Maximizing dose reductions with cardiac CT

Multidetector computed tomography has come a long way in a short time, quickly becoming a standard tool in the cardiac imaging armamentarium. The promise of plaque imaging, combined with both anatomical visualization and stenosis detection, has made this a preferred first line test of many cardiologists and radiologists. This test is well suited to rule out coronary artery disease (obstruction) and still diagnosing subclinical plaque, with may be a good target for anti-atherosclerotic therapies. There has been recent criticism against CT imaging, and cardiac CT specifically, due to the high radiation doses that being employed. New advances have allowed for dramatic dose reductions. These include more routinely performed methods such as dose modulation, and newer methods such as prospective gating or minimizing the field of view. This paper will review the different applications to reduce cardiac CT radiation doses to nominal levels, potentially expanding the applications of cardiac CT by removing one of the biggest barriers

Functional assessment of coronary artery flow using adenosine stress dual-energy CT: a preliminary study

We attempted to assess coronary artery flow using adenosine-stress and dual-energy mode with dual-source CT (DE-CT). Data of 18 patients with suspected coronary arteries disease who had undergone cardiac DE-CT were retrospectively analyzed. The patients were divided into two groups: 10 patients who performed adenosine stress CT, and 8 patients who performed rest CT as controls. We reconstructed an iodine map and composite images at 120 kV (120 kV images) using raw data with scan parameters of 100 and 140 kV. We measured mean attenuation in the coronary artery proximal to the distal portion on both the iodine map and 120 kV images. Coronary enhancement ratio (CER) was calculated by dividing mean attenuation in the coronary artery by attenuation in the aortic root, and was used as an estimate of coronary enhancement. Coronary stenosis was identified as a reduction in diameter of >50% on CT angiogram, and myocardial ischemia was diagnosed by adenosine-stress myocardial perfusion scintigraphy. The iodine map showed that CER was significantly lower for ischemic territories (0.76 ± 0.06) or stenosed coronary arteries (0.77 ± 0.06) than for non-ischemic territories (0.95 ± 0.21, P = 0.02) or non-stenosed coronary arteries (1.07 ± 0.33, P < 0.001). The 120 kV images showed no difference in CER between these two groups. Use of CER on the iodine map separated ischemic territories from non-ischemic territories with a sensitivity of 86% and a specificity of 75%. Our quantification is the first non-invasive analytical technique for assessment of coronary artery flow using cardiac CT. CER on the iodine map is a candidate method for demonstration of alteration in coronary artery flow under adenosine stress, which is related to the physiological significance of coronary artery disease

Reduction in downstream test utilization following introduction of coronary computed tomography in a cardiology practice

To compare utilization of non-invasive ischemic testing, invasive coronary angiography (ICA), and percutaneous coronary intervention (PCI) procedures before and after introduction of 64-slice multi-detector row coronary computed tomographic angiography (CCTA) in a large urban primary and consultative cardiology practice. We utilized a review of electronic medical records (NotesMD®) and the electronic practice management system (Megawest®) encompassing a 4-year period from 2004 to 2007 to determine the number of exercise treadmill (TME), supine bicycle exercise echocardiography (SBE), single photon emission computed tomography (SPECT) myocardial perfusion stress imaging (MPI), coronary calcium score (CCS), CCTA, ICA, and PCI procedures performed annually. Test utilization in the 2 years prior to and 2 years following availability of CCTA were compared. Over the 4-year period reviewed, the annual utilization of ICA decreased 45% (2,083 procedures in 2004 vs. 1,150 procedures in 2007, P < 0.01) and the percentage of ICA cases requiring PCI increased (19% in 2004 vs. 28% in 2007, P < 0.001). SPECT MPI decreased 19% (3,223 in 2004 vs. 2,614 in 2007 P < 0.02) and exercise stress treadmill testing decreased 49% (471 in 2004 vs. 241 in 2007 P < 0.02). Over the same period, there were no significant changes in measures of practice volume (office and hospital) or the annual incidence of PCI (405 cases in 2004 vs. 326 cases in 2007) but a higher percentage of patients with significant disease undergoing PCI 19% in 2004 vs. 29% in 2007 P < 0.01. Implementation of CCTA resulted in a significant decrease in ICA and a corresponding significant increase in the percentage of ICA cases requiring PCI, indicating that CCTA resulted in more accurate referral for ICA. The reduction in unnecessary ICA is associated with avoidance of potential morbidity and mortality associated with invasive diagnostic testing, reduction of downstream SPECT MPI and TME as well as substantial savings in health care dollars

