Engineering a 3D ultrasound system for image-guided vascular modelling

Atherosclerosis is often diagnosed using an ultrasound (US) examination in the carotid and femoral arteries and the abdominal aorta. A decision to operate requires two measures of disease severity: the degree of stenosis measured using B-mode US; and the blood flow patterns in the artery measured using spectral Doppler US. However other biomechanical factors such as wall shear stress (WSS) and areas of flow recirculation are also important in disease development and rupture. These are estimated using an image-guided modelling approach, where a three-dimensional computational mesh of the artery is simulated. To generate a patient-specific arterial 3D computational mesh, a 3D ultrasound (3DUS) system was developed. This system uses a standard clinical US scanner with an optical position sensor to measure the position of the transducer; a video capture card to record video images from the scanner; and a PC running Stradwin software to reconstruct 3DUS data. The system was characterised using an industry-standard set of calibration phantoms, giving a reconstruction accuracy of ± 0.17 mm with a 12MHz linear array transducer. Artery movements from pulsatile flow were reduced using a retrospective gating technique. The effect of pressure applied to the transducer moving and deforming the artery was reduced using an image-based rigid registration technique. The artery lumen found on each 3DUS image was segmented using a semi-automatic segmentation technique known as ShIRT (the Sheffield Image Registration Toolkit). Arterial scans from healthy volunteers and patients with diagnosed arterial disease were segmented using the technique. The accuracy of the semi-automatic technique was assessed by comparing it to manual segmentation of each artery using a set of segmentation metrics. The mean accuracy of the semi-automatic technique ranged from 85% to 99% and depended on the quality of the images and the complexity of the shape of the lumen. Patient-specific 3D computational artery meshes were created using ShIRT. An idealised mesh was created using key features of the segmented 3DUS scan. This was registered and deformed to the rest of the segmented dataset, producing a mesh that represents the shape of the artery. Meshes created using ShIRT were compared to meshes created using the Rhino solid modelling package. ShIRT produced smoother meshes; Rhino reproduced the shape of arterial disease more accurately. The use of 3DUS with image-guided modelling has the potential to be an effective tool in the diagnosis of atherosclerosis. Simulations using these data reflect in vivo studies of wall shear stress and recirculation in diseased arteries and are comparable with results in the literature created using MRI and other 3DUS systems

UCDs in the Coma Cluster

As part of the HST/ACS Coma Cluster Treasury Survey, we have undertaken a Keck/LRIS spectroscopic campaign to determine membership for faint dwarf galaxies. In the process, we discovered a population of Ultra Compact Dwarf galaxies (UCDs) in the core region of the Coma cluster. At the distance of Coma, UCDs are expected to have angular sizes 0.01 < R_e < 0.2 arcsec. With ACS imaging, we can resolve all but the smallest ones with careful fitting. Candidate UCDs were chosen based on magnitude, color, and degree of resolution. We spectroscopically confirm 27 objects as bona fide UCD members of the Coma cluster, a 60% success rate for objects targeted with M_R < -12. We attribute the high success rate in part to the high resolution of HST data and to an apparent large population of UCDs in Coma. We find that the UCDs tend to be strongly clustered around giant galaxies, at least in the core region of the cluster, and have a distribution and colors that are similar to globular clusters. These findings suggest that UCDs are not independent galaxies, but rather have a star cluster origin. This current study provides the dense environment datapoint necessary for understanding the UCD population.Comment: 6 pages, 9 figures, to appear in the conference proceedings of "A Universe of Dwarf Galaxies" (Lyon, June 14-18, 2010

