Abstract
The purpose of the presented research is estimation of the performance characteristics of the economic total-body Jagiellonian-PET system (TB-J-PET) constructed from plastic scintillators. ...The characteristics are estimated according to the NEMA NU-2-2018 standards utilizing the GATE package. The simulated detector consists of 24 modules, each built out of 32 plastic scintillator strips (each with cross section of 6 mm times 30 mm and length of 140 or 200 cm) arranged in two layers in regular 24-sided polygon circumscribing a circle with the diameter of 78.6 cm. For the TB-J-PET with an axial field-of-view (AFOV) of 200 cm, a spatial resolutions (SRs) of 3.7 mm (transversal) and 4.9 mm (axial) are achieved. The noise equivalent count rate (NECR) peak of 630 kcps is expected at 30 kBq cc
−1
. Activity concentration and the sensitivity at the center amounts to 38 cps kBq
−1
. The scatter fraction (SF) is estimated to 36.2 %. The values of SF and SR are comparable to those obtained for the state-of-the-art clinical PET scanners and the first total-body tomographs: uExplorer and PennPET. With respect to the standard PET systems with AFOV in the range from 16 to 26 cm, the TB-J-PET is characterized by an increase in NECR approximately by factor of 4 and by the increase of the whole-body sensitivity by factor of 12.6 to 38. The time-of-flight resolution for the TB-J-PET is expected to be at the level of CRT = 240 ps full width at half maximum. For the TB-J-PET with an AFOV of 140 cm, an image quality of the reconstructed images of a NEMA IEC phantom was presented with a contrast recovery coefficient and a background variability parameters. The increase of the whole-body sensitivity and NECR estimated for the TB-J-PET with respect to current commercial PET systems makes the TB-J-PET a promising cost-effective solution for the broad clinical applications of total-body PET scanners. TB-J-PET may constitute an economic alternative for the crystal TB-PET scanners, since plastic scintillators are much cheaper than BGO or LYSO crystals and axial arrangement of the strips significantly reduces the costs of readout electronics and SiPMs.
Summary
The FREEDOM study and its Extension provide long-term information about the effects of denosumab for the treatment of postmenopausal osteoporosis. Treatment for up to 8 years was associated ...with persistent reduction of bone turnover, continued increases in bone mineral density, low fracture incidence, and a favorable benefit/risk profile.
Introduction
This study aims to report the results through year 5 of the FREEDOM Extension study, representing up to 8 years of continued denosumab treatment in postmenopausal women with osteoporosis.
Methods
Women who completed the 3-year FREEDOM study were eligible to enter the 7-year open-label FREEDOM Extension in which all participants are scheduled to receive denosumab, since placebo assignment was discontinued for ethical reasons. A total of 4550 women enrolled in the Extension (2343 long-term; 2207 cross-over). In this analysis, women in the long-term and cross-over groups received denosumab for up to 8 and 5 years, respectively.
Results
Throughout the Extension, sustained reduction of bone turnover markers (BTMs) was observed in both groups. In the long-term group, mean bone mineral density (BMD) continued to increase significantly at each time point measured, for cumulative 8-year gains of 18.4 and 8.3 % at the lumbar spine and total hip, respectively. In the cross-over group, mean BMD increased significantly from the Extension baseline for 5-year cumulative gains of 13.1 and 6.2 % at the lumbar spine and total hip, respectively. The yearly incidence of new vertebral and nonvertebral fractures remained low in both groups. The incidence of adverse and serious adverse events did not increase over time. Through Extension year 5, eight events of osteonecrosis of the jaw and two events of atypical femoral fracture were confirmed.
Conclusions
Denosumab treatment for up to 8 years was associated with persistent reductions of BTMs, continued BMD gains, low fracture incidence, and a consistent safety profile.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We present a study of the application of the Jagiellonian positron emission tomograph (J-PET) for the registration of gamma quanta from decays of ortho-positronium (o-Ps). The J-PET is the first ...positron emission tomography scanner based on organic scintillators in contrast to all current PET scanners based on inorganic crystals. Monte Carlo simulations show that the J-PET as an axially symmetric and high acceptance scanner can be used as a multi-purpose detector well suited to pursue research including e.g. tests of discrete symmetries in decays of ortho-positronium in addition to the medical imaging. The gamma quanta originating from o-Ps decay interact in the plastic scintillators predominantly via the Compton effect, making the direct measurement of their energy impossible. Nevertheless, it is shown in this paper that the J-PET scanner will enable studies of the
o-Ps
→
3
γ
decays with angular and energy resolution equal to
σ
(
θ
)
≈
0
.
4
∘
and
σ
(
E
)
≈
4.1
keV
, respectively. An order of magnitude shorter decay time of signals from plastic scintillators with respect to the inorganic crystals results not only in better timing properties crucial for the reduction of physical and instrumental background, but also suppresses significantly the pile-ups, thus enabling compensation of the lower efficiency of the plastic scintillators by performing measurements with higher positron source activities.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A detection system of the conventional PET tomograph is set-up to record data from annihilation into two photons with energy of 511 keV, and it gives information on the density distribution of a ...radiopharmaceutical in the body of the object. In this paper we explore the possibility of performing the three gamma photons imaging based on ortho-positronium annihilation, as well as the possibility of positronium mean lifetime imaging with the J-PET tomograph constructed from plastic scintillators. For this purposes simulations of the ortho-positronium formation and its annihilation into three photons were performed taking into account distributions of photons' momenta as predicted by the theory of quantum electrodynamics and the response of the J-PET tomograph. In order to test the proposed ortho-positronium lifetime image reconstruction method, we concentrate on the decay of the ortho-positronium into three photons and applications of radiopharmaceuticals labeled with isotopes emitting a prompt gamma. The proposed method of imaging is based on the determination of hit-times and hit-positions of registered photons which enables the reconstruction of the time and position of the annihilation point as well as the lifetime of the ortho-positronium on an event-by-event basis. We have simulated the production of the positronium in point-like sources and in a cylindrical phantom composed of a set of different materials in which the ortho-positronium lifetime varied from 2.0 ns to 3.0 ns, as expected for ortho-positronium created in the human body. The presented reconstruction method for total-body J-PET like detector allows to achieve a mean lifetime resolution of 40 ps. Recent positron annihilation lifetime spectroscopy measurements of cancerous and healthy uterine tissues show that this sensitivity may allow to study the morphological changes in cell structures.
Recent tests of a single module of the Jagiellonian Positron Emission Tomography system (J-PET) consisting of 30 cm long plastic scintillator strips have proven its applicability for the detection of ...annihilation quanta (0.511 MeV) with a coincidence resolving time (CRT) of 0.266 ns. The achieved resolution is almost by a factor of two better with respect to the current TOF-PET detectors and it can still be improved since, as it is shown in this article, the intrinsic limit of time resolution for the determination of time of the interaction of 0.511 MeV gamma quanta in plastic scintillators is much lower. As the major point of the article, a method allowing to record timestamps of several photons, at two ends of the scintillator strip, by means of matrix of silicon photomultipliers (SiPM) is introduced. As a result of simulations, conducted with the number of SiPM varying from 4 to 42, it is shown that the improvement of timing resolution saturates with the growing number of photomultipliers, and that the configuration at two ends allowing to read twenty timestamps, constitutes an optimal solution. The conducted simulations accounted for the emission time distribution, photon transport and absorption inside the scintillator, as well as quantum efficiency and transit time spread of photosensors, and were checked based on the experimental results. Application of the matrix of SiPM allows for achieving the coincidence resolving time in positron emission tomography of 0.170 ns for 15 cm axial field-of-view (AFOV) and 0.365 ns for 100 cm AFOV. The results open perspectives for construction of a cost-effective TOF-PET scanner with significantly better TOF resolution and larger AFOV with respect to the current TOF-PET modalities.
