Search for the Lepton Flavor Violating Decays B

We present a search for the lepton flavor violating decays B^{+}→K^{+}τ^{±}ℓ^{∓}, with ℓ=(e,µ), using the full data sample of 772×10^{6} BB[over ¯] pairs recorded by the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. We use events in which one B meson is fully reconstructed in a hadronic decay mode. We find no evidence for B^{±}→K^{±}τℓ decays and set upper limits on their branching fractions at the 90% confidence level in the (1-3)×10^{-5} range. The obtained limits are the world's best results.

Longitudinal changes in 18 F-THK5351 positron emission tomography in corticobasal syndrome.

BACKGROUND AND PURPOSE: Corticobasal syndrome (CBS) is pathologically characterized by tau deposits in neuronal and glial cells and by reactive astrogliosis. In several neurodegenerative disorders, 18 F-THK5351 has been observed to bind to reactive astrocytes expressing monoamine oxidase B. In this study, the aim was to investigate the progression of disease-related pathology in the brains of patients with CBS using positron emission tomography with 18 F-THK5351. METHODS: Baseline and 1-year follow-up imaging were acquired using magnetic resonance imaging and positron emission tomography with 18 F-THK5351 in 10 subjects: five patients with CBS and five age-matched normal controls (NCs). RESULTS: The 1-year follow-up scan images revealed that 18 F-THK5351 retention had significantly increased in the superior parietal gyrus of the patients with CBS compared with the NCs. The median increases in 18 F-THK5351 accumulation in the patients with CBS were 6.53% in the superior parietal gyrus, 4.34% in the precentral gyrus and 4.33% in the postcentral gyrus. In contrast, there was no significant increase in the regional 18 F-THK5351 retention in the NCs. CONCLUSIONS: Longitudinal increases in 18 F-THK5351 binding can be detected over a short interval in the cortical sites of patients with CBS. A monoamine oxidase B binding radiotracer could be useful in monitoring the progression of astrogliosis in CBS.

Coexistence of insulin-derived amyloidosis and an overlying acanthosis nigricans-like lesion at the site of insulin injection.

A 59-year-old patient with diabetes mellitus had been treated with human recombinant insulin for 4 years. He developed a solid mass on his left abdomen at the insulin injection site, which had an overlying pigmented verrucous plaque and keratinized papules, similar to acanthosis nigricans (AN). On histological examination, the mass was found to contain a deposit of amyloid in the dermis, with hyperkeratosis, papillomatosis and acanthosis in the epidermis. Using immunohistochemistry, the amyloid deposits were found to be positive for insulin. A few cases of localized insulin-derived amyloid deposits at injection sites have been reported previously, but none had significant epidermal changes. The coexistence of dermal insulin-derived amyloidosis and an overlying AN-like change, as found in our patient, has not been reported previously, to our knowledge. The presence of a tumour-like lesion at the injection site should be carefully examined, as injection of insulin into amyloid deposits can result in insulin resistance.

Application of positron emission tomography in physical medicine.

Positron emission tomography (PET) is widely used in the fields of clinical and basic medicine. The PET device utilizes coincidence logic to detect annihilation photons emitted from positrons and estimates physiological functions of human organs in vivo. Radiopharmaceutical 18F- fluorodeoxyglucose (FDG), an analogue of glucose, is trapped metabolically in cells after being administered into the body, and can be substantially used for evaluating physiological and biochemical functions in vivo. Here, we attempted to describe the basics of PET as well as to apply the technique together with 18F-FDG as a tracer for evaluating organ glucose metabolism induced by exercise. Three-dimensional (3D) FDG-PET was applied to normal volunteers who performed exercise to evaluate whole-body glucose metabolism. Regions of interest analysis were drawn on visually defined regions (i.e., lower limbs, thigh, liver, intestine, brain, heart, etc.) to determine radioactivity distribution. FDG-PET clearly showed the recruitment of energy resources from abdominal organs to lower limb skeletal muscles to balance energy expenditures. The results suggested that 3D FDG-PET can be applied as an imaging tool to physical medicine.

Performance evaluation of the small-animal PET scanner ClairvivoPET using NEMA NU 4-2008 Standards.

