Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Development of a Practical Calibration Procedure for a Clinical SPECT/MRI System Using a Single INSERT Prototype Detector and Multimini Slit-Slat Collimator

In the context of the INSERT project, we have been developing a clinical single photon emission computed tomography (SPECT) insert for a magnetic resonance imaging (MRI) system, in order to perform simultaneous SPECT/MRI of the human brain. This system will consist of 20 CsI:Tl scintillation detectors, 5-cm wide and 10-cm long, with a 72-channel silicon photomultiplier (SiPM) readout per detector, and a multimini slit-slat (MSS) collimator set up in a stationary partial ring. Additionally the system has a custom-built transmit/receive MR coil to ensure compatibility with the SPECT system. Due to the novel design of the system/collimator, existing geometric calibration methods are not suitable. Therefore we propose a novel and practical calibration procedure that consists of a set of specific independent measurements to determine the geometric parameters of the collimator. This procedure was developed utilizing a prototype system that consists of a reduced-size single detector with a 36-channel SiPM-based readout and a single MSS collimator module. Validation was performed by reconstructing different imaging phantoms, using a rotating stage to simulate a tomographic acquisition. Regarding uniformity, the coefficient of variation (COV) for the cylinder phantom reconstructed with correct calibration parameters is 6.7%, whereas the COV using incorrect parameters is 9.4%. The quality of the phantom reconstructions provide evidence of the applicability of the proposed method to the calibration of the prototype system. This procedure can be easily adapted for the final INSERT system

Development of a Practical Calibration Procedure for a Clinical SPECT/MRI System Using a Single INSERT Prototype Detector and Multimini Slit-Slat Collimator

In the context of the INSERT project, we have been developing a clinical single photon emission computed tomography (SPECT) insert for a magnetic resonance imaging (MRI) system, in order to perform simultaneous SPECT/MRI of the human brain. This system will consist of 20 CsI:Tl scintillation detectors, 5-cm wide and 10-cm long, with a 72-channel silicon photomultiplier (SiPM) readout per detector, and a multimini slit-slat (MSS) collimator set up in a stationary partial ring. Additionally the system has a custom-built transmit/receive MR coil to ensure compatibility with the SPECT system. Due to the novel design of the system/collimator, existing geometric calibration methods are not suitable. Therefore we propose a novel and practical calibration procedure that consists of a set of specific independent measurements to determine the geometric parameters of the collimator. This procedure was developed utilizing a prototype system that consists of a reduced-size single detector with a 36-channel SiPM-based readout and a single MSS collimator module. Validation was performed by reconstructing different imaging phantoms, using a rotating stage to simulate a tomographic acquisition. Regarding uniformity, the coefficient of variation (COV) for the cylinder phantom reconstructed with correct calibration parameters is 6.7%, whereas the COV using incorrect parameters is 9.4%. The quality of the phantom reconstructions provide evidence of the applicability of the proposed method to the calibration of the prototype system. This procedure can be easily adapted for the final INSERT system

A SiPM-based detection module for SPECT/MRI systems

In the present work we present the development of a Silicon PhotoMultiplier (SiPM)-based detection module for hybrid SPECT/MRI instruments. The module is designed for preclinical SPECT systems for mouse and rat brain imaging, but can also be exploited for clinical SPECT brain scanners. The gamma-ray detection module is designed on the well established Anger architecture, with a continuous 5 cm × 5 cm CsI:Tl scintillator read by an array of SiPMs (RGB-HD with 25 μm SPAD cells) from Fondazione Bruno Kessler. The current signals are conveyed to a 36-channel ASIC realized in 0.35 μm CMOS technology and digitized by an external data acquisition system. An operative temperature of 0◦C is mandatory to reduce the dark count rate of the SiPM array and to enhance the final performance of the detector in terms of energy and spatial resolution. For this purpose, an MRI-compatible heat sink is realized with a plastic material (Coolpolymer D5506) with a glycol-water mixture as cooling fluid. Gamma-ray measurements with Co-57 (122 keV) have provided an energy resolution better than 14% and an average intrinsic spatial resolution below 1.0 mm

No indication of strict host associations in a widespread mycoparasite: Grapevine Powdery Mildew (Erysiphe necator) is attacked by phylogenetically distant Ampelomyces strains in the field

Pycnidial fungi belonging to the genus Ampelomyces are common intracellular mycoparasites of powdery mildews worldwide. Some strains have already been developed as commercial biocontrol agents (BCAs) of Erysiphe necator and other powdery mildew species infecting important crops. One of the basic, and still debated, questions concerning the tritrophic relationships between host plants, powdery mildew fungi, and Ampelomyces mycoparasites is whether Ampelomyces strains isolated from certain species of the Erysiphales are narrowly specialized to their original mycohosts or are generalist mycoparasites of many powdery mildew fungi. This is also important for the use of Ampelomyces strains as BCAs. To understand this relationship, the nuclear ribosomal DNA internal transcribed spacer (ITS) and partial actin gene (act1) sequences of 55 Ampelomyces strains from E. necator were analyzed together with those of 47 strains isolated from other powdery mildew species. These phylogenetic analyses distinguished five major clades and strains from E. necator that were present in all but one clade. This work was supplemented with the selection of nine inter-simple sequence repeat (ISSR) markers for strain-specific identification of Ampelomyces mycoparasites to monitor the environmental fate of strains applied as BCAs. The genetic distances among strains calculated based on ISSR patterns have also highlighted the genetic diversity of Ampelomyces mycoparasites naturally occurring in grapevine powdery mildew. Overall, this work showed that Ampelomyces strains isolated from E. necator are genetically diverse and there is no indication of strict mycohost associations in these strains. However, these results cannot rule out a certain degree of quantitative association between at least some of the Ampelomyces lineages identified in this work and their original mycohosts

Development of a SiPM-based Anger camera for INSERT, a new multi-modality SPECT/MRI system for preclinical and clinical imaging

A new multi-modality imaging tool is under development in the framework of the INSERT (INtegrated SPECT/MRI for Enhanced Stratification in Radio-chemoTherapy) project, supported by the European Community. A custom SPECT apparatus, used as an insert for commercially available MRI systems, could enhance the treatment of brain tumors (primarily glioma) by offering more effective and earlier diagnosis with potentially better outcome in survival. In this work we briefly describe the architecture of the gamma-ray photo-detection module with focus on the Silicon PhotoMultiplier (SiPM) detectors and their performance with low-energy gamma-rays (57Co - 122 keV). The camera has a 50.40 mm × 51.70 mm photo-detection area, comprising of 144 SiPMs with 36 readout channels, each one composed of four short-circuited SiPMs for an 8 mm × 8 mm active area. We have developed an Anger camera to characterize and qualify the array when coupled to a CsI:Tl scintillator (8 mm thick). We have measured an intrinsic spatial resolution better than 1.35 mm and an energy resolution below 14% using a 57Co source, when the tile is cooled down to -17°C to reduce the impact of the dark count rate on the measurements