Positron Probe Research Articles

Improvement of phoswich detector-based β+/γ-ray discrimination algorithm with deep learning.

Positron probes can accurately localize malignant tumors by directly detecting positrons emitted from positron-emitting radiopharmaceuticals that accumulate in malignant tumors. In the conventional method for direct positron detection, multilayer scintillator detection and pulse shape discrimination techniques are used. However, some γ-rays cannot be distinguished by conventional methods. Accordingly, these γ-rays are misidentified as positrons, which may increase the error rate of positron detection. To analyze the energy distribution in each scintillator of the multilayer scintillator detector to distinguish true positrons and γ-rays and to improve the positron detection algorithm by discriminating true and false positrons. We used Autoencoder, an unsupervised deep learning architecture, to obtain the energy distribution data in each scintillator of the multilayer scintillator detector. The Autoencoder was trained to separate the combined signals generated from the multilayer scintillator detector into two signals of each scintillator. An energy window was then applied to the energy distribution obtained using the trained Autoencoder to distinguish true positrons from false positrons. Finally, the performance of the proposed method and conventional positron detection algorithm was evaluated in terms of the sensitivity and error rate for positron detection. The energy distribution map obtained using the trained Autoencoder was proven to be similar to that of the simulated results. Furthermore, the proposed method demonstrated a 29.79% (+0.42%p) increase in positron detection sensitivity compared to the conventional method, both having an equal error rate of 0.48%. However, when both methods were set to have the same sensitivity of 1.83%, the proposed method had an error rate that was 25.0% (-0.16%p) lower than that of the conventional method. We proposed and developed an Autoencoder-based positron detection algorithm that can discriminate between true and false positrons with a smaller error rate than conventional methods. We verified that the proposed method could increase the positron detection sensitivity while maintaining a low error rate compared to the conventional method. If the proposed algorithm is implemented in handheld positron detection probes or cameras, diseases such as cancers can be more accurately localized in a shorter time compared with using traditional methods.

Diagnostic and therapeutic agents that target alpha-synuclein in Parkinson's disease.

The development of disease-modifying drugs and differential diagnostic agents is an urgent medical need in Parkinson’s disease. Despite the complex pathophysiological pathway, the misfolding of alpha-synuclein has been identified as a putative biomarker for detecting the onset and progression of the neurodegeneration associated with Parkinson’s disease. Identifying the most appropriate alpha-synuclein-based diagnostic modality with clinical translation will revolutionize the diagnosis of Parkinson’s. Likewise, molecules that target alpha-synuclein could alter the disease pathway that leads to Parkinson’s and may serve as first-in class therapeutics compared to existing treatment options such as levodopa and dopamine agonist that do not necessarily modify the disease pathway. Notwithstanding the promising benefits that alpha-synuclein presents to therapeutics and diagnostics development for Parkinson’s disease, finding ways to address potential challenges such as inadequate preclinical models, safety and efficacy will be paramount to achieving clinical translation. In this comprehensive review paper, we described the role of alpha-synuclein in the pathogenesis of Parkinson’s disease, as well as how its structure and function relationship delineate disease onset and progression. We further discussed different alpha-synuclein-based diagnostic modalities including biomolecular assays and molecular imaging. Finally, we presented current small molecules and biologics that are being developed as disease-modifying drugs or positron emission tomography imaging probes for Parkinson’s disease.

Momentum density spectroscopy of Pd: Comparison of 2D-ACAR and Compton scattering using a 1D-to-2D reconstruction method

Two-dimensional angular correlation of annihilation radiation (2D-ACAR) and Compton scattering are both powerful techniques to investigate the bulk electronic structure of crystalline solids through the momentum density of the electrons. Here we apply both methods to a single crystal of Pd to study the electron momentum density and the occupancy in the first Brillouin zone, and to point out the complementary nature of the two techniques. To retrieve the 2D spectra from 1D Compton profiles, a new direct inversion method (DIM) is implemented and benchmarked against the well-established Cormack's method. The comparison of experimental spectra with first principles density functional theory calculations of the electron momentum density and the two photon momentum density clearly reveals the importance of positron probing effects on the determination of the electronic structure. While the calculations are in good agreement with the experimental data, our results highlight some significant discrepancies.