The aim of this study was to evaluate the performance of ClairvivoPET using NEMA NU4 standards. The ClairvivoPET incorporates a LYSO dual depth-of-interaction detector system with 151 mm axial field of view (FOV). Spatial resolution, sensitivity, counting rate capabilities, and image quality were evaluated using NEMA NU4-2008 standards. Normal mouse imaging was also performed for 10 min after intravenous injection of (18)F(-)-NaF. Data were compared with 19 other preclinical PET scanners. Spatial resolution measured using full width at half maximum on FBP-ramp reconstructed images was 2.16 mm at radial offset 5 mm of the axial centre FOV. The maximum absolute sensitivity for a point source at the FOV centre was 8.72%. Peak noise equivalent counting rate (NECR) was 415 kcps at 14.6 MBq ml(-1). The uniformity with the image-quality phantom was 4.62%. Spillover ratios in the images of air and water filled chambers were 0.19 and 0.06, respectively. Our results were comparable with the 19 other preclinical PET scanners based on NEMA NU4 standards, with excellent sensitivity because of the large FOV. The ClairvivoPET with iterative reconstruction algorithm also provided sufficient visualization of the mouse spine. The high sensitivity and resolution of the ClairvivoPET scanner provided high quality images for preclinical studies.

Measurement of the ratio of cerebral oxygen consumption to glucose utilization by positron emission tomography: its consistency with the values determined by the Kety-Schmidt method in normal volunteers.

The regional interrelationship between cerebral oxygen consumption (CMRO2) and cerebral glucose utilization (CMRGlc) was studied in normal subjects using positron emission tomography (PET) and the 15O steady-state inhalation and the [18F]fluoro deoxyglucose method. The use of standard sets of rate constants and the model lumped constant of 0.52 as well as the regional blood-brain partition coefficient for water and the blood volume correction for oxygen extraction fraction provided a CMRO2/CMRGlc ratio of 4.89 in the cortical gray matter, 5.27 in the basal ganglia and 5.82 in the centrum semiovale (white matter). The values of CMRO2/CMRGlc for the basal ganglia and the white matter were consistent with those reported for the whole brain with the Kety-Schmidt method. There was no significant difference in the CMRO2/CMRGlc between the basal ganglia and the white matter indicating the similar nature of in vivo oxidative metabolism of glucose in neuron-rich region and glial cell-rich region.

Estimation of absorbed doses in humans due to intravenous administration of fluorine-18-fluorodeoxyglucose in PET studies.

Radiation absorbed doses due to intravenous administration of fluorine-18-fluorodeoxyglucose in positron emission tomography (PET) studies were estimated in normal volunteers. The time-activity curves were obtained for seven human organs (brain, heart, kidney, liver, lung, pancreas, and spleen) by using dynamic PET scans and for bladder content by using a single detector. These time-activity curves were used for the calculation of the cumulative activity in these organs. Absorbed doses were calculated by the MIRD method using the absorbed dose per unit of cumulated activity, "S" value, transformed for the Japanese physique and the organ masses of the Japanese reference man. The bladder wall and the heart were the organs receiving higher doses of 1.2 x 10(-1) and 4.5 x 10(-2) mGy/MBq, respectively. The brain received a dose of 2.9 x 10(-2) mGy/MBq, and other organs received doses between 1.0 x 10(-2) and 3.0 x 10(-2) mGy/MBq. The effective dose equivalent was estimated to be 2.4 x 10(-2) mSv/MBq. These results were comparable to values of absorbed doses reported by other authors on the radiation dosimetry of this radiopharmaceutical.

18F-FDG PET imaging of muscle activity in runners.

UNLABELLED: PET with three-dimensional data acquisition using 18F-fluorodeoxyglucose (FDG) was applied to evaluate skeletal muscle activity in runners. METHODS: Seven healthy adult male volunteers were studied. They ran for a total of 35 min, 15 min before and 20 min after intravenous injection of FDG. Another 7 adult male control subjects were also examined at rest. Images obtained through a set of whole-body PET scans were analyzed. Regions of interest (ROIs) were manually drawn on images of muscles of both thighs, legs and feet, and the standardized uptake ratio (SUR) and total radioactivity distribution (TRD) for each region were calculated. RESULTS: The work load was below the anaerobic threshold. SUR of foot, leg and thigh were low at rest but during running increased 5.19, 4.30 and 1.74 times, respectively. The SUR of posterior-to- anterior compartment of the leg was 1.1+/-0.1 at rest and 1.6+/-0.5 (P < 0.01) during running. The laterality index of both SUR and TRD changed significantly only in the foot of the dominant side during running. TRD of the leg, less than half that of the thigh at rest, became equivalent to that of the thigh during running. TRD of the foot did not change significantly. CONCLUSION: Sole muscles showed highest metabolic activation per unit volume during running, which was higher in the dominant side. Comparison of whole muscle activity during running indicated the highest metabolic activation was in the posterior compartment of the leg, whereas thigh muscles showed relatively little changes during running. Our data indicate that whole-body FDG PET, especially three-dimensional data acquisition, is a useful tool for the investigation of muscular activity during exercise.

