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Introduction: Brain positron emission tomography/computed tomography (PET/CT) scans are useful for identifying the cause of dementia by evaluating glucose metabolism in the brain with F-18-fluorodeoxyglucose or Aβ deposition with F-18-florbetaben. However, since imaging time ranges from 10 to 30 minutes, movements during the examination might result in image artifacts, which interfere with diagnosis. To solve this problem, data-driven brain motion correction (DDBMC) techniques are capable of performing motion corrected reconstruction using highly accurate motion estimates with high temporal resolution. In this study, we investigated the effectiveness of DDBMC techniques on PET/CT images using a Hoffman phantom, involving continuous rotational and tilting motion, each expanded up to approximately 20 degrees. Materials and methods: Listmode imaging was performed using a Hoffman phantom that reproduced rotational and tilting motions of the head. Brain motion correction processing was performed on the obtained data. Reconstructed images with and without brain motion correction processing were compared. Visual evaluations by a nuclear medicine specialist and quantitative parameters of images with correction and reference still images were compared. Results: Normalized Mean Squared Error (NMSE) results demonstrated the effectiveness of DDBMC in compensating for rotational and tilting motions during PET imaging. In Cases 1 and 2 involving rotational motion, NMSE decreased from 0.15–0.2 to approximately 0.01 with DDBMC, indicating a substantial reduction in differences from the reference image across various brain regions. In the Structural Similarity Index (SSIM), DDBMC improved it to above 0.96 Contrast assessment revealed notable improvements with DDBMC. In continuous rotational motion, % contrast increased from 42.4% to 73.5%, In tilting motion, % contrast increased from 52.3% to 64.5%, eliminating significant differences from the static reference image. These findings underscore the efficacy of DDBMC in enhancing image contrast and minimizing motion induced variations across different motion scenarios. Conclusions: DDBMC processing can effectively compensate for continuous rotational and tilting motion of the head during PET, with motion angles of approximately 20 degrees. However, a significant limitation of this study is the exclusive validation of the proposed method using a Hoffman phantom; its applicability to the human brain has not been investigated. Further research involving human subjects is necessary to assess the generalizability and reliability of the presented motion correction technique in real clinical scenarios. [ABSTRACT FROM AUTHOR]

The interaction of ionizing radiation with matter is a stochastic process and statistical analysis of such a process would be a crucial step in understanding radioactivity. Geiger–Müller (GM) counter is a widely used radiation detector used in nuclear radiation surveying, which produces counts upon exposure to a radioactive source. There are a variety of multi-purpose software that can be used to perform statistical analysis of measured counts from a GM counter. However, statistical analysis is a lengthy, error prone and time-consuming process, which gets more tedious when the number of measurements increases. In the present work, we have developed an open-source and easy-to-use graphical user interface (GUI) computer program named RadStat for statistical analysis of counts measured by a GM counter. RadStat has its own scripting syntaxes and bundled with gnuplot for quick visualization of output results. We believe the present open-source GUI program would be a useful tool for research and teaching of nuclear radiation physics. [ABSTRACT FROM AUTHOR]

Some concepts in nuclear radiation physics are abstract and intellectually demanding. In the present paper, an "MCHP platform" (MCHP was an acronym for Monte Carlo simulations + Human Phantoms) was proposed to provide assistance to the students through visualization. The platform involved Monte Carlo simulations of interactions between ionizing radiations and the Oak Ridge National Laboratory (ORNL) adult male human phantom. As an example to demonstrate the benefits of the proposed MCHP platform, the present paper investigated the variation of the absorbed photon dose per photon from a 137Cs source in three selected organs, namely, brain, spine and thyroid of an adult male for concrete and lead shields with varying thicknesses. The results were interesting but not readily comprehensible without direct visualization. Graphical visualization snapshots as well as video clips of real time interactions between the photons and the human phantom were presented for the involved cases, and the results were explained with the help of such snapshots and video clips. It is envisaged that, if the platform is found useful and effective by the readers, the readers can also propose examples to be gradually added onto this platform in future, with the ultimate goal of enhancing students' understanding and learning the concepts in an undergraduate nuclear radiation physics course or a related course. [ABSTRACT FROM AUTHOR]

The purpose of this study is to evaluate the feasibility of extending a previously developed amyloid biomathematical screening methodology to support the screening of tau radiotracers during compound development. 22 tau-related PET radiotracers were investigated. For each radiotracer, in silico MLogP, Vx, and in vitro KD were input into the model to predict the in vivo K1, k2, and BPND under healthy control (HC), mild cognitive impaired (MCI), and Alzheimer's disease (AD) conditions. These kinetic parameters were used to simulate the time activity curves (TACs) in the target regions of HC, MCI, and AD and a reference region. Standardized uptake value ratios (SUVR) were determined from the integrated area under the TACs of the target region over the reference region within a default time window of 90–110 min. The predicted K1, k2, and BPND values were compared with the clinically observed values. The TACs and SUVR distributions were also simulated with population variations and noise. Finally, the clinical usefulness index (CUI) ranking was compared with clinical comparison results. The TACs and SUVR distributions differed for tau radiotracers with lower tau selectivity. The CUI values ranged from 0.0 to 16.2, with 6 out of 9 clinically applied tau radiotracers having CUI values higher than the recommend CUI value of 3.0. The differences between the clinically observed TACs and SUVR results showed that the evaluation of the clinical usefulness of tau radiotracer based on single target binding could not fully reflect in vivo tau binding. The screening methodology requires further study to improve the accuracy of screening tau radiotracers. However, the higher CUI rankings of clinically applied tau radiotracers with higher signal-to-noise ratio supported the use of the screening methodology in radiotracer development by allowing comparison of candidate radiotracers with clinically applied radiotracers based on SUVR, with respect to binding to a single target. [ABSTRACT FROM AUTHOR]

Ultrahigh resolution small animal PET systems require small pixel size scintillators. We developed an ultrahigh resolution small animal PET system using fine LYSO pixels, which were 0.32 mm×0.5 mm×5.0 mm. The LYSO pixels were combined into a 22×15 matrix with a 0.1 mm thick BaSO 4 reflector between them. The LYSO block was 9.24 mm×9.0 mm×5 mm, and it was optically coupled to a 4×4 through silicon via silicon photomultiplier (TSV Si-PM) array that has smaller gaps between channels with a 1-mm thick light guide. We made eight Si-PM-based block detectors and arranged them octagonally to form a PET detector ring. At the center, the spatial resolution of the developed PET system, which was reconstructed by filtered back projection (FBP), was 0.6-mm FWHM. The sensitivity at the axial center was 0.5%. The peak noise equivalent count rate (NECR) was 12.5 k cps. We obtained high resolution images of phantoms and small animals with the developed PET system. With these results, we conclude that a high resolution PET system is possible with 0.32 mm pixel LYSO scintillators. [ABSTRACT FROM AUTHOR]

Introduction The purpose of this study was to compare two amyloid imaging agents, [ 11 C]BF227 and [ 18 F]FACT (derivative from [ 11 C]BF227) through quantitative pharmacokinetics analysis in human brain. Methods Positron emission tomography studies were performed on six elderly healthy control (HC) subjects and seven probable Alzheimer’s disease (AD) patients with [ 11 C]BF227 and 10 HC subjects and 10 probable AD patients with [ 18 F]FACT. Data from nine regions of interest were analyzed by several approaches, namely non-linear least-squared fitting methods with arterial input functions (one-tissue compartment model(1TCM), two-tissue compartment model (2TCM)), Logan plot, and linearized methods with reference region (Reference Logan plot (RefLogan), MRTM0, MRTM2). We also evaluated SUV and SUVR for both tracers. The parameters estimated by several approaches were compared between two tracers for detectability of differences between HC and AD patients. Results For [ 11 C]BF227, there were no significant difference of V T (2TCM, 1TCM) and SUV in all regions (Student t -test; p < 0.05) and significant differences in the DVRs (Logan, RefLogan, and MRTM2) and SUVRs in six neocortical regions ( p < 0.05) between the HC and AD groups. For [ 18 F]FACT, significant differences in DVRs (RefLogan, MRTM0, and MRTM2) were observed in more than four neocortical regions between the HC and AD groups (p < 0.05), and the significant differences were found in SUVRs for two neocortical regions (inferior frontal coretex and lateral temporal coretex). Our results showed that both tracers can clearly distinguish between HC and AD groups although the pharmacokinetics and distribution patterns in brain for two tracers were substantially different. Conclusion This study revealed that although the PET amyloid imaging agents [ 11 C]BF227 and [ 18 F]FACT have similar chemical and biological properties, they have different pharmacokinetics, and caution must be paid for usage of the tracers. [ABSTRACT FROM AUTHOR]

