Left Ventricular Trabeculations Decrease the Wall Shear Stress and Increase the Intra-Ventricular Pressure Drop in CFD Simulations

The aim of the present study is to characterize the hemodynamics of left ventricular (LV) geometries to examine the impact of trabeculae and papillary muscles (PMs) on blood flow using high performance computing (HPC). Five pairs of detailed and smoothed LV endocardium models were reconstructed from high-resolution magnetic resonance images (MRI) of ex-vivo human hearts. The detailed model of one LV pair is characterized only by the PMs and few big trabeculae, to represent state of art level of endocardial detail. The other four detailed models obtained include instead endocardial structures measuring ≥1 mm2 in cross-sectional area. The geometrical characterizations were done using computational fluid dynamics (CFD) simulations with rigid walls and both constant and transient flow inputs on the detailed and smoothed models for comparison. These simulations do not represent a clinical or physiological scenario, but a characterization of the interaction of endocardial structures with blood flow. Steady flow simulations were employed to quantify the pressure drop between the inlet and the outlet of the LVs and the wall shear stress (WSS). Coherent structures were analyzed using the Q-criterion for both constant and transient flow inputs. Our results show that trabeculae and PMs increase the intra-ventricular pressure drop, reduce the WSS and disrupt the dominant single vortex, usually present in the smoothed-endocardium models, generating secondary small vortices. Given that obtaining high resolution anatomical detail is challenging in-vivo, we propose that the effect of trabeculations can be incorporated into smoothed ventricular geometries by adding a porous layer along the LV endocardial wall. Results show that a porous layer of a thickness of 1.2·10−2 m with a porosity of 20 kg/m2 on the smoothed-endocardium ventricle models approximates the pressure drops, vorticities and WSS observed in the detailed models.This paper has been partially funded by CompBioMed project, under H2020-EU.1.4.1.3 European Union’s Horizon 2020 research and innovation programme, grant agreement n◦ 675451. FS is supported by a grant from Severo Ochoa (n◦ SEV-2015-0493-16-4), Spain. CB is supported by a grant from the Fundació LaMarató de TV3 (n◦ 20154031), Spain. TI and PI are supported by the Institute of Engineering in Medicine, USA, and the Lillehei Heart Institute, USA.Peer ReviewedPostprint (published version

PREVALENCE RATE DIFFERENCES BASED ON HERDMATE COMPARISONS

A non-random survey of ovine progressive pneumonia (OPP) seropositive prevalence rates among 16,827 sheep in 29 states in the United states revealed large breed differences, a higher prevalence rate among older sheep and an unexplainable female rate that was more that three times the male rate. The herdmate comparison procedure, successfully used in evaluating dairy bulls, was adapted to compare the prevalence of a breed to the rate of its herdmates within herds. Likewise, sex and age differences in OPP prevalence were compared within herds that contained animals of both sexes and several ages. Using herdmate comparisons, breed and age differences in OPP prevalence remained but the sex difference disappeared

Value of cardiovascular MR in diagnosing left ventricular non-compaction cardiomyopathy and in discriminating between other cardiomyopathies

Objectives: To analyse the value of cardiovascular magnetic resonance (CMR)-derived myocardial parameters to differentiate left ventricular non-compaction cardiomyopathy (LVNC) from other cardiomyopathies and controls. Methods: We retrospectively analysed 12 patients with LVNC, 11 with dilated and 10 with hypertrophic cardiomyopathy and compared them to 24 controls. LVNC patients had to fulfil standard echocardiographic criteria as well as additional clinical and imaging criteria. Cine steady-state free precession and late gadolinium enhancement (LGE) imaging was performed. The total LV myocardial mass index (LV-MMI), compacted (LV-MMI(compacted)), non-compacted (LV-MMI(non-compacted)), percentage LV-MM(non-compacted), ventricular volumes and function were calculated. Data were compared using analysis of variance and Dunnett's test. Additionally, semi-quantitative segmental analyses of the occurrence of increased trabeculation were performed. Results: Total LV-MMI(non-compacted) and percentage LV-MM(non-compacted) were discriminators between patients with LVCN, healthy controls and those with other cardiomyopathies with cut-offs of 15 g/m(2) and 25 %, respectively. Furthermore, trabeculation in basal segments and a ratio of non-compacted/compacted myocardium of >/=3:1 were criteria for LVNC. A combination of these criteria provided sensitivities and specificities of up to 100 %. None of the LVNC patients demonstrated LGE. Conclusions: Absolute CMR quantification of the LV-MMI(non-compacted) or the percentage LV-MM(non-compacted) and increased trabeculation in basal segments allows one to reliably diagnose LVNC and to differentiate it from other cardiomyopathies. Key Points: Cardiac magnetic resonance imaging can reliably diagnose left ventricular non-compaction cardiomyopathy. Differentiation of LVNC from other cardiomyopathies and normal hearts is possible. The best diagnostic performance can be achieved if combined MRI criteria for the diagnosis are used

