Mouse sperm energy restriction and recovery (SER) revealed novel metabolic pathways

Mammalian sperm must undergo capacitation to become fertilization-competent. While working on mice, we recently developed a new methodology for treating sperm in vitro, which results in higher rates of fertilization and embryo development after in vitro fertilization. Sperm incubated in media devoid of nutrients lose motility, although they remain viable. Upon re-adding energy substrates, sperm resume motility and become capacitated with improved functionality. Here, we explore how sperm energy restriction and recovery (SER) treatment affects sperm metabolism and capacitation-associated signaling. Using extracellular flux analysis and metabolite profiling and tracing via nuclear magnetic resonance (NMR) and mass spectrometry (MS), we found that the levels of many metabolites were altered during the starvation phase of SER. Of particular interest, two metabolites, AMP and L-carnitine, were significantly increased in energy-restricted sperm. Upon re-addition of glucose and initiation of capacitation, most metabolite levels recovered and closely mimic the levels observed in capacitating sperm that have not undergone starvation. In both control and SER-treated sperm, incubation under capacitating conditions upregulated glycolysis and oxidative phosphorylation. However, ATP levels were diminished, presumably reflecting the increased energy consumption during capacitation. Flux data following the fate of 13C glucose indicate that, similar to other cells with high glucose consumption rates, pyruvate is converted into 13C-lactate and, with lower efficiency, into 13C-acetate, which are then released into the incubation media. Furthermore, our metabolic flux data show that exogenously supplied glucose is converted into citrate, providing evidence that in sperm cells, as in somatic cells, glycolytic products can be converted into Krebs cycle metabolites

Aortic endovascular surgery

The continuous technological improvements of medical instruments and devices make minimally-invasive approaches a real and valid alternative to standard open surgery in more and more cases. Recent developments in cardiovascular surgery, in particular, have led to the success of thoracic endovascular repair (TEVAR) and transcatheter aortic valve implantation (TAVI). If, on the one hand, minimally-invasive interventions induce shorter hospital stays, faster recovery, and thus reduced costs, on the other hand, since, for obvious reasons, the direct control of the operator on the procedure is much more limited, operation planning and decision-making steps cover a crucial importance. In this context, computational tools have demonstrated to play a remarkable role, providing the surgeon with predictive information regarding the potential optimality of the treatment strategy. In the present chapter, we aim at describing recent developments of TEVAR and TAVI modeling, from both the structural and fluid-dynamic point of view

Benchmarking a Hemodynamics Application on Intel Based HPC Systems

Three different INTEL based HPC systems are used to benchmark an application of the LifeV library for running simulations of patient-specific cardiovascular hemodynamics. The targeted INTEL architectures rely on the Hashwell-Broadwell family of processors. Running times and scalability measures are collected with two real-size experiments. A third small-size test case is used to profile the code, exposing the effect of compiler vectorization, MPI efficiency and memory footprint. Profiling showed an unexpected low degree of floating point functional units usage, and a low percentage of effective vectorization. Extensive code redesign is likely necessary to best exploit the architectural features available in INTEL Knight Landing processors

Patient-specific computational fluid dynamics analysis of transcatheter aortic root replacement with chimney coronary grafts

OBJECTIVES: Transcatheter aortic root repair (TARR) consists of the simultaneous endovascular replacement of the aortic valve, the root and the proximal ascending aorta. The aim of the study is to set-up a computational model of TARR to explore the impact of the endovascular procedure on the coronary circulation supported by chimney grafts. METHODS: Computed tomography of a patient with dilated ascending aorta was segmented to obtain a 3-dimensional representation of the proximal thoracic aorta, including aortic root and supra-aortic branches. Computed assisted design tools were used to modify the geometry to create the post-procedural TARR configuration featuring the main aortic endograft integrated with 2 chimney grafts for coronary circulation. Computational Fluid Dynamics simulations were run in both pre- and post-procedural configurations using a pulsatile inflow and lumped parameter models at the outflows to simulate peripheral aortic and coronary circulation. Differences in coronary flow and pressure along the cardiac cycle were evaluated. RESULTS: After the virtual implant of the TARR device with coronary grafts, the flow became more organized and less recirculation was seen in the ascending aorta. Coronary perfusion was guaranteed with negligible flow differences between pre- and post-procedural configurations. However, despite being well perfused by chimney grafts, the procedure induces an increase of the pressure drop between the coronary ostia and the ascending aorta of 8 mmHg. CONCLUSIONS: The proposed numerical simulations, in the specific case under investigation, suggest that the TARR technique maintains coronary perfusion through the chimney grafts. This study calls for experimental validation and further analyses of the impact of TARR on cardiac afterload, decrease of aortic compliance and local pressure drop induced by the coronary chimney grafts

Computational simulation of TEVAR in the ascending aorta for optimal endograft selection: A patient-specific case study

Thoracic endovascular aortic repair of the ascending aorta is becoming an option for patients considered unfit for open surgery. Such an endovascular procedure requires careful pre-operative planning and the customization of prosthesis design. The patient-specific tailoring of the procedure may call for dedicated tools to investigate virtual treatment scenarios. Given such considerations, the present study shows a computational framework for choosing and deploying stent-grafts via Finite Element Analysis, by supporting the device sizing and selection in a real case dealing with the endovascular treatment of a pseudoaneurysm. In particular, three devices with various lengths and materials were examined. Two off-the-shelf devices were computationally tested: one composed of Stainless Steel rings with a nominal length of 60 mm and another one with Nitinol rings and a distal free flow extension, with a nominal length of 70 mm. In third place, a custom-made stent-graft, also with Nitinol rings and containing both proximal and distal bare extensions with a nominal length of 75 mm, was deployed. The latter solution based on patient morphology and virtually benchmarked in this simulation framework, enhanced the apposition to the wall by reducing the distance between the skirt and the vessel from more than 6 mm to less than 2 mm in the distal sealing zone. Our experience shows that in-silico simulations can help choosing the right endograft for the ascending aorta as well as the right deployment sequence. This process may also encourage vendors to develop new devices for cases where open repair is unfeasible

