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

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

Big Data Analyses To Identify Physiologic Adaptive Responses In The American Black Bear (Ursus Americanus): From Basic Biological Knowledge To Clinical Applications

University of Minnesota Ph.D. dissertation. November 2017. Major: Biomedical Informatics and Computational Biology. Advisor: Paul Iaizzo. 1 computer file (PDF); ix, 205 pages.The purpose of our research investigations is primarily to characterize the cardiovascular and ecological adaptations of the American black bear (Ursus americanus) during extended periods of overwintering. The over-arching goal of these is to provide new insights into clinical solutions for human patients. Hibernation physiology has long been of interest to many research groups, and several species have been studied. Here we have an incredible opportunity to utilize a bioinformatics and “big data” approach, in addition to clinical diagnostics, to study the American black bear. In general, it is considered that the secrets of the bears’ physiologic modifications during hibernation are of scientific importance due to a variety of potential applications, from medicine to ecology to applied basic research. The first series of studies aims to investigate elicited blood chemistries and metabolomics of the black bear during denning. Part two of my thesis will focus on a comprehensive literature review performed and a model for administering pharmaceutical compounds to the pericardial space surrounding the heart. In addition, to models that can be used to test paradigms and compounds for their potential translational applications: i.e., first, those in cardiac surgery or cardiac transplantation and a methods paper to test compounds to identify their effect on cardiac arrhythmias, overall function and transplant viability. I will also describe an evaluated model of ex vivo lung perfusion as a platform to test these pharmaceutical agents and compounds in lung transplantation. Part three of my dissertation will focus on a set of investigations designed to detail data collected from implantable cardiac monitors to evaluate cardiovascular adaptions to hibernation. The overall goals of these studies is to Further identify unique modifications of cardiac and respiratory responses associated with black bear hibernation, by utilizing bioinformatics methodologies to analyze the data we continue to collect from these animals utilizing multiple methodologies

Merit of an Ursodeoxycholic Acid Clinical Trial in COVID-19 Patients

Corona Virus Disease 2019 (COVID-19) has affected over 8 million people worldwide. We underscore the potential benefits of conducting a randomized open-label unblinded clinical trial to evaluate the role of ursodeoxycholic acid (UDCA) in the treatment of COVID-19. Some COVID-19 patients are characterized with cytokine storm syndrome that can cause severe and irreversible damage to organs leading to multi-organ failure and death. Therefore, it is critical to control both programmed cell death (apoptosis) and the hyper-immune inflammatory response in COVID-19 patients to reduce the rising morbidity and mortality. UDCA is an existing drug with proven safety profiles that can reduce inflammation and prevent cell death. National Geographic reported that, “China Promotes Bear Bile as Coronavirus Treatment”. Bear bile is rich in UDCA, comprising up to 40–50% of the total bile acid. UDCA is a logical and attainable replacement for bear bile that is available in pill form and merits clinical trial consideration

Patient independent representation of the detailed cardiac ventricular anatomy

Reparameterization of surfaces is a widely used tool in computer graphics known mostly from the remeshing algorithms. Recently, the surface reparameterization techniques started to gain popularity in the field of medical imaging, but mostly for convenient 2D visualization of the information initially represented on 3D surfaces (e.g. continuous bulls-eye plot). However, by consistently mapping the 3D information to the same 2D domain, surface reparameterization techniques allow us to put into correspondence anatomical shapes of inherently different geometry. In this paper, we propose a method for anatomical parameterization of cardiac ventricular anatomies that include myocardium, trabeculations, tendons and papillary muscles. The proposed method utilizes a quasi-conformal flattening of the myocardial surfaces of the left and right cardiac ventricles and extending it to cover the interior of the cavities using the local coordinates given by the solution of the Laplace’s equation. Subsequently, we define a geometry independent representation for the detailed cardiac left and right ventricular anatomies that can be used for convenient visualization and statistical analysis of the trabeculations in a population. Lastly we show how it can be used for mapping the detailed cardiac anatomy between different hearts, which is of considerable interest for detailed cardiac computational models or shape atlases.Paun is supported by the grant FI-DGR 2014 (2014 FI B01238) from the Generalitat de Catalunya. The research leading to these results has received funding from the EU FP7 for research, technological development and demonstration under grant agreement VP2HF (no. 611823) and from the Spanish Ministry of Economy and Competitiveness (grant TIN2011-28067, TIN2014-52923-R, the Maria de Maeztu Units of Excellence Programme MDM-2015-0502) and FEDER

Virtual Prototyping: Computational Device Placements within Detailed Human Heart Models

Data relative to anatomical measurements, spatial relationships, and device–tissue interaction are invaluable to medical device designers. However, obtaining these datasets from a wide range of anatomical specimens can be difficult and time consuming, forcing designers to make decisions on the requisite shapes and sizes of a device from a restricted number of specimens. The Visible Heart® Laboratories have a unique library of over 500 perfusion-fixed human cardiac specimens from organ donors whose hearts (and or lungs) were not deemed viable for transplantation. These hearts encompass a wide variety of pathologies, patient demographics, surgical repairs, and/or interventional procedures. Further, these specimens are an important resource for anatomical study, and their utility may be augmented via generation of 3D computational anatomical models, i.e., from obtained post-fixation magnetic resonance imaging (MRI) scans. In order to optimize device designs and procedural developments, computer generated models of medical devices and delivery tools can be computationally positioned within any of the generated anatomical models. The resulting co-registered 3D models can be 3D printed and analyzed to better understand relative interfaces between a specific device and cardiac tissues within a large number of diverse cardiac specimens that would be otherwise unattainable

Patient independent representation of the detailed cardiac ventricular anatomy

Reparameterization of surfaces is a widely used tool in computer graphics known mostly from the remeshing algorithms. Recently, the surface reparameterization techniques started to gain popularity in the field of medical imaging, but mostly for convenient 2D visualization of the information initially represented on 3D surfaces (e.g. continuous bulls-eye plot). However, by consistently mapping the 3D information to the same 2D domain, surface reparameterization techniques allow us to put into correspondence anatomical shapes of inherently different geometry. In this paper, we propose a method for anatomical parameterization of cardiac ventricular anatomies that include myocardium, trabeculations, tendons and papillary muscles. The proposed method utilizes a quasi-conformal flattening of the myocardial surfaces of the left and right cardiac ventricles and extending it to cover the interior of the cavities using the local coordinates given by the solution of the Laplace’s equation. Subsequently, we define a geometry independent representation for the detailed cardiac left and right ventricular anatomies that can be used for convenient visualization and statistical analysis of the trabeculations in a population. Lastly we show how it can be used for mapping the detailed cardiac anatomy between different hearts, which is of considerable interest for detailed cardiac computational models or shape atlases.Paun is supported by the grant FI-DGR 2014 (2014 FI B01238) from the Generalitat de Catalunya. The research leading to these results has received funding from the EU FP7 for research, technological development and demonstration under grant agreement VP2HF (no. 611823) and from the Spanish Ministry of Economy and Competitiveness (grant TIN2011-28067, TIN2014-52923-R, the Maria de Maeztu Units of Excellence Programme MDM-2015-0502) and FEDER