Understanding the role of hemodynamics in the initiation, progression, rupture, and treatment outcome of cerebral aneurysm from medical iamge-based computational studies

About a decade ago, the first image-based computational hemodynamic studies of cerebral aneurysms were presented. Their potential for clinical applications was the results of a right combination of medical image processing, vascular reconstruction, and grid generation techniques used to reconstruct personalziaed domains for computational fluid and solid dynamics solvers and data analysis and visualization techniques. A considerable number of studies have captivated the attention of clinicians, neurosurgeons, and neuroradiologists, who realized the ability of those tools to help in understanding the role played by hemodynamics in the natural history and management of intracranial aneurysms. This paper intends to summarize the most relevant results in the filed reported during the last years.Fil: Castro, Marcelo Adrian. Universidad Tecnológica Nacional. Facultad Regional Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Hemodynamic characteristics at anterior communicating artery before aneurysm initiation using patient-specific finite element blood flow simulations

The anterior communicating artery (AComA) is a unique vascular location that receives blood from two sources of inflow and redistributes it toward the anterior part of the brain through two efferent arteries. It is widely accepted that complexity in the flow pattern is associated with the high rate of aneurysm formation in that location observed in large studies. A previous computational hemodynamic study showed a possible association between high maximum intraaneurysmal wall shear stress (WSS) at the systolic peak with rupture in a cohort of AComA aneurysms. In another study it was observed a connection between location of aneurysm blebs and regions of high WSS in models where blebs were virtually removed. The purpose of this work is to study associations between hemodynamic patterns and AComA aneurysm initiation by comparing hemodynamics between the aneurysm models and the normal model where the aneurysm was computationally removed. Vascular models of both right and left circulation were independently reconstructed from three-dimensional rotational angiography images using deformable models after image registration of both images, and later fused using a surface merging algorithm. Afterwards, the geometric models were used to generate high-quality volumetric finite element grids composed several million tetrahedral elements with an advancing front technique. For each patient the second anatomical model was created by digitally removing the aneurysm. It was iteratively achieved by applying a Laplacian smoothing filter and remeshing the surface. Finite element blood flow numerical simulations were performed for both the pathological and normal models under the same flow conditions. Personalized pulsatile flow conditions were imposed at the inlets of both models with use of the Womersley solution. The Navier-Stokes equations were numerically integrated by using a fully implicit finite-element formulation. From analysis of WSS distributions it was observed that aneurysms initiated in regions of high and moderate WSS in the counterpart normal models. Adjacent or close to those regions, low WSS portions of the arterial wall were not affected by the disease. These results are in line with previous reported observations at other vascular locations.Fil: Castro, Marcelo Adrian. Universidad Tecnológica Nacional. Facultad Regional Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. George Mason University; Estados UnidosFil: Putman, Christopher M.. Inova Fairfax Hospital; Estados UnidosFil: Cebral, Juan Raúl. George Mason University; Estados Unido

Hemodynamic characteristics at anterior communicating artery before aneurysm initiation using patient-specific finite element blood flow simulations

The anterior communicating artery (AComA) is a unique vascular location that receives blood from two sources of inflow and redistributes it toward the anterior part of the brain through two efferent arteries. It is widely accepted that complexity in the flow pattern is associated with the high rate of aneurysm formation in that location observed in large studies. A previous computational hemodynamic study showed a possible association between high maximum intraaneurysmal wall shear stress (WSS) at the systolic peak with rupture in a cohort of AComA aneurysms. In another study it was observed a connection between location of aneurysm blebs and regions of high WSS in models where blebs were virtually removed. The purpose of this work is to study associations between hemodynamic patterns and AComA aneurysm initiation by comparing hemodynamics between the aneurysm models and the normal model where the aneurysm was computationally removed. Vascular models of both right and left circulation were independently reconstructed from three-dimensional rotational angiography images using deformable models after image registration of both images, and later fused using a surface merging algorithm. Afterwards, the geometric models were used to generate high-quality volumetric finite element grids composed several million tetrahedral elements with an advancing front technique. For each patient the second anatomical model was created by digitally removing the aneurysm. It was iteratively achieved by applying a Laplacian smoothing filter and remeshing the surface. Finite element blood flow numerical simulations were performed for both the pathological and normal models under the same flow conditions. Personalized pulsatile flow conditions were imposed at the inlets of both models with use of the Womersley solution. The Navier-Stokes equations were numerically integrated by using a fully implicit finite-element formulation. From analysis of WSS distributions it was observed that aneurysms initiated in regions of high and moderate WSS in the counterpart normal models. Adjacent or close to those regions, low WSS portions of the arterial wall were not affected by the disease. These results are in line with previous reported observations at other vascular locations.Fil: Castro, Marcelo Adrian. Universidad Tecnológica Nacional. Facultad Regional Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. George Mason University; Estados UnidosFil: Putman, Christopher M.. Inova Fairfax Hospital; Estados UnidosFil: Cebral, Juan Raúl. George Mason University; Estados Unido

