In Vitro Assessment of the Neuro-Compatibility of Fe-20Mn as a Potential Bioresorbable Material for Craniofacial Surgery.

Background and Objectives: Spring-assisted surgery is a popular option for the treatment of non-syndromic craniosynostosis. The main drawback of this procedure is the need for a second surgery for spring removal, which could be avoided if a distractor material could be metabolised over time. Iron-Manganese alloys (FeMn) have a good trade-off between degradation rate and strength; however, their biocompatibility is still debated. Materials and Methods: In this study, the neuro-compatibility of Fe-20Mn (wt.%) was assessed using standard assays. PC-12 cells were exposed to Fe-20Mn (wt.%) and stainless steel via indirect contact. To examine the cytotoxicity, a Cell Tox Green assay was carried out after 1, 2, and 3 days of incubation. Following differentiation, a neurite morphological examination after 1 and 7 days of incubation time was carried out. The degradation response in modified Hank's solution at 1, 3, and 7 days was investigated, too. Results: The cytotoxicity assay showed a higher toxicity of Fe-20Mn than stainless steel at earlier time points; however, at the latest time point, no differences were found. Neurite morphology was similar for cells exposed to Fe-20Mn and stainless steel. Conclusions: In conclusion, the Fe-20Mn alloy shows promising neuro-compatibility. Future studies will focus on in vivo studies to confirm the cellular response to Fe-20Mn.

Fetal face shape analysis from prenatal 3D ultrasound images.

3D ultrasound imaging of fetal faces has been predominantly confined to qualitative assessment. Many genetic conditions evade diagnosis and identification could assist with parental counselling, pregnancy management and neonatal care planning. We describe a methodology to build a shape model of the third trimester fetal face from 3D ultrasound and show how it can objectively describe morphological features and gestational-age related changes of normal fetal faces. 135 fetal face 3D ultrasound volumes (117 appropriately grown, 18 growth-restricted) of 24-34 weeks gestation were included. A 3D surface model of each face was obtained using a semi-automatic segmentation workflow. Size normalisation and rescaling was performed using a growth model giving the average size at every gestation. The model demonstrated a similar growth rate to standard head circumference reference charts. A landmark-free morphometry model was estimated to characterize shape differences using non-linear deformations of an idealized template face. Advancing gestation is associated with widening/fullness of the cheeks, contraction of the chin and deepening of the eyes. Fetal growth restriction is associated with a smaller average facial size but no morphological differences. This model may eventually be used as a reference to assist in the prenatal diagnosis of congenital anomalies with characteristic facial dysmorphisms.

Spring-assisted posterior vault expansion: a parametric study to improve the intracranial volume increase prediction.

Spring-assisted posterior vault expansion has been adopted at the London Great Ormond Street Hospital for Children to treat raised intracranial pressure in patients affected by syndromic craniosynostosis, a congenital calvarial anomaly causing the premature fusion of skull sutures. This procedure involves elastic distractors used to dynamically reshape the skull and increase the intracranial volume (ICV). In this study, we developed and validated a patient-specific model able to predict the ICV increase and carried out a parametric study to investigate the effect of surgical parameters on that final volume. Pre- and post-operative computed tomography data relative to 18 patients were processed to extract simplified patient-specific skull shape, replicate surgical cuts, and simulate spring expansion. A parametric study was performed to quantify each parameter's impact on the surgical outcome: for each patient, the osteotomy location was varied in a pre-defined range; local sensitivity of the predicted ICV to each parameter was analysed and compared. Results showed that the finite element model performed well in terms of post-operative ICV prediction and allowed for parametric optimization of surgical cuts. The study indicates how to optimize the ICV increase according to the type of procedure and provides indication on the most robust surgical strategy.

Towards a radiation free numerical modelling framework to predict spring assisted correction of scaphocephaly.

