Development of a GPU-based Monte Carlo dose calculation code for coupled electron-photon transport

Monte Carlo simulation is the most accurate method for absorbed dose calculations in radiotherapy. Its efficiency still requires improvement for routine clinical applications, especially for online adaptive radiotherapy. In this paper, we report our recent development on a GPU-based Monte Carlo dose calculation code for coupled electron-photon transport. We have implemented the Dose Planning Method (DPM) Monte Carlo dose calculation package (Sempau et al, Phys. Med. Biol., 45(2000)2263-2291) on GPU architecture under CUDA platform. The implementation has been tested with respect to the original sequential DPM code on CPU in phantoms with water-lung-water or water-bone-water slab geometry. A 20 MeV mono-energetic electron point source or a 6 MV photon point source is used in our validation. The results demonstrate adequate accuracy of our GPU implementation for both electron and photon beams in radiotherapy energy range. Speed up factors of about 5.0 ~ 6.6 times have been observed, using an NVIDIA Tesla C1060 GPU card against a 2.27GHz Intel Xeon CPU processor.Comment: 13 pages, 3 figures, and 1 table. Paper revised. Figures update

A Monte Carlo simulation of the Sudbury Neutrino Observatory proportional counters

The third phase of the Sudbury Neutrino Observatory (SNO) experiment added an array of 3He proportional counters to the detector. The purpose of this Neutral Current Detection (NCD) array was to observe neutrons resulting from neutral-current solar neutrino-deuteron interactions. We have developed a detailed simulation of the current pulses from the NCD array proportional counters, from the primary neutron capture on 3He through the NCD array signal-processing electronics. This NCD array Monte Carlo simulation was used to model the alpha-decay background in SNO's third-phase 8B solar-neutrino measurement.Comment: 38 pages; submitted to the New Journal of Physic

GATE : a simulation toolkit for PET and SPECT

Monte Carlo simulation is an essential tool in emission tomography that can assist in the design of new medical imaging devices, the optimization of acquisition protocols, and the development or assessment of image reconstruction algorithms and correction techniques. GATE, the Geant4 Application for Tomographic Emission, encapsulates the Geant4 libraries to achieve a modular, versatile, scripted simulation toolkit adapted to the field of nuclear medicine. In particular, GATE allows the description of time-dependent phenomena such as source or detector movement, and source decay kinetics. This feature makes it possible to simulate time curves under realistic acquisition conditions and to test dynamic reconstruction algorithms. A public release of GATE licensed under the GNU Lesser General Public License can be downloaded at the address http://www-lphe.epfl.ch/GATE/

Validation of a small-animal PET simulation using GAMOS: a Geant4-based framework

onte Carlo-based modelling is a powerful tool to help in the design and optimization of positron emission tomography (PET) systems. The performance of these systems depends on several parameters, such as detector physical characteristics, shielding or electronics, whose effects can be studied on the basis of realistic simulated data. The aim of this paper is to validate a comprehensive study of the Raytest ClearPET small-animal PET scanner using a new Monte Carlo simulation platform which has been developed at CIEMAT (Madrid, Spain), called GAMOS (GEANT4-based Architecture for Medicine-Oriented Simulations). This toolkit, based on the GEANT4 code, was originally designed to cover multiple applications in the field of medical physics from radiotherapy to nuclear medicine, but has since been applied by some of its users in other fields of physics, such as neutron shielding, space physics, high energy physics, etc. Our simulation model includes the relevant characteristics of the ClearPET system, namely, the double layer of scintillator crystals in phoswich configuration, the rotating gantry, the presence of intrinsic radioactivity in the crystals or the storage of single events for an off-line coincidence sorting. Simulated results are contrasted with experimental acquisitions including studies of spatial resolution, sensitivity, scatter fraction and count rates in accordance with the National Electrical Manufacturers Association (NEMA) NU 4-2008 protocol. Spatial resolution results showed a discrepancy between simulated and measured values equal to 8.4% (with a maximum FWHM difference over all measurement directions of 0.5 mm). Sensitivity results differ less than 1% for a 250–750 keV energy window. Simulated and measured count rates agree well within a wide range of activities, including under electronic saturation of the system (the measured peak of total coincidences, for the mouse-sized phantom, was 250.8 kcps reached at 0.95 MBq mL−1 and the simulated peak was 247.1 kcps at 0.87 MBq mL−1). Agreement better than 3% was obtained in the scatter fraction comparison study. We also measured and simulated a mini-Derenzo phantom obtaining images with similar quality using iterative reconstruction methods. We concluded that the overall performance of the simulation showed good agreement with the measured results and validates the GAMOS package for PET applications. Furthermore, its ease of use and flexibility recommends it as an excellent tool to optimize design features or image reconstruction techniques

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402