Procedural recommendations of cardiac PET/CT imaging:standardization in inflammatory-, infective-, infiltrative-, and innervation (4Is)-related cardiovascular diseases: a joint collaboration of the EACVI and the EANM

With this document, we provide a standard for PET/(diagnostic) CT imaging procedures in cardiovascular diseases that are inflammatory, infective, infiltrative, or associated with dysfunctional innervation (4Is). This standard should be applied in clinical practice and integrated in clinical (multicenter) trials for optimal procedural standardization. A major focus is put on procedures using [18F]FDG, but 4Is PET radiopharmaceuticals beyond [18F]FDG are also described in this document. Whilst these novel tracers are currently mainly applied in early clinical trials, some multicenter trials are underway and we foresee in the near future their use in clinical care and inclusion in the clinical guidelines. Finally, PET/MR applications in 4Is cardiovascular diseases are also briefly described. Diagnosis and management of 4Is-related cardiovascular diseases are generally complex and often require a multidisciplinary approach by a team of experts. The new standards described herein should be applied when using PET/CT and PET/MR, within a multimodality imaging framework both in clinical practice and in clinical trials for 4Is cardiovascular indications.</p

Folate receptor-β imaging using 99mTc-folate to explore distribution of polarized macrophage populations in human atherosclerotic plaque

UNLABELLED: In atherosclerotic plaques, the risk of rupture is increased at sites of macrophage accumulation. Activated macrophages express folate receptor-β (FR-β), which can be targeted by folate coupled to radioactive ligands to visualize vulnerability. The aim of this study was to explore the presence of activated macrophages in human atherosclerotic plaques by (99m)Tc-folate imaging and to evaluate whether this technique can discriminate between an M1-like and M2-like macrophage phenotype. METHODS: Carotid endarterectomy specimens of 20 patients were incubated with (99m)Tc-folate, imaged using micro-SPECT, and divided into 3-mm slices. The mean accumulation was calculated per slice, and the distribution of M1-like and M2-like macrophages per slice was quantified by immunohistochemical staining for CD86 as well as inducible nitric oxide synthase (iNOS) for M1 and CD163 and FR-β for M2 macrophages. Monocytes from healthy donors were differentiated toward M1-like or M2-like phenotype by in vitro culturing. Messenger RNA levels of specific M1 and M2 markers were measured by reverse-transcription polymerase chain reaction and expression of FR-β, CD86, and CD163 by flow cytometry. RESULTS: There was a heterogeneous accumulation of (99m)Tc-folate in plaques (median, 2.45 [0.77-6.40] MBq/g). Slices with the highest (99m)Tc-folate accumulation of each plaque showed significantly more expression of FR-β and CD163, compared with slices with the lowest (99m)Tc-folate accumulation, which showed significantly more expression of iNOS. In in vitro polarized macrophages, messenger RNA expression of FR-β, mannose receptor, IL-10, and matrix metalloproteinase-9 was significantly increased in M2-like macrophages, compared with M1-like macrophages. On a receptor level, CD86 was shown to be overexpressed on M1-like macrophages whereas FR-β and CD163 were overexpressed on M2-like macrophages measured by flow cytometry. CONCLUSION: Higher numbers of M2-like macrophages were present in areas of high (99m)Tc-folate accumulation than areas with low accumulation. It is anticipated that (99m)Tc-folate imaging using SPECT as a marker for M2-like macrophages in atherosclerosis might be a good indicator for plaque vulnerability

Procedural recommendations of cardiac PET/CT imaging: standardization in inflammatory-, infective-, infiltrative-, and innervation- (4Is) related cardiovascular diseases: a joint collaboration of the EACVI and the EANM: summary

With this summarized document we share the standard for positron emission tomography (PET)/(diagnostic)computed tomography (CT) imaging procedures in cardiovascular diseases that are inflammatory, infective, infiltrative, or associated with dysfunctional innervation (4Is) as recently published in the European Journal of Nuclear Medicine and Molecular Imaging. This standard should be applied in clinical practice and integrated in clinical (multicentre) trials for optimal standardization of the procedurals and interpretations. A major focus is put on procedures using [18F]-2-fluoro-2-deoxyglucose ([18F]FDG), but 4Is PET radiopharmaceuticals beyond [18F]FDG are also described in this summarized document. Whilst these novel tracers are currently mainly applied in early clinical trials, some multicentre trials are underway and we foresee in the near future their use in clinical care and inclusion in the clinical guidelines. Diagnosis and management of 4Is related cardiovascular diseases are generally complex and often require a multidisciplinary approach by a team of experts. The new standards described herein should be applied when using PET/CT and PET/magnetic resonance, within a multimodality imaging framework both in clinical practice and in clinical trials for 4Is cardiovascular indications.</p

Procedural recommendations of cardiac PET/CT imaging: standardization in inflammatory-, infective-, infiltrative-, and innervation (4Is)-related cardiovascular diseases: a joint collaboration of the EACVI and the EANM