Sagittal Craniosynostosis (SC) is a congenital craniofacial malformation, involving premature sagittal suture ossification; spring-assisted cranioplasty (SAC) - insertion of metallic distractors for skull reshaping - is an established method for treating SC. Surgical outcomes are predictable using numerical modelling, however published methods rely on computed tomography (CT) scans availability, which are not routinely performed. We investigated a simplified method, based on radiation-free 3D stereophotogrammetry scans.Eight SAC patients (age 5.1 ± 0.4 months) with preoperative CT and 3D stereophotogrammetry scans were included. Information on osteotomies, spring model and post-operative spring opening were recorded. For each patient, two preoperative models (PREOP) were created: i) CT model and ii) S model, created by processing patient specific 3D surface scans using population averaged skin and skull thickness and suture locations. Each model was imported into ANSYS Mechanical (Analysis System Inc., Canonsburg, PA) to simulate spring expansion. Spring expansion and cranial index (CI - skull width over length) at times equivalent to immediate postop (POSTOP) and follow up (FU) were extracted and compared with in-vivo measurements.Overall expansion patterns were very similar for the 2 models at both POSTOP and FU. Both models had comparable outcomes when predicting spring expansion. Spring induced CI increase was similar, with a difference of 1.2%±0.8% for POSTOP and 1.6%±0.6% for FU.This work shows that a simplified model created from the head surface shape yields acceptable results in terms of spring expansion prediction. Further modelling refinements will allow the use of this predictive tool during preoperative planning.

Spring-assisted cranioplasty (SAC) ­insertion of metallic distractors helping skull reshaping ­ is a method for treating sagittal craniosynostosis, caused by premature sagittal suture closure. We present a method for predicting SAC outcomes, relying on radiation-free 3D stereophotogrammetry scans. Eight patients with preoperative CT and 3D stereophotogrammetry scans were recruited; results of spring expansion simulation were compared between models created using CT versus 3D scan data. Expansion patterns and extent of reshaping were very similar. This work proves that SAC preoperative planning can be carried out using non-ionising imaging. Further modelling refinements will allow clinical adoption of this predictive tool.

Current treatment strategies in managing side effects associated with domiciliary positive airway pressure (PAP) therapy for patients with sleep disordered breathing: A systematic review and meta-analysis.

Sleep disordered breathing is commonly treated with positive airway pressure therapy. Positive airway pressure therapy is delivered via a tight-fitting mask with common side effects including: leak, ineffective treatment, residual sleep disordered breathing, eye irritation, nasal congestion, pressure ulcers and poor concordance with therapy. This systematic review and meta-analysis aimed to identify the effectiveness of current treatment strategies for managing side effects associated with positive airway pressure therapy. Five databases were searched and 10,809 articles were screened, with 36 articles included in the review. Studies investigated: dressings, nasal spray/douche, chin straps, heated humidification and interfaces. No intervention either improved or detrimentally affected: positive airway pressure concordance, Epworth Sleepiness Score, residual apnoea hypopnea index or interface leak. The review was limited by study heterogeneity, particularly for outcome measures. Additionally, patient demographics were not reported, making it difficult to apply the findings to a broad clinical population. This review highlights the paucity of evidence supporting treatment strategies to manage side effects of positive airway pressure therapy.

Mapping the use of computational modelling and simulation in clinics: A survey.