LES-based Study of the Roughness Effects on the Wake of a Circular Cylinder from Subcritical to Transcritical Reynolds Numbers

This paper investigates the effects of surface roughness on the flow past a circular cylinder at subcritical to transcritical Reynolds numbers. Large eddy simulations of the flow for sand grain roughness of size k/D = 0.02 are performed (D is the cylinder diameter). Results show that surface roughness triggers the transition to turbulence in the boundary layer at all Reynolds numbers, thus leading to an early separation caused by the increased momentum deficit, especially at transcritical Reynolds numbers. Even at subcritical Reynolds numbers, boundary layer instabilities are triggered in the roughness sublayer and eventually lead to the transition to turbulence. The early separation at transcritical Reynolds numbers leads to a wake topology similar to that of the subcritical regime, resulting in an increased drag coefficient and lower Strouhal number. Turbulent statistics in the wake are also affected by roughness; the Reynolds stresses are larger due to the increased turbulent kinetic energy production in the boundary layer and separated shear layers close to the cylinder shoulders.We acknowledge “Red Española de Surpercomputación” (RES) for awarding us access to the MareNostrum III machine based in Barcelona, Spain (Ref. FI-2015-2-0026 and FI-2015-3-0011). We also acknowledge PRACE for awarding us access to Fermi and Marconi Supercomputers at Cineca, Italy (Ref. 2015133120). Oriol Lehmkuhl acknowledges a PDJ 2014 Grant by AGAUR (Generalitat de Catalunya). Ugo Piomelli acknowledges the support of the Natural Sciences and Engineering Research Council (NSERC) of Canada under the Discovery Grant Programme (Grant No. RGPIN-2016-04391). Ricard Borrell acknowledges a Juan de la Cierva postdoctoral grant (IJCI-2014-21034). Ivette Rodriguez, Oriol Lehmkuhl, Ricard Borrell and Assensi Oliva acknowledge Ministerio de Economía y Competitividad, Secretaría de Estado de Investigación, Desarrollo e Innovación, Spain (ref. ENE2014-60577-R).Peer ReviewedPostprint (author's final draft

Evaluating the roles of detailed endocardial structures on right ventricular haemodynamics by means of CFD simulations

Computational modelling plays an important role in right ventricular (RV) haemodynamic analysis. However, current approaches use smoothed ventricular anatomies. The aim of this study is to characterise RV haemodynamics including detailed endocardial structures like trabeculae, moderator band, and papillary muscles. Four paired detailed and smoothed RV endocardium models (2 male and 2 female) were reconstructed from ex vivo human hearts high‐resolution magnetic resonance images. Detailed models include structures with ≥1 mm2 cross‐sectional area. Haemodynamic characterisation was done by computational fluid dynamics simulations with steady and transient inflows, using high‐performance computing. The differences between the flows in smoothed and detailed models were assessed using Q‐criterion for vorticity quantification, the pressure drop between inlet and outlet, and the wall shear stress. Results demonstrated that detailed endocardial structures increase the degree of intra‐ventricular pressure drop, decrease the wall shear stress, and disrupt the dominant vortex creating secondary small vortices. Increasingly turbulent blood flow was observed in the detailed RVs. Female RVs were less trabeculated and presented lower pressure drops than the males. In conclusion, neglecting endocardial structures in RV haemodynamic models may lead to inaccurate conclusions about the pressures, stresses, and blood flow behaviour in the cavity.The DICOMdatasetswere provided by the Visible Heart R Laboratory, obtained byMRI scanning of perfusion fixed hearts that were graciously donated by the organ donors and their families through LifeSource. Part of the simulation hours were provided by the CompBioMed project in the Archer supercomputer, EPCC, UK.Peer ReviewedPostprint (author's final draft

A single codon insertion in PICALM is associated with development of familial subvalvular aortic stenosis in Newfoundland dogs

Familial subvalvular aortic stenosis (SAS) is one of the most common congenital heart defects in dogs and is an inherited defect of Newfoundlands, golden retrievers and human children. Although SAS is known to be inherited, specific genes involved in Newfoundlands with SAS have not been defined. We hypothesized that SAS in Newfoundlands is inherited in an autosomal dominant pattern and caused by a single genetic variant. We studied 93 prospectively recruited Newfoundland dogs, and 180 control dogs of 30 breeds. By providing cardiac screening evaluations for Newfoundlands we conducted a pedigree evaluation, genome-wide association study and RNA sequence analysis to identify a proposed pattern of inheritance and genetic loci associated with the development of SAS. We identified a three-nucleotide exonic insertion in phosphatidylinositol-binding clathrin assembly protein (PICALM) that is associated with the development of SAS in Newfoundlands. Pedigree evaluation best supported an autosomal dominant pattern of inheritance and provided evidence that equivocally affected individuals may pass on SAS in their progeny. Immunohistochemistry demonstrated the presence of PICALM in the canine myocardium and area of the subvalvular ridge. Additionally, small molecule inhibition of clathrin-mediated endocytosis resulted in developmental abnormalities within the outflow tract (OFT) of Xenopus laevis embryos. The ability to test for presence of this PICALM insertion may impact dog-breeding decisions and facilitate reduction of SAS disease prevalence in Newfoundland dogs. Understanding the role of PICALM in OFT development may aid in future molecular and genetic investigations into other congenital heart defects of various species

