Patient-specific tissue engineered vascular graft for aortic arch reconstruction.

Objectives: The complexity of aortic arch reconstruction due to diverse 3-dimensional geometrical abnormalities is a major challenge. This study introduces 3-dimensional printed tissue-engineered vascular grafts, which can fit patient-specific dimensions, optimize hemodynamics, exhibit antithrombotic and anti-infective properties, and accommodate growth. Methods: We procured cardiac magnetic resonance imaging with 4-dimensional flow for native porcine anatomy (n = 10), from which we designed tissue-engineered vascular grafts for the distal aortic arch, 4 weeks before surgery. An optimal shape of the curved vascular graft was designed using computer-aided design informed by computational fluid dynamics analysis. Grafts were manufactured and implanted into the distal aortic arch of porcine models, and postoperative cardiac magnetic resonance imaging data were collected. Pre- and postimplant hemodynamic data and histology were analyzed. Results: Postoperative magnetic resonance imaging of all pigs with 1:1 ratio of polycaprolactone and poly-L-lactide-co-ε-caprolactone demonstrated no specific dilatation or stenosis of the graft, revealing a positive growth trend in the graft area from the day after surgery to 3 months later, with maintaining a similar shape. The peak wall shear stress of the polycaprolactone/poly-L-lactide-co-ε-caprolactone graft portion did not change significantly between the day after surgery and 3 months later. Immunohistochemistry showed endothelization and smooth muscle layer formation without calcification of the polycaprolactone/poly-L-lactide-co-ε-caprolactone graft. Conclusions: Our patient-specific polycaprolactone/poly-L-lactide-co-ε-caprolactone tissue-engineered vascular grafts demonstrated optimal anatomical fit maintaining ideal hemodynamics and neotissue formation in a porcine model. This study provides a proof of concept of patient-specific tissue-engineered vascular grafts for aortic arch reconstruction.

In vitro investigation of axial mechanical support devices implanted in the novel convergent cavopulmonary connection Fontan.

OBJECTIVES: The 2 opposing inflows and 2 outflows in a total cavopulmonary connection make mechanical circulatory support (MCS) extremely challenging. We have previously reported a novel convergent cavopulmonary connection (CCPC) Fontan design that improves baseline characteristics and provides a single inflow and outflow, thus simplifying MCS. This study aims to assess the feasibility of MCS of this novel configuration using axial flow pumps in an in vitro benchtop model. METHODS: Three-dimensional segmentations of 12 single-ventricle patients (body surface area 0.5-1.75 m2) were generated from cardiovascular magnetic resonance images. The CCPC models were designed by connecting the inferior vena cava and superior vena cava to a shared conduit ascending to the pulmonary arteries, optimized in silico. The 12 total cavopulmonary connection and their corresponding CCPC models underwent in vitro benchtop characterization. Two MCS devices were used, the Impella RP® and the PediPump. RESULTS: MCS successfully and symmetrically reduced the pressure in both vena cavae by >20 mmHg. The devices improved the hepatic flow distribution balance of all CCPC models (Impella RP®P = 0.045, PediPump P = 0.055). CONCLUSIONS: The CCPC Fontan design provides a feasible MCS solution for a failing Fontan by balancing hepatic flow distribution and symmetrically decompressing the central venous pressure. Cardiac index may also improve with MCS. Additional studies are needed to evaluate this concept for managing Fontan failure.

Virtual Planning and Patient-Specific Graft Design for Aortic Repairs.