Measurement of D2 dopamine receptor-specific carbon-11-YM-09151-2 binding in the canine brain by PET: importance of partial volume correction.

Carbon-11-YM-09151-2 binds highly selectively to D2 dopamine receptors in the brain. Using this ligand, D2 dopamine receptor density (Bmax) and affinity (Kd) in canine striatum were measured. After administering various doses of the ligand in nine experiments, regional uptake was followed by repeated PET scanning for up to 80 min. D2 dopamine receptor specific binding at equilibrium was defined as striatal minus occipital activity after partial volume correction. Bmax and Kd were estimated by Scatchard analysis to be 40.3 pmole/ml of tissue and 22.9 nM, respectively. When a low mass dose of the ligand was administered, the bound-to-free ligand ratio in the striatum at equilibrium was consistent with the Bmax/Kd value obtained from the Scatchard analysis. The present study demonstrates the importance of partial volume correction and the Bmax/Kd measurement in a single PET study with carbon-11-YM-09151-2.

Quantitative evaluation of L-[methyl-C-11] methionine uptake in tumor using positron emission tomography.

Tumor uptake of L-[methyl-11C]methionine ([11C]Met) was assessed in six patients with brain tumors and three patients with lung cancer using positron emission tomography (PET). In arterial plasma samples taken at 5, 15, 30, and 60 min after injection, a fraction of [11C]Met was measured using high performance liquid chromatography in individual patients. Employing curve fitting, a history of [11C]Met activity was obtained as an input function. By means of sequential PET scannings and graphic analysis, uptake rate and distribution volume of [11C]Met in tumor tissue were calculated. In two studies irreversible uptake into the tumors was not seen when total plasma 11C activity was used as the input; however when [11C]Met plasma activity was used, definite irreversible uptake was seen, indicating tumor viability. In other studies, up to 24% underestimation of uptake rate was found. The present results demonstrated the importance of measuring [11C]Met in plasma for quantitative assessment of in vivo amino acid metabolism in tumors.

Biodistribution of a positron-emitting suicide inactivator of monoamine oxidase, carbon-11 pargyline, in mice and a rabbit.

Carbon-11 (11C) pargyline, which is a suicide inactivator of Type B monoamine oxidase (MAO), was synthesized by the reaction of N-demethylpargyline with 11CH3I. Biodistribution was investigated in mice, and positron tomographic images of the heart and lung in a rabbit were obtained. The distribution of 11C after administration of [11C]pargyline was measured in several organs and blood at various time intervals. After 30 min its concentrations in the organs were constant. Subcellular distribution studies in the brain, lung, liver, and kidney showed that 59-70% of the 11C became acid-insoluble and 9-33% was present in the crude mitochondrial fraction at 60 min after injection. However, a high loading dose influenced the subcellular distribution but had little effect on tissue distribution. The uptakes of the 11C in each organ except for the kidney and spleen seemed to correlate with the in vitro enzymatic activity of Type B MAO. At high loading dose a nonspecific uptake was observed.

Metabolic imaging in hemianopsia using positron emission tomography with 18F-deoxyfluoroglucose.

To evaluate the usefulness of metabolic mapping by positron emission tomography using 18F-deoxyfluoroglucose as a tracer in the diagnosis of hemianopsia, we examined eight patients who had had cerebrovascular accident, and four controls. Neuro-ophthalmologic examination disclosed hemianopsia in five and incomplete hemianopsia in three patients; computed tomography showed low-density areas in four patients; and nuclear magnetic resonance imaging demonstrated a prolonged T2 area in five patients. The cerebral metabolic rate for glucose without visual stimulation in the visual cortex was 7.4 +/- 1.0 mg/min/100 g of brain without interhemispheric asymmetry. Light stimulation increased cerebral metabolic rate for glucose in the visual cortex of the nonaffected hemisphere and decreased it in the affected hemisphere. Asymmetry in the metabolic rate in the posterior medial occipital cortex in complete hemianopsia was 22% 12% (P less than .01).

6-[18F]fluorodopa metabolism in patients with hemiparkinsonism studied by positron emission tomography.

