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Respiratory tract infections play a considerable pathogenetic role in many cases of sudden infant death (SID). Frequently, clinicians encounter difficulties in diagnosing the disease because of its often unspecific clinical and radiological presentation. We report three cases of sudden unexpected death in infancy (SUDI), involving two males and one female admitted to hospital due to mild respiratory distress. In all three cases, complete post-mortem investigations were successful in uncovering interstitial lung disease as the cause of death. These cases highlight the key role of infection-related interstitial lung diseases in the pathogenesis of some currently unexplained SUDI/SIDS and the diagnostic difficulties due to the variable clinical and histological pattern, thereby explaining the importance of performing complete post-mortem investigations whenever an infant dies suddenly and unexpectedly.

Abusive head trauma (AHT) represents a commonly misdiagnosed condition. In fact, there is no pathognomonic sign that allows the diagnosis in children. Therefore, it is such an important medico-legal challenge to evaluate reliable diagnostic tools. The aim of this review is to evaluate the current scientific evidence to assess what the best practice is in order to diagnose AHT. We have focused particularly on evaluating the importance of circumstantial evidence, clinical history, the use of postmortem radiological examinations (such as CT and MRI), and the performance of the autopsy. After autopsy, histological examination of the eye and brain play an important role, with attention paid to correlation with symptoms found in vivo.

Post-mortem diagnosis of sepsis is often very difficult to make, especially in the elderly affected by multiple comorbidities. However, clinical evaluation following histology, immunohistochemistry, microbiological tests, immunoassays and proteomics can improve reliability of this post-mortem diagnosis.

Anatomic landmark detection is crucial during preoperative planning of transcatheter aortic valve implantation (TAVI) to select the proper device size and assess the risk of complications. The detection is currently a time-consuming manual process influenced by the image quality and subject to operator variability. In this work, we propose a novel automatic method to detect the relevant aortic landmarks from MDCT images using deep learning techniques. We trained three convolutional neural networks (CNNs) with 344 multidetector computed tomography (MDCT) acquisitions to detect five anatomical landmarks relevant for TAVI planning: the three basal attachment points of the aortic valve leaflets and the left and right coronary ostia. The detection strategy used these three CNN models to analyse a single MDCT image and yield three segmentation volumes as output. These segmentation volumes were averaged into one final segmentation volume, and the final predicted landmarks were obtained during a postprocessing step. Finally, we constructed the aortic annular plane, defined by the three predicted hinge points, and measured the distances from this plane to the predicted coronary ostia (i.e., coronary height). The methodology was validated on 100 patients. The automatic landmark detection was able to detect all the landmarks and showed high accuracy as the median distance between the ground truth and predictions is lower than the interobserver variations (1.5 mm [1.1-2.1], 2.0 mm [1.3-2.8] with a paired difference -0.5 ± 1.3 mm and p value <0.001). Furthermore, a high correlation is observed between predicted and manually measured coronary heights (for both R 2  = 0.8). The image analysis time per patient was below one second. The proposed method is accurate, fast, and reproducible. Embedding this tool based on deep learning in the preoperative planning routine may have an impact in the TAVI environments by reducing the time and cost and improving accuracy., Competing Interests: The following disclosures have been reported by the authors: Peter de Jaegere is a consultant for Medtronic. Johan Bosmans is a consultant for Medtronic. Ole De Backer has been a consultant for Abbott. Matthieu De Beule and Peter Mortier are shareholders of FEops. Francesco Iannaccone is an employee of FEops. Joni Dambre and Patricio Astudillo have no conflicts of interest to declare., (Copyright © 2020 Patricio Astudillo et al.)