With this document, we provide a standard for PET/(diagnostic) CT imaging procedures in cardiovascular diseases that are inflammatory, infective, infiltrative, or associated with dysfunctional innervation (4Is). This standard should be applied in clinical practice and integrated in clinical (multicenter) trials for optimal procedural standardization. A major focus is put on procedures using [18F]FDG, but 4Is PET radiopharmaceuticals beyond [18F]FDG are also described in this document. Whilst these novel tracers are currently mainly applied in early clinical trials, some multicenter trials are underway and we foresee in the near future their use in clinical care and inclusion in the clinical guidelines. Finally, PET/MR applications in 4Is cardiovascular diseases are also briefly described. Diagnosis and management of 4Is-related cardiovascular diseases are generally complex and often require a multidisciplinary approach by a team of experts. The new standards described herein should be applied when using PET/CT and PET/MR, within a multimodality imaging framework both in clinical practice and in clinical trials for 4Is cardiovascular indications.</p

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

The Multi-Scale Infrastructure for Chemistry and Aerosols (MUSICA)

To explore the various couplings across space and time and between ecosystems in a consistent manner, atmospheric modeling is moving away from the fractured limited-scale modeling strategy of the past toward a unification of the range of scales inherent in the Earth system. This paper describes the forward-looking Multi-Scale Infrastructure for Chemistry and Aerosols (MUSICA), which is intended to become the next-generation community infrastructure for research involving atmospheric chemistry and aerosols. MUSICA will be developed collaboratively by the National Center for Atmospheric Research (NCAR) and university and government researchers, with the goal of serving the international research and applications communities. The capability of unifying various spatiotemporal scales, coupling to other Earth system components, and process-level modularization will allow advances in both fundamental and applied research in atmospheric composition, air quality, and climate and is also envisioned to become a platform that addresses the needs of policy makers and stakeholders

Entdeckung und Charakterisierung von tierischen small RNA in deep sequencing Daten

Discoveries in the last decade have shown that small RNAs (such as microRNAs) perform a number of important functions, including post-transcriptional gene regulation, transposon silencing, DNA methylation, chromatin modifications and chromosome segregation. The ability of the new deep sequencing technologies to sequence millions of short RNAs in a few hours have made them the method of choice for simultaneous discovery and profiling of small RNAs. However, when the sequenced RNAs are mapped to the reference genome, they typically locate to millions of distinct loci, only a few of which are loci that produce regulatory small RNAs. To distinguish the few loci that produce regulatory small RNAs from the many loci that are sources of other short RNAs like degradation products is a non-trivial computational challenge. In my doctorate works I have formalized knowledge of small RNA biology and biogenesis into computational models that can accurately identify regulatory small RNAs of different classes in much larger pools of sequenced RNAs. As part of collaborations, I have used these models to discover hundreds of novel small RNA genes in more than ten animal species including humans, mice, fruit flies, nematodes and planarian flatworms. We find evidence that a number of these small RNA genes have roles in disease or in stem cell function. Further, some of the novel regulatory small RNAs are in fact cleaved bona fide snoRNAs, revealing cross-talk between two RNA pathways. Last, I have developed methods for precise quantitation of individual small RNAs as well as entire small RNA populations between deep sequencing samples.Die Entdeckungen des letzten Jahrzehnts haben gezeigt, dass so genannte small RNAs, wie zum Beispiel microRNAs, bedeutenden Einfluss auf viele Zellabläufe haben. Dazu zählen unter anderem posttranskriptionelle Regulation, Chromatin Modifikationen sowie Segregation der Chromosomen. So genannte next generation sequencer Maschinen sind dazu in der Lage Millionen von kurzen RNA Molekülen innerhalb nur werniger Stunden zu sequenzieren, weshalb sie heutzutage das Mittel Wahl sind um sowohl neue regulatorische small RNAs zu entdecken als auch Expressionsprofile von diesen zu erstellen. Wenn die sequenzierten RNAs auf das Genom gemappt werden gibt es normalerweise Millionen von verschieden Moeglichkeiten von dem sie stammen koennten, aber nur einige von Ihnen produzieren kleine regulatorische RNAs. Die Identifikation genau dieser wenigen Loci, von denen die kleinen regulatorischen RNA Stücke stammen, ist eine computertechnisch anspruchsvolle Aufgabe. In meiner Doktorarbeit habe ich computerbasierte Modelle auf der Grundlage von der Biologie und Biogenese kleiner RNAs erstellt. Diese Modelle sind dazu in der Lage die Loci der verschiedenen kleinen regulatorischen RNAs zuverlaessig zu identifizieren. Während diverser Kollaborationen mit anderen Arbeitsgruppe habe ich meine Modelle dazu benutzt hunderte von noch nicht detektierten kleinen RNA Genen in mehr als zehn verschiedenen Tierspezies zu identifizieren. Dazu zählen Menschen, Mäuse, Fruchtfliegen und Flachwürmer. Wir haben Evidenz dafür gefunden, dass eine Vielzahl dieser kleinen RNAs eine Rolle in diversen Krankheiten oder Stammzellfunktion spielen. Des Weiteren sind einiger dieser kleinen RNAs tatsächlich prozessierte snoRNAs sind, was auf eine Interaktion der verschiedenen RNA Pathways nahelegt. Als Letzes habe ich noch Methoden entwickelt, die eine präzise Quantifikation von einzelnen kleinen RNAs sowie gesamter Populationen von kleinen RNAs zwischen Proben erlauben