The HST/ACS Coma Cluster Survey. II. Data Description and Source Catalogs

The Coma cluster was the target of a HST-ACS Treasury program designed for deep imaging in the F475W and F814W passbands. Although our survey was interrupted by the ACS instrument failure in 2007, the partially completed survey still covers ~50% of the core high-density region in Coma. Observations were performed for 25 fields that extend over a wide range of cluster-centric radii (~1.75 Mpc) with a total coverage area of 274 arcmin^2. The majority of the fields are located near the core region of Coma (19/25 pointings) with six additional fields in the south-west region of the cluster. In this paper we present reprocessed images and SExtractor source catalogs for our survey fields, including a detailed description of the methodology used for object detection and photometry, the subtraction of bright galaxies to measure faint underlying objects, and the use of simulations to assess the photometric accuracy and completeness of our catalogs. We also use simulations to perform aperture corrections for the SExtractor Kron magnitudes based only on the measured source flux and half-light radius. We have performed photometry for ~73,000 unique objects; one-half of our detections are brighter than the 10-sigma point-source detection limit at F814W=25.8 mag (AB). The slight majority of objects (60%) are unresolved or only marginally resolved by ACS. We estimate that Coma members are 5-10% of all source detections, which consist of a large population of unresolved objects (primarily GCs but also UCDs) and a wide variety of extended galaxies from a cD galaxy to dwarf LSB galaxies. The red sequence of Coma member galaxies has a constant slope and dispersion across 9 magnitudes (-21<M_F814W<-13). The initial data release for the HST-ACS Coma Treasury program was made available to the public in 2008 August. The images and catalogs described in this study relate to our second data release.Comment: Accepted for publication in ApJS. A high-resolution version is available at http://archdev.stsci.edu/pub/hlsp/coma/release2/PaperII.pd

GTOSat: Radiation Belt Dynamics from the Inside

GTOSat, a 6U SmallSat integrated and tested at NASA Goddard Space Flight Center (GSFC), has a scheduled launch date of July 31st, 2022, on an Atlas V. From a low inclination geosynchronous transfer orbit (GTO), GTOSat has the primary science goal of advancing our quantitative understanding of acceleration and loss of relativistic electrons in the Earth’s outer radiation belt. It will measure energy spectra and pitch angles of both the seed and the energized electron populations simultaneously using a compact, high-heritage Relativistic Electron Magnetic Spectrometer (REMS) built by The Aerospace Corporation. A boom-mounted Fluxgate Magnetometer (FMAG), developed by NASA GSFC, will provide 3-axis knowledge of the ambient local magnetic field. The spacecraft bus uses a combination of commercial and in-house/custom designed components. Design, integration, and testing of the spacecraft bus was performed by a small, dedicated team at GSFC. Throughout development GTOSat has encountered numerous challenges, expected and unexpected, that we’re ready to share with the community

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma

SummaryWe describe a comprehensive genomic characterization of adrenocortical carcinoma (ACC). Using this dataset, we expand the catalogue of known ACC driver genes to include PRKAR1A, RPL22, TERF2, CCNE1, and NF1. Genome wide DNA copy-number analysis revealed frequent occurrence of massive DNA loss followed by whole-genome doubling (WGD), which was associated with aggressive clinical course, suggesting WGD is a hallmark of disease progression. Corroborating this hypothesis were increased TERT expression, decreased telomere length, and activation of cell-cycle programs. Integrated subtype analysis identified three ACC subtypes with distinct clinical outcome and molecular alterations which could be captured by a 68-CpG probe DNA-methylation signature, proposing a strategy for clinical stratification of patients based on molecular markers

No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study

It is well known that inbreeding increases the risk of recessive monogenic diseases, but it is less certain whether it contributes to the etiology of complex diseases such as schizophrenia. One way to estimate the effects of inbreeding is to examine the association between disease diagnosis and genome-wide autozygosity estimated using runs of homozygosity (ROH) in genome-wide single nucleotide polymorphism arrays. Using data for schizophrenia from the Psychiatric Genomics Consortium (n = 21,868), Keller et al. (2012) estimated that the odds of developing schizophrenia increased by approximately 17% for every additional percent of the genome that is autozygous (β = 16.1, CI(β) = [6.93, 25.7], Z = 3.44, p = 0.0006). Here we describe replication results from 22 independent schizophrenia case-control datasets from the Psychiatric Genomics Consortium (n = 39,830). Using the same ROH calling thresholds and procedures as Keller et al. (2012), we were unable to replicate the significant association between ROH burden and schizophrenia in the independent PGC phase II data, although the effect was in the predicted direction, and the combined (original + replication) dataset yielded an attenuated but significant relationship between Froh and schizophrenia (β = 4.86,CI(β) = [0.90,8.83],Z = 2.40,p = 0.02). Since Keller et al. (2012), several studies reported inconsistent association of ROH burden with complex traits, particularly in case-control data. These conflicting results might suggest that the effects of autozygosity are confounded by various factors, such as socioeconomic status, education, urbanicity, and religiosity, which may be associated with both real inbreeding and the outcome measures of interest