A group of 10 healthy control subjects and 10 patients with hemiparkinsonism (HD) were studied by positron emission tomography (PET) using 6-[18F]fluorodopa (FDOPA). FDOPA metabolism in the caudate nucleus and the putamen was separately estimated by measuring target-to-background ratios (TBRs) using composite images added between 30 and 60 min after FDOPA injection and by TBR-versus-time slopes during PET study. TBRs in the caudate nucleus and the putamen were 1.81 +/- 0.23 (mean +/- SD) and 1.92 +/- 0.28 in the 10 controls, respectively. In HD patients, on the dominantly affected hemisphere related to main clinical symptoms, TBRs were significantly decreased in the caudate nucleus (P < 0.01) and the putamen (P < 0.05) compared with those in the corresponding areas on the contralateral hemisphere, though those TBRs on both hemispheres were significantly decreased compared with the TBRs of normal subjects (P < 0.01). TBRs and TBR slopes in both the caudate nucleus and the putamen were correlated with disease severity according to Hoehn and Yahr. On the dominantly affected hemisphere, TBR and TBR slopes in the putamen were well correlated with individual clinical measures for bradykinesia and rigidity, and those in the caudate nucleus were also correlated with the severity of tremor. Our data suggest that in HD patients, PET study using FDOPA may provide unique and efficient information on the dysfunction of the dominantly affected caudate nucleus and the putamen which are correlated with diseased severity and individual clinical symptoms.

Differential gene transcriptional regulation of Gi isoforms and Gs protein expression in diabetic rat hearts.

Many cardiac diseases can be associated with alterations in the function and quantity of G proteins. We examined the gene expressions and protein levels of Gi-1alpha, Gi-2alpha, Gi-3alpha and G(s alpha) in ventricular myocardial preparations from rats 4-6 weeks after induction of diabetes with streptozotocin in comparison with those from age-matched control rats. Diabetic rat myocardium exhibited reductions in the protein levels of Gi-2alpha and Gi-3alpha by 22+/-2% and 57+/-2%, respectively. In diabetes, 22% and 53% reductions in myocardial mRNA levels of Gi-2alpha and Gi-3alpha were observed. Although a faint protein signal of Gi-1alpha was detectable, no apparent expression of mRNA for Gi-1alpha was found in either control or diabetic myocardium. The reduced protein and mRNA levels of Gi-2alpha and Gi-3alpha were prevented by insulin therapy. No change was found in the protein and mRNA levels of G(s alpha) in diabetic myocardium. In conclusion, diabetes leads to a differential regulation of protein expressions of G(i alpha) isoforms and G(s alpha) in ventricular myocardium. The reduced expression of Gi-2alpha and Gi-3alpha proteins can be explained, at least in part, by the decreases in the transcriptional levels.

Absorbed dose estimates in positron emission tomography studies based on the administration of 18F-labeled radiopharmaceuticals.

Absorbed doses were estimated after intravenous administration of 18F-labeled radiopharmaceuticals in Positron Emission Tomography (PET) studies. These radiopharmaceuticals, [18F]-2-Fluoro-2-Deoxy-D-Glucose (FDG), 6-[18F]Fluoro-L-Dopa (FDOPA) and 18F-5-Fluorodeoxyuridine (FdUR), are used in clinical research at the Cyclotron and Radioisotope Center of Tohoku University. Radiopharmaceutical biokinetic values were measured in humans or extrapolated from animal experiments. Selective organ uptake and rapid clearance of activity from the blood were observed. High activity in the bladder contents of humans was found. Calculations were made by the MIRD method, modified to account for the differences in physique and organ mass between the Caucasian Reference Man and the Japanese one. The bladder wall receives the highest dose (more than 1.23 x 10(-1) mGy/MBq) when any of these compounds are administered. Other organs receiving high doses are the heart, brain and kidneys from FDG; the kidneys and pancreas from FDOPA, and the kidneys and small intestine from FdUR. These organs received absorbed doses of more than 2.7 x 10(-2) mGy/MBq. Effective dose equivalents of 2.4 x 10(-2), 2.6 x 10(-2) and 3.3 x 10(-2) mSv/MBq were estimated in the intravenous administration of 18F-FDG, 18F-FDOPA and 18F-FdUR, respectively.

Endoscopic and clinicopathological features of primary gastric lymphoma.

Thirty-three patients with primary gastric lymphoma over a period of 32 years were studied. Endoscopic findings indicated that there were many cases of multiple lymphoma in the stomach, or with extensive tumor-infiltration, and that it was necessary to carefully inspect the entire stomach to determine the scope of resection and improve diagnostic accuracy. It is also particularly important not to damage the tissue during biopsy and to take deep large specimens from the ulcer margin, surrounding wall, and area of erosion. As compared clinicopathologically with gastric carcinoma, primary gastric lymphoma is found more frequently in younger females, with invasion of the entire stomach and extensive lymph node infiltration. By performing adequate resection of lymph nodes, as is done for gastric carcinoma, and administering appropriate combination chemotherapy, postoperative longterm results were similar to, or better than, those obtained with gastric carcinoma.