A total of 420 day old chicks were divided into seven groups (5 replicates of 12 chicks/group) fed isoproteic and isoenergetic diets. The control group was fed diets containing 0.50%, 0.45% and 0.40% of non-phytic phosphorous (nPP) in starter (1-35), grower (37-56) and finisher (57-64 d) periods, respectively. The three intermediate nPP (IntnPP) groups were fed diets with 0.40%, 0.35% and 0.30% nPP according to the growth period and were submitted to three dietary treatments: unsupplemented; supplemented with 500 FTU/kg diet of an Aspergillus niger phytase (IntnPP&#95;fp) and supplemented with 500 FTU/kg diet of an Escherichia coli phytase (IntnPP&#95;bp). The three low nPP groups fed diets contained 0.30%, 0.25% and 0.20% nPP and were submitted to the same dietary treatments than IntnPP to obtain LnPP, LnPP&#95;fp and LnPP&#95;bp groups. IntnPP and LnPP groups had lower body weight gain and feed, crude protein (CP) and metabolizable energy (ME) intake ( p < 0.05) than the control. Feed conversion ratio of IntnPP was more favorable ( p < 0.01) than the LnPP group. CP and ME conversion ratios worsened ( p < 0.01) in IntnPP and LnPP groups in comparison to the control. The nPP conversion ratio improved ( p < 0.01) from the control to the LnPP group. Fungal phytase reduced ( p < 0.05) feed, CP, ME and nPP intake than the bacterial one. IntnPP and LnPP diets had a lower digestibility of CP ( p < 0.01) and CF ( p = 0.01) than the control. IntnPP and LnPP groups showed a higher ( p < 0.05) economic efficiency than the control. Blood total protein was the lowest ( p < 0.05) in the LnPP group, the control group showed the lowest ( p < 0.05) level of albumin and IntnPP group had the lowest ( p < 0.01) globulin level. The use of bacterial phytase increased ( p < 0.01) total protein and globulin and decreased ( p < 0.05) the plasma cholesterol in comparison to fungal phytase. Decreasing nPP levels in colored slow-growing broilers diet negatively affects growth performance and the use of phytase can partly alleviate these negative effects, but the efficiency of different enzyme sources (bacterial or fungal) was tied to the dietary nPP levels.

Background: Percutaneous left atrial appendage (LAA) closure can be optimised through diligent preprocedural planning. Cardiac computational tomography (CCT) is increasingly recognised as a valuable tool in this process. A CCT-based computational model (FEops HEARTguide™, Belgium) has been developed to simulate the deployment of the two most commonly used LAA closure devices into patient-specific LAA anatomies., Objective: The aim of this study was to validate this computational model based on real-life percutaneous LAA closure procedures and post-procedural CCT imaging., Methods: Thirty patients having undergone LAA closure (Amulet™ n = 15, Watchman™ n = 15) and having a pre- and post-procedural CCT-scan were selected for this validation study. Virtually implanted devices were directly compared to actual implants for device frame deformation and LAA wall apposition., Results: The coefficient of determination (R 2 ) and the difference in measurements between model and actual device (area, perimeter, minimum diameter, maximum diameter) were ≥0.91 and ≤ 5%, respectively. For both device types, the correlation coefficient between predicted and observed measurements was higher than 0.90. Furthermore, predicted device apposition correlated well with observed leaks based on post-procedural CCT., Conclusion: Computational modelling accurately predicts LAA closure device deformation and apposition and may therefore potentiate more accurate LAA closure device sizing and better preprocedural planning., (Copyright © 2020 Society of Cardiovascular Computed Tomography. All rights reserved.)

Herein we report an unusual case of sudden death occurring in a 65 year old woman during a minor oral surgery. The subject, who had a medically treated anxiety, had a history of two reversible left ventricle dysfunction episodes consistent with recurrent Takotsubo Syndrome that had occurred seven and six years before, respectively. She also suffered from moderate, well treated post-menopausal systemic hypertension. Post-mortem examination showed apical biventricular ballooning of the heart with no cardiac rupture, coronary artery lesion or other cardiac/extra-cardiac disease. Toxicological tests and forensic investigations excluded unnatural causes of death, including pharmacological or iatrogenic causes related to medical malpractice. Only non-specific contraction bands and mild hypertrophy were observed by histology in the left ventricle myocytes. Takotsubo syndrome is usually an acute and reversible heart failure syndrome with acute left ventricle apex ballooning, no coronary artery disease or other macroscopic or microscopic cardiac changes; physical or emotional stress are well known triggering factors. Nevertheless, recurrent forms, major cardiac adverse events and even sudden death may occur in a minority of cases, meaning that a diagnosis of Takotsubo syndrome must be considered in cases of sudden death and in forensic investigations.

Background: Pain physicians have long been seen as subspecialists that commonly prescribe opioid medications, but the reality exists that primary care, oncologists, and surgical subspecialists find themselves embroiled in these clinical decisions just as frequently. It is a reasonable hope that pain physicians emerge as leaders in navigating these muddy waters, and the most important time to engrave practice standards is during clinical training., Objectives: It was our hope to survey Accreditation Council for Graduate Medical Education (ACGME) pain fellowship programs throughout the United States in regard to practice behaviors for opioid prescribing in chronic noncancer pain (CNCP), and to assess what future pain physicians are learning during their training., Study Design: We developed a succinct, 8-question survey that attempted to gauge several aspects of opioid prescribing practices for CNCP. A survey was prepared in electronic format and e-mailed to each program director or chair of every ACGME accredited pain program in the United States., Methods: Our results were anonymously collected and percentage of response to each question was presented in bar graph format. The survey was prepared and initially sent out in November 2017 and intermittently redistributed through April 2018., Results: Of the 117 surveys sent through Survey Monkey, 42 responses were returned and collected, 39 fully completed surveys, and 3 partial completions, an estimate of roughly one-third of US ACGME pain fellowship programs., Limitations: Completion of our survey was voluntary, roughly 35% of ACGME programs submitted a response., Conclusions: Data displayed in collected responses illustrate that although there is variance in opioid prescribing practices for CNCP, many programs are limiting what they use opioids for and have substantial nonopioid pharmacologic and or interventional aspects to their practice. Future pain physicians throughout the country are learning diverse methods of pain management, with opioids being only a part of their toolbox., Key Words: Opioids, ACGME, pain management fellowship, guidelines, teaching.

Purpose : To assess the efficacy and tolerability of interferon (IFN) alpha-2a in post-infectious uveitis secondary to presumed intraocular tuberculosis (IOTB). Methods : Patients with chronic uveitis secondary to presumed IOTB who, after completing an antitubercular treatment, showed poor response to treatments or recurred after tapering oral corticosteroids to ≤7.5 mg/day were enrolled. All patients were treated with IFN alpha-2a subcutaneous injections. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), and inflammatory signs were compared between baseline and follow-up visits up to six months. Results : Twelve eyes (six patients) were enrolled. Mean BCVA improved from 0.64 ± 0.55 logMAR at baseline to 0.32 ± 0.31 logMAR at 6 months ( p  = 0.03). Mean CRT decreased from 372 ± 132.2 μm to 274.66 ± 34.9 μm at six months ( p  = 0.01). Inflammatory signs (vitritis, vasculitis) also decreased overtime. No major complications or tuberculosis reactivations were recorded. Conclusions : IFN alpha-2a was efficacious and safe in treating chronic post-infectious uveitis secondary to presumed IOTB.