In silico medicine describes the application of computational modelling and simulation (CM&S) to the study, diagnosis, treatment or prevention of a disease. Tremendous research advances have been achieved to facilitate the use of CM&S in clinical applications. Nevertheless, the uptake of CM&S in clinical practice is not always timely and accurately reflected in the literature. A clear view on the current awareness, actual usage and opinions from the clinicians is needed to identify barriers and opportunities for the future of in silico medicine. The aim of this study was capturing the state of CM&S in clinics by means of a survey toward the clinical community. Responses were collected online using the Virtual Physiological Human institute communication channels, engagement with clinical societies, hospitals and individual contacts, between 2020 and 2021. Statistical analyses were done with R. Participants (n = 163) responded from all over the world. Clinicians were mostly aged between 35 and 64 years-old, with heterogeneous levels of experience and areas of expertise (i.e., 48% cardiology, 13% musculoskeletal, 8% general surgery, 5% paediatrics). The CM&S terms "Personalised medicine" and "Patient-specific modelling" were the most well-known within the respondents. "In silico clinical trials" and "Digital Twin" were the least known. The familiarity with different methods depended on the medical specialty. CM&S was used in clinics mostly to plan interventions. To date, the usage frequency is still scarce. A well-recognized benefit associated to CM&S is the increased trust in planning procedures. Overall, the recorded level of trust for CM&S is high and not proportional to awareness level. The main barriers appear to be access to computing resources, perception that CM&S is slow. Importantly, clinicians see a role for CM&S expertise in their team in the future. This survey offers a snapshot of the current situation of CM&S in clinics. Although the sample size and representativity could be increased, the results provide the community with actionable data to build a responsible strategy for accelerating a positive uptake of in silico medicine. New iterations and follow-up activities will track the evolution of responses over time and contribute to strengthen the engagement with the medical community.

Shape-driven deep neural networks for fast acquisition of aortic 3D pressure and velocity flow fields.

Computational fluid dynamics (CFD) can be used to simulate vascular haemodynamics and analyse potential treatment options. CFD has shown to be beneficial in improving patient outcomes. However, the implementation of CFD for routine clinical use is yet to be realised. Barriers for CFD include high computational resources, specialist experience needed for designing simulation set-ups, and long processing times. The aim of this study was to explore the use of machine learning (ML) to replicate conventional aortic CFD with automatic and fast regression models. Data used to train/test the model consisted of 3,000 CFD simulations performed on synthetically generated 3D aortic shapes. These subjects were generated from a statistical shape model (SSM) built on real patient-specific aortas (N = 67). Inference performed on 200 test shapes resulted in average errors of 6.01% ±3.12 SD and 3.99% ±0.93 SD for pressure and velocity, respectively. Our ML-based models performed CFD in ∼0.075 seconds (4,000x faster than the solver). This proof-of-concept study shows that results from conventional vascular CFD can be reproduced using ML at a much faster rate, in an automatic process, and with reasonable accuracy.

Does the Mutation Type Affect the Response to Cranial Vault Expansion in Children With Apert Syndrome?

LEVEL OF EVIDENCE: III.

Comparison of Internal and External Distraction in Frontofacial Monobloc Advancement: A Three-Dimensional Quantification.

BACKGROUND: Crouzon syndrome is characterized by complex craniosynostosis and midfacial hypoplasia. Where frontofacial monobloc advancement (FFMBA) is indicated, the method of distraction used to achieve advancement holds an element of equipoise. This two-center retrospective cohort study quantifies the movements produced by internal or external distraction methods used for FFMBA. Using shape analysis, this study evaluates whether the different distraction forces cause plastic deformity of the frontofacial segment, producing distinct morphologic outcomes. METHODS: Patients with Crouzon syndrome who underwent FFMBA with internal distraction [Hôpital Necker-Enfants Malades (Paris, France)] or external distraction [Great Ormond Street Hospital for Children (London, United Kingdom)] were compared. Digital Imaging and Communications in Medicine files of preoperative and postoperative computed tomographic scans were converted to three-dimensional bone meshes and skeletal movements were assessed using nonrigid iterative closest point registration. Displacements were visualized using color maps and statistical analysis of the vectors was undertaken. RESULTS: Fifty-one patients met the strict inclusion criteria. Twenty-five underwent FFMBA with external distraction and 26 with internal distraction. External distraction provides a preferential midfacial advancement, whereas internal distractors produce a more positive movement at the lateral orbital rim. This confers good orbital protection but does not advance the central midface to the same extent. Vector analysis confirmed this to be statistically significant ( P < 0.01). CONCLUSIONS: Morphologic changes resulting from monobloc surgery differ depending on the distraction technique used. Although the relative merits of internal and external distraction still stand, it may be that external distraction is more suited to addressing the midfacial biconcavity seen in syndromic craniosynostosis. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Two-Center Review of Posterior Vault Expansion following a Staged or Expectant Treatment of Crouzon and Apert Craniosynostosis.