Preclinical evaluation of [68Ga]Ga-MALAT-1-antisense oligonucleotides for specific PET imaging of MALAT-1 expressing tumours.

The present study was to explore the feasibility of developing positron molecular probes for the metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), to evaluate the distribution and pharmacokinetics, and to explore whether the probe can be used for the imaging of malignant tumours with high MALAT-1 expression in vivo. [68Ga]Ga labelling of MALAT-1 antisense oligonucleotides ([68Ga]Ga-MALAT-1-ASO) was synthesized by the conjugation of MALAT-1-NOTA-ASO and [68Ga] Ga3+. The radiochemical purity was shown by radio-HPLC. Pharmacokinetic studies and cellular uptake studies were performed. The biodistribution and metabolism of [68Ga] Ga-MALAT-1-ASO in normal ICR and MHCC-LM3 xenograft-bearing nude mice were studied in vitro and in vivo. [68Ga]Ga-MALAT-1-ASO was obtained in 98% radiochemical yield from a 10-min synthesis with 100 ± 50 MBq/nmol specific activity and >99% radiochemical purity. The Log D was -2.53 ± 0.19. The tracer displayed excellent stability in vitro. 68Ga-MALAT-1 ASO showed satisfactory binding ability to MHCC-LM3 cells; the biodistribution of [68Ga]Ga-MALAT-1-ASO in MHCC-LM3 tumour-bearing mice demonstrated specific uptake of the radiotracer (3.04 ± 0.11%ID/g). Micro-PET images of the MHCC-LM3 cell xenograft mouse model provided further evidence to support the hypothesis that [68Ga]Ga-MALAT-1-ASO can target tumours in vivo. We conclude that [68Ga]Ga labelling of MALAT-1 ASO is a convenient approach. The high accumulation of [68Ga]Ga-MALAT-1-ASO for tumours expressing MALAT-1 suggests that this radio compound may be used as a potential positron molecular probe. Molecular structure optimization studies need to be more in-depth to further reduce its background uptake and enhance tumour targeting.

Studies on healthy and neoplastic tissues using positron annihilation lifetime spectroscopy and focused histopathological imaging

Samples of healthy and neoplastic myometrial tissues were investigated using Positron Annihilation Lifetime Spectroscopy (PALS). Meaningful differences between normal and diseased tissues were observed for each patient. The differences were also clearly visible for various kinds of lesions in each patient. The set of lifetimes and intensities obtained from PALS was correlated with the histopathological examinations of the same fragments of tissues. Strong coincidence between PALS parameters and histopathological findings was observed only in the case of a very precise correlation of the investigated area in both techniques. Measurements and discussion presented here were carried out to develop a method for measuring the sub-nanometric structure of human tissues. This kind of investigation, using positron probe, creates an opportunity of a new application in Positron Emission Tomography (PET).

MAPSSIC, a communicating MAPS-based intracerebral positrons probe for deep brain imaging in awake and freely-moving rats

Radioisotope imaging is a powerful tool to understand the biological mechanisms in-vivo, especially in the brain of small animals, providing a significant model to study the human brain. In this context, we have developed and built a pixelated intracerebral positron probe to be embedded on awake and freely moving small animals, typically rats. This pixelated probe will represent a key instrument for neuroscientists to study neural mechanisms and correlate them to behavioral experiments. We describe in this paper the simulations carried out to design the intracerebral sensor, its architecture, and the detection of positrons in a volume with a couple of sensors assembled back-to-back. We also depict the architecture of the wireless acquisition system. Finally, we present the first measurements performed in real-time by this miniaturized probe with sealed radioactive sources and a 18F solution.

A new positron-gamma discriminating phoswich detector based on wavelength discrimination (WLD)

Abstract The intra-operative positron probe, used in the field of nuclear medicine, has been developed to localize positron ( β +) emitted from positron emission tomography (PET) radiopharmaceuticals by selectively detecting β + particles in the presence of background gamma ( γ ) radiation. In this research, we propose a new method for real-time discrimination of radiation types in a mixed radiation field of positron ( β +) and gamma ( γ ) radiation, based on simple electronics and signal processing. Scintillators often have distinct emission wavelengths, and this method exploits the scintillator’s emission wavelength, as opposed to conventional pulse shape discrimination (PSD) approach. In this study, we used a two-layer phoswich detector consisting of europium-doped calcium fluoride (CaF2(Eu)) and Ce 3 + doped Lu3Al5O12 (Ce:LuAG), with dimensions of 3 mm × 3 mm × 0.5 mm and 3 mm × 3 mm × 10 mm, and emission wavelengths of 380–450 nm and 480–700 nm respectively. This phoswich detector was placed at the center of two adjacent optical filters (one short pass and one long pass filter), and each coupled to a silicon photomultiplier (SiPM). The optical filters are used for directing a specific scintillator photon wavelength to its corresponding SiPM for identification of the crystal of interaction. This proposed method allows us to realize a high sensitivity (true positive rate) positron probe, that can also double as a γ -probe, while simplifying readout electronic and signal processing. A Na-22 positron( β +) source and Cs-137 γ -source were used to validate the proposed approach experimentally. Results indicate the possibility of discriminating β + and γ -radiations in real time, with an excellent γ -rejection ratio exceeding 99.9 %.

MAPSSIC, a Novel CMOS Intracerebral Positrons Probe for Deep Brain Imaging in Awake and Freely Moving Rats: A Monte Carlo Study

Preclinical behavior neuroimaging gathers simultaneous assessment of behavior and functional brain imaging. It is a potential key breakthrough to improve the understanding of brain processes and assess the validity of preclinical studies in drug development. Achieving such a combination is difficult, anesthesia or restraints inherent to conventional nuclear imaging preclude its use for behavior studies. In that context, we have proposed an original strategy using submillimetric probes to directly measures positrons inside the rat brain. This paper gives the results of Monte Carlo simulations of a new generation of intracerebral positron probe based on a complementary metal oxide semi-conductor monolithic active pixel sensor. We present the results obtained for a probe into a large homogeneous volume of radioactive water (18F) leading to a sensitivity of 0.88 cps ${\cdot }$ Bq $^{ {-1}} {\cdot }$ mm3 and a mean energy deposition by positrons of 15.1 keV. Simulation in simplified brain-shaped sources modeling a 11C-raclopride experiment shows that the implanted volume modeling the left putamen contribute to 92.4% of the signal from positrons. We also investigate the effects of the thickness of the sensitive layer, the energy threshold and pixel dimensions on the detection capacities of the sensor. We demonstrate that an increase in the sensitive thickness from 18 to 190 $ \mu \text{m}$ would lead to an increase of positrons sensitivity by a factor of 1.74, but to a decrease of the direct (positrons) to indirect ( $ \gamma $ -rays and electrons) sensitivity ratio by a factor of 1.59. Finally, we show that for a threshold lower than about 5 keV the effect of the pixel dimensions is negligible.

Implantable CMOS pixel sensor for positron imaging in rat brain

IMIC is a Monolithic Active Pixel Sensor prototype designed for the MAPSSIC project, which aims at developing wireless intracerebral probes dedicated to image positron-emitting source activity in the brain of awake and freely moving rats. Former experiments with the PIXSIC positron probe based on a passive sensor have validated the proof of concept, but have also shown limitations with regards to the probe robustness and to its transparency to annihilation photons. The IMIC circuit features a matrix of 16 × 128 active pixels of 30 × 50 µm2 size and targets to overcome the PIXSIC probe drawbacks by exploiting a thin sensitive layer of 18 µm, still featuring an overall thickness close to 300 µm. Additionally, by using a low power (55 nW/pixel) in-pixel front-end architecture providing binary output, IMIC solves the challenge of implanting an active sensor in tissues where overheating is forbidden.The needle-shaped sensor 610 µm × 12000 µm was fabricated and tested in laboratory. The whole sensor dissipates 160 µW and its imaging capabilities were asserted with various sources: 55Fe, 90Sr and 18F. These tests also demonstrated robust count-rate measurement with IMIC in the range 10–1000 counts/matrix/s. Finally, a dedicated setup qualitatively confirmed excellent in-sensitivity to 511 keV γ-rays.In this paper, we present the sensor requirements and its detailed design. We also discuss the first characterisation results and the outlook for the integration of IMIC into an implantable probe.

Measurement of Transverse Wakefields Induced by a Misaligned Positron Bunch in a Hollow Channel Plasma Accelerator.

Hollow channel plasma wakefield acceleration is a proposed method to provide high acceleration gradients for electrons and positrons alike: a key to future lepton colliders. However, beams which are misaligned from the channel axis induce strong transverse wakefields, deflecting beams and reducing the collider luminosity. This undesirable consequence sets a tight constraint on the alignment accuracy of the beam propagating through the channel. Direct measurements of beam misalignment-induced transverse wakefields are therefore essential for designing mitigation strategies. We present the first quantitative measurements of transverse wakefields in a hollow plasma channel, induced by an off-axis 20GeV positron bunch, and measured with another 20GeV lower charge trailing positron probe bunch. The measurements are largely consistent with theory.

Gamma-background rejection method for a dual scintillator positron probe dedicated to radio-guided surgery

We developed a positron intraoperative probe with high sensitivity dedicated to real-time assessment of the resection margins of tumors and control of the surgical cavity. Its main limitation comes from the annihilation photon background generated by distal non-specific radiotracer uptakes. This study is a proof of concept for a dual-scintillator intraoperative probe with background subtraction capability. It associates a highly p-terphenyl β-sensitive scintillator and a highly γ-sensitive LYSO:Ce. Both scintillator are readout by a single pixelated photodetector based on SiPMs and the shape and intensity of the light distribution is used to identify in which scintillator the interactions occurred to allow further discrimination of the signals and subsequent quantification of this background can be utilized to have it subtracted from the raw images. We describe in this study the design of the probe and the analysis to achieve this identification with a good accuracy. An average efficiency of events identification of 97.90 ± 0.06% is reported on the whole field of view.

Positron probing of open vacancy volume of phosphorus‐vacancy complexes in float‐zone n‐type silicon irradiated by 0.9‐MeV electrons and by 15‐MeV protons

For the first time the samples, cut from the same wafer of crystals of float‐zone silicon, n−FZ−Si(P) and n−FZ−Si(Bi), were subjected to irradiation with 0.9‐MeV electrons and 15‐MeV protons at RT for studying them by low‐temperature positron annihilation lifetime spectroscopy. Measurements of Hall effect have been used for the materials characterization. The discussion is focused on the open vacancy volume (Vop) of the thermally stable group‐V‐impurity‐vacancy complexes comprising the phosphorus atoms; the bismuth‐related vacancy complexes are briefly considered. The data of positron probing of PV pairs (E‐centers), divacancies, and the thermally stable defects in the irradiated n−FZ−Si(P) materials are compared. Beyond a reliable detecting of the defect‐related positron annihilation lifetime in the course of isochronal annealing at ∼ 500 °C, the recovery of concentration of phosphorus‐related shallow donor states continues up to ∼650–700 °C. The open vacancy volumes Vop to be characterized by long positron lifetimes Δτ2 ∼271–289 ps in (gr.‐V‐atom)–Vop complexes are compared with theoretical data available for the vacancies, τ(V1), and divacancies, τ(V2). The extended semi‐vacancies, 2Vs‐ext, and relaxed vacancies, 2Vinw, are proposed as the open volume Vop in (gr.‐V‐atom)–Vop complexes. It is argued that at high annealing temperature the defect Ps–Vop–Ps is decomposed.

Tunable monoenergy positron annihilation spectroscopy of polyethylene glycol thin films**Project supported by the National Natural Science Foundation of China (Grant Nos. 11575205, 11475197, 11675188, and 11475193).

Doppler broadening and coincidence Doppler broadening of annihilation radiation experiments have been performed in three kinds of polyethylene glycol (PEG) membrane formed with different average molecular weight using the tunable monoenergy slow positron probe as a function of implantion energy. The obtained positron annihilation parameters are interpreted from two aspects: surface effect and differences in micro-structure or chemical environment of positron annihilation. The experimental results show that the regulation of densification of PEG molecular packing and distribution uniformity from the near surface layer to the bulk region in the film forming process can be well realized by changing its molecular weight. Combining a variable monoenergetic slow positron beam and these two positron annihilation spectroscopy methods is a powerful tool to study positron annihilation characteristics and for polymeric thin-film fine structure analysis.

Positron probing of disordered regions in neutron‐irradiated silicon

The vacancy‐rich disordered regions (DR) playing a key role in improving the thermoelectric figure‐of‐merit of silicon thermoelectric generators by reducing (by ∼90%) the thermal conductivity, have been probed with positrons. The DR were created by irradiating n‐Cz‐Si(P) material with the fast reactor neutrons. The parameter of the electron density rs′ ≈ 2.18 a.u. contacting positrons in DR has been reconstructed using the data of the angular correlation of the annihilation radiation (ACAR); the amendments to the rs′ value associated with the ion core electrons were taken into account. It is argued that the ion cores of atoms of silicon as well as the ones of the as‐grown impurities (O, C) are involved in the open vacancy volume to be probed with positrons: a relaxation of the ion cores directed inward toward the vacancy volume seems to take place. These positron traps are formed beyond the vacancy‐rich area of the disordered region. In the course of isochronal annealing, the traps are stable up to Tanneal. ≈ 520 °C when a recovery of ACAR parameters begins and then it continues up to ∼1050 °C.A vacancy center containing positrons in the open vacancy volume beyond the vacancy‐rich area of the disordered region is shown schematically. The emission of electron–positron annihilation gamma‐quanta dominates from within these positron traps. The values of both the electron–positron ion core radius (rm) and electron density (parameter rs′) suggest a relaxation directed toward inwards the open vacancy volume: the impurity atoms of oxygen and carbon are, perhaps, involved in the center.

Development of a PET/OMRI combined system for simultaneous imaging of positron and free radical probes for small animals.

Positron emission tomography (PET) has high sensitivity for imaging radioactive tracer distributions in subjects. However, it is not possible to image free radical distribution in a subject by PET. Since free radicals are quite reactive, they are related to many diseases, including but not limited to cancer, inflammation, strokes, and heart disease. The Overhauser enhanced magnetic resonance imaging (OMRI) is so far the only method that images free radical distribution in vivo. By combining PET and OMRI, a new hybrid imaging modality might be developed that can simultaneously image the radioactive tracer and free radical distributions. For this purpose, the authors developed a PET/OMRI combined system for small animals. The developed PET/OMRI system used an optical fiber-based PET system combined with a permanent magnet-based OMRI system. The optical fiber-based PET system uses flexible optical fiber bundles. Eight optical fiber-based block detectors were arranged in a 56 mm diameter ring to form a PET system. The LGSO blocks were located inside the field-of-view (FOV) of the OMRI, and the position sensitive photomultiplier tubes were positioned behind the OMRI to minimize the interference between the PET and the OMRI. The OMRI system used a 0.0165 T permanent magnet. The system has an electron spin resonance coil to enhance the MRI signal using the Overhauser effect to image the free radical in the FOV of the PET/OMRI system. The spatial resolution and sensitivity of the optical fiber-based PET system were 1.2 mm FWHM and 1.2% at the central FOV, respectively. The OMRI system imaged the distribution of a nitroxyl radical (NXR) solution. The interference between PET and OMRI was small. Simultaneous imaging of the positron radiotracer and the NXR solution was successfully conducted with the developed PET/OMRI system for phantom and small animal studies. The authors developed a PET/OMRI combined system with the potential to provide interesting new results in molecular imaging research, such as in vivo molecular and free radical distributions.

실리콘 광증폭기와 반응깊이 측정방법을 이용한 수술용 베타 영상/감마 프로브 가능성 연구

Radiopharmaceutical agents for positron emission tomography (PET), such as -FDG and , have been used not only for whole-body PET imaging but also for intraoperative radionuclide-guided surgery due to their quantitative and sensitive imaging characteristics. Current intraoperative probes detect gamma or beta particles, but not both of them. Gamma probes have low sensitivities since a collimator has to be used to reduce backgrounds. Positron probes have a high tumor-to-background ratio, but they have a 1-2 mm depth limitation from the body surface. Most of current intraoperative probes produce only audible sounds proportional to count rates without providing tumor images. This research aims to detect both positrons and annihilation photons from using plastic scintillators and a GAGG scintillation crystal attached to silicon photomultiplier (SiPM). The depth-of-interaction (DOI) along the plastic scintillator can be used to obtain the 2-D images of tumors near the body surface. The front and rear part of the intraoperative probe consists of plastic scintillators () for positron detection and a Ce:GAGG scintillation crystal () for annihilation photon detection, respectively. The DOI resolution of along the plastic scintillator was obtained by using the 3M enhanced specular reflector (ESR) with rectangular holes between the plastic scintillators, which showed the feasibility of a 2-D image pixel size of (X-direction Y-direction).

Positron annihilation study of Fe-ion irradiated reactor pressure vessel model alloys

The degradation of reactor pressure vessel steels under irradiation, which results from the hardening and embrittlement caused by a high number density of nanometer scale damage, is of increasingly crucial concern for safe nuclear power plant operation and possible reactor lifetime prolongation. In this paper, the radiation damage in model alloys with increasing chemical complexity (Fe, Fe-Cu, Fe-Cu-Si, Fe-Cu-Ni and Fe-Cu-Ni-Mn) has been studied by Positron Annihilation Doppler Broadening spectroscopy after 1.5 MeV Fe-ion implantation at room temperature or high temperature (290 oC). It is found that the room temperature irradiation generally leads to the formation of vacancy-type defects in the Fe matrix. The high temperature irradiation exhibits an additional annealing effect for the radiation damage. Besides the Cu-rich clusters observed by the positron probe, the results show formation of vacancy-Mn complexes for implantation at low temperatures.

The Positron Probe Microanalyser Studies of Defect Distribution Induced by Machining of Copper, Iron and Titanium

We demonstrate the application of the new experimental technique: positron probe microanalyser for studies of the defect profiles induced by milling. Metal foils of Cu, Fe and Ti were subjected to machining in a milling machine with different cutting speed. This technique revealed well-defined profiles of defects below the machined surface which was extended up to hundreds of micrometres. The extent of the profile depended on the metal and the cutting speed. The positron probe microanalyser allowed us to trace the evolution of the profile after annealing in different temperatures. Surprisingly, the high thermal stability of a few tens of micrometres thick layer adjacent to the machined surface was detected.

Positron probing of phosphorus-vacancy complexes in silicon irradiated with 15 MeV protons

Defects in phosphorus-doped silicon samples of floating-zone material, n-FZ-Si(P), produced under irradiation with 15 MeV protons at room temperature are studied by positron annihilation lifetime spectroscopy over the temperature range of ∼ 30 K - 300 K and by low- temperature Hall effect measurements. After annealing of E-centersand divacancies, we detected for the first time high concentrations of positron traps which had not been observed earlier. These defects are isochronally annealed over the temperature interval of ∼ 320 °C - 700 °C; they manifest themselves as electrically neutral deep donor centersin the material of n-type. A long-lived component of the positron lifetime, τ2(I2 < 60%) ∼ 280 ps, attributed to these centers, suggests a relaxed configuration involving two vacancies. The enthalpy and entropy of annealing of these centersare Ea ∼ 1.05(0.21) eV and ΔSm ≈ 3.1(0.6)kB, respectively. It is argued that the microstructure of the defect consists of two vacancies, VV, and one atom of phosphorus, P. The split configuration of the VPV complex is shortly discussed.

Positron probing of electron momentum re-distribution at the superconducting transition in Ba(Fe1−xCox)2As2 single crystals

Superconducting Ba(Fe0.943Co0.057)2As2 single crystals with Tc (R=0)=19.5K, and non-superconducting BaFe2As2 single crystals have been studied by coincidence Doppler broadening of positron annihilation radiation line-shape (coincidence DBPARL) down to ~14K. This appears to be the first reporting of positron probing of any Fe-based superconductor. The superconducting sample shows, on cooling below ~40K and towards Tc, a sharp decrease of S, the line-shape parameter, which gives the fraction of suitably defined low momentum electrons as probed by the positrons. No such decrease of S for the non-superconducting sample indicates the effect to be induced by superconductivity. The ratio curve analysis of the coincidence DBPARL spectra suggests that in the superconducting state the positrons are annihilating less with the 3d electrons of Fe and Co and more with the 5s and 4d electrons of Ba. In addition, a novel double measurement of coincidence DBPARL for the a–b plane and planes normal to the a–b plane of the single crystalline sample shows a nearly isotropic distribution of the lower electron momentum in this Fe-based superconductor.