Quaternary ammonium compounds containing N-trimethylamino moiety, such as choline derivatives and carnitine, abundant in meat and dairy products, are metabolic precursors of trimethylamine (TMA). A similar fate is reported for N ε -trimethyllysine and γ-butyrobetaine. With the aim at investigating the metabolic profile of such metabolites in most employed animal dietary sources, HPLC-ESI-MS/MS analyses on ruminant and non-ruminant milk and meat were performed. Results demonstrate, for the first time, the presence of δ-valerobetaine, occurring at levels higher than γ-butyrobetaine in all ruminant samples compared to non-ruminants. Demonstration of δ-valerobetaine metabolic origin, surprisingly, showed that it originates from rumen through the transformation of dietary N ε -trimethyllysine. These results highlight our previous findings showing the ubiquity of free N ε -trimethyllysine in vegetable kingdom. Furthermore, δ-valerobetaine, similarly to γ-butyrobetaine, can be degraded by host gut microbiota producing TMA, precursor of the proatherogenic trimethylamine N-oxide (TMAO), unveiling its possible role in the biosynthetic route of TMAO., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The combined effect of six consecutive timed artificial inseminations (TAIs) on pregnancy rates, following two different synchronization protocols on buffalo heifers, over a period of seven months typically characterized by low breeding performances, were investigated in this study. A total of 2189 TAIs were performed on 1463 buffalo heifers within a large buffalo farm in the south of Italy. Individual animals were allowed to undergo synchronization protocol (either a slightly modified Ovsynch or Progesterone treatment) and TAI until establishment of pregnancy or else for not more than six consecutive times. Semen of seven proven bulls was used throughout the study, which was carried out from March to September of the same year. Therefore, other than the effect given by consecutive TAIs over time, a monthly and a seasonal effect could also be tested, once the entire period was split into a Low Breeding Season (LBS) from March to June, and a Transition to Breeding Season (TBS) from July to September. From the data recorded in this study and the statistical analysis performed, it can be stated that the two protocols for the synchronization of ovulation were similar in efficiency in determining pregnancies with an overall fertility rate of 89.4% when the comparison was run both on a monthly basis or when months were grouped into two different seasons. In addition, an average of 1.83 AI/pregnancy was reported, slightly higher for the Ovsynch when compared to the Progesterone protocol: 1.91 vs 1.70, respectively. Finally, when considering the number of progressive synchronization treatments implemented over time as covariate, neither Ovsynch nor Progesterone treatment significantly affected pregnancy rates following the first of the six synchronization sessions. However, repeating the synchronization procedure, the progesterone based protocol resulted in significantly higher probability of success in terms of established pregnancies during the second and third re-synchronization sessions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: Stent implantation for the treatment of aortic coarctation has become a standard approach for the management of older children and adults. Criteria for optimal stent design and construction remain undefined. This study used computational modelling to compare the performance of two generations of the Cheatham-Platinum stent (NuMED, Hopkinton, NY, USA) deployed in aortic coarctation using finite element analysis., Design: Three-dimensional models of both stents, reverse engineered from microCT scans, were implanted in the aortic model of one representative patient. They were virtually expanded in the vessel with a 16 mm balloon and a pressure of 2 atm., Results: The conventional stent foreshortened to 96.5% of its initial length, whereas the new stent to 99.2% of its initial length. Diameters in 15 slices across the conventional stent were 11.6-15 mm (median 14.2 mm) and slightly higher across the new stent: 10.7-15.3 mm (median 14.5 mm) (p= 0.021). Apposition to the vessel wall was similar: conventional stent 31.1% and new stent 28.6% of total stent area., Conclusions: The new design Cheatham-Platinum stent showed similar deployment results compared to the conventional design. The new stent design showed slightly higher expansion, using the same delivery balloon. Patient-specific computational models can be used for virtual implantation of new aortic stents and promise to inform subsequent in vivo trials.

In the original publication of the article, Tables 2 and 3 were published with error. The correct tables are provided below (Tables 2, 3). The original version of the article has also been corrected.

Background: The extent to which pressure generated by the valve on the aortic root plays a role in the genesis of conduction abnormalities after transcatheter aortic valve replacement (TAVR) is unknown. This study elucidates the role of contact pressure and contact pressure area in the development of conduction abnormalities after TAVR using patient-specific computer simulations., Methods and Results: Finite-element computer simulations were performed to simulate TAVR of 112 patients who had undergone TAVR with the self-expanding CoreValve/Evolut R valve. On the basis of preoperative multi-slice computed tomography, a patient-specific region of the aortic root containing the atrioventricular conduction system was determined by identifying the membranous septum. Contact pressure and contact pressure index (percentage of area subjected to pressure) were quantified and compared in patients with and without new conduction abnormalities. Sixty-two patients (55%) developed a new left bundle branch block or a high-degree atrioventricular block after TAVR. Maximum contact pressure and contact pressure index (median [interquartile range]) were significantly higher in patients with compared with those without new conduction abnormalities (0.51 MPa [0.43-0.70 MPa] and 33% [22%-44%], respectively, versus 0.29 MPa [0.06-0.50 MPa] and 12% [1%-28%]). By multivariable regression analysis, only maximum contact pressure (odds ratio, 1.35; confidence interval, 1.1-1.7; P =0.01) and contact pressure index (odds ratio, 1.52; confidence interval, 1.1-2.1; P =0.01) were identified as independent predictors for conduction abnormalities, but not implantation depth., Conclusions: Patient-specific computer simulations revealed that maximum contact pressure and contact pressure index are both associated with new conduction abnormalities after CoreValve/Evolut R implantation and can predict which patient will have conduction abnormalities., (© 2018 American Heart Association, Inc.)

Despite all technological innovations in esophageal stent design over the past 20 years, the association between the stent design's mechanical behavior and its effect on the clinical outcome has not yet been thoroughly explored. A parametric numerical model of a commercially available esophageal bioresorbable polymeric braided wire stent is set up, accounting for stent design aspects such as braiding angle, strut material, wire thickness, degradation and friction between the wires comprising a predictive tool on the device's mechanical behavior. Combining this tool with complex multilayered numerical models of the pathological in vivo stressed, actively contracting and buckling esophagus could provide clinicians and engineers with a patient-specific window into the mechanical aspects of stent-based esophageal intervention. This study integrates device and soft tissue mechanics in one computational framework to potentially aid in the understanding of the occurrence of specific symptoms and complications after stent placement.

Shear wave elastography (SWE) is an ultrasound (US) diagnostic method for measuring the stiffness of soft tissues based on generated shear waves (SWs). SWE has been applied to bulk tissues, but in arteries it is still under investigation. Previously performed studies in arteries or arterial phantoms demonstrated the potential of SWE to measure arterial wall stiffness-a relevant marker in prediction of cardiovascular diseases. This study is focused on numerical modelling of SWs in ex vivo equine aortic tissue, yet based on experimental SWE measurements with the tissue dynamically loaded while rotating the US probe to investigate the sensitivity of SWE to the anisotropic structure. A good match with experimental shear wave group speed results was obtained. SWs were sensitive to the orthotropy and nonlinearity of the material. The model also allowed to study the nature of the SWs by performing 2D FFT-based and analytical phase analyses. A good match between numerical group velocities derived using the time-of-flight algorithm and derived from the dispersion curves was found in the cross-sectional and axial arterial views. The complexity of solving analytical equations for nonlinear orthotropic stressed plates was discussed.

Local hemodynamics has been identified as one main determinant in the onset and progression of atherosclerotic lesions at coronary bifurcations. Starting from the observation that atherosensitive hemodynamic conditions in arterial bifurcation are majorly determined by the underlying anatomy, the aim of the present study is to investigate how peculiar coronary bifurcation anatomical features influence near-wall and intravascular flow patterns. Different bifurcation angles and cardiac curvatures were varied in population-based, idealized models of both stenosed and unstenosed bifurcations, representing the left anterior descending (LAD) coronary artery with its diagonal branch. Local hemodynamics was analyzed in terms of helical flow and exposure to low/oscillatory shear stress by performing computational fluid dynamics simulations. Results show that bifurcation angle impacts lowly hemodynamics in both stenosed and unstenosed cases. Instead, curvature radius influences the generation and transport of helical flow structures, with smaller cardiac curvature radius associated to higher helicity intensity. Stenosed bifurcation models exhibit helicity intensity values one order of magnitude higher than the corresponding unstenosed cases. Cardiac curvature radius moderately affects near-wall hemodynamics of the stenosed cases, with smaller curvature radius leading to higher exposure to low shear stress and lower exposure to oscillatory shear stress. In conclusion, the proposed controlled benchmark allows investigating the effect of various geometrical features on local hemodynamics at the LAD/diagonal bifurcation, highlighting that cardiac curvature influences near wall and intravascular hemodynamics, while bifurcation angle has a minor effect., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Aims: Mechanisms of lumen compromise after provisional side branch (SB) stenting are poorly understood. In this study we aimed to investigate the impact of bifurcation angle, plaque composition, and procedural strategy on SB compromise., Methods and Results: Computer simulations of stent implantation were performed in Medina (1,1,1) bifurcation models. Provisional SB stenting was replicated including post-dilation after main branch stenting. Two bifurcation angles (45°, 70°) and four plaque types (fully lipid, fully fibrous, lipid with half and fully calcified ring distal to the carina) were tested. Two post-dilation balloons of different lengths (15 mm and 9 mm) were also investigated. Provisional stenting caused an ovalisation of the SB ostium (i.e., increase of ellipticity from 0.27 to 0.58±0.21, p<0.05) that might appear as a significant stenosis on two-dimensional angiography, although SB ostium area was preserved (-3.3±10.3%) in the absence of calcifications. However, in the presence of calcifications, SB lumen volume compromise was evident (-0.89±0.15 mm3). Plaque type had a higher impact than bifurcation angle on SB ostium shape. A shorter balloon (9 mm) for proximal optimisation reduced SB lumen volume compromise from -1.11 mm3 to -0.72 mm3., Conclusions: Simulations showed ovalisation of the SB ostium, generally without significant lumen compromise. Provisional stenting in the presence of calcifications resulted in a more severe outcome for the SB ostium.

