Search

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]

Background: The cardiac support device supports the heart and mechanically reduces left ventricular (LV) diastolic wall stress. Although it has been shown to halt LV remodeling in dilated cardiomyopathy, its therapeutic efficacy is limited by its lack of biological effects. In contrast, the slow-release synthetic prostacyclin agonist ONO-1301 enhances reversal of LV remodeling through biological mechanisms such as angiogenesis and attenuation of fibrosis. We therefore hypothesized that ONO-1301 plus a cardiac support device might be beneficial for the treatment of ischemic cardiomyopathy. Methods: Twenty-four dogs with induced anterior wall infarction were assigned randomly to 1 of 4 groups at 1 week postinfarction as follows: cardiac support device alone, cardiac support device plus ONO-1301 (hybrid therapy), ONO-1301 alone, or sham control. Results: At 8 weeks post-infarction, LV wall stress was reduced significantly in the hybrid therapy group compared with the other groups. Myocardial blood flow, measured by positron emission tomography, and vascular density were significantly higher in the hybrid therapy group compared with the cardiac support device alone and sham groups. The hybrid therapy group also showed the least interstitial fibrosis, the greatest recovery of LV systolic and diastolic functions, assessed by multidetector computed tomography and cardiac catheterization, and the lowest plasma N-terminal pro-B-type natriuretic peptide levels (P < .05). Conclusions: The combination of a cardiac support device and the prostacyclin agonist ONO-1301 elicited a greater reversal of LV remodeling than either treatment alone, suggesting the potential of this hybrid therapy for the clinical treatment of ischemia-induced heart failure. [Copyright &y& Elsevier]

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]

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]

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) 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]

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]

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]

• A Tungsten-based fiducial marker was developed for multi-modal image registration. • The Tungsten solution has characteristics of high T1 and T2 contrasts and density. • The Tungsten-based marker allowed accurate registration and cortical functional mapping. Multi-modal brain image registration is a prerequisite for accurate mapping of brain structure and function in neuroscience. Image registration is commonly performed using automated software; however, its accuracy decreases when images differ in modality, contrast, uniformity, and resolution. This limitation could be overcome by using an external reference point; however, high-contrast agents in multi-modal imaging have not been previously reported. Here, we propose a novel multi-modal fiducial marker that contains Tungsten solution and provides high contrast in magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET). The basic characteristics of this multi-modal marker were investigated by assessing major sources of image contrast in the following modalities: density and T1-, T2-relaxivity in comparison with conventional contrast agents. Tungsten solution had lower T1- and T2-relaxivity and high solubility, and showed high contrast in T1- and T2-weighted MR and CT images at a high-density concentration (˜3.0 g/mL), whereas other conventional solutions did not show sufficient contrast in either CT or MRI. The use of this Tungsten-based multi-modal marker allowed more accurate registration than a software-only method in phantom and animal experiments. Application of this method demonstrated accurate cortical surface mapping of neurotransmitter function (dopamine transporter, DAT) using PET and MRI, and provided a neurobiologically relevant cortical distribution consistent with previous literature on histology-based DAT immunoreactivity. The Tungsten-based multi-modal fiducial marker is non-radioactive, easy to handle, and aids precise registration across different modalities of brain imaging. [ABSTRACT FROM AUTHOR]

We proposed use of astatine-210 in preclinical study. Astatine-210 has higher yield of production and is easier to quantify than astatine-211. We produced astatine-210 with Bi target and 40 MeV alpha beam accelerated by cyclotron, free astatine-210 was separated and injected to normal rats. Three male rats (blocking group) were injected non-radioactive iodide before injection of astatine-210. Compared with the control group, the astatine-210 accumulations in the blocking group decreased to 24% in the thyroid. [ABSTRACT FROM AUTHOR]

Astatine-211 is a promising radionuclide for targeted radiotherapy. It is required to image the distribution of targeted radiotherapeutic agents in a patient's body for optimization of treatment strategies. We proposed to image 211 At with high-energy photons to overcome some problems in conventional planar or single-photon emission computed tomography imaging. We performed an imaging experiment of a point-like 211 At source using a Compton camera, and demonstrated the capability of imaging 211 At with the high-energy photons for the first time. [ABSTRACT FROM AUTHOR]