BACKGROUND: The timing of posterior cranial expansion for the management of intracranial pressure can be "staged" by age and dysmorphology or "expectant" by pressure monitoring. The authors report shared outcome measures from one center performing posterior vault remodeling (PCVR) or distraction (PVDO) following a staged approach and another performing spring-assisted expansion (SAPVE) following an expectant protocol. METHODS: Apert or Crouzon syndrome patients who underwent posterior expansion younger than 2 years were included. Perioperative outcomes and subsequent cranial operations were recorded up to last follow-up and intracranial volume changes measured and adjusted using growth curves. RESULTS: Thirty-eight patients were included. Following the expectant protocol, Apert patients underwent SAPVE at a younger age (8 months) than Crouzon patients (16 months). The initial surgery time was shorter but total operative time, including device removal, was longer for PVDO (3 hours 52 minutes) and SAPVE (4 hours 34 minutes) than for PCVR (3 hours 24 minutes). Growth-adjusted volume increase was significant and comparable. Fourteen percent of PCVR, 33% of PVDO, and 11% of SAPVE cases had complications, but without long-term deficits. Following the staged approach, 5% underwent only PVDO, 85% had a staged posterior followed by anterior surgery, and 10% required a third expansion. Following the expectant approach, 42% of patients had only posterior expansion at last follow-up, 32% had a secondary cranial surgery, and 26% had a third cranial expansion. CONCLUSION: Two approaches involving posterior vault expansion in young syndromic patients using three techniques resulted in comparable early volume expansion and complication profiles. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

The Accuracy of Computer-Assisted Surgical Planning in Predicting Soft Tissue Responses After Le Fort I Osteotomy: Retrospective Analysis.

PURPOSE: Mismatch between preoperative planning and surgical outcome in maxillofacial surgery relate to on-table replication of presurgical planning and predictive algorithm inaccuracy: software error was hereby decoupled from planning inaccuracy to assess a commercial software. The hypothesis was that soft tissue prediction error would be minimized if the surgical procedure was replicated precisely as planned and is independent of the extent of bone repositioning. MATERIALS AND METHODS: Cone-beam computed tomography scans of 16 Le Fort I osteotomy patients were collected at Boston Children's Hospital. Preoperative and postoperative models of bone and soft tissue were constructed and the maxilla repositioning was replicated. Each model was subdivided into 6 regions: mouth, nose, eyes, and cheeks. Soft tissue prediction (performed using Proplan CMF-Materialise) for each patient was compared with the relative postoperative reconstruction and error was determined. P <0.05 was considered significant. RESULTS: Le Fort I segment repositioning was replicated within 0.70±0.18 mm. The highest prediction error was found in the mouth (1.49±0.77 mm) followed by the cheeks (0.98±0.34 mm), nose (0.86±0.23 mm), and eyes (0.76±0.32). Prediction error on cheeks correlated significantly with mouth ( r =0.63, P < 0.01) and nose ( r =0.67, P < 0.01). Mouth prediction error correlated with total advancement ( r =0.52, P =0.04). CONCLUSIONS: ProPlan CMF is a useful outcome prediction tool; however, accuracy decreases with the extent of maxillary advancement even when errors in surgical replication are minimized.

Use of virtual reality in complex double outlet right ventricle cases.