Quantitative reconstruction of precipitation changes on the NE Tibetan Plateau since the Last Glacial Maximum – extending the concept of pollen source area to pollen-based climate reconstructions from large lakes

Pollen records from large lakes have been used for quantitative palaeoclimate reconstruction, but the influences that lake size (as a result of species-specific variations in pollen dispersal patterns that smaller pollen grains are more easily transported to lake centre) and taphonomy have on these climatic signals have not previously been systematically investigated. We introduce the concept of pollen source area to pollen-based climate calibration using the north-eastern Tibetan Plateau as our study area. We present a pollen data set collected from large lakes in the arid to semi-arid region of central Asia. The influences that lake size and the inferred pollen source areas have on pollen compositions have been investigated through comparisons with pollen assemblages in neighbouring lakes of various sizes. Modern pollen samples collected from different parts of Lake Donggi Cona (in the north-eastern part of the Tibetan Plateau) reveal variations in pollen assemblages within this large lake, which are interpreted in terms of the species-specific dispersal and depositional patterns for different types of pollen, and in terms of fluvial input components. We have estimated the pollen source area for each lake individually and used this information to infer modern climate data with which to then develop a modern calibration data set, using both the multivariate regression tree (MRT) and weighted-averaging partial least squares (WA-PLS) approaches. Fossil pollen data from Lake Donggi Cona have been used to reconstruct the climate history of the north-eastern part of the Tibetan Plateau since the Last Glacial Maximum (LGM). The mean annual precipitation was quantitatively reconstructed using WA-PLS: extremely dry conditions are found to have dominated the LGM, with annual precipitation of around 100 mm, which is only 32% of present-day precipitation. A gradually increasing trend in moisture conditions during the Late Glacial is terminated by an abrupt reversion to a dry phase that lasts for about 1000 yr and coincides with "Heinrich event 1" in the North Atlantic region. Subsequent periods corresponding to the Bølling/Allerød interstadial, with annual precipitation (<i>P</i>_ann) of about 350 mm, and the Younger Dryas event (about 270 mm <i>P</i>_ann) are followed by moist conditions in the early Holocene, with annual precipitation of up to 400 mm. A drier trend after 9 cal. ka BP is followed by a second wet phase in the middle Holocene, lasting until 4.5 cal. ka BP. Relatively steady conditions with only slight fluctuations then dominate the late Holocene, resulting in the present climatic conditions. The climate changes since the LGM have been primarily driven by deglaciation and fluctuations in the intensity of the Asian summer monsoon that resulted from changes in the Northern Hemisphere summer solar insolation, as well as from changes in the North Atlantic climate through variations in the circulation patterns and intensity of the westerlies

Regional aerosol deposition in the human airways: the SimInhale benchmark case and a critical assessment of in silico methods

Regional deposition effects are important in the pulmonary delivery of drugs intended for the topical treatment of respiratory ailments. They also play a critical role in the systemic delivery of drugs with limited lung bioavailability. In recent years, significant improvements in the quality of pulmonary imaging have taken place, however the resolution of current imaging modalities remains inadequate for quantifying regional deposition. Computational Fluid-Particle Dynamics (CFPD) can fill this gap by providing detailed information about regional deposition in the extrathoracic and conducting airways. It is therefore not surprising that the last 15 years have seen an exponential growth in the application of CFPD methods in this area. Survey of the recent literature however, reveals a wide variability in the range of modelling approaches used and in the assumptions made about important physical processes taking place during aerosol inhalation. The purpose of this work is to provide a concise critical review of the computational approaches used to date, and to present a benchmark case for validation of future studies in the upper airways. In the spirit of providing the wider community with a reference for quality assurance of CFPD studies, in vitro deposition measurements have been conducted in a human-based model of the upper airways, and several groups within MP1404 SimInhale have computed the same case using a variety of simulation and discretization approaches. Here, we report the results of this collaborative effort and provide a critical discussion of the performance of the various simulation methods. The benchmark case, in vitro deposition data and in silico results will be published online and made available to the wider community. Particle image velocimetry measurements of the flow, as well as additional numerical results from the community, will be appended to the online database as they become available in the future