Effects of Casson rheology on aneurysm wall shear stress

It is widely accepted that wall shear stress plays an important role in cerebral aneurysm initiation, progress and rupture. Previous works have shown strong evidence in support of the high wall shear stress as a risk factor associated to those biomechanical processes. Patient-specific imagebased computational hemodynamic modeling of vascular systems harboring cerebral aneurysms has demonstrated to be a fast and reliable way to compute quantities difficult or impossible to be measured in-vivo. The accuracy of the simulation results have been successfully validated in the past. Additionally, most model assumptions have shown no impact on the flow characterization whose association with the mentioned processes was investigated. Particularly, the incorporation of the blood rheology in large arterial systems containing aneurysms resulted in similar hemodynamic characterizations for most aneurysms. However, large aneurysms, especially those containing blebs are expected to have flow rates in the range where Newtonian and non-Newtonian models exhibit the largest differences. In order to study the impact of blood rheology in vascular systems harboring specific intracranial aneurysms, unsteady finite element blood flow simulations were carried out over patient-specific models. Those models were reconstructed from rotational angiographic images using region growing and deformable model algorithms. Unstructured finite element meshes were generated using and advancing front technique. Walls were assumed as rigid, traction-free boundary conditions were imposed at the outlets of the models, and a flow rate wave form was imposed at the inlets after scaling according to the Murray's Law for optimal arterial networks. The Casson model was incorporated as a velocity gradient dependent apparent viscosity and the results were compared to those using the Newtonian rheology. Regions with differentiated wall shear stress values and orientations were studied.Fil: Castro, Marcelo Adrian. Universidad Tecnológica Nacional. Secretaria de Ciencia y Técnica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ahumada, Maria Carolina. Universidad Favaloro. Facultad de Ingeniería y Ciencias Exactas y Naturales; ArgentinaFil: Putman, Christopher M.. Innova Fairfax Hospital; Estados UnidosFil: Cebral, Juan Raúl. George Mason University; Estados Unido

Effects of Casson rheology on aneurysm wall shear stress

It is widely accepted that wall shear stress plays an important role in cerebral aneurysm initiation, progress and rupture. Previous works have shown strong evidence in support of the high wall shear stress as a risk factor associated to those biomechanical processes. Patient-specific imagebased computational hemodynamic modeling of vascular systems harboring cerebral aneurysms has demonstrated to be a fast and reliable way to compute quantities difficult or impossible to be measured in-vivo. The accuracy of the simulation results have been successfully validated in the past. Additionally, most model assumptions have shown no impact on the flow characterization whose association with the mentioned processes was investigated. Particularly, the incorporation of the blood rheology in large arterial systems containing aneurysms resulted in similar hemodynamic characterizations for most aneurysms. However, large aneurysms, especially those containing blebs are expected to have flow rates in the range where Newtonian and non-Newtonian models exhibit the largest differences. In order to study the impact of blood rheology in vascular systems harboring specific intracranial aneurysms, unsteady finite element blood flow simulations were carried out over patient-specific models. Those models were reconstructed from rotational angiographic images using region growing and deformable model algorithms. Unstructured finite element meshes were generated using and advancing front technique. Walls were assumed as rigid, traction-free boundary conditions were imposed at the outlets of the models, and a flow rate wave form was imposed at the inlets after scaling according to the Murray's Law for optimal arterial networks. The Casson model was incorporated as a velocity gradient dependent apparent viscosity and the results were compared to those using the Newtonian rheology. Regions with differentiated wall shear stress values and orientations were studied.Fil: Castro, Marcelo Adrian. Universidad Tecnológica Nacional. Secretaria de Ciencia y Técnica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ahumada, Maria Carolina. Universidad Favaloro. Facultad de Ingeniería y Ciencias Exactas y Naturales; ArgentinaFil: Putman, Christopher M.. Innova Fairfax Hospital; Estados UnidosFil: Cebral, Juan Raúl. George Mason University; Estados Unido