Plasmodium APC3 mediates chromosome condensation and cytokinesis during atypical mitosis in male gametogenesis

The anaphase promoting complex/cyclosome (APC/C) is a highly conserved multi-subunit E3 ubiquitin ligase that controls mitotic division in eukaryotic cells by tagging cell cycle regulators for proteolysis. APC3 is a key component that contributes to APC/C function. Plasmodium, the causative agent of malaria, undergoes atypical mitotic division during its life cycle. Only a small subset of APC/C components has been identified in Plasmodium and their involvement in atypical cell division is not well understood. Here, using reverse genetics we examined the localisation and function of APC3 in Plasmodium berghei. APC3 was observed as a single focus that co-localised with the centriolar plaque during asexual cell division in schizonts, whereas it appeared as multiple foci in male gametocytes. Functional studies using gene disruption and conditional knockdown revealed essential roles of APC3 during these mitotic stages with loss resulting in a lack of chromosome condensation, abnormal cytokinesis and absence of microgamete formation. Overall, our data suggest that Plasmodium utilises unique cell cycle machinery to coordinate various processes during ndomitosis, and this warrants further investigation in future studies

Automatic centerline extraction of coronary arteries in coronary computed tomographic angiography

Coronary computed tomographic angiography (CCTA) is a non-invasive imaging modality for the visualization of the heart and coronary arteries. To fully exploit the potential of the CCTA datasets and apply it in clinical practice, an automated coronary artery extraction approach is needed. The purpose of this paper is to present and validate a fully automatic centerline extraction algorithm for coronary arteries in CCTA images. The algorithm is based on an improved version of Frangi’s vesselness filter which removes unwanted step-edge responses at the boundaries of the cardiac chambers. Building upon this new vesselness filter, the coronary artery extraction pipeline extracts the centerlines of main branches as well as side-branches automatically. This algorithm was first evaluated with a standardized evaluation framework named Rotterdam Coronary Artery Algorithm Evaluation Framework used in the MICCAI Coronary Artery Tracking challenge 2008 (CAT08). It includes 128 reference centerlines which were manually delineated. The average overlap and accuracy measures of our method were 93.7% and 0.30 mm, respectively, which ranked at the 1st and 3rd place compared to five other automatic methods presented in the CAT08. Secondly, in 50 clinical datasets, a total of 100 reference centerlines were generated from lumen contours in the transversal planes which were manually corrected by an expert from the cardiology department. In this evaluation, the average overlap and accuracy were 96.1% and 0.33 mm, respectively. The entire processing time for one dataset is less than 2 min on a standard desktop computer. In conclusion, our newly developed automatic approach can extract coronary arteries in CCTA images with excellent performances in extraction ability and accuracy

The emerging structure of the Extended Evolutionary Synthesis: where does Evo-Devo fit in?

The Extended Evolutionary Synthesis (EES) debate is gaining ground in contemporary evolutionary biology. In parallel, a number of philosophical standpoints have emerged in an attempt to clarify what exactly is represented by the EES. For Massimo Pigliucci, we are in the wake of the newest instantiation of a persisting Kuhnian paradigm; in contrast, Telmo Pievani has contended that the transition to an EES could be best represented as a progressive reformation of a prior Lakatosian scientific research program, with the extension of its Neo-Darwinian core and the addition of a brand-new protective belt of assumptions and auxiliary hypotheses. Here, we argue that those philosophical vantage points are not the only ways to interpret what current proposals to ‘extend’ the Modern Synthesis-derived ‘standard evolutionary theory’ (SET) entail in terms of theoretical change in evolutionary biology. We specifically propose the image of the emergent EES as a vast network of models and interweaved representations that, instantiated in diverse practices, are connected and related in multiple ways. Under that assumption, the EES could be articulated around a paraconsistent network of evolutionary theories (including some elements of the SET), as well as models, practices and representation systems of contemporary evolutionary biology, with edges and nodes that change their position and centrality as a consequence of the co-construction and stabilization of facts and historical discussions revolving around the epistemic goals of this area of the life sciences. We then critically examine the purported structure of the EES—published by Laland and collaborators in 2015—in light of our own network-based proposal. Finally, we consider which epistemic units of Evo-Devo are present or still missing from the EES, in preparation for further analyses of the topic of explanatory integration in this conceptual framework

Evidence for strong, widespread chlorine radical chemistry associated with pollution outflow from continental Asia