Summary
Transitioning postmenopausal women with osteoporosis from a bisphosphonate to denosumab appears to be safe and more effective at improving BMD than continuing treatment with a bisphosphonate.
...Introduction
We conducted a patient-level pooled analysis of four studies to estimate the efficacy and safety of transitioning to denosumab vs. continuing bisphosphonate treatment in postmenopausal women who previously received oral bisphosphonates.
Methods
Patients received 60 mg denosumab once every 6 months or a bisphosphonate (oral alendronate, risedronate, ibandronate, or intravenous zoledronic acid). Endpoints were change from baseline in lumbar spine, total hip, femoral neck, and 1/3 radius BMD at month 12, change from baseline in serum CTX-1 and P1NP, and incidence of adverse events.
Results
A total of 2850 randomized patients (1424 bisphosphonate:1426 denosumab) were included in the analysis. Percentage change in BMD was significantly greater (
p
< 0.001) for denosumab vs. bisphosphonate at each skeletal site; differences in BMD changes ranged from 0.6 to 2.0%. Percentage decrease in serum CTX-1 and P1NP was significantly greater (
p
< 0.0001) for denosumab vs. bisphosphonate at months 1, 6, and 12; in the denosumab group only, percentage change in serum CTX-1 at month 1 was significantly correlated with percentage change in lumbar spine and total hip BMD at month 12. The incidences of adverse events were similar between treatment groups. Three patients (one bisphosphonate and two denosumab) had atypical femoral fractures, all from the denosumab vs. zoledronic acid study.
Conclusion
Postmenopausal women can safely transition from a bisphosphonate to denosumab, which is more effective at improving BMD than continuing with a bisphosphonate.
Clinical trials registration
NCT00377819, NCT00919711, NCT00936897, NCT01732770.
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Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Charged lepton system symmetry under combined charge, parity, and time-reversal transformation (CPT) remains scarcely tested. Despite stringent quantum-electrodynamic limits, discrepancies ...in predictions for the electron–positron bound state (positronium atom) motivate further investigation, including fundamental symmetry tests. While CPT noninvariance effects could be manifested in non-vanishing angular correlations between final-state photons and spin of annihilating positronium, measurements were previously limited by knowledge of the latter. Here, we demonstrate tomographic reconstruction techniques applied to three-photon annihilations of ortho-positronium atoms to estimate their spin polarisation without magnetic field or polarised positronium source. We use a plastic-scintillator-based positron-emission-tomography scanner to record ortho-positronium (o-Ps) annihilations with single-event estimation of o-Ps spin and determine the complete spectrum of an angular correlation operator sensitive to CPT-violating effects. We find no violation at the precision level of 10
−4
, with an over threefold improvement on the previous measurement.
J-PET is a detector optimized for registration of photons from the electron–positron annihilation via plastic scintillators where photons interact predominantly via Compton scattering. Registration ...of both primary and scattered photons enables to determinate the linear polarization of the primary photon on the event by event basis with a certain probability. Here we present quantitative results on the feasibility of such polarization measurements of photons from the decay of positronium with the J-PET and explore the physical limitations for the resolution of the polarization determination of 511 keV photons via Compton scattering. For scattering angles of about 82
∘
(where the best contrast for polarization measurement is theoretically predicted) we find that the single event resolution for the determination of the polarization is about 40
∘
(predominantly due to properties of the Compton effect). However, for samples larger than ten thousand events the J-PET is capable of determining relative average polarization of these photons with the precision of about few degrees. The obtained results open new perspectives for studies of various physics phenomena such as quantum entanglement and tests of discrete symmetries in decays of positronium and extend the energy range of polarization measurements by five orders of magnitude beyond the optical wavelength regime.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK