively). CONCLUSION: Preprocedural MRI strain, right-to-left pulmonary artery flow, diameter ratio and morphological features of the right ventricular outflow tract were significantly different between the two groups. A transcatheter approach may be recommended for patients with branch pulmonary artery stenosis, since both pulmonary valve replacement and branch pulmonary artery stenting can be performed in the same session.

Myocardial Biomechanics and the Consequent Differentially Expressed Genes of the Left Atrial Ligation Chick Embryonic Model of Hypoplastic Left Heart Syndrome.

Left atrial ligation (LAL) of the chick embryonic heart is a model of the hypoplastic left heart syndrome (HLHS) where a purely mechanical intervention without genetic or pharmacological manipulation is employed to initiate cardiac malformation. It is thus a key model for understanding the biomechanical origins of HLHS. However, its myocardial mechanics and subsequent gene expressions are not well-understood. We performed finite element (FE) modeling and single-cell RNA sequencing to address this. 4D high-frequency ultrasound imaging of chick embryonic hearts at HH25 (ED 4.5) were obtained for both LAL and control. Motion tracking was performed to quantify strains. Image-based FE modeling was conducted, using the direction of the smallest strain eigenvector as the orientations of contractions, the Guccione active tension model and a Fung-type transversely isotropic passive stiffness model that was determined via micro-pipette aspiration. Single-cell RNA sequencing of left ventricle (LV) heart tissues was performed for normal and LAL embryos at HH30 (ED 6.5) and differentially expressed genes (DEG) were identified.After LAL, LV thickness increased by 33%, strains in the myofiber direction increased by 42%, while stresses in the myofiber direction decreased by 50%. These were likely related to the reduction in ventricular preload and underloading of the LV due to LAL. RNA-seq data revealed potentially related DEG in myocytes, including mechano-sensing genes (Cadherins, NOTCH1, etc.), myosin contractility genes (MLCK, MLCP, etc.), calcium signaling genes (PI3K, PMCA, etc.), and genes related to fibrosis and fibroelastosis (TGF-ß, BMP, etc.). We elucidated the changes to the myocardial biomechanics brought by LAL and the corresponding changes to myocyte gene expressions. These data may be useful in identifying the mechanobiological pathways of HLHS.

Embryonic aortic arch material properties obtained by optical coherence tomography-guided micropipette aspiration.

It is challenging to determine the in vivo material properties of a very soft, mesoscale arterial vesselsof size âˆ¼ 80 to 120 µm diameter. This information is essential to understand the early embryonic cardiovascular development featuring rapidly evolving dynamic microstructure. Previous research efforts to describe the properties of the embryonic great vessels are very limited. Our objective is to measure the local material properties of pharyngeal aortic arch tissue of the chick-embryo during the early Hamburger-Hamilton (HH) stages, HH18 and HH24. Integrating the micropipette aspiration technique with optical coherence tomography (OCT) imaging, a clear vision of the aspirated arch geometry is achieved for an inner pipette radius of Rp = 25 µm. The aspiration of this region is performed through a calibrated negatively pressurized micro-pipette. A computational finite element model is developed to model the nonlinear behaviour of the arch structure by considering the geometry-dependent constraints. Numerical estimations of the nonlinear material parameters for aortic arch samples are presented. The exponential material nonlinearity parameter (a) of aortic arch tissue increases statistically significantly from a = 0.068 ± 0.013 at HH18 to a = 0.260 ± 0.014 at HH24 (p = 0.0286). As such, the aspirated tissue length decreases from 53 µm at HH18 to 34 µm at HH24. The calculated NeoHookean shear modulus increases from 51 Pa at HH18 to 93 Pa at HH24 which indicates a statistically significant stiffness increase. These changes are due to the dynamic changes of collagen and elastin content in the media layer of the vessel during development.

Cardiac magnetic resonance T2* mapping in patients with COVID-19 pneumonia is associated with serum ferritin level?

The coronavirus disease of 2019 (COVID-19)-related myocardial injury is an increasingly recognized complication and cardiac magnetic resonance imaging (MRI) has become the most commonly used non-invasive imaging technique for myocardial involvement. This study aims to assess myocardial structure by T2*-mapping which is a non-invasive gold-standard imaging tool for the assessment of cardiac iron deposition in patients with COVID-19 pneumonia without significant cardiac symptoms. Twenty-five patients with COVID-19 pneumonia and 20 healthy subjects were prospectively enrolled.Cardiac volume and function parameters, myocardial native-T1, and T2*-mapping were measured. The association of serum ferritin level and myocardial mapping was analyzed. There was no difference in terms of cardiac volume and function parameters. The T2*-mapping values were lower in patients with COVID-19 compared to controls (35.37 [IQR 31.67-41.20] ms vs. 43.98 [IQR 41.97-46.88] ms; p < 0.0001), while no significant difference was found in terms of native-T1 mapping value(p = 0.701). There was a positive correlation with T2*mapping and native-T1 mapping values (r = 0.522, p = 0.007) and negative correlation with serum ferritin values (r = - 0.653, p = 0.000), while no correlation between cardiac native-T1 mapping and serum ferritin level. Negative correlation between serum ferritin level and T2*-mapping values in COVID-19 patients may provide a non-contrast-enhanced alternative to assess tissue structural changes in patients with COVID-19. T2*-mapping may provide a non-contrast-enhanced alternative to assess tissue alterations in patients with COVID-19. Adding T2*-mapping cardiac MRI in patients with myocardial pathologies would improve the revealing of underlying mechanisms. Further in vivo and ex vivo animal or human studies designed with larger patient cohorts should be planned.

Optimizing percutaneous pulmonary valve implantation with patient-specific 3D-printed pulmonary artery models and hemodynamic assessment.

Background: Percutaneous pulmonary valve implantation (PPVI) has emerged as a less invasive alternative for treating severe pulmonary regurgitation after tetralogy of Fallot (TOF) repair in patients with a native right ventricular outflow tract (RVOT). However, the success of PPVI depends on precise patient-specific valve sizing, the avoidance of oversizing complications, and optimal valve performance. In recent years, innovative adaptations of commercially available cardiovascular mock loops have been used to test conduits in the pulmonary position. These models are instrumental in facilitating accurate pulmonic valve sizing, mitigating the risk of oversizing, and providing insight into the valve performance before implantation. This study explored the utilization of custom-modified mock loops to implant patient-specific 3D-printed pulmonary artery geometries, thereby advancing PPVI planning and execution. Material and Methods: Patient-specific 3D-printed pulmonary artery geometries of five patients who underwent PPVI using Pulsta transcatheter heart valve (THV) ® were tested in a modified ViVitro pulse duplicator system®. Various valve sizes were subjected to 10 cycles of testing at different cardiac output levels. The transpulmonary systolic and regurgitation fractions of the valves were also recorded and compared. Results: A total of 39 experiments were conducted using five different patient geometries and several different valve sizes (26, 28, 30, and 32 mm) at 3, 4, and 5 L/min cardiac output at heart rates of 70 beats per minute (bpm) and 60/40 systolic/diastolic ratios. The pressure gradients and regurgitation fractions of the tested valve sizes in the models were found to be similar to the pressure gradients and regurgitation fractions of valves used in real procedures. However, in two patients, different valve sizes showed better hemodynamic values than the actual implanted valves. Discussion: The use of 3D printing technology, electromagnetic flow meters, and the custom-modified ViVitro pulse duplicator system® in conjunction with patient-specific pulmonary artery models has enabled a comprehensive assessment of percutaneous pulmonic valve implantation performance. This approach allows for accurate valve sizing, minimization of oversizing risks, and valuable insights into hemodynamic behavior before implantation. The data obtained from this experimental setup will contribute to advancing PPVI procedures and offer potential benefits in improving patient outcomes and safety.

In vitro measurement of hepatic flow distribution in Fontan vascular conduits: Towards rapid validation techniques.

Fontan operation is the last stage of single-ventricle surgical reconstructions that connects superior and inferior vena cava (SVC, IVC) to the pulmonary arteries. The key design objectives in total cavopulmonary connections (TCPC) are to achieve low power loss (PL) and balanced hepatic flow distribution (HFD). Computational fluid dynamics (CFD) played a pivotal role in pre-surgical design of single-ventricle patients. However, the clinical application of current CFD techniques is limited due to their complexity, high computational time and untested accuracy for HFD prediction. This study provides a performance assessment of computationally low-cost steady Reynolds-Averaged Navier-Stokes (RANS) k-ɛ turbulent models for simulation of Fontan hemodynamics. The performance is evaluated based on prediction accuracy for three clinically important Fontan hemodynamic indices: HFD, PL and total pulmonary flow split (TPFS). For this purpose, a low-cost experimental technique is developed for rapid quantification of Fontan performance indices. Experiments and simulations are performed for both an idealized and a complex 3D reconstructed patient-specific TCPC. Time-averaged flow data from phase contrast MRI was used as the boundary conditions for the patient-specific model. For the idealized model, different SVC/IVC flow ratios corresponding to different cardiac outputs and Reynolds' numbers were examined. This study revealed that steady RANS k-ɛ models are able to estimate the Fontan hemodynamic indices with acceptable accuracy within minutes. Among these, standard k-ɛ two-layer was found to deliver the best agreement with the in vitro data with an average error percentage of 1.7, 2.0 and, 3.9 for HFD, TPFS and, PL, respectively for all cases.

Mechanical support of pulmonary blood flow as a strategy to support the Norwood circulation-lumped parameter model study.

OBJECTIVES: We hypothesize that mechanical assistance of the pulmonary blood flow in a Norwood circulation can increase systemic blood flow and oxygen delivery. The aim of the study was to compare haemodynamics of an unassisted Norwood Blalock-Taussig shunt circulation with a mechanically assisted pulmonary flow-based Norwood circulation, using a lumped parameter computational model. METHODS: A neonatal circulatory lumped parameter model was developed to simulate a Norwood circulation with a 3.5-mm Blalock-Taussig shunt in a 3.5-kg neonate. A roller pump circulatory assist device with an inflow bladder was incorporated into the Norwood circulation to mechanically support the pulmonary circulation. Computer simulations were used to compare the haemodynamics of the assisted and unassisted circulations. Assisted and unassisted models with normal (56%) and reduced ejection fraction (30%) were compared. RESULTS: Compared to the unassisted Norwood circulation, the systemic flow in the assisted Norwood increased by 25% (ejection fraction = 56%) and 41% (ejection fraction = 30%). The central venous pressure decreased by up to 3 mmHg (both ejection fraction = 56% and ejection fraction = 30%) at a maximum pulmonary assist flow of 800 ml/min. Initiation of assisted pulmonary flow increased the arterial oxygen saturation by up to 15% and mixed venous saturation by up to 20%. CONCLUSIONS: This study demonstrates that an assisted pulmonary flow-based Norwood circulation has higher systemic flow and oxygen delivery compared to a standard Norwood Blalock-Taussig shunt circulation.

Soft-Tissue Material Properties and Mechanogenetics during Cardiovascular Development.

During embryonic development, changes in the cardiovascular microstructure and material properties are essential for an integrated biomechanical understanding. This knowledge also enables realistic predictive computational tools, specifically targeting the formation of congenital heart defects. Material characterization of cardiovascular embryonic tissue at consequent embryonic stages is critical to understand growth, remodeling, and hemodynamic functions. Two biomechanical loading modes, which are wall shear stress and blood pressure, are associated with distinct molecular pathways and govern vascular morphology through microstructural remodeling. Dynamic embryonic tissues have complex signaling networks integrated with mechanical factors such as stress, strain, and stiffness. While the multiscale interplay between the mechanical loading modes and microstructural changes has been studied in animal models, mechanical characterization of early embryonic cardiovascular tissue is challenging due to the miniature sample sizes and active/passive vascular components. Accordingly, this comparative review focuses on the embryonic material characterization of developing cardiovascular systems and attempts to classify it for different species and embryonic timepoints. Key cardiovascular components including the great vessels, ventricles, heart valves, and the umbilical cord arteries are covered. A state-of-the-art review of experimental techniques for embryonic material characterization is provided along with the two novel methods developed to measure the residual and von Mises stress distributions in avian embryonic vessels noninvasively, for the first time in the literature. As attempted in this review, the compilation of embryonic mechanical properties will also contribute to our understanding of the mature cardiovascular system and possibly lead to new microstructural and genetic interventions to correct abnormal development.

A novel Fontan Y-graft for interrupted inferior vena cava and azygos continuation.

OBJECTIVES: To evaluate the hemodynamicdynamic advantage of a new Fontan surgical template that is intended for complex single-ventricle patients with interrupted inferior vena cava-azygos and hemi-azygos continuation. The new technique has emerged from a comprehensive pre-surgical simulation campaign conducted to facilitate a balanced hepatic flow and somatic Fontan pathway growth after Kawashima procedure. METHODS: For 9 patients, aged 2 to18 years, majority having poor preoperative oxygen saturation, a pre-surgical computational fluid dynamics customization is conducted. Both the traditional Fontan pathways and the proposed novel Y-graft templates are considered. Numerical model was validated against in vivo phase-contrast magnetic resonance imaging data and in vitro experiments. RESULTS: The proposed template is selected and executed for 6 out of the 9 patients based on its predicted superior hemodynamic performance. Pre-surgical simulations performed for this cohort indicated that flow from the hepatic veins (HEP) do not reach to the desired lung. The novel Y-graft template, customized via a right- or left-sided displacement of the total cavopulmonary connection anastomosis location resulted a drastic increase in HEP flow to the desired lung. Orientation of HEP to azygos direct shunt is found to be important as it can alter the flow pattern from 38% in the caudally located direct shunt to 3% in the cranial configuration with significantly reversed flow. The postoperative measurements prove that oxygen saturation increased significantly (P-value = 0.00009) to normal levels in 1 year follow-up. CONCLUSIONS: The new Y-graft template, if customized for the individual patient, is a viable alternative to the traditional surgical pathways. This template addresses the competing hemodynamic design factors of low physiological venous pressure, high postoperative oxygen saturation, low energy loss and balanced hepatic growth factor distribution possibly assuring adequate lung development. DATE AND NUMBER OF IRB APPROVAL: 25 October 2019, 280011928-604.01.01.

A novel method for hemodynamic analysis of penile erection.

Measurement of blood flow velocity through the cavernosal arteries via penile color Doppler ultrasound (PDUS) is the most common objective method for the assessment of erectile function. However, in some clinical cases, this method needs to be augmented via the invasive intracavernosal pressure (ICP) measurement, which is arguably a more direct index for erectile function. The aim of this study is to develop a lumped parameter model (LPM) of the penile circulation mechanism integrated to a pulsatile, patient-specific, bi-ventricular circulation system to estimate ICP values non-invasively. PDUS data obtained from four random patients with erectile dysfunction are used to develop patient-specific LPMs. Cardiac output is estimated from the body surface area. Systemic pressure is obtained by a sphygmomanometer. Through the appropriate parameter set determined by optimization, patient-specific ICP values are predicted with only using PDUS data and validated by pre- and post-papaverine injection cavernosometry measurements. The developed model predicts the ICP with an average error value of 3 mmHg for both phases. Penile size change during erection is predicted with a ~15% error, according to the clinical size measurements. The developed mathematical model has the potential to be used as an effective non-invasive tool in erectile function evaluation, expanding the existing clinical decision parameters significantly.

Single-center experience with routine clinical use of 3D technologies in surgical planning for pediatric patients with complex congenital heart disease.

PURPOSE: This study was planned to assess the application of three-dimensional (3D) cardiac modeling in preoperative evaluation for complex congenital heart surgeries. METHODS: From July 2015 to September 2019, 18 children diagnosed with complex congenital heart diseases (CHDs) were enrolled in this study (double outlet right ventricle in nine patients, complex types of transposition of the great arteries in six patients, congenitally corrected transposition of the great arteries in two patients, and univentricular heart in one patient). The patients' age ranged from 7 months to 19 years (median age, 14 months). Before the operation, 3D patient-specific cardiac models were created based on computed tomography (CT) data. Using each patient's data, a virtual computer model (3D mesh) and stereolithographic (SLA) file that would be printed as a 3D model were generated. These 3D cardiac models were used to gather additional data about cardiac anatomy for presurgical decision-making. RESULTS: All 18 patients successfully underwent surgeries, and there were no mortalities. The 3D patient-specific cardiac models led to a change from the initial surgical plans in 6 of 18 cases (33%), and biventricular repair was considered feasible. Moreover, the models helped to modify the planned biventricular repair in five cases, for left ventricular outflow tract obstruction removal and ventricular septal defect enlargement. 3D cardiac models enable pediatric cardiologists to better understand the spatial relationships between the ventricular septal defect and great vessels, and they help surgeons identify risk structures more clearly for detailed planning of surgery. There was a strong correlation between the models of the patients and the anatomy encountered during the operation. CONCLUSION: 3D cardiac models accurately reveal the patient's anatomy in detail and are therefore beneficial for planning surgery in patients with complex intracardiac anatomy.