Background: Studies of radiofrequency ablation (RFA) of genicular nerves have reportedly significantly decreased pain up to 3 months post ablation, but no longer term effects have been reported. We performed an analysis of long-term pain relief of 31 RFA procedures of the genicular nerves to analyze the degree of pain relief past 3 months, culminating at 6 months., Study Design: Chart review and study design was approved by Newark Health Sciences Institutional Review Board (IRB). Chart review and follow-up was performed on all patients who underwent genicular nerve RFA during the period of February 2014 through August of 2015. During this inclusion period 41 genicular nerve RFAs were performed on 31 patients, 5 patients received RFA procedure in both knees. Patient follow-up was performed via telephone interview or in-office visit at least 3 months and 6 months post RFA., Settings: Procedures were performed in Medical Special Procedures at University Hospital in Newark, NJ, and the Pain Management Center at Overlook Medical Arts Center in Summit, NJ., Methods: Chart review and study design was approved by Newark Health Sciences IRB. Chart review was performed from February 2014 and continued through August 2015. Patient follow-up was conducted at 3 and at least 6 months post treatment to gauge degree of pain relief (0 - none, 100% - complete), their current day's pain score, other treatment modalities tried before RFA, and the medications used. Patients were asked to quantify their satisfaction with procedure length, pre-procedure anxiety, complications, and if they would recommend this procedure to others. Primary and secondary goals were the duration of pain relief after RFA, the quality of pain relief, and the efficacy of our approach for RFA of genicular nerves versus prior published techniques., Results: At 3 month follow-up, the average pain relief was 67% improvement from baseline knee pain, 0% being no relief and 100% being complete relief, and average 0 - 10 pain score was 2.9. At 6 month follow-up, of those who described pain relief at 3 months, 95% still described pain relief. This group's average percent pain relief was 64% and average day's 0 - 10 pain score 3.3., Limitations: Our study included a retrospective component in chart review followed by prospective follow-up, only 76% of patients were able to participate in the interview process. Furthermore, some patients suffered from other chronic pain ailments, most commonly chronic back pain, which at times disturbed the patient's ability to focus on solely knee pain., Conclusions: Based on patient interviews and data collection, RFA of genicular nerves can supply on average greater than 60% pain relief in our patient population for as long as 6 months.Key words: Osteoarthritis, knee osteoarthritis, chronic knee pain, radiofrequency ablation, nerve ablation, genicular nerves, long-term pain relief.

Three-dimensional (3-D) strain estimation might improve the detection and localization of high strain regions in the carotid artery (CA) for identification of vulnerable plaques. This paper compares 2-D versus 3-D displacement estimation in terms of radial and circumferential strain using simulated ultrasound (US) images of a patient-specific 3-D atherosclerotic CA model at the bifurcation embedded in surrounding tissue generated with ABAQUS software. Global longitudinal motion was superimposed to the model based on the literature data. A Philips L11-3 linear array transducer was simulated, which transmitted plane waves at three alternating angles at a pulse repetition rate of 10 kHz. Interframe (IF) radio-frequency US data were simulated in Field II for 191 equally spaced longitudinal positions of the internal CA. Accumulated radial and circumferential displacements were estimated using tracking of the IF displacements estimated by a two-step normalized cross-correlation method and displacement compounding. Least-squares strain estimation was performed to determine accumulated radial and circumferential strain. The performance of the 2-D and 3-D methods was compared by calculating the root-mean-squared error of the estimated strains with respect to the reference strains obtained from the model. More accurate strain images were obtained using the 3-D displacement estimation for the entire cardiac cycle. The 3-D technique clearly outperformed the 2-D technique in phases with high IF longitudinal motion. In fact, the large IF longitudinal motion rendered it impossible to accurately track the tissue and cumulate strains over the entire cardiac cycle with the 2-D technique.