Virtual reality has been incorporated into clinical practice for planning complex congenital cardiac operations at the Great Ormond Street Hospital for Children since 2018 [1]. Virtual reality allows for 3-dimensional exploration of patient-specific models, created through the segmentation of 3-dimensional imaging data sets. Along with 3-dimensional printed models and 3-dimensional PDFs, this technology has enabled a new approach in planning and reviewing surgical interventions. It is particularly important in intracardiac repairs involving ventricular septal defects [2] and double outlet right ventricle cases presenting with various phenotypes of interventricular communication [3,4]. We present the virtual reality environment of two complex cases of double outlet right ventricle, illustrating the potential of virtual reality as a clinical tool to aid anatomical understanding and surgical planning of complex congenital heart disease.

Automatic segmentation of the great arteries for computational hemodynamic assessment.

BACKGROUND: Computational fluid dynamics (CFD) is increasingly used for the assessment of blood flow conditions in patients with congenital heart disease (CHD). This requires patient-specific anatomy, typically obtained from segmented 3D cardiovascular magnetic resonance (CMR) images. However, segmentation is time-consuming and requires expert input. This study aims to develop and validate a machine learning (ML) method for segmentation of the aorta and pulmonary arteries for CFD studies. METHODS: 90 CHD patients were retrospectively selected for this study. 3D CMR images were manually segmented to obtain ground-truth (GT) background, aorta and pulmonary artery labels. These were used to train and optimize a U-Net model, using a 70-10-10 train-validation-test split. Segmentation performance was primarily evaluated using Dice score. CFD simulations were set up from GT and ML segmentations using a semi-automatic meshing and simulation pipeline. Mean pressure and velocity fields across 99 planes along the vessel centrelines were extracted, and a mean average percentage error (MAPE) was calculated for each vessel pair (ML vs GT). A second observer (SO) segmented the test dataset for assessment of inter-observer variability. Friedman tests were used to compare ML vs GT, SO vs GT and ML vs SO metrics, and pressure/velocity field errors. RESULTS: The network's Dice score (ML vs GT) was 0.945 (interquartile range: 0.929-0.955) for the aorta and 0.885 (0.851-0.899) for the pulmonary arteries. Differences with the inter-observer Dice score (SO vs GT) and ML vs SO Dice scores were not statistically significant for either aorta or pulmonary arteries (p = 0.741, p = 0.061). The ML vs GT MAPEs for pressure and velocity in the aorta were 10.1% (8.5-15.7%) and 4.1% (3.1-6.9%), respectively, and for the pulmonary arteries 14.6% (11.5-23.2%) and 6.3% (4.3-7.9%), respectively. Inter-observer (SO vs GT) and ML vs SO pressure and velocity MAPEs were of a similar magnitude to ML vs GT (p > 0.2). CONCLUSIONS: ML can successfully segment the great vessels for CFD, with errors similar to inter-observer variability. This fast, automatic method reduces the time and effort needed for CFD analysis, making it more attractive for routine clinical use.

Computational investigation of the haemodynamics shows criticalities of central venous lines used for chronic haemodialysis in children.

Background: Haemodialysis is a life-saving treatment for children with kidney failure. The majority of children have haemodialysis through central venous lines (CVLs). The use of CVLs in pediatric patients is often associated to complications which can lead to their replacement. The aim of this study is to investigate haemodynamics of pediatric CVLs to highlight the criticalities of different line designs. Methods: Four models of CVLs for pediatric use were included in this study. The selected devices varied in terms of design and sizes (from 6.5 Fr to 14 Fr). Accurate 3D models of CVLs were reconstructed from high-resolution images including venous and arterial lumens, tips and side holes. Computational fluid dynamics (CFD) analyses were carried out to simulate pediatric working conditions of CVLs in ideal and anatomically relevant conditions. Results: The arterial lumens of all tested CVLs showed the most critical conditions with the majority of blood flowing through the side-holes. A zone of low flow was identified at the lines' tip. The highest shear stresses distribution (>10 Pa) was found in the 8 Fr line while the highest platelet lysis index in the 10 Fr model. The analysis on the anatomical geometry showed an increase in wall shear stress measured in the 10 F model compared to the idealised configuration. Similarly, in anatomical models an increased disturbance and velocity of the flow was found inside the vein after line placement. Conclusion: This study provided a numerical characterization of fluid dynamics in pediatric CVLs highlighting performance criticalities (i.e. high shear stresses and areas of stagnation) associated to specific sizes (8 Fr and 10 Fr) and conditions (i.e. anatomical test).

Relationship between Pulmonary Regurgitation and Ventriculo-Arterial Interactions in Patients with Post-Early Repair of Tetralogy of Fallot: Insights from Wave-Intensity Analysis.

This study aimed to investigate the effect of pulmonary regurgitation (PR) on left ventricular ventriculo-arterial (VA) coupling in patients with repaired tetralogy of Fallot (ToF). It was hypothesised that increasing PR severity results in a smaller forward compression wave (FCW) peak in the aortic wave intensity, because of right-to-left ventricular interactions. The use of cardiovascular magnetic resonance (CMR)-derived wave-intensity analysis provided a non-invasive comparison between patients with varying PR degrees. A total of n = 201 patients were studied and both hemodynamic and wave-intensity data were compared. Wave-intensity peaks and areas of the forward compression and forward expansion waves were calculated as surrogates of ventricular function. Any extent of PR resulted in a significant reduction in the FCW peak. A correlation was found between aortic distensibility and the FCW peak, suggesting unfavourable (VA) coupling in patients that also present stiffer ascending aortas. Data suggest that VA coupling is affected by increased impedance.

Assessment of cardiac dimensions in children diagnosed with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is an inherited autosomal dominant heart disease, characterized by increased left ventricular wall thickness and abnormal loading conditions. Imaging modalities are the first choice for diagnosis and risk stratification. Although heart dimensions have been characterized widely in HCM adults from cardiac imaging, there is limited information about children affected by HCM. The aim of this study is to evaluate left ventricular function and left heart dimensions in a small population of children diagnosed with HCM. METHODS: A total of 16 (seven male, nine female) pediatric patients with an average age of 14.0 ± 2.5 years diagnosed with HCM at Great Ormond Street Hospital for Children were included in this study. Cardiac magnetic resonance (CMR) images were used to measure left and right ventricular dimensions, and septal and left ventricular free wall thicknesses in Simpleware ScanIP. The gender groups were compared using student t-test or non-parametric Mann-Whitney U-test depending on the sample distribution. RESULTS: Differences in heart rate, left ventricular end-diastolic volume and end-diastolic volume index, left ventricular stroke volume and stroke volume index, left ventricular end-systolic long axis length, left ventricular end-systolic long axis length index, left ventricular end-diastolic mid-cavity diameter, left ventricular end-diastolic free wall thickness, left ventricular end-diastolic free wall thickness index, right ventricular end-diastolic long axis length were statistically significant in males and females. CONCLUSION: Left ventricular wall and intraventricular septal thickness increase affecting left ventricle cavity dimensions and there may be differences in anatomical and physiological parameters in males and females affected by HCM.

Aortic Arch Phenotypes in Double Outlet Right Ventricle (DORV)-Implications for Surgery and Multi-Modal Imaging.

Abnormal aortic arches (AAAs) cover a spectrum of malformations, including abnormal laterality, branching patterns, and flow-limiting narrowing, which themselves vary from tubular hypoplasia, through discrete coarctation, to complete interruption of the arch. Neonatal surgery within the first days of life is necessary for most of these morphologies. Patch aortoplasty is widely used as it can offer a good haemodynamic result, being tailored to each combination of presenting pathologies. Our study hypothesis was that arch malformations are frequent in DORV and exhibit a plethora of phenotypes. We reviewed 54 post-mortem heart specimens from the UCL Cardiac Archive, analysing morphological features that would potentially influence the surgical repair, and taking relevant measurements of surgical importance. AAAs were found in half of the specimens, including 22.2% with aortic arch narrowing. In total, 70% and 30% of narrow arches had a subpulmonary and subaortic interventricular defect, respectively. Z-scores were significantly negative for all cases with tubular hypoplasia. We concluded that arch malformations are a common finding among hearts with DORV. Surgery on the neonatal aortic arch in DORV, performed in conjunction with other interventions that aim to balance pulmonary to systemic flow (Qp/Qs), should be anticipated and form an important part of multi-modal imaging.

Growth patterns and shape development of the paediatric mandible - A 3D statistical model.

Background/aim: To develop a 3D morphable model of the normal paediatric mandible to analyse shape development and growth patterns for males and females. Methods: Computed tomography (CT) data was collected for 242 healthy children referred for CT scan between 2011 and 2018 aged between 0 and 47 months (mean, 20.6 ± 13.4 months, 59.9% male). Thresholding techniques were used to segment the mandible from the CT scans. All mandible meshes were annotated using a defined set of 52 landmarks and processed such that all meshes followed a consistent triangulation. Following this, the mandible meshes were rigidly aligned to remove translation and rotation effects, while size effects were retained. Principal component analysis (PCA) was applied to the processed meshes to construct a generative 3D morphable model. Partial least squares (PLS) regression was also applied to the processed data to extract the shape modes with which to evaluate shape differences for age and sex. Growth curves were constructed for anthropometric measurements. Results: A 3D morphable model of the paediatric mandible was constructed and validated with good generalisation, compactness, and specificity. Growth curves of the assessed anthropometric measurements were plotted without significant differences between male and female subjects. The first principal component was dominated by size effects and is highly correlated with age at time of scan (Spearman's r = 0.94, p < 0.01). As with PCA, the first extracted PLS mode captures much of the size variation within the dataset and is highly correlated with age (Spearman's r = -0.94, p < 0.01). Little correlation was observed between extracted shape modes and sex with either PCA or PLS for this study population. Conclusion: The presented 3D morphable model of the paediatric mandible enables an understanding of mandibular shape development and variation by age and sex. It allowed for the construction of growth curves, which contains valuable information that can be used to enhance our understanding of various disorders that affect the mandibular development. Knowledge of shape changes in the growing mandible has potential to improve diagnostic accuracy for craniofacial conditions that impact the mandibular morphology, objective evaluation, surgical planning, and patient follow-up.

Beating heart implantation of transventricular artificial cordae: How can access site selection and leaflet insertion improve mitral regurgitation correction?

NeoChord-DS1000-System (NC) and The Harpoon-Mitral-Repair-System (H-MRS) are two trans-apical chordal implantation devices developed for the treatment of degenerative mitral valve (MV) regurgitation (DMR) either if as Fibroelastic-Deficiency (FED), Forma-Frusta (FF), or Barlow (B) presentation. The aim of this study is to evaluate some of the advantages and disadvantages of these two different devices by performing numerical simulation analyses focused on different transventricular access sites in all subsets of DMR presentations. By applying a novel approach for the development of patient-specific MV domains we worked out a set of numerical simulations of the artificial chordae implantation. Different leaflet insertions and ventricle access sites were investigated, and resulting contact-area (CA), tensioning-forces (F) and leaflet's stress (LS) were calculated. The analyses showed that: i) NC-approach maintains low LS when performed with a posterior access site and optimizes the overlap between the leaflets at the systolic peak; ii) H-MRS-system presents better results in case of a more anterior ventricular entry site; however, for FED prolapse large variation of F and LS with respect to NC-approach are found; iii) an accidental contact between artificial sutures and the anterior leaflet may occur when valve function is restored through an excessive anterior access site. Present findings set light on specific technical aspects of transapical off-pump chords implantation, either performed with NC and H-MRS systems and highlight the advantages and disadvantages proper to the two devices. Our study also paves the basis for a systematic application of computational methodology, in order to plan a patient-specific mini-invasive approach thus maximizing the outcomes.