The chlorine radical is a potent atmospheric oxidant, capable of perturbing tropospheric oxidative cycles normally controlled by the hydroxyl radical. Significantly faster reaction rates allow chlorine radicals to expedite oxidation of hydrocarbons, including methane, and in polluted environments, to enhance ozone production. Here we present evidence, from the CARIBIC airborne dataset, for extensive chlorine radical chemistry associated with Asian pollution outflow, from airborne observations made over the Malaysian Peninsula in winter. This region is known for persistent convection that regularly delivers surface air to higher altitudes and serves as a major transport pathway into the stratosphere. Oxidant ratios inferred from hydrocarbon relationships show that chlorine radicals were regionally more important than hydroxyl radicals for alkane oxidation and were also important for methane and alkene oxidation (>10%). Our observations reveal pollution-related chlorine chemistry that is both widespread and recurrent, and has implications for tropospheric oxidizing capacity, stratospheric composition and ozone chemistry

Role of the Cellular Prion Protein in Oligodendrocyte Precursor Cell Proliferation and Differentiation in the Developing and Adult Mouse CNS

There are numerous studies describing the signaling mechanisms that mediate oligodendrocyte precursor cell (OPC) proliferation and differentiation, although the contribution of the cellular prion protein (PrPc) to this process remains unclear. PrPc is a glycosyl-phosphatidylinositol (GPI)-anchored glycoprotein involved in diverse cellular processes during the development and maturation of the mammalian central nervous system (CNS). Here we describe how PrPc influences oligodendrocyte proliferation in the developing and adult CNS. OPCs that lack PrPc proliferate more vigorously at the expense of a delay in differentiation, which correlates with changes in the expression of oligodendrocyte lineage markers. In addition, numerous NG2-positive cells were observed in cortical regions of adult PrPc knockout mice, although no significant changes in myelination can be seen, probably due to the death of surplus cells

Prevalence of anatomical variants and coronary anomalies in 543 consecutive patients studied with 64-slice CT coronary angiography

The aim of our study was to assess the prevalence of variants and anomalies of the coronary artery tree in patients who underwent 64-slice computed tomography coronary angiography (CT-CA) for suspected or known coronary artery disease. A total of 543 patients (389 male, mean age 60.5 ± 10.9) were reviewed for coronary artery variants and anomalies including post-processing tools. The majority of segments were identified according to the American Heart Association scheme. The coronary dominance pattern results were: right, 86.6%; left, 9.2%; balanced, 4.2%. The left main coronary artery had a mean length of 112 ± 55 mm. The intermediate branch was present in the 21.9%. A variable number of diagonals (one, 25%; two, 49.7%; more than two, 24%; none, 1.3%) and marginals (one, 35.2%; two, 46.2%; more than two, 18%; none, 0.6%) was visualized. Furthermore, CT-CA may visualize smaller branches such as the conus branch artery (98%), the sinus node artery (91.6%), and the septal branches (93%). Single or associated coronary anomalies occurred in 18.4% of the patients, with the following distribution: 43 anomalies of origin and course, 68 intrinsic anomalies (59 myocardial bridging, nine aneurisms), three fistulas. In conclusion, 64-slice CT-CA provides optimal visualization of the variable and complex anatomy of coronary arteries because of the improved isotropic spatial resolution and flexible post-processing tool

Influence of Microbial Biofilms on the Preservation of Primary Soft Tissue in Fossil and Extant Archosaurs

Background: Mineralized and permineralized bone is the most common form of fossilization in the vertebrate record. Preservation of gross soft tissues is extremely rare, but recent studies have suggested that primary soft tissues and biomolecules are more commonly preserved within preserved bones than had been presumed. Some of these claims have been challenged, with presentation of evidence suggesting that some of the structures are microbial artifacts, not primary soft tissues. The identification of biomolecules in fossil vertebrate extracts from a specimen of Brachylophosaurus canadensis has shown the interpretation of preserved organic remains as microbial biofilm to be highly unlikely. These discussions also propose a variety of potential mechanisms that would permit the preservation of soft-tissues in vertebrate fossils over geologic time. Methodology/Principal Findings: This study experimentally examines the role of microbial biofilms in soft-tissue preservation in vertebrate fossils by quantitatively establishing the growth and morphology of biofilms on extant archosaur bone. These results are microscopically and morphologically compared with soft-tissue extracts from vertebrate fossils from the Hell Creek Formation of southeastern Montana (Latest Maastrichtian) in order to investigate the potential role of microbial biofilms on the preservation of fossil bone and bound organic matter in a variety of taphonomic settings. Base