Since a high resolution PET system is needed for small animal imaging, especially for mouse studies, we developed a new small animal PET system that decreased the size of the scintillators to less than 1 mm. Our developed PET system used 0.5 × 0.7 × 5 mm3 LYSO pixels arranged in an 11 × 13 matrix to form a block with a 0.1 mm BaSO4 reflector between the pixels. Two LYSO blocks were optically coupled to two optical fiber based angled image guides. These LYSO blocks and image guides were coupled to a Si-PM array (Hamamatsu MPPC S11064–050P) to form a block detector. Eight block detectors (16 LYSO blocks) were arranged in a 34 mm inner diameter ring to form a small animal PET system. The block detector showed good separation for the 22 × 13 LYSO pixels in the two-dimensional position histogram. The energy resolution was 20% full-with at half-maximum (FWHM) for 511 keV gamma photons. The transaxial resolution reconstructed by filtered backprojection was 0.71 to 0.75 mm FWHM and the axial resolution was 0.70 mm. The point source sensitivity was 0.24% at the central axial field-of-view. High resolution mouse images were obtained using our PET system. The developed ultrahigh resolution PET system showed attractive images for small animal studies and has a potential to provide new findings in molecular imaging researches. [ABSTRACT FROM AUTHOR]

Abstract: A silicon photomultiplier (Si-PM) is a promising photodetector for high resolution PET systems due to its small channel size and high gain. Using Si-PMs, it will be possible to develop a high resolution imaging systems. For this purpose, we developed a small field-of-view (FOV) ultrahigh-resolution Si-PM-based dual-head coincidence imaging system for small animals and plant research. A new scintillator, Ce doped Gd3Al12Ga3O12 (GAGG), was selected because of its high light output and its emission wavelength matched with the Si-PM arrays and contained no radioactivity. Each coincidence imaging block detector consists of 0.5×0.5×5mm3 GAGG pixels combined with a 0.1-mm thick reflector to form a 20×17 matrix that was optically coupled to a Si-PM array (Hamamatsu MPPC S11064-050P) with a 1.5-mm thick light guide. The GAGG block size was 12.0×10.2mm2. Two GAGG block detectors were positioned face to face and set on a flexible arm based detector stand. All 0.5mm GAGG pixels in the block detectors were clearly resolved in the 2-dimensional position histogram. The energy resolution was 14.4% FWHM for the Cs-137 gamma ray. The spatial resolution was 0.7mm FWHM measured using a 0.25mm diameter Na-22 point source. Small animal and plant images were successfully obtained. We conclude that our developed ultrahigh-resolution Si-PM-based dual-head coincidence imaging system is promising for small animal and plant imaging research. [Copyright &y& Elsevier]

Purpose: To clarify the mechanism of prostaglandin (PG) analogue-dependent relaxation in ciliary arteries from wild-type (WT) and prostanoid receptor-deficient mice. Methods: The intracellular-free calcium concentration ([Ca2+]i) in isolated WT mouse ciliary arteries was measured by fluorescence photometry. Reduction of [Ca2+]i leading to vascular relaxation by PG analogues latanoprost, isopropyl unoprostone, or tafluprost was compared to the maximum increase of [Ca2+]i by 50 mM KCl. The cyclooxygenase inhibitor indomethacin and the NO synthase inhibitor NG-nitro-L-arginine methylester (L-NAME) were added to investigate the involvement of vascular endothelial factors. Moreover, PG analogue-dependent reduction of [Ca2+]i was measured in ciliary artery strips from FP, EP1, EP2, and EP3 receptor-deficient mice. Results: The 3 PG analogues reduced K+-dependent increase in [Ca2+]i in a concentration-dependent manner. Indomethacin (10 μM) had little effect. The reductions of [Ca2+]i induced by 10 μM PG analogues were not significantly affected by the treatment with the NO synthase inhibitor L-NAME (10−4 M). The effect of all 3 PG analogues in FP and EP3 receptor-deficient arteries was similar to the effect in WT arteries. Latanoprost significantly enhanced the reduction of [Ca2+]i in ciliary arteries from prostanoid EP1 and EP2 receptor-deficient mice compared to WT mice. Tafluprost had a similar effect in arteries from EP2 receptor-deficient mice. Conclusions: PG analogues latanoprost, isopropyl unoprostone, and tafluprost reduced the K+-dependent increase in [Ca2+]i in isolated mouse ciliary arteries. Endothelial-derived factors and FP and EP3 receptors were not involved in the responses. The increased effectiveness of latanoprost and tafluprost in reducing [Ca2+]i in EP1 and EP2 receptor-deficient arteries suggests that the PG analogues may act, at least partially, through nonprostanoid receptor pathways. For glaucoma patients, PG analogues can be selected to reduce the intraocular pressure and increase the ocular blood flow. [ABSTRACT FROM AUTHOR]

Purpose: Recently, photomultiplier tubes (PMTs) and position sensitive PMTs (PSPMTs) with higher quantum efficiencies (HQE) have been developed. However, it remains unclear whether they actually improve such performances as the energy and spatial resolution for PET and SPECT detectors. Methods: The authors evaluated the quantum efficiencies (QEs) for PMTs and PSPMTs and measured the energy resolution of a 3-in. round HQE PMT combined with various scintillators and compared the results with a conventional normal quantum efficiency (NQE) PMT of the same type. The authors also measured the position and energy performance of a 2-in. square HQE PSPMT combined with scintillator blocks and compared them with a NQE PSPMT of the same size. Results: The energy resolution of the 3-in. round HQE PMT showed higher energy resolution than the NQE with all scintillators. The improvement of the energy resolution was smaller, for all measurements, than the expected value from the quantum efficiency of the PMT but was higher for the scintillators with smaller light outputs. The energy and position performance of the HQE PSPMT based block detectors showed higher position and energy performance than those with NQE. Conclusions: From these results, the authors conclude that both HQE PMT and PSPMT contribute to improve the energy and position performance for PET and SPECT detectors. Significant performance improvements will be expected in PET and SPECT systems by the use of the HQE PMTs or PSPMTs. [ABSTRACT FROM AUTHOR]

Purpose: The simultaneous measurement of PET and magnetic resonance imaging (MRI) is an emerging field for molecular imaging research. Although optical fiber based PET/MRI systems have advantages on less interference between PET and MRI, there is a drawback in reducing the scintillation light due to the fiber. To reduce the problem, the authors newly developed flexible optical fiber bundle based block detectors and employed them for a high resolution integrated PET/MRI system. Methods: The flexible optical fiber bundle used 0.5 mm diameter, 80 cm long double clad fibers which have dual 12 mm × 24 mm rectangular inputs and a single 24 mm × 24 mm rectangular output. In the input surface, LGSO scintillators of 0.025 mol.% (decay time: ∼31 ns: 0.9 mm × 1.3 mm × 5 mm) and 0.75 mol.% (decay time: ∼46 ns: 0.9 mm × 1.3 mm × 6 mm) were optically coupled in depth direction to form depth-of-interaction detector, arranged in 11 × 13 matrix and optically coupled to the fiber bundle. The two inputs of the bundle are bent for 90°, bound to one, and are optically coupled to a Hamamatsu 1-in. square position sensitive photomultiplier tube. Results: Light loss due to the fiber bundle could be reduced and the performance of the block detectors was improved. Eight optical fiber based block detectors (16 LGSO blocks) were arranged in a 56 mm diameter ring to form a PET system. Spatial resolution and sensitivity were 1.2 mm full-width at half-maximum and 1.2% at the central field-of-view, respectively. Sensitivity change was less than 1% for 2 °C temperature changes. This PET system was integrated with a 0.3 T permanent magnet MRI system which has 17 cm diameter hole at the yoke area for insertion of the PET detector ring. There was no observable interference between PET and MRI. Simultaneous imaging of PET and MRI was successfully performed for small animal studies. Conclusions: The authors confirmed that the developed high resolution PET/MRI system is promising for molecular imaging research. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Measurement of regional cerebral blood flow (rCBF) in rodents can provide knowledge of pathophysiology of the cerebral circulation, but generally requires blood sampling for analysis during positron emission tomography (PET). We therefore tested the feasibility of using an arteriovenous (AV) shunt in rats for less invasive blood analysis. Methods: Six anesthetized rats received [15O]H2O and [15O]CO PET scans with their femoral artery and vein connected by an AV shunt, the activity within which was measured with a germanium ortho-oxysilicate scintillation detector. The [15O]H2O was intravenously injected either at a faster or slower injection rate, while animals were placed either with their head or heart centered in the gantry. The time–activity curve (TAC) from the AV shunt was compared with that from the cardiac ventricle in PET image. The rCBF values were calculated by a nonlinear least-square method using the dispersion-corrected AV-shunt TAC as an input. Results: The AV-shunt TAC had higher signal-to-noise ratio, but also had delay and dispersion compared with the image-derived TAC. The delay time between the AV-shunt TAC and image-based TAC ranged from 11 to 21 s, while the dispersion was estimated to be ∼5 s as a time constant of the dispersion model of exponential function, and both were properly corrected. In a steady-state condition of [15O]CO PET, the blood activity concentration by AV-shunt TAC was also comparable in height with the image-based TAC corrected for partial volume. Whole-brain CBF values measured by [15O]H2O were 0.37±0.04 (mean±S.D.) ml/g/min, partition coefficient was 0.73±0.04 ml/g, and the CBF varied in a linear relationship with partial pressure of carbon dioxide during each scan. Conclusions: The AV-shunt technique allows less invasive, quantitative and reproducible measurement of rCBF in [15O]H2O PET studies in rats than direct blood sampling and radioassay. [Copyright &y& Elsevier]

Abstract: Introduction: This study is intended to evaluate the feasibility of using a high-resolution pinhole SPECT system and iodine-123-N-isopropyl-4-iodoamphetamine (123I-IMP) for three-dimensional (3D) absolute quantitation of regional cerebral blood flow (rCBF) in mice. Methods: The pinhole SPECT system consists of a rotating stage and a pinhole collimator attached to a clinical gamma camera. The collimator''s focal length is 251 mm. Phantom studies were performed to evaluate sensitivity and full-width half-maximum (FWHM) spatial resolution. The aperture-to-object distance was 15 mm. Six mice were studied. Cerebral infarctions were induced by ligating and disconnecting the distal portion of the left middle cerebral artery. Ex vivo SPECT studies were performed using harvested brains and skulls. The CBF volumetric image was computed using the standardized input function. Results: Excellent spatial resolution of 0.9-mm FWHM and uniform sensitivity throughout the 3D volume were demonstrated in the phantom experiments. The CBF images showed a defect in the infarcted areas and a reduction of CBF values in the infarcted region as compared with the control region. Conclusions: This study demonstrated the feasibility of the 3D quantitation of rCBF in mice using a high-resolution pinhole SPECT system and 123I-IMP. [Copyright &y& Elsevier]

Quantitative interpretation of brain [F]FDOPA PET data has been made possible by several kinetic modeling approaches, which are based on different assumptions about complex [F]FDOPA metabolic pathways in brain tissue. Simple kinetic macro parameters are often utilized to quantitatively evaluate metabolic and physiological processes of interest, which may include DDC activity, vesicular storage, and catabolism from F-labeled dopamine to DOPAC and HVA. A macro parameter most sensitive to the changes of these processes would be potentially beneficial to identify impaired processes in a neurodegenerative disorder such as Parkinson's disease. The purpose of this study is a systematic comparison of several [F]FDOPA macro parameters in terms of sensitivities to process-specific changes in simulated time-activity curve (TAC) data of [F]FDOPA PET. We introduced a multiple-compartment kinetic model to simulate PET TACs with physiological changes in the dopamine pathway. TACs in the alteration of dopamine synthesis, storage, and metabolism were simulated with a plasma input function obtained by a non-human primate [F]FDOPA PET study. Kinetic macro parameters were calculated using three conventional linear approaches (Gjedde-Patlak, Logan, and Kumakura methods). For simulated changes in dopamine storage and metabolism, the slow clearance rate ( k) as calculated by the Kumakura method showed the highest sensitivity to these changes. Although k performed well at typical ROI noise levels, there was large bias at high noise level. In contrast, for simulated changes in DDC activity it was found that K and V, estimated by Gjedde-Patlak and Logan method respectively, have better performance than k. Synapse 2011. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Purpose: In normotensive eyes, reduced ocular blood flow can lead to glaucoma pathogenesis. Drugs that reduce intraocular pressure (IOP) often cause vasodilation of the ciliary arteries and improve blood flow to the eye. A novel class of drugs called Rho-associated coiled coil-forming protein kinase (ROCK) inhibitors can lower IOP. Therefore, we tested the ability of two ROCK inhibitors, Y-27632 and Y39983, to relax rabbit ciliary arteries. Methods: We measured in vitro ciliary artery smooth muscle contractions by isometric tension recordings and changes of intracellular free calcium concentration ([Ca]) by fluorescence photometry. Results: Both Y-27632 and Y-39983 induced a concentration-dependent relaxation in rabbit ciliary arteries precontracted with a high-potassium (high-K) solution. The amplitude of relaxation induced by Y-27632 and Y-39983 was not affected by either 100 μM N-nitro- l-arginine methyl ester ( l-NAME) or 10 μM indomethacin. In Ca-free solution, Y-27632 and Y-39983 significantly inhibited the transient contraction of ciliary arteries induced by 10 μM histamine. However, neither Y-27632 nor Y-39983 affected the elevation of [Ca] induced by high-K solution and histamine. Conclusions: We concluded that Y-27632 and Y-39983 relaxed isolated rabbit ciliary artery segments in vitro. The mechanism of relaxation was not dependent on endothelial-derived factors such as nitric oxide (NO) or prostacyclin, nor was it dependent on changes in intracellular Ca concentration. [ABSTRACT FROM AUTHOR]

Abstract: We investigated the effects of prostaglandin F2α (PGF2α) analogues on the endothelin-1 (ET-1)-induced impairment of optic nerve head (ONH) blood flow and on ET-1-induced contraction in isolated ciliary artery segments. In male rabbits, one of four PGF2α analogues [0.0015% tafluprost, 0.0015% 15-hydroxyl tafluprost (15-OH tafluprost), 0.005% latanoprost, or 0.004% travoprost] was topically administered at various pretreatment times before intravitreal ET-1 injection. ONH blood flow was estimated by the laser speckle method, which expresses blood velocity as a quantitative index, the squared blur rate (SBR). SBR was measured just before (baseline value) and at 30, 60, and 120 min after ET-1 injection. SBR was significantly decreased from 4.47 ± 0.20 to 3.50 ± 0.10 (78.6 ± 2.4% of baseline) at 120 min after intravitreal ET-1 injection (5 pmol/eye). The ET-1-induced decrease was almost completely prevented by tafluprost and significantly inhibited by the other three analogues. The inhibitory effect lasted longest with tafluprost, as indicated by the effective pretreatment times (tafluprost: 90, 120, or 240 min; 15-OH tafluprost: 90, but not 120 or 240 min; latanoprost and travoprost: 120, but not 240 min). In vitro, the effects of PGF2α analogues on ET-1-induced contractions in male rabbit ciliary arteries were evaluated using an isometric tension recording system. Tafluprost, latanoprost, travoprost, and 15-OH tafluprost concentration-dependently relaxed the 10 nM ET-1-induced ciliary artery contraction. Improvement of the ocular circulation may be superior with tafluprost than with the other PGF2α analogues. The underlying mechanism may involve relaxation of ocular resistance vessels. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) with [11C]raclopride has been used to investigate the density (Bmax) and affinity (Kd) of dopamine D2 receptors related to several neurological and psychiatric disorders. However, in assessing the Bmax and Kd, multiple PET scans are necessary under variable specific activities of administered [11C]raclopride, resulting in a long study period and unexpected physiological variations. In this paper, we have developed a method of multiple-injection graphical analysis (MI-GA) that provides the Bmax and Kd values from a single PET scan with three sequential injections of [11C]raclopride, and we validated the proposed method by performing numerous simulations and PET studies on monkeys. In the simulations, the three-injection protocol was designed according to prior knowledge of the receptor kinetics, and the errors of Bmax and Kd estimated by MI-GA were analyzed. Simulations showed that our method could support the calculation of Bmax and Kd, despite a slight overestimation compared with the true magnitudes. In monkey studies, we could calculate the Bmax and Kd of diseased or normal striatum in a 150 mins scan with the three-injection protocol of [11C]raclopride. Estimated Bmax and Kd values of D2 receptors in normal or partially dopamine-depleted striatum were comparable to the previously reported values. [ABSTRACT FROM AUTHOR]

Abstract: Vascular peripheral resistance is increased during hypertension, and endothelium-derived hyperpolarizing factor (EDHF) is an important for regulating vasodilation in small arteries. Therefore we characterized the role of EDHF in regulating vascular resistance of ocular ciliary arteries from spontaneous hypertensive rats (SHR) and age-matched Wistar Kyoto rats (WKY). Isometric tension recordings were used in isolated ocular ciliary artery segments from SHR and WKY. Ocular ciliary arteries pre-contracted with 100 μM norepinephrine exhibited a concentration-dependent relaxation to acetylcholine, and the effect on SHR arteries was smaller than that on WKY arteries (P < 0.05). The EDHF-mediated component of this relaxation, determined in the presence of 100 μM l-NAME plus 10 μM indomethacin, was also smaller in SHR than in WKY arteries (P < 0.05). Apamin (1 μM), a blocker of small-conductance calcium-activated K+ (KCa) channels, had no effect on EDHF-mediated relaxation in either preparation. However, charybdotoxin (0.1 μM), which blocks intermediate- and large-conductance KCa channels, and iberiotoxin (0.1 μM), which blocks large-conductance KCa channels, almost completely suppressed EDHF-mediated relaxation in both preparations. The tension of ciliary arteries from both SHR and WKY was increased above baseline by 100 μM l-NAME plus 10 μM indomethacin. In these preparations, apamin had no effect on the tension in arteries from either SHR or WKY. However, both charybdotoxin and iberiotoxin further increased tension above that induced by l-NAME and indomethacin. The increase was smaller for SHR than WKY (P < 0.05). In summary, the ability of EDHF to relax ocular ciliary artery vascular tone in SHR is smaller than in WKY. The large-conductance calcium-activated K+ channel is utilized in EDHF-signaling pathway. [Copyright &y& Elsevier]

Abstract: Positron emission tomography (PET) with [11C]raclopride is widely used to investigate temporal changes in the dopamine D2 receptor system attributed to the dopamine release. The simplified reference tissue model (SRTM) can be used to determine the binding potential (BPND) value using the time–activity curve (TAC) of the reference region as input function. However, in assessing temporal changes in BPND using the SRTM, multiple [11C]raclopride PET scans are required, and a second scan must be performed after the disappearance of the [11C]raclopride administered in the first scan. In this study, we have developed an extended multiple-injection SRTM to estimate the BPND change, from a single PET scan with multiple injections of [11C]raclopride, and we have validated this approach by performing numerous simulations and studies on monkeys. In the computer simulations, TACs were generated for dual injections of [11C]raclopride, in which binding conditions changed during the scans, and the BPND values before, and after, the second injection were estimated by the proposed method. As a result, the reduction in BPND was correlated, either with the integral of released dopamine, or with the administered mass of raclopride. This method was applied to studies on monkeys, and was capable of determining two identical BPND values when there were no changes in binding conditions. The BPND after the second injection decreased when binding conditions changed due to an increase in administered raclopride. An advantage of the proposed method is the shortened scan period for the quantitative assessment of the BPND change for neurotransmitter competition studies. [Copyright &y& Elsevier]

Abstract: Our objective was to determine if tafluprost, a newly synthesized antiglaucoma drug, can relax precontracted rabbit ciliary arteries, and if so, to elucidate the underlying mechanism. We used isometric tension recordings of smooth muscle contractions and fluorescence photometry to monitor the change of intracellular free calcium concentration ([Ca2+]i) in isolated rabbit ciliary artery segments. Tafluprost induced a concentration-dependent relaxation in rabbit ciliary arteries precontracted with a high-K solution. The amplitude of relaxation induced by tafluprost was unchanged by 100μM l-NAME, 10μM indomethacin, denudation of vascular endothelium, 30μM thapsigargin, or 100μM ouabain. In Ca2+-free solution, 30μM tafluprost did not decrease the amplitude of contraction induced by 1μM histamine or the amplitude of the [Ca2+]i increase induced by 10μM histamine. The mechanism of tafluprost-induced relaxation was different from diltiazem, a voltage-dependent Ca2+ channel blocker. However, in thapsigargin-pretreated preparations incubated in Ca2+-free solution, tafluprost attenuated the capacitative increase of [Ca2+]i upon Ca2+ reintroduction to the extracellular medium. Thus, we conclude that tafluprost relaxed isolated rabbit ciliary artery segments precontracted with a high-K solution. The relaxing mechanism was not dependent on endothelial-derived factors, and not affected by the intracellular Ca2+ cycles or the Ca2+ extrusion component of the extracellular Ca2+ cycles. Relaxation of rabbit ciliary artery smooth muscle by tafluprost may be due, at least in part, to inhibition of capacitative Ca2+ entry from the extracellular space. [Copyright &y& Elsevier]

Abstract: A new method has been developed for diffusible tracers, to quantify CBF at rest and after pharmacological stress from a single session of dynamic scans with dual bolus administration of a radiotracer. The calculation process consisted of three steps, including the procedures of incorporating background radioactivity contaminated from the previous scan. Feasibility of this approach was tested on clinical SPECT studies on 16 subjects. Two sequential SPECT scans, 30 min apart, were carried out on each subject, after each of two split-dose administrations of 111 MBq IMP. Of these, 11 subjects received acetazolamide at 10 min before the second IMP injection. Additional PET scans were also carried out on 6 subjects on a separate day, at rest and after acetazolamide administration. The other 5 subjects were scanned only at rest during the whole study period. Quantitative CBF obtained by this method was in a good agreement with those determined with PET (y(ml/100 g/min)=1.07×(ml/100 g/min)−1.14, r =0.94). Vasareactivity was approximately 40% over the whole cerebral area on healthy controls, which was consistent with a literature value. Reproducibility of CBF determined in the rest–rest study was 1.5±5.7%. Noise enhancement of CBF images, particularly the second CBF, was reduced, providing reasonable image quality. Repeat assessment of quantitative CBF from a single session of scans with split-dose IMP is accurate, and may be applied to clinical research for assessing vascular reactivity in patients with chronic cerebral vascular disease. [Copyright &y& Elsevier]

Purpose: An image-based scatter correction (IBSC) method was developed to convert scatter-uncorrected into scatter-corrected SPECT images. The purpose of this study was to validate this method by means of phantom simulations and human studies with 99mTc-labeled tracers, based on comparison with the conventional triple energy window (TEW) method. Methods: The IBSC method corrects scatter on the reconstructed image IACμb with Chang's attenuation correction factor. The scatter component image is estimated by convolving IACμb with a scatter function followed by multiplication with an image-based scatter fraction function. The IBSC method was evaluated with Monte Carlo simulations and 99mTc-ethyl cysteinate dimer SPECT human brain perfusion studies obtained from five volunteers. The image counts and contrast of the scatter-corrected images obtained by the IBSC and TEW methods were compared. Results: Using data obtained from the simulations, the image counts and contrast of the scatter-corrected images obtained by the IBSC and TEW methods were found to be nearly identical for both gray and white matter. In human brain images, no significant differences in image contrast were observed between the IBSC and TEW methods. Conclusion: The IBSC method is a simple scatter correction technique feasible for use in clinical routine. [ABSTRACT FROM AUTHOR]

Abstract: Recently, lactate has been receiving great attention as an energy substrate in the brain. In this study, the role of lactate was evaluated by “bioradiography” system with 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG), which is a positron emitting radiotracer for glucose uptake quantification. “Bioradiography” is the dynamic living tissue slice imaging system for positron-emitter labeled compounds. We investigated the brain energy metabolism under resting state and neural activated conditions induced by KCl addition. The monocarboxylate transporter inhibitor, α-cyano-4-hydroxycinnamate (4-CIN), had no effect on [18F]FDG uptake rate in rat brain slices before KCl addition. On the other hand, addition of 4-CIN induced larger [18F]FDG uptake rates under the activated condition in comparison with the control condition. Because neurons cannot utilize lactate under the 4-CIN loaded conditions, this indicates that activated neurons consume lactate as an energy substrate. The lactate concentration in the incubation medium was increased with KCl treatment in both groups and the extent was slightly greater in 4-CIN group. These results suggested that: (1) the brain mainly uses glucose, not lactate, as an energy substrate in resting state; (2) when neuron is stimulated, excess amounts of lactate might be produced in astrocytes and the lactate is mobilized as an energy substrate. [Copyright &y& Elsevier]

Pinhole single-photon emission computed tomography (SPECT) is able to provide information on the biodistribution of several radioligands in small laboratory animals, but has limitations associated with non-uniform spatial resolution or axial blurring. We have hypothesised that this blurring is due to incompleteness of the projection data acquired by a single circular pinhole orbit, and have evaluated a new strategy for accurate image reconstruction with better spatial resolution uniformity. A pinhole SPECT system using two circular orbits and a dedicated three-dimensional ordered subsets expectation maximisation (3D-OSEM) reconstruction method were developed. In this system, not the camera but the object rotates, and the two orbits are at 90° and 45° relative to the object’s axis. This system satisfies Tuy’s condition, and is thus able to provide complete data for 3D pinhole SPECT reconstruction within the whole field of view (FOV). To evaluate this system, a series of experiments was carried out using a multiple-disk phantom filled with 99mTc solution. The feasibility of the proposed method for small animal imaging was tested with a mouse bone study using 99mTc-hydroxymethylene diphosphonate. Feldkamp’s filtered back-projection (FBP) method and the 3D-OSEM method were applied to these data sets, and the visual and statistical properties were examined. Axial blurring, which was still visible at the edge of the FOV even after applying the conventional 3D-OSEM instead of FBP for single-orbit data, was not visible after application of 3D-OSEM using two-orbit data. 3D-OSEM using two-orbit data dramatically reduced the resolution non-uniformity and statistical noise, and also demonstrated considerably better image quality in the mouse scan. This system may be of use in quantitative assessment of bio-physiological functions in small animals. [ABSTRACT FROM AUTHOR]

Motion of the head during brain positron emission tomography (PET) acquisitions has been identified as a source of artifact in the reconstructed image. A number of techniques have been proposed to correct for this motion artifact, but they are unable to correct for a motion during an acquisition. The aim of this study was to develop a sinogram-based motion correction (SBMC) technique to correct directly the head motion during a PET scan using a motion tracking system and list-mode data acquisition. This method uses a rebinning procedure whereby the lines of response (LOR) are geometrically transformed according to the current values of six-dimensional motion data. A Michelogram was recomposed using the rebinned LOR, and the motion-corrected sinogram was generated. In the motion corrected image, the blurring artifact due to the motion was reduced by the SBMC technique. This technique was applied to actual PET data acquired in the list-mode, and demonstrated the potential for real-time motion correction of head movements during a PET acquisition. [ABSTRACT FROM AUTHOR]

Transmission-dependent convolution subtraction (TDCS) is a promising technique in quantitative SPECT for subtracting the scatter components from emission images. Usually, a 20% photopeak energy window is used in SPECT acquisitions. To date, no investigation has assessed the effects of energy windows in the subtraction of scatter components from emission images with the TDCS technique. To evaluate the energy dependence of the TDCS technique, we analyzed photopeak energy windows of 5%, 10%, 15%, 20%, 25%, 30%, and 35% using 99mTc radionuclide. The scatter fractions for a point source placed in a water phantom were estimated using the triple-energy-window (TEW) technique. These estimates were used to establish the parameters of the TDCS equation as a function of transmission. The estimated parameters were applied to the TDCS technique to subtract the scatter components from data of corresponding energy windows using nonuniform and uniform phantoms. All data were reconstructed with the OSEM algorithm. The energy window dependence of the TDCS technique was verified by comparing the coefficients of variance (COV) of the data from the uniform phantom of each energy window. Ten Poisson deviates were generated from each projection's data from the uniform phantom. The nonuniform phantom results showed that the estimated parameters effectively estimated the scatter component from the projection image for each energy window. The COV for the 5%, 10%, 15%, 20%, 25%, 30%, and 35% windows were 2.10%, 1.76%, 1.44 %, 1.39%, 1.34%, 1.37%, and 1.61%, respectively. In the TDCS technique, any photopeak energy window from 15% to 30% may work almost as well as judged by the COV measured for a uniform phantom in this study. The best window by that measure was the 25% window. [ABSTRACT FROM AUTHOR]

Pinhole single-photon emission computed tomography (SPECT) with high spatial-resolution is suitable for small-animal imaging, but has limitations associated with spatial-resolution inhomogeneity or axial blurring. We have hypothesized that this blurring is due to incompleteness of projection data acquired by a single circular pinhole orbit. And we have developed a pinhole SPECT system with two circular orbits which satisfy Tuy''s condition so as to provide complete data for 3D pinhole SPECT reconstruction within the whole field-of-view (FOV); a dedicated 3D ordered subsets expectation maximization (3D-OSEM) reconstruction method for two-orbit data. This study is aimed at evaluating accuracy and impact of this system. In this system, not the camera but the object rotates and the two orbits are 90° and 45° relative to object''s axis. Experiments using a multiple-disk phantom filled with 99mTc solution and a mouse bone scan using 99mTc-labeled HMDP agent were carried out. The Feldkamp''s filtered back-projection (FBP) method and the 3D-OSEM method were applied to these data sets. The axial blurring was apparent on images reconstructed by FBP for single-orbit data, while the 3D-OSEM using two-orbit data dramatically improved the resolution homogeneity and statistical noise property, and also demonstrated considerably better image quality in the mouse scan. [Copyright &y& Elsevier]

Head movement during positron emission tomography (PET) studies causes loss of image quality and quantity and is problematic for brain PET study. During the PET scan, the head of the subject is often fixed by a head holder. However, the head holder is not perfect and it is sometimes difficult to use the head holder for a less cooperative patient. Moreover, head fixation might generate unwanted signals in neural activation studies. There are several software packages, such as AIR and SPM, offering software tools to correct head motion between two scans. These tools, however, cannot correct head motions during scanning. We developed a system to correct the head motion during PET scanning using list-mode acquisition and an optical tracking system. To compensate for escaped photon from the FOV of the PET scanner, the concept of a “virtual ring” was introduced. The present system has the potential to do real-time motion correction during PET scanning and makes it possible to scan a subject without any head fixation, which provides a new aspect of brain research using PET. [Copyright &y& Elsevier]

Presents information on a study which investigated the relationship between scatter and collimator design for the use of the transmission-dependent convolution subtraction method. Methodology; Results and discussion; Conclusions.

Presents a study which developed the profile fitting method to measure the input function from positron emission tomography images of the aorta. Discussions on positron emission tomography; How the diameter of the aorta was determined; Methods used in the study; Discussion on the results of the study.

AbstractThe fundamental prompt neutron delayed constant α, the effective delayed neutron fraction $${\beta _{eff}}$$βeff, and the effective neutron generation time $${\Lambda _{eff}}$$Λeff are important for accurate measurements of keff in subcritical systems. In this paper, based on the open-source program OpenMC, a module with the function of calculating the α-eigenvalue is developed based on the k-α iterative method. Based on the nodal expansion method (NEM), an adjoint neutron flux calculation program was developed, which in turn used the idea of coupling the k-α iterative method with the NEM to obtain the neutron kinetics parameters (α, $${\beta _{eff}}$$βeff, and $${\Lambda _{eff}}$$Λeff) of the subcritical system and allowed for a more accurate keff under the subcritical system as compared to the traditional k-mode program.In this paper, the results of the α-eigenvalues calculated by the program are validated using the Godiva benchmark and the MUSE-4 device as computational objects. The accuracy of the results for $${\beta _{eff}}$$βeff and $${\Lambda _{eff}}$$Λeff was verified with the KUCA (Kyoto University Critical Assembly) benchmark. The results of the keff calculations using k-mode and α-mode are compared with the ADS benchmark.The results show that the calculation program (α-mode) can obtain keff under the subcritical system more accurately, which makes up for the shortcomings of the traditional program, which cannot be calculated under the deep subcritical system. The relative error between the calculated and reference values was less than 750 pcm at deep subcriticality (keff = 0.899). The error was less than 400 pcm at the deeper subcritical system (keff = 0.952), which can satisfy the demand for neutron dynamics parameters and keff calculation in the subcritical system. The program can also continue to be upgraded in the later stage in the calculation method and other aspects. [ABSTRACT FROM AUTHOR]

Acute cardiovascular physical exercise improves cognitive performance, as evidenced by a reduction in reaction time (RT). However, the mechanistic understanding of how this occurs is elusive and has not been rigorously investigated in humans. Here, using positron emission tomography (PET) with [11C]raclopride, in a multi‐experiment study we investigated whether acute exercise releases endogenous dopamine (DA) in the brain. We hypothesized that acute exercise augments the brain DA system, and that RT improvement is correlated with this endogenous DA release. The PET study (Experiment 1: n = 16) demonstrated that acute physical exercise released endogenous DA, and that endogenous DA release was correlated with improvements in RT of the Go/No‐Go task. Thereafter, using two electrical muscle stimulation (EMS) studies (Experiments 2 and 3: n = 18 and 22 respectively), we investigated what triggers RT improvement. The EMS studies indicated that EMS with moderate arm cranking improved RT, but RT was not improved following EMS alone or EMS combined with no load arm cranking. The novel mechanistic findings from these experiments are: (1) endogenous DA appears to be an important neuromodulator for RT improvement and (2) RT is only altered when exercise is associated with central signals from higher brain centres. Our findings explain how humans rapidly alter their behaviour using neuromodulatory systems and have significant implications for promotion of cognitive health. Key points: Acute cardiovascular exercise improves cognitive performance, as evidenced by a reduction in reaction time (RT). However, the mechanistic understanding of how this occurs is elusive and has not been rigorously investigated in humans.Using the neurochemical specificity of [11C]raclopride positron emission tomography, we demonstrated that acute supine cycling released endogenous dopamine (DA), and that this release was correlated with improved RT.Additional electrical muscle stimulation studies demonstrated that peripherally driven muscle contractions (i.e. exercise) were insufficient to improve RT.The current study suggests that endogenous DA is an important neuromodulator for RT improvement, and that RT is only altered when exercise is associated with central signals from higher brain centres. [ABSTRACT FROM AUTHOR]

(R,S)‐ketamine exerts robust antidepressant effects in patients with depression when given at sub‐anesthetic doses. Each of the enantiomers in this racemic mixture, (R)‐ketamine and (S)‐ketamine, have been reported to exert antidepressant effects individually. However, the neuropharmacological effects of these enantiomers and the mechanisms underlying their antidepressive actions have not yet been fully elucidated. Therefore, we investigated the effect of (R,S)‐, (R)‐, and (S)‐ketamine on brain activity by functional MRI (fMRI) in conscious rats and compared these with that of N‐methyl‐D‐aspartate receptor (NMDAR) antagonist MK‐801 (n = 5~7). We also assessed their pharmacokinetic profiles (n = 4) and their behavioral effects (n = 7~9). This pharmacological MRI study revealed a significant positive response to (S)‐ketamine specifically in the cortex, nucleus accumbens and striatum. In contrast, negative fMRI responses were observed in various brain regions after (R)‐ketamine administration. (R,S)‐ketamine, evoked significant positive fMRI responses specifically in the cortex, nucleus accumbens and striatum, and this fMRI response pattern was comparable with that of (S)‐ketamine. MK‐801‐induced similar fMRI response pattern to (S)‐ketamine. The fMRI responses to (S)‐ketamine and MK‐801 showed differential temporal profiles, which corresponded with brain concentration profiles. (S)‐ketamine and MK‐801 significantly increased locomotor activity, while (R)‐ketamine produced no noticeable change. (R,S)‐ketamine tended to increase locomotor activity. Our novel fMRI findings show that (R)‐ketamine and (S)‐ketamine induce completely different fMRI response patterns on rat, and that the response produced by the latter is similar to that elicited by an NMDAR antagonist. Our findings provide insight into the antidepressant mechanism of (R,S)‐ketamine. [ABSTRACT FROM AUTHOR]

It is well known that higher-dimensional black objects with translational invariance are unstable, which is called Gregory-Laflamme instability. There is a question if this instability is eliminated by adding a scalar hair to the black objects. For the first step, we investigate a regular topological string solution and its stability in the five-dimensional Einstein-Higgs system. Linear analysis shows that the string solution is stable against non-uniform perturbations. [ABSTRACT FROM AUTHOR]

This work reports on the differential and various angle integrated cross sections for the scattering of electrons and positrons by silicon atoms. Moreover, the Sherman function S (θ) and two other spin asymmetry parameters U (θ) and T (θ) have been calculated. Critical minima in the elastic differential cross sections and maximum spin polarization points were identified for this element. Dirac partial wave method with a complex optical model potential is used to carry out these investigations. Transport characteristics of electrons in silicon vapors and mixtures of inert gases (helium, argon) with silicon vapor were calculated using the Monte Carlo method. For electric field strengths ranging from 1 to 100 Td, drift velocity, average electron energy, diffusion and mobility coefficients, and electron energy distribution function are studied. We have shown that impurities of silicon vapor significantly affect electron transport in noble gases. [ABSTRACT FROM AUTHOR]

In clinical situations, various breast-dedicated positron emission tomography (PET) systems have been used. However, clinical breast-dedicated PET systems have polygonal detector ring. Polygonal detector ring sometimes causes image artifact, so complicated reconstruction algorithm is needed to reduce artifact. Consequently, we developed a circular detector ring for breast-dedicated PET to obtain images without artifact using a simple reconstruction algorithm. We used Lu 1.9 Gd 0.1 SiO 5 (LGSO) scintillator block which was made of 1.5 x 1.9 x 15 mm pixels that were arranged in an 8 x 24 matrix. As photodetectors, we used silicon photomultiplier (Si-PM) arrays whose channel size was 3 x 3 mm. A detector unit was composed of four scintillator blocks, 16 Si-PM arrays and a light guide. The developed detector unit had angled configuration since the light guide was bending. A detector unit had three gaps with an angle of 5.625° between scintillator blocks. With these configurations, we could arrange 64 scintillator blocks in nearly circular shape (regular 64-sided polygon) using 16 detector units. The use of the smaller number of detector units could reduce the size of the front–end electronics circuits. The inner diameter of the developed detector ring was 260 mm. This size was similar to those of brain PET systems, so our breast-dedicated PET detector ring can measure not only breast but also brain. Measured radial, tangential and axial spatial resolution of the detector ring reconstructed by the filtered back-projection (FBP) algorithm were 2.1 mm FWHM, 2.0 mm FWHM and 1.7 mm FWHM at center of field of view (FOV), respectively. The sensitivity was 2.0% at center of the axial FOV. With the developed detector ring, we could obtain high resolution image of the breast phantom and the brain phantom. We conclude that our developed Si-PM-based detector ring is promising for a high resolution breast-dedicated PET system that can also be used for brain PET system. [ABSTRACT FROM AUTHOR]

The present work reports the theoretical investigation of the scattering of electrons and positrons by the ethane (C 2 H 6 ) molecule over the energy range 1 eV–1 MeV. The investigation was carried out by taking into account the screening correction arising from a semiclassical analysis of the atomic geometrical overlapping of the scattering observables calculated in the independent atom approximation. The study is presented through the calculations of a broad spectrum of observable quantities, namely differential, integrated elastic, momentum transfer, viscosity, inelastic, grand total, and total ionization cross-sections and the Sherman functions. A comparative study was carried out between scattering observables for electron impact with those for positron impact to exhibit the similarity and dissimilarity arising out of the difference of the collisions of impinging projectiles with the target. Partial-wave decomposition of the scattering states within the Dirac relativistic framework employing a free-atom complex optical model potential was used to calculate the corresponding observable quantities of the constituent atoms. The results, calculated using our recipe, were compared with the experimental and theoretical works available in the literature. The Sherman function for a e ± – C 2 H 6 scattering system is presented for the first time in the literature. The addition of the screening correction to the independent atom approximation method was found to substantially reduce the scattering cross-sections, particularly at forward angles for lower incident energies. [ABSTRACT FROM AUTHOR]

The present work introduced a framework to investigate the effectiveness of proton boron fusion therapy (PBFT) at the cellular level. The framework consisted of a cell array generator program coupled with PHITS Monte Carlo package with a dedicated terminal-based code editor that was developed in this work. The framework enabled users to model large cell arrays with normal, all boron, and random boron filled cytoplasm, to investigate the underlying mechanism of PBFT. It was found that alpha particles and neutrons could be produced in absence of boron mainly because of nuclear reaction induced by proton interaction with 16O, 12C and 14N nuclei. The effectiveness of PBFT is highly dependent on the incident proton energy, source size, cell array size, buffer medium thickness layer, concentration and distribution of boron in the cell array. To quantitatively assess the effectiveness of PBFT, of the total energy deposition by alpha particle for different cases were determined. The number of alpha particle hits in cell cytoplasm and nucleus for normal and 100 ppm boron were determined. The obtained results and the developed tools would be useful for future development of PBFT to objectively determine the effectiveness of this treatment modality. [ABSTRACT FROM AUTHOR]

• An efficient method for the isolation of radium from thorium was reported. • Separation behaviors in batch and column modes were systematically investigated. • Hot test demonstrated that 228Ra and 224Ra was easily separated from 232Th. • Separation mechanism was illustrated successfully by the species distribution. In recent years, targeted-α-nuclide therapy (TAT) has been widely concerned in the world. As one of the few representative TAT nuclides, 212Pb showed good efficacy in cancer treatment; however, the amount remains scarce. Separating 228Ra and 224Ra from 232Th is expected to fundamentally solve this issue, since they both are the parent nuclides of 212Pb and can be used in generators. In this work, an efficient method for trace radium isolation from bulk thorium was proposed and verified through a systematic investigation of the adsorption behaviors of an anion exchanger denoted IRA900 toward thorium and barium/radium. Batch experiments suggested that IRA900 had unique selectivity for thorium in nitric acid solution, with almost no barium adsorbed. The thorium adsorption performance kept improving with increasing concentration of nitric acid and decreasing temperature. The adsorption kinetics and adsorption isotherm could be well fitted by the pseudo-second-order kinetic model and the Langmuir model, respectively. Column experiments suggested that thorium could be effectively immobilized by a column packed with IRA900, while barium was directly penetrated. For desorbing the fixed thorium, 0.1 M HNO 3 was optimal. A final hot test demonstrated the successful radium isolation from bulk thorium, with high chemical yield and purity. The selective separation mechanism was attributed to the formation of an anionic [Th(NO 3) 5 ]− complex, while barium or radium existed in the cationic form in any nitric acid concentration. This work provides a promising method for separating trace radium from thorium, which will be significant for promoting the large-scale utilization of 212Pb. [ABSTRACT FROM AUTHOR]

The theoretical investigation of differential, integrated elastic, momentum transfer, viscosity, inelastic, grand total and total ionisation cross sections along with the Sherman functions for the scattering of electrons and positrons by polar NH3 molecule in the energy range 1 eV–1 MeV are reported in the present work. We carry out calculations using the independent atom model (IAM) and IAM with screening correction. The scattering observables are calculated using a complex optical model potential in the framework of the Dirac partial wave analysis. The application of screening correction to the IAM substantially improves the cross sections particularly at lower incident energies. The results obtained from the present study are compared with the available experimental and theoretical works found in the literature. [ABSTRACT FROM AUTHOR]

A PET system for small animals requires a small detector ring to obtain high-spatial resolution images. However, when we use a relatively large size of photodetector such as a position-sensitive photomultiplier tube (PSPMT), the detector ring is arranged in a hexagonal- or octagonal-shape, and the PET system has large gaps between the block detectors. The large gaps produce image distortion, and the reconstruction algorithm is difficult. To solve these problems, we proposed to arrange two scintillator blocks on one PSPMT using two angled optical fiber-based image guides. We could set two scintillator blocks angled at 22.5° on a PSPMT so that these scintillator blocks are arranged in a nearly circular (hexadecagonal) shape with eight developed block detectors. We used Gd 2 SiO 5 (GSO) scintillators with Ce concentrations of 1.5 mol% (decay time: 39 ns) and 0.4 mol% (decay time: 63 ns). Sizes of these GSO cells were 1.6×2.4×7.0 mm 3 and 1.6×2.4×8.0 mm 3 for 1.5 mol% Ce and 0.4 mol% Ce, respectively. These two types of GSO were arranged in an 11×15 matrix and optically coupled in the depth direction to form a depth-of-interaction (DOI) detector. Two GSO blocks and two optical fiber-based image guides were optically coupled to a 2-in. PSPMT (Hamamatsu Photonics H8500: 8×8 anodes). We measured the performances of the block detector with Cs-137 gamma photons (662-keV). We could resolve almost all pixels clearly in a two-dimensional position histogram. The average peak-to-valley ratios (P/Vs) of the two-dimensional position histogram along profiles were 2.6 and 4.8 in horizontal and vertical directions, respectively. The energy resolution was 28.4% full-width at half-maximum (FWHM). The pulse shape spectra showed good separation with a P/V of 5.2. The developed block detector performed well and shows promise for the development of high-sensitivity and high-spatial resolution PET systems. [ABSTRACT FROM AUTHOR]

Small animal PET provides the biodistribution of administrated radiotracer in vivo and have a potential to contribute on dosimetry study. The aim of this study is to investigate the effect of region-of-interest (ROI)-delineation in whole-body rat PET image toward non-invasive estimation of human dosimetry of 18F-FDG. After administration of 18F-FDG (averaged 11.7 MBq), 3.5-h PET and 20-min CT scans were sequentially performed for three rats by Clairvivo PET/CT system. Seven source organs, and the remainder of the body, were studied to extrapolate %ID(t) and estimate time-integrated activity coefficients [kBq-h/MBq] in human. The mean absorbed dose in each target organ and the effective dose were estimated by MIRD method. Effects of ROI-definitions on both extrapolated %ID(t) in human and estimated doses were also investigated by using (i) small ROIs of high uptake region and (ii) whole organ ROIs. Averaged effective doses of 18F-FDG in human by using high-uptake and whole-organ ROIs were 27.8 ± 6.54 and 19.3 ± 2.72 μSv/MBq, respectively. The use of small animal PET scanner, which allows repeatedly PET scans, have a potential to contribute on the reduction of the number of experimental animals. However, the ways of ROI drawing influences on the estimated effective dose and safe-side ROI definition may be preferred. • Whole-body small animal PET was used for the dosimetry in human. • Estimated effective dose of this study was comparable with previous effective dose estimated from human study. • Image analysis of whole-body small animal PET influences on the estimated dose. [ABSTRACT FROM AUTHOR]

The Monte Carlo method is employed in this study to simulate the proton irradiation of a water-gel phantom. Positron-emitting radionuclides such as 11C, 15O, and 13N are scored using the Particle and Heavy Ion Transport Code System Monte Carlo code package. Previously, it was reported that as a result of 16O(p,2p2n)13N nuclear reaction, whose threshold energy is relatively low (5.660 MeV), a 13N peak is formed near the actual Bragg peak. Considering the generated 13N peak, we obtain offset distance values between the 13N peak and the actual Bragg peak for various incident proton energies ranging from 45 to 250 MeV, with an energy interval of 5 MeV. The offset distances fluctuate between 1.0 and 2.0 mm. For example, the offset distances between the 13N peak and the Bragg peak are 2.0, 2.0, and 1.0 mm for incident proton energies of 80, 160, and 240 MeV, respectively. These slight fluctuations for different incident proton energies are due to the relatively stable energy-dependent cross-section data for the 16O(p,2p2n)13N nuclear reaction. Hence, we develop an open-source computer program that performs linear and non-linear interpolations of offset distance data against the incident proton energy, which further reduces the energy interval from 5 to 0.1 MeV. In addition, we perform spectral analysis to reconstruct the 13N Bragg peak, and the results are consistent with those predicted from Monte Carlo computations. Hence, the results are used to generate three-dimensional scatter plots of the 13N radionuclide distribution in the modeled phantom. The obtained results and the developed methodologies will facilitate future investigations into proton range monitoring for therapeutic applications. [ABSTRACT FROM AUTHOR]

Polymeric nanoparticles (NPs) comprised of hydrophilic poly(γ-glutamic acid) in the main chain and hydrophobic phenylalanine in the side chain (γ-PGA-Phe) are a promising vaccine carrier for various kinds of diseases. However, little is known about the fate of subcutaneously administered γ-PGA-Phe NPs. Therefore, we newly synthesized γ-PGA graft phenylalanine and tyrosine conjugates (γ-PGA-Phe-Tyr), and then γ-PGA-Phe-Tyr NPs were labeled with 125I for monitoring their biodistribution (γ-PGA-Phe-Tyr(125I) NPs). Dynamic light scattering (DLS) measurements showed that γ-PGA-Phe-Tyr(125I) NPs showed 200nm in diameter and a negative ζ-potential, which was comparable to those of their precursors. γ-scintigraphic images showed that in mice, subcutaneously injected γ-PGA-Phe-Tyr(125I) NPs were mainly observed at the site of injection (SOI), but not other organs 1h after administration. However, γ-PGA-PheTyr(125I) NPs were almost undetectable at the SOI and other organs at 11days postinjection. Similar results were observed when γ-PGA-Phe-Tyr(125I) NPs were subcutaneously injected into rats. Furthermore, at 11days postinjection, 73±3% of the injected dose of γ-PGA-Phe-Tyr(125I) NPs was detected in the feces (14±1%) and urine (59±1%). These results clearly showed that subcutaneously injected γ-PGA-Phe-Tyr(125I) NPs were cleared from the body, and γ-PGA-Phe NPs were safe and effective vaccine carriers. [ABSTRACT FROM AUTHOR]

Background: Neurodegenerative diseases including Parkinson's and Alzheimer's diseases progress slowly and steadily over years or decades. They show significant between-subject variation in progress and clinical symptoms, which makes it difficult to predict the course of long-term disease progression with or without treatments. Recent technical advances in biomarkers have facilitated earlier, preclinical diagnoses of neurodegeneration by measuring or imaging molecules linked to pathogenesis. However, there is no established "biomarker model" by which one can quantitatively predict the progress of neurodegeneration. Here, we show predictability of a model with riskbased kinetics of neurodegeneration, whereby neurodegeneration proceeds as probabilistic events depending on the risk. Results: We used five experimental glaucomatous animals, known for causality between the increased intraocular pressure (IOP) and neurodegeneration of visual pathways, and repeatedly measured IOP as well as white matter integrity by diffusion tensor imaging (DTI) as a biomarker of axonal degeneration. The IOP in the glaucomatous eye was significantly increased than in normal and was varied across time and animals; thus we tested whether this measurement is useful to predict kinetics of the integrity. Among four kinds of models of neurodegeneration, constant-rate, constant-risk, variable-risk and heterogeneity models, goodness of fit of the model and F-test for model selection showed that the time course of optic nerve integrity was best explained by the variable-risk model, wherein neurodegeneration kinetics is expressed in an exponential function across cumulative risk based on measured IOP. The heterogeneity model with stretched exponential decay function also fit well to the data, but without statistical superiority to the variable-risk model. The variable-risk model also predicted the number of viable axons in the optic nerve, as assessed by immunohistochemistry, which was also confirmed to be correlated with the pre-mortem integrity of the optic nerve. In addition, the variable-risk model identified the disintegrity in the higher-order visual pathways, known to underlie the transsynaptic degeneration in this disease. Conclusions: These findings indicate that the variable-risk model, using a risk-related biomarker, could predict the spatiotemporal progression of neurodegeneration. This model, virtually equivalent to survival analysis, may allow us to estimate possible effect of neuroprotection in delaying progress of neurodegeneration. [ABSTRACT FROM AUTHOR]

In clinical cardiac positron emission tomography using 15O-water, significant tracer accumulation is observed not only in the heart but also in the liver and lung, which are partially outside the field-of-view. In this work, we investigated the effects of scatter on quantitative myocardium blood flow (MBF) and perfusable tissue fraction (PTF) by a precise Monte Carlo simulation (Geant4) and a numerical human model. We assigned activities to the heart, liver, and lung of the human model with varying ratios of organ activities according to an experimental time activity curve and created dynamic sinograms. The sinogram data were reconstructed by filtered backprojection. By comparing a scatter-corrected image (SC) with a true image (TRUE), we evaluated the accuracy of the scatter correction. TRUE was reconstructed using a scatter-eliminated sinogram, which can be obtained only in simulations. A scatter-uncorrected image (W/O SC) and an attenuation-uncorrected image (W/O AC) were also constructed. Finally, we calculated MBF and PTF with a single tissue-compartment model for four types of images. As a result, scatter was corrected accurately, and MBFs derived from all types of images were consistent with the MBF obtained from TRUE. Meanwhile, the PTF of only the SC was in agreement with the PTF of TRUE. From the simulation results, we concluded that quantitative MBF is less affected by scatter and absorption in 3D-PET using 15O-water. However, scatter correction is essential for accurate PTF. [ABSTRACT FROM AUTHOR]