The 137Cs soil contamination has detrimental effects on human health. The penetration and distribution of 137Cs radionuclides at different soil depths were investigated. Two sampling campaigns in 2001 and 2018 were performed to determine the 137Cs activity in soil at 11 locations around the city of Kragujevac in central Serbia. The ICRP and ORNL humanoid phantom models were used to determine equivalent and effective doses from the experimentally measured data, and conversion coefficients were obtained from Monte Carlo computations. The results show a general decrease in 137Cs concentration in samples that were taken in 2018. However, variation of 137Cs concentration was observed at different locations that did not match the expected reduction of 137Cs concentration based on its half-life. Considering the computational results, no significant difference between the estimated equivalent dose rate per unit activity of 137Cs (conversion coefficients) between ICRP and ORNL phantoms was observed. In addition, two open-source computer programs for PC and Android devices were developed for users to determine the equivalent and effective doses for their specific cases; this gives the users an easy-to-use interface and portable tools to determine dosimetric quantities. The obtained results and the developed tools would be useful for future investigations related to soil contamination by 137Cs radionuclides that require extensive future studies. • Cs-137 in soil measured in two campaign. • Cs-137 in soil vertical distribution. • Effective dose from Cs-137 in soil as the source of external irradiation. • Comparison between ORNL and voxel humanoid phantoms. [ABSTRACT FROM AUTHOR]

Objective The purpose of this study is to investigate the correlation between the liver kinetics of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) and liver histopathology in a mouse model of NASH by using dynamic contrast-enhanced MRI. Materials and methods Twenty male C57/BL6 mice aged 8 weeks were fed a methionine–choline-deficient (MCD) diet for 2, 4 and 6 weeks (MCD groups: MCD 2w, 4w, or 6w). Gd-EOB-DTPA-enhanced MR imaging of the liver was performed at 2, 4 and 6 weeks after the MCD feeding. The signal intensity of the liver was obtained from dynamic MR images and relative enhancement (RE), and the time to maximum RE (T max ) and half-life of elimination RE (T 1/2 ) were calculated. After MRI scan, histopathological scores of hepatic steatosis and inflammation and blood biochemistry data, such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, were obtained. Results Plasma AST and ALT levels were significantly increased in mice fed MCD. Histopathological scores indicated that steatohepatitis progressed with the MCD feeding period from 2 to 6 weeks, but significant fibrosis was observed only in mice fed MCD for 6 weeks. Gd-EOB-DTPA-enhanced MRI showed that T max was significantly prolonged in the livers of the 6-week group compared to the control group (control, 4.0 ± 0.7 min; MCD 6w, 12.1 ± 1.6 min), although there was no alteration in the 2- and 4-week groups. T 1/2 was significantly prolonged in mice fed MCD for 4 and 6 weeks compared to the control group (control, 19.9 ± 2.0 min; MCD 4w, 46.7 ± 8.7 min; MCD 6w, 65.4 ± 8.8 min). The parameters of Gd-EOB-DTPA kinetics (T max and T 1/2 ) in the liver were positively correlated with the liver histopathological score (steatosis vs T max , rho = 0.69, P = 0.0007; inflammation vs T max , rho = 0.66, P = 0.00155; steatosis vs T 1/2 , rho = 0.77, P < 0.0001; inflammation vs T 1/2 , rho = 0.73, P = 0.0003). Conclusions The liver kinetics of Gd-EOB-DTPA correlated well with the inflammation score in the mouse model of NASH, suggesting the possibility of detecting the steatohepatitis stage without fibrosis by Gd-EOB-DTPA-enhanced MR imaging. [ABSTRACT FROM AUTHOR]

We developed a new gamma camera specifically for plant nutritional research and successfully performed live imaging of the uptake and partitioning of 137 Cs in intact plants. The gamma camera was specially designed for high-energy gamma photons from 137 Cs (662 keV). To obtain reliable images, a pinhole collimator made of tungsten heavy alloy was used to reduce penetration and scattering of gamma photons. A single-crystal scintillator, Ce-doped Gd 3 Al 2 Ga 3 O 12 , with high sensitivity, no natural radioactivity, and no hygroscopicity was used. The array block of the scintillator was coupled to a high-quantum efficiency position sensitive photomultiplier tube to obtain accurate images. The completed gamma camera had a sensitivity of 0.83 count s −1 MBq −1 for 137 Cs with an energy window from 600 keV to 730 keV, and a spatial resolution of 23.5 mm. We used this gamma camera to study soybean plants that were hydroponically grown and fed with 2.0 MBq of 137 Cs for 6 days to visualize and investigate the transport dynamics in aerial plant parts. 137 Cs gradually appeared in the shoot several hours after feeding, and then accumulated preferentially and intensively in growing pods and seeds; very little accumulation was observed in mature leaves. Our results also suggested that this gamma-camera method may serve as a practical analyzing tool for breeding crops and improving cultivation techniques resulting in low accumulation of radiocesium into the consumable parts of plants. [ABSTRACT FROM AUTHOR]