The Modified Arch Landing Areas Nomenclature identifies hostile zones for endograft deployment: a confirmatory biomechanical study in patients treated by thoracic endovascular aortic repair†

OBJECTIVES: Our goal was to confirm whether the Modified Arch Landing Areas Nomenclature (MALAN) for thoracic endovascular aortic repair, in which each landing area is described by indicating both the proximal landing zone (PLZ) and the type of arch (e.g. 0/I), identifies unfavourable landing zones for endograft deployment in diseased aortas. METHODS: Preoperative computed tomography angiography scans of 10 patients scheduled for thoracic endovascular aortic repair for aneurysm or penetrating ulcer of the arch and with a potential hostile PLZ were reviewed. Five had proximal deployment planned in MALAN area 3/III and 5, in MALAN area 2/III. The angulation of each PLZ was calculated. Computational fluid dynamics modelling was used to compute magnitude and orientation of pulsatile displacement forces in each PLZ. Normalized values based on PLZ areas (i.e. equivalent surface traction) were calculated. Results were compared to those obtained in healthy controls stratified by the MALAN. RESULTS: Angulation was severe (>60\ub0) in MALAN areas 3/III and 2/III, which was consistent with the findings obtained in healthy controls. Increased magnitude (P\u2009=\u20090.021) and unfavourable orientation (i.e. orthogonal to the longitudinal aortic axis) of equivalent surface traction (P\u2009=\u20090.011) was also found in these areas compared to the adjacent ones, following the same pattern seen in the controls. Adverse events related to proximal endograft performance were reported in 3/10 cases. CONCLUSIONS: This study confirms in diseased aortas initial proof-of-concept findings on the predictive value of the MALAN to identify landing areas with a geometric and haemodynamic environment hostile for thoracic endovascular aortic repair. These adverse biomechanical features may entail an increased risk of dismal endograft performance

Fast Approximate Quantification of Endovascular Stent Graft Displacement Forces in the Bovine Aortic Arch Variant

Purpose: Displacement forces (DF s) identify hostile landing zones for stent graft deployment in thoracic endovascular aortic repair (TEVAR). However, their use in TEVAR planning is hampered by the need for time-expensive computational fluid dynamics (CFD). We propose a novel fast-approximate computation of DF s merely exploiting aortic arch anatomy, as derived from the computed tomography (CT) and a measure of central aortic pressure. Materials and Methods: We tested the fast-approximate approach against CFD gold-standard in 34 subjects with the “bovine” aortic arch variant. For each dataset, a 3-dimensional (3D) model of the aortic arch lumen was reconstructed from computed tomography angiography and CFD then employed to compute DF s within the aortic proximal landing zones. To quantify fast-approximate DF s, the wall shear stress contribution to the DF was neglected and blood pressure space-distribution was averaged on the entire aortic wall to reliably approximate the patient-specific central blood pressure. Also, DF values were normalized on the corresponding proximal landing zone area to obtain the equivalent surface traction (EST). Results: Fast-approximate approach consistently reflected (r2=0.99, p<0.0001) the DF pattern obtained by CFD, with a −1.1% and 0.7° bias in DF s magnitude and orientation, respectively. The normalized EST progressively increased (p<0.0001) from zone 0 to zone 3 regardless of the type of arch, with proximal landing zone 3 showing significantly greater forces than zone 2 (p<0.0001). Upon DF normalization to the corresponding aortic surface, fast-approximate EST was decoupled in blood pressure and a dimensionless shape vector (S) reflecting aortic arch morphology. S showed a zone-specific pattern of orientation and proved a valid biomechanical blueprint of DF impact on the thoracic aortic wall. Conclusion: Requiring only a few seconds and quantifying clinically relevant biomechanical parameters of proximal landing zones for arch TEVAR, our method suits the real preoperative decision-making process. It paves the way toward analyzing large population of patients and hence to define threshold values for a future patient-specific preoperative TEVAR planning

Anomalous aortic origin of coronary artery biomechanical modeling: Toward clinical application

Objectives: Anomalous aortic origin of the coronary artery can be associated with sudden cardiac death and ischemic events. Anatomic static characteristics mainly dictated surgical indications, although adverse events are usually related to dynamic physical effort. We developed a computational model able to simulate anomalous coronary behavior, and we aimed to assess its clinical applicability and to investigate coronary characteristics at increasing loading stress conditions. Methods: We selected 5 patients with anomalous aortic origin of the coronary artery and 5 control subjects. For each of them, we construct a 3-dimensional model resembling the aortic root and coronary arteries based on 25 parameters obtained from computed tomography. Structural finite element analysis simulations were run to simulate pressure increasing in the aortic root during exercise (+40 mm Hg, +100 mm Hg with respect baseline condition, assumed at 80 mm Hg) and investigate coronary lumen characteristics. Results: The 25 parameters were obtainable in all subjects with a consistent interobserver agreement. In control subjects, the right coronary artery had a more significant lumen expansion at loading conditions compared with anomalous aortic origin of coronary artery (6%-19.2% vs 1.8%-8.1%, P = .008), which also showed an inability to expand within the intramural segment. Conclusions: The proposed anomalous aortic origin of coronary artery model is able to represent the pathogenic disease mechanism after being populated with patient-specific data. It can assess the impaired expansion of anomalous right coronary at loading conditions, a process that cannot be quantified in any clinical set-up. This first clinical application showed promising results on quantifying pathological behavior, potentially helping in patient-specific risk stratification