Estimation of Aneurysm Wall Motion from 4D Computerized Tomographic Angiography Images

It is widely accepted that wall shear stressis associated to aneurysm formation, growthand rupture. Early identification of potential risk factors may contribute to decide the treatment and improve patient care. Previous studies have shown associations between high aneurysm wall shear stress values and both elevated risk of rupture and localization of regions of aneurysm progression. Based on the assumption that damaged regions of the endothelium have different mechanical properties, regions with differentiated wall displacement amplitudes are expected. A previous approach based on the analysis ofbidimensional dynamic tomographic angiography images at a limited number of points during the cardiac cycle showed only small displacements in some patients using that simplified and semi-automatic low resolution methodology. The purpose of this work is to overcome some of those limitations. High time and spatial resolution four dimensional computerized tomographic angiography images of cerebral aneurysms were acquired and analyzed in order to identify and characterize wall motion. Images were filtered andsegmented at nineteentime points during the cardiac cycle.An average image was computed to generate the vascular model. Anunstructured mesh of tetrahedral elements was generated using an advancing front technique. A finite element blood flow simulationwas carried out under personalized pulsatile flow conditions. A fuzzy c-means clustering algorithm was used to estimate regions that exhibit wall motion within the aneurysm sac. A good correlation between localization of regions of elevated wall shear stress and regionsexhibiting wall motion was found.Fil: Castro, Marcelo Adrian. Universidad Tecnológica Nacional. Facultad Regional Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ahumada Olivares, María C.. Universidad Favaloro; ArgentinaFil: Putman, Christopher M. . Inova Fairfax Hospital. Department of Interventional Neuroradiology; Estados UnidosFil: Cebral, Juan R.. George Mason University. Department of Computational and Data Sciences; Estados Unido

Delayed Puberty Due to a WDR11 Truncation at Its N-Terminal Domain Leading to a Mild Form of Ciliopathy Presenting With Dissociated Central Hypogonadism: Case Report

Pubertal delay in males is frequently due to constitutional delay of growth and puberty, but pathologic hypogonadism should be considered. After general illnesses and primary testicular failure are ruled out, the main differential diagnosis is central (or hypogonadotropic) hypogonadism, resulting from a defective function of the gonadotropin-releasing hormone (GnRH)/gonadotropin axis. Ciliopathies arising from defects in non-motile cilia are responsible for developmental disorders affecting the sense organs and the reproductive system. WDR11-mediated signaling in non-motile cilia is critical for fetal development of GnRH neurons. Only missense variants of WDR11 have been reported to date in patients with central hypogonadism, suggesting that nonsense variants could lead to more complex phenotypes. We report the case of a male patient presenting with delayed puberty due to Kallmann syndrome (central hypogonadism associated with hyposmia) in whom the next-generation sequencing analysis identified a novel heterozygous base duplication, leading to a frameshift and a stop codon in the N-terminal region of WDR11. The variant was predicted to undergo nonsense-mediated decay and classified as probably pathogenic following the American College of Medical Genetics and Genomics (ACMG) criteria. This is the first report of a variant in the WDR11 N-terminal region predicted to lead to complete expression loss that, contrary to expectations, led to a mild form of ciliopathy resulting in isolated Kallmann syndrome.Fil: Castro, Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Brunello, Franco Gino. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Sanso, Elsa Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Scaglia, Paula Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Esnaola Azcoiti, María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Izquierdo, Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Villegas, Florencia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Bergadá, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Ropelato, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Marti, Marcelo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Rey, Rodolfo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología; ArgentinaFil: Grinspon, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentin

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO