A new detector concept based on the prompt gamma radiation analysis for In vivo boron monitoring in BNCT.

The problem of boron concentration monitoring during the boron neutron capture therapy (BNCT) therapy is one of the main challenges of this type of radiotherapy and is directly related to the nature of the interaction of neutrons with mater. Among the available in vivo methods of boron monitoring positron emission tomography seems to be very promising but it requires a new boron carrier with a ß+ emitter, which is not yet clinically available. An alternative solution may be the prompt gamma radiation analysis (PGRA) based on the secondary radiation emitted in the interaction of neutrons with the patient's tissues. This method requires, however, compact gamma radiation detection systems sustaining high counting rates and characterized by very good energy resolution. In this contribution, we present state-of-the-art solutions for monitoring in BNCT based on PGRA. Moreover, we describe a new concept of such a system based on position-sensitive scintillator detectors equipped with an anti-Compton shield and data analysis supported with modern artificial intelligence algorithms.

Efficiency determination of J-PET: first plastic scintillators-based PET scanner.

BACKGROUND: The Jagiellonian Positron Emission Tomograph is the 3-layer prototype of the first scanner based on plastic scintillators, consisting of 192 half-metre-long strips with readouts at both ends. Compared to crystal-based detectors, plastic scintillators are several times cheaper and could be considered as a more economical alternative to crystal scintillators in future PETs. JPET is also a first multi-photon PET prototype. For the development of multi-photon detection, with photon characterized by the continuous energy spectrum, it is important to estimate the efficiency of J-PET as a function of energy deposition. The aim of this work is to determine the registration efficiency of the J-PET tomograph as a function of energy deposition by incident photons and the intrinsic efficiency of the J-PET scanner in detecting photons of different incident energies. In this study, 3-hit events are investigated, where 2-hits are caused by 511 keV photons emitted in [Formula: see text] annihilations, while the third hit is caused by one of the scattered photons. The scattered photon is used to accurately measure the scattering angle and thus the energy deposition. Two hits by a primary and a scattered photon are sufficient to calculate the scattering angle of a photon, while the third hit ensures the precise labeling of the 511 keV photons. RESULTS: By comparing experimental and simulated energy distribution spectra, the registration efficiency of the J-PET scanner was determined in the energy deposition range of 70-270 keV, where it varies between 20 and 100[Formula: see text]. In addition, the intrinsic efficiency of the J-PET was also determined as a function of the energy of the incident photons. CONCLUSION: A method for determining registration efficiency as a function of energy deposition and intrinsic efficiency as a function of incident photon energy of the J-PET scanner was demonstrated. This study is crucial for evaluating the performance of the scanner based on plastic scintillators and its applications as a standard and multi-photon PET systems. The method may be also used in the calibration of Compton-cameras developed for the ion-beam therapy monitoring and simultaneous multi-radionuclide imaging in nuclear medicine.

Comparative studies of the sensitivities of sparse and full geometries of Total-Body PET scanners built from crystals and plastic scintillators.

BACKGROUND: Alongside the benefits of Total-Body imaging modalities, such as higher sensitivity, single-bed position, low dose imaging, etc., their final construction cost prevents worldwide utilization. The main aim of this study is to present a simulation-based comparison of the sensitivities of existing and currently developed tomographs to introduce a cost-efficient solution for constructing a Total-Body PET scanner based on plastic scintillators. METHODS: For the case of this study, eight tomographs based on the uEXPLORER configuration with different scintillator materials (BGO, LYSO), axial field-of-view (97.4 cm and 194.8 cm), and detector configurations (full and sparse) were simulated. In addition, 8 J-PET scanners with different configurations, such as various axial field-of-view (200 cm and 250 cm), different cross sections of plastic scintillator, and multiple numbers of plastic scintillator layers (2, 3, and 4), based on J-PET technology have been simulated by GATE software. Furthermore, Siemens' Biograph Vision has been simulated to compare the results with standard PET scans. Two types of simulations have been performed. The first one with a centrally located source with a diameter of 1 mm and a length of 250 cm, and the second one with the same source inside a water-filled cylindrical phantom with a diameter of 20 cm and a length of 183 cm. RESULTS: With regards to sensitivity, among all the proposed scanners, the ones constructed with BGO crystals give the best performance ([Formula: see text] 350 cps/kBq at the center). The utilization of sparse geometry or LYSO crystals significantly lowers the achievable sensitivity of such systems. The J-PET design gives a similar sensitivity to the sparse LYSO crystal-based detectors while having full detector coverage over the body. Moreover, it provides uniform sensitivity over the body with additional gain on its sides and provides the possibility for high-quality brain imaging. CONCLUSION: Taking into account not only the sensitivity but also the price of Total-Body PET tomographs, which till now was one of the main obstacles in their widespread clinical availability, the J-PET tomography system based on plastic scintillators could be a cost-efficient alternative for Total-Body PET scanners.

Simulating NEMA characteristics of the modular total-body J-PET scanner-an economic total-body PET from plastic scintillators.

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.

Testing CPT symmetry in ortho-positronium decays with positronium annihilation tomography.

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.

3D TOF-PET image reconstruction using total variation regularization.

In this paper we introduce a semi-analytic algorithm for 3-dimensional image reconstruction for positron emission tomography (PET). The method consists of the back-projection of the acquired data into the most likely image voxel according to time-of-flight (TOF) information, followed by the filtering step in the image space using an iterative optimization algorithm with a total variation (TV) regularization. TV regularization in image space is more computationally efficient than usual iterative optimization methods for PET reconstruction with full system matrix that use TV regularization. The efficiency comes from the one-time TOF back-projection step that might also be described as a reformatting of the acquired data. An important aspect of our work concerns the evaluation of the filter operator of the linear transform mapping an original radioactive tracer distribution into the TOF back-projected image. We obtain concise, closed-form analytical formula for the filter operator. The proposed method is validated with the Monte Carlo simulations of the NEMA IEC phantom using a one-layer, 50 cm-long cylindrical device called Jagiellonian PET scanner. The results show a better image quality compared with the reference TOF maximum likelihood expectation maximization algorithm.

Estimating relationship between the time over threshold and energy loss by photons in plastic scintillators used in the J-PET scanner.

PURPOSE: The time-over-threshold (TOT) technique is being used widely due to itsimplications in developing the multi-channel readouts, mainly when fast signal processing is required. Using the TOT technique, as a measure of energy loss instead of charge integration methods, significantly reduces the signal readout costs by combining the time and energy information. Therefore, this approach can potentially be utilized in J-PET tomograph which is built from plastic scintillators characterized by fast light signals. The drawback in adopting this technique lies in the non-linear correlation between input energy loss and TOT of the signal. The main motivation behind this work is to develop the relationship between TOT and energy loss and validate it by the J-PET tomograph setup. METHODS: The experiment was performed using a 22Na beta emitter source placed in the center of the J-PET tomograph. This isotope produces photons of two different energies: 511 keV photons from the positron annihilation (direct annihilation or through the formation of a para-positronium atom or pick-off process of ortho-positronium atoms) and a 1275 keV prompt photon. This allows the study of the correlation between TOT values and energy loss for energy ranges up to 1000 keV. Since the photon interacts predominantly via Compton scattering inside the plastic scintillator, there is no direct information of the energy deposition. However, using the J-PET geometry, one can measure the scattering angle of the interacting photon. Since the 22Na source emits photons of two different energies, it is necessary to know unambiguously the energy of incident photons and their corresponding scattering angles in order to estimate energy deposition. In summary, this work presents a dedicated algorithm developed to tag photons of different energies and studying their scattering angles to calculate the energy deposition by the interacting photons. RESULTS: A new method was elaborated to measure the energy loss by photons interacting with plastic scintillators used in the J-PET tomograph. We find the relationship between the energy loss and TOT is non-linear and can be described by the functions TOT = A0 + A1 * ln(E dep + A2) + A3 * (ln(E dep + A2))2 and TOT = A0 - A1 * A2[Formula: see text]. In addition, we also introduced a theoretical model to calculate the TOT as a function of energy loss in plastic scintillators. CONCLUSIONS: A relationship between TOT and energy loss by photons interacting inside the plastic scintillators used in J-PET scanner is established for a deposited energy range of 100-1000 keV.

Performance assessment of the 2 γpositronium imaging with the total-body PET scanners.

PURPOSE: In living organisms, the positron-electron annihilation (occurring during the PET imaging) proceeds in about 30% via creation of a metastable ortho-positronium atom. In the tissue, due to the pick-off and conversion processes, over 98% of ortho-positronia annihilate into two 511 keV photons. In this article, we assess the feasibility for reconstruction of the mean ortho-positronium lifetime image based on annihilations into two photons. The main objectives of this work include the (i) estimation of the sensitivity of the total-body PET scanners for the ortho-positronium mean lifetime imaging using 2γ annihilations and (ii) estimation of the spatial and time resolution of the ortho-positronium image as a function of the coincidence resolving time (CRT) of the scanner. METHODS: Simulations are conducted assuming that radiopharmaceutical is labeled with 44Sc isotope emitting one positron and one prompt gamma. The image is reconstructed on the basis of triple coincidence events. The ortho-positronium lifetime spectrum is determined for each voxel of the image. Calculations were performed for cases of total-body detectors build of (i) LYSO scintillators as used in the EXPLORER PET and (ii) plastic scintillators as anticipated for the cost-effective total-body J-PET scanner. To assess the spatial and time resolution, the four cases were considered assuming that CRT is equal to 500 ps, 140 ps, 50 ps, and 10 ps. RESULTS: The estimated total-body PET sensitivity for the registration and selection of image forming triple coincidences (2γ+γprompt) is larger by a factor of 13.5 (for LYSO PET) and by factor of 5.2 (for plastic PET) with respect to the sensitivity for the standard 2γ imaging by LYSO PET scanners with AFOV = 20 cm. The spatial resolution of the ortho-positronium image is comparable with the resolution achievable when using TOF-FBP algorithms already for CRT = 50 ps. For the 20-min scan, the resolution better than 20 ps is expected for the mean ortho-positronium lifetime image determination. CONCLUSIONS: Ortho-positronium mean lifetime imaging based on the annihilations into two photons and prompt gamma is shown to be feasible with the advent of the high sensitivity total-body PET systems and time resolution of the order of tens of picoseconds.

A vitamin K epoxide reductase-oxidase complex gene polymorphism (-1639G>A) and interindividual variability in the dose-effect of vitamin K antagonists.

A daily dose of vitamin K antagonists (VKAs) may vary and its range depends on various interrelated factors. Low responsiveness to VKA (defined as a failure to achieve a target international normalized ratio [INR]) is associated with polymorphisms of the vitamin K epoxide reductase-oxidase complex gene (VKORC1). A highly prevalent promoter single-nucleotide polymorphism (VKORC1-1639 G>A, rs17878363) impairs VKORC1 expression and determines the interindividual variability of the target INR. We studied 57 patients receiving oral anticoagulation, including 50 subjects treated with acenocoumarol (mean dose: 5.7+/-2.3 mg/day) and 7 treated with warfarin (mean dose: 9.6+/-4.2 mg/day). The indications for the use of oral anticoagulant therapy were as follows: deep-vein thrombosis (N = 23); pulmonary embolism (N = 20); arterial thrombosis (N = 5); stroke (N = 4); atrial fibrillation with transient ischemic attacks (N = 2), and history of multiple thromboembolic events (N = 3). Identification of the VKORC1 genomic variation was performed using DNA sequencing methods. The prevalence of the mutated allele (VKORC1 -1639A) was 41%. The VKORC1 -1639G allele carriers required a higher daily dose of acenocoumarol (5.9+/-1.9 mg) than the noncarriers (4.1+/-3.3 mg; P < 0.001). All of 5 low responders (who failed to achieve a target INR using standard dose requirements of VKAs) were homozygous for the 1639G allele. Low responders did not differ from good responders with respect to age, gender, and body mass index. Our findings suggest the potential benefits from pharmacogenetic testing, and provide evidence that the VKORC1 -1639 G>A gene polymorphism may explain at least in part the low responsiveness to acenocoumarol.

Feasibility study of the positronium imaging with the J-PET tomograph.

A detection system of the conventional PET tomograph is set-up to record data from [Formula: see text] 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.

The proteome analysis of rat platelet with nano-liquid chromatography-matrix-assisted laser desorption/ionization time-of-flight mass spectrometry technique.

Recently, the proteomic analysis has become an ideal tool to study the structure and function of platelets. We proposed a nano-liquid chromatography (nano-LC) technique coupled off-line with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF-MS) for rat platelet proteome analysis. In this study, we attempted to analyze the rat platelet proteome in two different subcellular fractions: cytosol and membrane. Platelet-rich plasma was collected from healthy rats. The platelet samples were extracted with Subcellular Proteome Extraction Kit to collect subcellular compartments. For further investigations, platelet lysate, cytosol and membrane fractions were used. Enzymatic digestion of proteins was performed using Filter Aided Sample Preparation method with trypsin as a proteolytic enzyme. Tryptic peptides were analyzed using nano-LC-MALDI-TOF/TOF-MS. Platelet proteins identification was performed using the Mascot engine. We identified 238 proteins in the platelet lysate, 210 in the cytosol, and 148 in the membrane fraction. Among them, 45 were unique for platelet lysate, 55 for cytosol, and 34 for the membrane fraction. The gene ontology analysis showed that there were differences in the proteome of cytosol and membrane fractions related to the molecular functions, i.e. coagulative activity. Our results may suggest that the membrane or cytosol location of the proteins with coagulative activity may be responsible for the acute or delayed platelet response to an agonist. The nano-LC-MALDI-TOF/TOF-MS method can be used for identifying proteins of subcellular fraction in rat platelets.

Changes in morphology of human skin fibroblasts induced by local anaesthetics: role of actomyosin contraction.

Local anaesthetics block action potentials in the membranes of excitable cells but their effects on non-excitable cells are less well known. Some local anaesthetics are applied directly onto the skin, and for this reason the effect of procaine (p-aminobenzoic acid diethylamino-etyl ester hydrochloride) and tetracaine (4-[butylamino]benzoic acid 2-[dimethylamino]ethyl ester) upon the morphology and cytoskeleton organisation of human skin fibroblasts was investigated. The time lapse video recording of fibroblasts cultured in serum-enriched medium revealed that the cells rapidly change shape after the addition of the anaesthetic. These effects were fully reversible. The microscopic observations were confirmed by quantitative analysis of projected cell area and cell shape parameters. Local anaesthetics significantly changed the actin cytoskeleton organisation, inducing total disappearance of stress fibres. Serum-starvation or myosin light chain kinase inhibitors, KT 5926 inhibitor (8R*,9S*,11S*)-(-)-9-hydroxy-9-methoxycarbonyl-8-methyl-14-n-propoxy-2,3 ,9, 10-tetrahydro-8,11-epoxy,1H,8H,11H-2,7b,11a-triazadibenzo[a,g]c ycloocta[cde] trinden-1-one or wortmannin, which induce the 'relaxed' morphology of the cells, prevent both the anaesthetic-induced changes in cell shape and the disassembly of stress fibres. Together, the observations suggest that local anaesthetics affect the actomyosin system, inducing contraction.

Effect of temperature and 4,6'-diamidine-2-phenylindole on restriction of supercoiled Col E1 DNA by Eco RI endonuclease.

Supercoiled Col E1 DNA is split by Eco RI endonuclease at 37 degrees C without intermediate formation of open circular DNA. Accumulation of this restriction product is observed at low temperature. The fluorescent dye, 4,6'-diamidine-2-phenylindole (DAPI) inhibits restriction by Eco RI endonuclease. This effect is due to the DAPI:DNA rather than to the DAPI:Eco RI interactions.

Osmometric studies on self-association of pyrimidines in aqueous solutions: evidence for involvement of hydrophobic interactions.

Vapour pressure osmometric studies were performed on stacking self-association of 25 uracil derivatives variously C- and N-substituted with polar and alkyl groups in aqueous solution at various temperatures. The respective equilibrium association constants Kst were computed on the assumption of the isodesmic model of self-association (K2=K3=...=Kn=Kst). Enthalpies of association for most of the compounds studied were obtained from the temperature-dependence of Kst, according to the van 't Hoff equation. Analysis of the equilibrium and thermodynamic parameters in terms of the association mechanism demonstrated the involvement of classical hydrophobic interactiors in the stabilization of complexes of di-and higher alkylated uracils. Data for the derivatives substituted with polar groups proved consistent with the predominant involvement of dipole-induced dipole forces in the association.

Cerebral blood flow assessed by brain SPECT with 99mTc-HMPAO utilising the acetazolamide test in systemic lupus erythematosus.

BACKGROUND: Cerebrovascular diseases are one of the most important complications of systemic lupus erythematosus (SLE). The diagnostic imaging of neuropsychiatric SLE complications presents many problems. This study was undertaken to investigate cerebral blood flow char s and its reactivity to hypercapnia by means of acetazolamide test in SLE patients. METHODS: Brain SPELT studies using 99mTc-HMPAO were performed in 50 patients with SLE. Acetazolamide test was performed in 35 patients 3 days after the baseline study by means of repetitive scanning 20 min after i.v. injection of 1.0 g of acetazolamide. RESULTS: Significant interhemispheric hypoperfusion areas were shown in 76.3% of all patients, 83.8% symptomatic and 63.1 % asymptomatic. Patients with antiphospholipid syndrome showed multifocal perfusion deficits. The reaction of cerebral perfusion to acetazolamide was heterogenous and showed increase, decrease, no change or mixed reaction of baseline-study-found focal hypoperfusion. Acetazolamide test revealed hypoperfusion in two patients with normal baseline study. MRI scanning revealed cerebral lesions in 41 % of patients. CONCLUSIONS: CBF asymmetries in symptomatic and asymptomatic patients with SLE are frequent. Regional CBF alterations seem to be different in patients with and without antiphospholipid syndrome. The part of the patients with SLE shows no or paradoxically inversed reaction to acetazolamide.

[Levels of troponin I, tropoinin T, isoenzyme MB creatine kinase and myoglobins in blood serum for perioperative diagnosis of myocardial infarction in patients after coronary artery bypass graft surgery with extracorporeal circulation]. / Poziomy troponiny I, troponiny T, izoenzymu MB kinazy kreatyny oraz mioglobiny w surowicy krwi w diagnostyce okolooperacyjnego zawalu miesnia sercowego u chorych po operacjach naczyn wiencowych z uzyciem krazenia pozaustrojowego.

UNLABELLED: We studied plasma levels of troponin I (cTnI), troponin T (cTnT), creatine kinase MB (CKMBmass) and myoglobin (MB) in patients undergoing coronary artery bypass surgery with extracorporeal circulation and cardioplegia. In group 1 (25 patients without perioperative myocardial infarction) plasma levels of all markers studied were elevated after operation. In group 2 (24 patients with perioperative myocardial infarction) plasma concentrations of all markers exceeded several times levels observed in patients without myocardial infarction with maximal value for MB at 12 hours after operation; for cTnI and CKMBmass at 16 hours after surgery and for cTnT at 32 hours after the end of operation. ROC curves show cut-off value for CKMBmass 20.3 ng/ml (sensitivity 79% and specificity 89%); for cTnI cut-off value was 0.8 ng/ml (sensitivity 80% and specificity 94%) for cTnT the cut-off value was 0.41 ng/ml (sensitivity 86% and specificity 88%) and for MB the cut-off value was 419 ng/ml (sensitivity 85% and specificity 70%). CONCLUSION: All markers studied are reliable biochemical tests for perioperative myocardial infarction, however, the analysis of ROC curves suggested that cTnI and cTnT might be more useful for diagnosis of perioperative myocardial infarction after conventional coronary artery bypass surgery.

[Use of polymerase chain reaction in medical diagnosis]. / Zastosowanie lancuchowej reakcji polimerazy do diagnostyki medycznej.

Principles of the polymerase chain reaction (PCR) and its modifications are discussed: reverse transcription-PCR (RT-PCR), nested PCR, restriction fragment length polymorphism-PCR (RFLP-PCR). Different methods of the PCR products detection used in routine diagnostics and research are presented: electrophoresis and chromatography techniques, immunoenzymatic methods, hybridisation and sequencing. Applications of PCR reaction in diagnostics of infectious diseases (viral and bacterial), genetic diseases and genotyping in transplantation are discussed and examples of commercial tests based on PCR reaction and another molecular biology methods used in fast, routine diagnostics are listed.