PURPOSE: Patients presenting with coarctation of the aorta (CoA) may also suffer from co-existing transverse arch hypoplasia (TAH). Depending on the risks associated with the surgery and the severity of TAH, clinicians may decide to repair only CoA, and monitor the TAH to see if it improves as the patient grows. While acutely successful, eventually hemodynamics may become suboptimal if TAH is left untreated. The objective of this work aims to develop a patient-specific surgical planning framework for predicting and assessing postoperative outcomes of simple CoA repair and comprehensive repair of CoA and TAH. METHODS: The surgical planning framework consisted of virtual clamp placement, stenosis resection, and design and optimization of patient-specific aortic grafts that involved geometrical modeling of the graft and computational fluid dynamics (CFD) simulation for evaluating various surgical plans. Time-dependent CFD simulations were performed using Windkessel boundary conditions at the outlets that were obtained from patient-specific non-invasive pressure and flow data to predict hemodynamics before and after the virtual repairs. We applied the proposed framework to investigate optimal repairs for six patients (n = 6) diagnosed with both CoA and TAH. Design optimization was performed by creating a combination of a tubular graft and a waterslide patch to reconstruct the aortic arch. The surfaces of the designed graft were parameterized to optimize the shape. RESULTS: Peak systolic pressure drop (PSPD) and time-averaged wall shear stress (TAWSS) were used as performance metrics to evaluate surgical outcomes of various graft designs and implantation. The average PSPD improvements were 28% and 44% after the isolated CoA repair and comprehensive repair, respectively. Maximum values of TAWSS were decreased by 60% after CoA repair and further improved by 22% after the comprehensive repair. The oscillatory shear index was calculated and the values were confirmed to be in the normal range after the repairs. CONCLUSION: The results showed that the comprehensive repair outperforms the simple CoA repair and may be more advantageous in the long term in some patients. We demonstrated that the surgical planning and patient-specific flow simulations could potentially affect the selection and outcomes of aorta repairs.

Computational Fontan Analysis: Preserving Accuracy While Expediting Workflow.

Background: Postoperative outcomes of the Fontan operation have been linked to geometry of the cavopulmonary pathway, including graft shape after implantation. Computational fluid dynamics (CFD) simulations are used to explore different surgical options. The objective of this study is to perform a systematic in vitro validation for investigating the accuracy and efficiency of CFD simulation to predict Fontan hemodynamics. Methods: CFD simulations were performed to measure indexed power loss (iPL) and hepatic flow distribution (HFD) in 10 patient-specific Fontan models, with varying mesh and numerical solvers. The results were compared with a novel in vitro flow loop setup with 3D printed Fontan models. A high-resolution differential pressure sensor was used to measure the pressure drop for validating iPL predictions. Microparticles with particle filtering system were used to measure HFD. The computational time was measured for a representative Fontan model with different mesh sizes and numerical solvers. Results: When compared to in vitro setup, variations in CFD mesh sizes had significant effect on HFD (P = .0002) but no significant impact on iPL (P = .069). Numerical solvers had no significant impact in both iPL (P = .50) and HFD (P = .55). A transient solver with 0.5 mm mesh size requires computational time 100 times more than a steady solver with 2.5 mm mesh size to generate similar results. Conclusions: The predictive value of CFD for Fontan planning can be validated against an in vitro flow loop. The prediction accuracy can be affected by the mesh size, model shape complexity, and flow competition.

Location matters: Offset in tissue-engineered vascular graft implantation location affects wall shear stress in porcine models.

Objective: Although surgical simulation using computational fluid dynamics has advanced, little is known about the accuracy of cardiac surgical procedures after patient-specific design. We evaluated the effects of discrepancies in location for patient-specific simulation and actual implantation on hemodynamic performance of patient-specific tissue-engineered vascular grafts (TEVGs) in porcine models. Methods: Magnetic resonance angiography and 4-dimensional (4D) flow data were acquired in porcine models (n = 11) to create individualized TEVGs. Graft shapes were optimized and manufactured by electrospinning bioresorbable material onto a metal mandrel. TEVGs were implanted 1 or 3 months postimaging, and postoperative magnetic resonance angiography and 4D flow data were obtained and segmented. Displacement between intended and observed TEVG position was determined through center of mass analysis. Hemodynamic data were obtained from 4D flow analysis. Displacement and hemodynamic data were compared using linear regression. Results: Patient-specific TEVGs were displaced between 1 and 8 mm during implantation compared with their surgically simulated, intended locations. Greater offset between intended and observed position correlated with greater wall shear stress (WSS) in postoperative vasculature (P < .01). Grafts that were implanted closer to their intended locations showed decreased WSS. Conclusions: Patient-specific TEVGs are designed for precise locations to help optimize hemodynamic performance. However, if TEVGs were implanted far from their intended location, worse WSS was observed. This underscores the importance of not only patient-specific design but also precision-guided implantation to optimize hemodynamics in cardiac surgery and increase reproducibility of surgical simulation.

Altered hemodynamics by 4D flow cardiovascular magnetic resonance predict exercise intolerance in repaired coarctation of the aorta: an in vitro study.