Cell-sheet transplantation induces angiogenesis for chronic myocardial infarction (MI), though insufficient capillary maturation and paucity of arteriogenesis may limit its therapeutic effects. Omentum has been used clinically to promote revascularization and healing of ischemic tissues. We hypothesized that cell-sheet transplantation covered with an omentum-flap would effectively establish mature blood vessels and improve coronary microcirculation physiology, enhancing the therapeutic effects of cell-sheet therapy. Rats were divided into four groups after coronary ligation; skeletal myoblast cell-sheet plus omentum-flap (combined), cell-sheet only, omentum-flap only, and sham operation. At 4 weeks after the treatment, the combined group showed attenuated cardiac hypertrophy and fibrosis, and a greater amount of functionally (CD31+/lectin+) and structurally (CD31+/α-SMA+) mature blood vessels, along with myocardial upregulation of relevant genes. Synchrotron-based microangiography revealed that the combined procedure increased vascularization in resistance arterial vessels with better dilatory responses to endothelium-dependent agents. Serial 13N-ammonia PET showed better global coronary flow reserve in the combined group, mainly attributed to improvement in the basal left ventricle. Consequently, the combined group had sustained improvements in cardiac function parameters and better functional capacity. Cell-sheet transplantation with an omentum-flap better promoted arteriogenesis and improved coronary microcirculation physiology in ischemic myocardium, leading to potent functional recovery in the failing heart. [ABSTRACT FROM AUTHOR]

Abstract: Positron-emission tomography (PET) can be used to visualize active stage cancer. Fluorine-18 ([18F])-labeled 2-([18F])2-deoxy-2-fluoroglucose (([18F])-FDG), which accumulates in glucose-dependent tissues, is a good cancer-targeting tracer. However, ([18F])-FDG is obscured in glucose-dependent normal tissues. In this study, we assessed the cancer-selective accumulation of zinc-labeled glycoconjugated 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (ZnGlc1–4), both in vitro and in vivo. Experiments using both normal and cancer cells confirmed the relationship between cancer cell-selective accumulation and the substitution numbers and orientations of glycoconjugated porphyrins. ZnGlctrans-2 accumulated at greater levels in cancer cells compared with other glycoconjugated porphyrins. PET imaging showed that ZnGlctrans-2 accumulated in tumor. [Copyright &y& Elsevier]

The coupling of cerebral blood flow (CBF) and metabolic rate of oxygen (CMRO2) during physiological and pathological conditions remains a subject of debate. We have developed a physiological model for oxygen delivery and metabolism, which allows the estimation of net oxygen diffusibility at the capillary level, termed “effective oxygen diffusibility (EOD).” The results of PET in monkeys showed dynamic changes in EOD in response to changes in oxygen delivery and consumption. EOD is defined as capillary volume and permeability product, but its change mainly reflects the pericapillary oxygen gradient as long as capillary architecture is preserved. EOD may have sufficient predictability to represent the tissue oxygen demand and application of the model to PET data. In the future, EOD may give us further insight to understand the physiological regulatory system for oxygen demand in the brain. [Copyright &y& Elsevier]

Xenon is a promising candidate for an exogenous MRI tracer because of its affinity for lipids and possible polarization. The estimation of net detectability of dissolved phase xenon in vivo is important for a development of diagnostic applications. The purposes of this study were to develop a hyperpolarized 129Xe experiment system on 3-T and to measure dissolved phase signal in a rat lung. The 129Xe gas was polarized using the optical pumping technique, was manually insufflated to male Sprague–Dawley rat under spontaneous respiration anesthetized by intraperitoneal injection of urethane (1 mg/g), and was measured in a rat lung by frequency selective spectroscopy. A full fractional optimum experiment of two-factor (flip angle, TR) and three-level (30°, 60°, 90°, 600, 1000, 1400 ms) was designed for SNR. A flip angle (∼60°) with 1 s TR made maximum signal in dissolved phase dynamic spectroscopy. Two dominant peaks of 212 for RBC and 201 ppm for tissue were observed, and their average signal ratio to that of gas was 5.6% and 4.4%, respectively. We have developed a hyperpolarized 129Xe experiment system, which could yield enough amount and polarization for dynamic analysis in a rat lung using the 3-T MRI system. [Copyright &y& Elsevier]

Motion of a subject during PET scanning is a significant source of errors in myocardial PET studies. We have developed a motion-correction system based on a rigid body model for thorax PET studies. The present study was intended to evaluate this system in the myocardial blood flow (MBF) study using 15O-labeled water on a normal volunteer. We artificially shifted the bed of the PET scanner horizontally by 30 mm to simulate the subject''s repositioning, in addition to a natural movement in the order of 10 mm. The shift was monitored successfully using the system developed. The motion correction provided values of myocardial blood flow with a better reproducibility as compared with those without the motion correction. [Copyright &y& Elsevier]

We proposed a novel PET protocol, which allows shortening of the total PET duration with sequential administration of two tracers. To calculate quantitative OEF, CBF and CMRO2 images, a mathematical formulation was developed. This formulation can be applied both in H215O–15O2 and 15O2–H215O, and enables estimating the quantitative functions from the PET scan by the residual radioactivity first administrated and built into a model. To test validity and applicability, accuracy and precision of quantitative values of OEF, CBF, and CMRO2 obtained by the present DARG, we compared them with the three-step ARG approach in our experimental study using monkeys. The accuracy of the functional values was confirmed and the enhancement of statistical noise was reasonably small. The global OEF values obtained by the present method also agreed well with those obtained by the arterial-sinus difference measurement. In addition, the simulation study showed that the error sensitivity of the present method was almost of the same degree as the three-step method. These findings suggest that the present protocol could be applicable to human studies. [Copyright &y& Elsevier]

Repetitive transcranial magnetic stimulation (rTMS) has recently been assessed as a non-invasive treatment modality for neuropsychiatric disorders. However, the mechanisms underlying the therapeutic effects are still not understood. Studies in rodents revealed lasting effects in limbic-related regions, but species difference in brain structures makes it difficult to infer the regional effect in primate brain. To reveal how rTMS affects primate brain function, we performed positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) and 11C-raclopride (RAC) in anaesthetized macaque monkeys. A total of 2000 pulses of 5Hz-rTMS were delivered on the unilateral primary motor cortex using a small coil. Voxel-based analysis revealed statistically robust changes in FDG activity in the motor, cingulate, and orbitofrontal cortices, as well as in binding potential of RAC in the ventral striatum. Interestingly, the change in FDG activity persisted at least 8 days. These results demonstrate that motor cortical rTMS induces dynamic functional changes in motor and limbic associated structures, suggesting its therapeutic effect on dysfunction of motor and motivation system. [Copyright &y& Elsevier]

Objectives: This study was intended to evaluate the feasibility and applicability of assessing absolute myocardial blood flow (MBF) using O-15 water and PET 14 times for various doses of vasodilator challenges in miniature pigs. Methods and results: MBFs were quantitated following intravenous injection of O-15 water during various administration doses of adenosine (25–800 μg/kg/min) and A2A-selective CGS-21680 (0.5–20 μg/kg) in six miniature pigs. A low dose of adenosine increased MBF but reached to a maximum, and gradually decreased MBF with reduced heart rate (HR), reduced systolic blood pressure (SBP), and thus decreased RPP, together with prolonged PR interval. Reduction in HR, SBP and RPP were also observed with CGS-21680, but were significantly less, and the maximum MBF was greater with CGS-21680. These findings were consistent and reproducible among all the six subjects. Discussion and conclusion: The technique of assessing MBF with O-15 water and PET appeared to be reproducible and useful for quantitative evaluation of the vascular reactivity for various pharmacological/physiological stresses. The ability of accurately correcting for the partial volume effect, and recent advances of generating functional parametric images from the dynamic O-15 water alone, would be the most important factors in clinical usage of this methodology. [Copyright &y& Elsevier]

: BackgroundRepetitive transcranial magnetic stimulation (rTMS) has been used as a treatment for neuropsychiatric disorders such as depression and Parkinson''s disease (PD). Despite the growing interest in therapeutic application of rTMS, precise mechanisms of its action remain unknown. With respect to PD, activation of the mesostriatal dopaminergic pathway is likely to be a candidate mechanism underlying the therapeutic effects; however, modulating effects of rTMS over the primary motor cortex (M1) on the dopaminergic system have not been studied.: MethodsWe used [11C]raclopride positron emission tomography to measure changes of extracellular dopamine concentration after 5Hz rTMS over the M1 in eight anesthetized monkeys.: ResultsrTMS over the right M1 induced a reduction of [11C]raclopride binding potential (BP) in the bilateral ventral striatum, including the nucleus accumbens, and a significant increase of BP in the right putamen; no significant BP reduction was found in the dorsal striatum. These data indicate that rTMS over the motor cortex induces a release of endogenous dopamine in the ventral striatum.: ConclusionsOur results suggest that therapeutic mechanisms of rTMS may be explained in part by an activation of the mesolimbic dopaminergic pathway, which plays critical roles in rewards, reinforcement, and incentive motivation. [Copyright &y& Elsevier]