Background: Coronary hemodynamics and physiology specific for bifurcation lesions was not well understood. To investigate the influence of the bifurcation angle on the intracoronary hemodynamics of side branch (SB) lesions computational fluid dynamics simulations were performed., Methods: A parametric model representing a left anterior descending-first diagonal coronary bifurcation lesion was created according to the literature. Diameters obeyed fractal branching laws. Proximal and distal main branch (DMB) stenoses were both set at 60 %. We varied the distal bifurcation angles (40°, 55°, and 70°), the flow splits to the DMB and SB (55 %:45 %, 65 %:35 %, and 75 %:25 %), and the SB stenoses (40, 60, and 80 %), resulting in 27 simulations. Fractional flow reserve, defined as the ratio between the mean distal stenosis and mean aortic pressure during maximal hyperemia, was calculated for the DMB and SB (FFRSB) for all simulations., Results: The largest differences in FFRSB comparing the largest and smallest bifurcation angles were 0.02 (in cases with 40 % SB stenosis, irrespective of the assumed flow split) and 0.05 (in cases with 60 % SB stenosis, flow split 55 %:45 %). When the SB stenosis was 80 %, the difference in FFRSB between the largest and smallest bifurcation angle was 0.33 (flow split 55 %:45 %). By describing the ΔPSB-QSB relationship using a quadratic curve for cases with 80 % SB stenosis, we found that the curve was steeper (i.e. higher flow resistance) when bifurcation angle increases (ΔP = 0.451*Q + 0.010*Q (2) and ΔP = 0.687*Q + 0.017*Q (2) for 40° and 70° bifurcation angle, respectively). Our analyses revealed complex hemodynamics in all cases with evident counter-rotating helical flow structures. Larger bifurcation angles resulted in more pronounced helical flow structures (i.e. higher helicity intensity), when 60 or 80 % SB stenoses were present. A good correlation (R(2) = 0.80) between the SB pressure drop and helicity intensity was also found., Conclusions: Our analyses showed that, in bifurcation lesions with 60 % MB stenosis and 80 % SB stenosis, SB pressure drop is higher for larger bifurcation angles suggesting higher flow resistance (i.e. curves describing the ΔPSB-QSB relationship being steeper). When the SB stenosis is mild (40 %) or moderate (60 %), SB resistance is minimally influenced by the bifurcation angle, with differences not being clinically meaningful. Our findings also highlighted the complex interplay between anatomy, pressure drops, and blood flow helicity in bifurcations.

The ApoE(-)(/)(-) mouse is a common small animal model to study atherosclerosis, an inflammatory disease of the large and medium sized arteries such as the carotid artery. It is generally accepted that the wall shear stress, induced by the blood flow, plays a key role in the onset of this disease. Wall shear stress, however, is difficult to derive from direct in vivo measurements, particularly in mice. In this study, we integrated in vivo imaging (micro-Computed Tomography-µCT and ultrasound) and fluid-structure interaction (FSI) modeling for the mouse-specific assessment of carotid hemodynamics and wall shear stress. Results were provided for 8 carotid bifurcations of 4 ApoE(-)(/)(-) mice. We demonstrated that accounting for the carotid elasticity leads to more realistic flow waveforms over the complete domain of the model due to volume buffering capacity in systole. The 8 simulated cases showed fairly consistent spatial distribution maps of time-averaged wall shear stress (TAWSS) and relative residence time (RRT). Zones with reduced TAWSS and elevated RRT, potential indicators of atherosclerosis-prone regions, were located mainly at the outer sinus of the external carotid artery. In contrast to human carotid hemodynamics, no flow recirculation could be observed in the carotid bifurcation region., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

In recent years the role of FSI (fluid-structure interaction) simulations in the analysis of the fluid-mechanics of heart valves is becoming more and more important, being able to capture the interaction between the blood and both the surrounding biological tissues and the valve itself. When setting up an FSI simulation, several choices have to be made to select the most suitable approach for the case of interest: in particular, to simulate flexible leaflet cardiac valves, the type of discretization of the fluid domain is crucial, which can be described with an ALE (Arbitrary Lagrangian-Eulerian) or an Eulerian formulation. The majority of the reported 3D heart valve FSI simulations are performed with the Eulerian formulation, allowing for large deformations of the domains without compromising the quality of the fluid grid. Nevertheless, it is known that the ALE-FSI approach guarantees more accurate results at the interface between the solid and the fluid. The goal of this paper is to describe the same aortic valve model in the two cases, comparing the performances of an ALE-based FSI solution and an Eulerian-based FSI approach. After a first simplified 2D case, the aortic geometry was considered in a full 3D set-up. The model was kept as similar as possible in the two settings, to better compare the simulations' outcomes. Although for the 2D case the differences were unsubstantial, in our experience the performance of a full 3D ALE-FSI simulation was significantly limited by the technical problems and requirements inherent to the ALE formulation, mainly related to the mesh motion and deformation of the fluid domain. As a secondary outcome of this work, it is important to point out that the choice of the solver also influenced the reliability of the final results.

Clinical studies have demonstrated the efficacy of stent supported coiling for intra-cranial aneurysm treatment. Despite encouraging outcomes, some matters are yet to be addressed. In particular closed stent designs are influenced by the delivery technique and may suffer from under-expansion, with the typical effect of "hugging" the inner curvature of the vessel which seems related to adverse events. In this study we propose a novel finite element (FE) environment to study potential failure able to reproduce the microcatheter "pull-back" delivery technique. We first verified our procedure with published in vitro data and then replicated the intervention on one patient treated with a 4.5 × 22 mm Enterprise microstent (Codman Neurovascular; Raynham MA, USA). Results showed good agreement with the in vitro test, catching both size and location of the malapposed area. A simulation of a 28 mm stent in the same geometry highlighted the impact of the delivery technique, which leads to larger area of malapposition. The patient specific simulation matched the global stent configuration and zones prone to malapposition shown on the clinical images with difference in tortuosity between actual and virtual treatment around 2.3%. We conclude that the presented FE strategy provides an accurate description of the stent mechanics and, after further in vivo validation and optimization, will be a tool to aid clinicians to anticipate the acute procedural outcome avoiding poor initial results.

Purpose: Carotid artery stenting (CAS) is an alternative procedure for the treatment of severely stenosed carotid artery lesions in high-risk patients. Appropriate patient selection and stent design are paramount to achieve a low stroke and death rate in these complex high-risk procedures. This study introduces and evaluates a novel virtual, patient-specific, pre-operative environment to quantify scaffolding parameters based on routine imaging techniques., Methods: Two patients who underwent CAS with two different sizes of the Acculink stent (Abbott Vascular, Santa Clara, CA, USA) were studied. Pre-operative data were used to build the numerical models for the virtual procedure. Numerical results were validated with post-operative angiography. Using novel virtual geometrical tools, incomplete stent apposition, free cell area and largest fitting sphere in the stent cell were evaluated in situ as quantitative measures of successful stent placement and to assess potential risk factors for CAS complications., Results: A quantitative validation of the numerical outcome with post-operative images noted differences in lumen diameter of 5.31 ± 8.05% and 4.12 ± 9.84%, demonstrating the reliability of the proposed methodology. The quantitative measurements of the scaffolding parameters on the virtually deployed stent geometry highlight the variability of the device behavior in relation to the target lesion. The free cell area depends on the target diameter and oversizing, while the largest fitting spheres and apposition values are influenced by the local concavity and convexity of the vessel., Conclusions: The proposed virtual environment may be an additional tool for endovascular specialists especially in complex anatomical cases where stent design and positioning may have a higher impact on procedural success and outcome.

Here, we consider the issue of generating a suitable controlled environment for the evaluation of phase contrast (PC) MRI measurements. The computational framework, tailored to build synthetic datasets, is based on a two-step approach, i.e., define and implement (1) an accurate CFD model and (2) an image generator able to mime the overall outcomes of a PC MRI acquisition starting from datasets retrieved by the computational model. About 20 different datasets were built by changing relevant image parameters (pixel size, slice thickness, time frames per cardiac cycle). Focusing our attention on the thoracic aorta, synthetic images were processed in order to: (1) verify to which extent the fluid dynamics into the aortic arch is influenced by the image parameters; (2) establish the effect of spatial and temporal interpolation. Our study demonstrates that the integral scale of the aortic bulk flow could be described satisfactorily even when using images which are nowadays acquirable with MRI scanners. However, attention must be paid to near-wall velocities that can be affected by large inaccuracy. In detail, in bulk flow regions error values are well bounded (below 5% for most of the analyzed resolutions), while errors greater than 100% are systematically present at the vessel's wall. Moreover, also the data interpolation process can be responsible for large inaccuracies in new data generation, due to the inherent complexity of the flow field in some connected regions.