BACKGROUND: Coarctation of the aorta (CoA) is associated with decreased exercise capacity despite successful repair. Altered flow patterns have been identified due to abnormal aortic arch geometry. Our previous work demonstrated aorta size mismatch to be associated with exercise intolerance in this population. In this study, we studied aortic flow patterns during simulations of exercise in repaired CoA using 4D flow cardiovascular magnetic resonance (CMR) using aortic replicas connected to an in vitro flow pump and correlated findings with exercise stress test results to identify biomarkers of exercise intolerance. METHODS: Patients with CoA repair were retrospectively analyzed after CMR and exercise stress test. Each aorta was manually segmented and 3D printed. Pressure gradient measurements from ascending aorta (AAo) to descending aorta (DAo) and 4D flow CMR were performed during simulations of rest and exercise using a mock circulatory flow loop. Changes in wall shear stress (WSS) and secondary flow formation (vorticity and helicity) from rest to exercise were quantified, as well as estimated DAo Reynolds number. Parameters were correlated with percent predicted peak oxygen consumption (VO2max) and aorta size mismatch (DAAo/DDAo). RESULTS: Fifteen patients were identified (VO2max 47 to 126% predicted). Pressure gradient did not correlate with VO2max at rest or exercise. VO2max correlated positively with the change in peak vorticity (R = 0.55, p = 0.03), peak helicity (R = 0.54, p = 0.04), peak WSS in the AAo (R = 0.68, p = 0.005) and negatively with peak WSS in the DAo (R = - 0.57, p = 0.03) from rest to exercise. DAAo/DDAo correlated strongly with change in vorticity (R = - 0.38, p = 0.01), helicity (R = - 0.66, p = 0.007), and WSS in the AAo (R = - 0.73, p = 0.002) and DAo (R = 0.58, p = 0.02). Estimated DAo Reynolds number negatively correlated with VO2max for exercise (R = - 0.59, p = 0.02), but not rest (R = - 0.28, p = 0.31). Visualization of streamline patterns demonstrated more secondary flow formation in aortic arches with better exercise capacity, larger DAo, and lower Reynolds number. CONCLUSIONS: There are important associations between secondary flow characteristics and exercise capacity in repaired CoA that are not captured by traditional pressure gradient, likely due to increased turbulence and inefficient flow. These 4D flow CMR parameters are a target of investigation to identify optimal aortic arch geometry and improve long term clinical outcomes after CoA repair.

Teachers' views related the middle school curriculum for distance education during the COVID-19 pandemic.

This qualitative study aims to examine teachers' opinions concerning the middle school curricula that have been in use for years, in order to determine its suitability for distance education during the COVID-19 pandemic. The participants consisted of eighteen middle school teachers from different subject areas in Turkey. A maximum variation sampling method was employed for participant selection. The data was collected through semi-structured interviews. Due to the pandemic, the interviews were conducted using video conferencing applications. The data was analyzed through content analysis. According to the findings, the teachers report that while they are effective in achieving cognitive objectives, they have difficulties in achieving affective and psychomotor objectives. In addition, the teachers do not prefer to design their own materials, rather they mainly benefit from ready-to-use materials during emergency distance education. The teachers also reveal that direct instruction and questioning were the teaching methods and techniques they preferred in online courses and that they were unable to adapt other methods and techniques to distance education, which resulted in students experiencing teacher-centered activities. Moreover, the teachers complain about students not attending the online courses on time or even at all, their disinterest, a lack of instant feedback, limited communication with students, and insufficient course lengths. Another critical finding was that the teachers only use homework, end-of-unit quizzes, and participation to online courses as measurement and evaluation tools and agree that they are unable to administer reliable and valid evaluation tools. The limitations of the study and implications for future research are later discussed.

Aorta size mismatch predicts decreased exercise capacity in patients with successfully repaired coarctation of the aorta.

OBJECTIVE: Coarctation of the aorta (CoA) is associated with decreased exercise capacity despite successful repair with no residual stenosis; however, the hemodynamic mechanism remains unknown. This study aims to correlate aortic arch geometry with exercise capacity in patients with successfully repaired CoA and explain hemodynamic changes using 3-dimensional-printed aorta models in a mock circulatory flow loop. METHODS: A retrospective chart review identified patients with CoA repair who had cardiac magnetic resonance imaging and an exercise stress test. Measurements included aorta diameters, arch height to diameter ratio, left ventricular function, and percent descending aorta (%DAo) flow. Each aorta was printed 3-dimensionally for the flow loop. Flow and pressure were measured at the ascending aorta (AAo) and DAo during simulated rest and exercise. Measurements were correlated with percent predicted peak oxygen consumption (VO2 max). RESULTS: Fifteen patients (mean age 26.8 ± 8.6 years) had a VO2 max between 47% and 126% predicted (mean 92 ± 20%) with normal left ventricular function. DAo diameter and %DAo flow positively correlated with VO2 (P = .007 and P = .04, respectively). AAo to DAo diameter ratio (DAAo/DDAo) negatively correlated with VO2 (P < .001). From flow loop simulations, the ratio of %DAo flow in exercise to rest negatively correlated with VO2 (P = .02) and positively correlated with DAAo/DDAo (P < .01). CONCLUSIONS: This study suggests aorta size mismatch (DAAo/DDAo) is a novel, clinically important measurement predicting exercise capacity in patients with successful CoA repair, likely due to increased resistance and altered flow distribution. Aorta size mismatch and %DAo flow are targets for further clinical evaluation in repaired CoA.

Non-invasive Prediction of Peak Systolic Pressure Drop across Coarctation of Aorta using Computational Fluid Dynamics.

This paper proposes a novel method to noninvasively measure the peak systolic pressure difference (PSPD) across coarctation of the aorta for diagnosing the severity of coarctation. Traditional non-invasive estimates of pressure drop from the ultrasound can underestimate the severity and invasive measurements by cardiac catheterization can carry risks for patients. To address the issues, we employ computational fluid dynamics (CFD) computation to accurately predict the PSPD across a coarctation based on cardiac magnetic resonance (CMR) imaging data and cuff pressure measurements from one arm. The boundary conditions of a patient-specific aorta model are specified at the inlet of the ascending aorta by using the time-dependent blood velocity, and the outlets of descending aorta and supra aortic branches by using a 3-element Windkessel model. To estimate the parameters of the Windkessel model, steady flow simulations were performed using the time-averaged flow rates in the ascending aorta, descending aorta, and two of the three supra aortic branches. The mean cuff pressure from one arm was specified at the outlet of one of the supra aortic branches. The CFD predicted PSPDs of 5 patients (n=5) were compared with the invasively measured pressure drops obtained by catheterization. The PSPDs were accurately predicted (mean µ=0.3mmHg, standard deviation σ =4.3mmHg) in coarctation of the aorta using completely non-invasive flow and cuff pressure data. The results of our study indicate that the proposed method could potentially replace invasive measurements for estimating the severity of coarctations.Clinical relevance-Peak systolic pressure drop is an indicator of the severity of coarctation of the aorta. It can be predicted without any additional risks to patients using non-invasive cuff pressure and flow data from CMR.

Automatic Shape Optimization of Patient-Specific Tissue Engineered Vascular Grafts for Aortic Coarctation.

This paper proposes a computational framework for automatically optimizing the shapes of patient-specific tissue engineered vascular grafts. We demonstrate a proof-of-concept design optimization for aortic coarctation repair. The computational framework consists of three main components including 1) a free-form deformation technique exploring graft geometries, 2) high-fidelity computational fluid dynamics simulations for collecting data on the effects of design parameters on objective function values like energy loss, and 3) employing machine learning methods (Gaussian Processes) to develop a surrogate model for predicting results of high-fidelity simulations. The globally optimal design parameters are then computed by multistart conjugate gradient optimization on the surrogate model. In the experiment, we investigate the correlation among the design parameters and the objective function values. Our results achieve a 30% reduction in blood flow energy loss compared to the original coarctation by optimizing the aortic geometry.

In vivo implantation of 3-dimensional printed customized branched tissue engineered vascular graft in a porcine model.

BACKGROUND: The customized vascular graft offers the potential to simplify the surgical procedure, optimize physiological function, and reduce morbidity and mortality. This experiment evaluated the feasibility of a flow dynamic-optimized branched tissue engineered vascular graft (TEVG) customized based on medical imaging and manufactured by 3-dimensional (3D) printing for a porcine model. METHODS: We acquired magnetic resonance angiography and 4-dimensional flow data for the native anatomy of the pigs (n = 2) to design a custom-made branched vascular graft of the pulmonary bifurcation. An optimal shape of the branched vascular graft was designed using a computer-aided design system informed by computational flow dynamics analysis. We manufactured and implanted the graft for pulmonary artery (PA) reconstruction in the porcine model. The graft was explanted at 4 weeks after implantation for further evaluation. RESULTS: The custom-made branched PA graft had a wall shear stress and pressure drop (PD) from the main PA to the branch PA comparable to the native vessel. At the end point, magnetic resonance imaging revealed comparable left/right pulmonary blood flow balance. PD from main PA to branch between before and after the graft implantation was unchanged. Immunohistochemistry showed evidence of endothelization and smooth muscle layer formation without calcification of the graft. CONCLUSIONS: Our animal model demonstrates the feasibility of designing and implanting image-guided, 3D-printed, customized grafts. These grafts can be designed to optimize both anatomic fit and hemodynamic properties. This study demonstrates the tremendous potential structural and physiological advantages of customized TEVGs in cardiac surgery.

Effects of simulated lateral canals on the accuracy of measurements by an electronic apex locator.

BACKGROUND: Accurate determination of the apical terminus plays a significant role in the success of root canal therapy, but accuracy may be affected by the presence of accessory canals. OBJECTIVE: To evaluate the accuracy of a ratio-based electronic apex locator for roots with simulated lateral canals. METHODS: Forty-two single-rooted human teeth were randomly divided into 2 groups. For each tooth, the root canal was prepared to the visually determined working length, and the working length was then measured with the Justy II electronic apex locator. Simulated lateral canals (of 2 different diameters) were then prepared at 3 mm (group A) or 6 mm (group B), and the working lengths were measured again with the same instrument. The measurements were analyzed by one-way analysis of variance. RESULTS: For both groups, there were no significant changes in working length after the creation of simulated canals (p > 0.05). CONCLUSION: Measurements obtained with the ratio-based electronic apex locator were not affected by the preparation of simulated lateral canals, and the instrument was able to accurately determine the location of the tooth apex.

Levels of PCDD/Fs in local and non-local food samples collected from a highly polluted area in Turkey.

A sampling and analysis program were conducted to determine the PCDD/F levels in various food samples collected in Kocaeli, one of the highly polluted areas in Turkey. Several food samples including animal (egg, chicken, meat and cow's milk) and plant (fruits, leafy vegetables, fruiting vegetables, rooty vegetables and flour) products were collected from both local and non-local (commercial) sources. The local food samples were taken from 20 sampling points selected by taking into account the location of the possible PCDD/F sources, dominant wind directions and representing the major part of the Turkish daily diet The PCDD/F concentrations in local eggs and milk samples were ranged from <1.16 to 10.94 pg TEQ g(-1) fat and from <0.43 to 3.29 pg TEQ g(-1) fat, respectively. On the other hand, the PCDD/F concentrations were measured between 0.28-1.81 pg EQ g(-1) fat in local meat samples and 0.15-2.92 pg TEQ g(-1) fat in local chicken samples. The PCDD/F concentrations in the plant products were relatively low and most of the congeners were measured below the detection limits except for the leafy vegetables. In addition, several commercial samples were analyzed in order to evaluate the differences of PCDD/F levels in samples collected from both the local and non-local sources. The results showed that the local animal products have higher PCDD/F concentrations than the non-local ones. Moreover, the commercial plant products showed undetectable concentrations for most of the congeners. Finally, the PCDD/F levels in some animal products were found to be higher than the national limit values.

The prevalence of molar incisor hypomineralization (MIH) in a group of children in a highly polluted urban region and a windfarm-green energy island.

BACKGROUND: Children's developing teeth may be sensitive to environmental pollutants such as polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans. The term molar incisor hypomineralization (MIH) was introduced to describe the clinical appearance of enamel hypomineralization of systemic origin affecting one or more permanent first molars (PFMs) that are associated frequently with affected incisors. AIM: The aim of this study was to determine the prevalance of MIH in children from the most industrialized and polluted region and the most green-energy island of Turkey. DESIGN: In September 2007, a retrospective study was initiated in two elementary schools: one, a group of children (N = 153) who fitted the criteria from Tavsancil, Kocaeli (N = 109) and the other from Bozcaada island, Canakkale (N = 44). The soil samples were collected from selected regions in order to determine the contamination levels in a heavily industrialized area and a non-industrialized area. RESULTS: Prevalance of MIH in children in Bozcaada island was 9.1%, while prevalance of MIH was 9.2% in Tavsancil. The PCDD/F levels in soil samples collected from Bozcaada and Tavsancil were determined as 1,12 and 8,4 I-TEQ ng/kg dry soil, respectively (P < 0.001). CONCLUSIONS: In this preliminary study with a small study population, prevalence of MIH did not seem to be associated with the levels of PCDD/Fs in the environment.