A case for multisite studies in critical care.

Studies in critical care settings are essential to improve critical care practice. Critical care research conducted at a single site may be limited with respect to sample size leading to large type II error, diminished statistical power, decreased generalizability, and inconclusive results. Multiple-site studies are more likely to change nursing practice in critical care. They allow for larger sample size, broader sampling, faster accrual rates, and meaningful subgroup analyses. Successful multisite research requires more thorough planning, and deliberate steps are required to ensure its feasibility and acceptability. Multisite research protocols can be challenging regarding communication, reliability, and data integrity. However, defining and addressing these challenges and selecting subjects and settings appropriately can lead to results that are more generalizable and relevant to practice.

Easy detection of tumor in oncologic whole-body PET by projection reconstruction images with maximum intensity projection algorithm.

Whole-body PET scanning for an oncology study produces a large number of transaxial images by data acquisition over multiple bed positions. The sagittal and coronal reformatted images are often used for better understanding of radioisotope distribution. We reduced the number of PET images by calculating projection images and evaluated the merit of additional data processing for the visualization and detection of tumors. After reconstructing whole-body 18F-FDG PET images (6-8 bed positions) of eight cancer patients, antero-posterior and lateral projection images were calculated by the maximum intensity projection (MIP) algorithm, the standard deviation projection (SD) algorithm and the summed voxel projection (SUM) algorithm. The projection images were compared with 2D whole-body images for visualizing foci. The focal uptakes of various positions in original whole-body PET data (294-392 transaxial images) were visualized on only two MIP reformatted images when superimposition of hot spots did not occur. Even if one hot spot was superimposed over the other hot spot, we could recognize the existence of at least one focus and determine the true positions of the hot spots from corresponding transaxial images. The SD image was found inferior for showing a contrast of small foci to the corresponding MIP images in the neck, mediastinum and abdomen. The SUM image failed to visualize many metastatic lesions. MIP is a promising technique for the easy preliminary assessment of tumor distribution in oncologic whole-body PET study.

Development of a new method for simultaneously evaluating mucociliary clearance and pulmonary epithelial permeability in rabbit experiments by means of 18FDG, three-dimensional positron emission tomography and rectilinear scan.

We tried to simultaneously obtain the elimination constant of mucociliary clearance and the pulmonary epithelial permeability constant after inhalation of 2-[18F]fluoro-2-deoxy-D-glucose (18FDG) solution by carrying out whole lung positron emission tomography and a rectilinear scan in rabbit experiments. The elimination constant of pulmonary epithelial permeability was obtained from the decrease in the amount of the radioactivity with time in the region of interest (ROI) confined to the lungs, trachea and tracheal cannula in the rectilinear scan. The total elimination constant of the radioactivity in the lungs was obtained from the ROI confined to the lungs in the tomography. The mucociliary clearance rate constant in the lungs was then obtained after subtracting the elimination constant of the pulmonary epithelial permeability from the total elimination constant of the 18FDG in the lungs. The mucociliary clearance constant in the trachea was calculated from the residual radioactivity in the trachea and the mucociliary clearance constant in the lungs. The mean pulmonary epithelial permeability constant was 0.0020% min(-1) obtained from the rectilinear scan. The mean mucociliary clearance constants of the lungs and the trachea were 0.0006 and 0.025% min(-1), respectively. These results indicated that the pulmonary epithelial permeability and mucociliary clearance could be evaluated simultaneously with 18FDG by using three-dimensional positron emission tomography and a rectilinear scan.

Evaluation of resting brain conditions measured by two different methods (i.v. and oral administration) with 18F-FDG-PET.

Our aim was to evaluate regional differences between brain activity in two resting control conditions measured by 3D PET after administration of FDG through either the intravenous (i.v.) or the oral route. Ten healthy male volunteers engaged in the study as the i.v. group (mean age, 26 +/- 9.3 years, +/- S.D.) who received FDG intravenously and another 10 volunteers as the oral group (mean age, 27.9 +/- 11.3 years, +/- S.D.) who received FDG per os. A set of 3D-PET scans (emission and transmission scans) were performed in both groups. To explore possible functional differences between the brains of the two groups, the SPM-96 software was used for statistical analysis. The results revealed that glucose metabolism was significantly higher in the superior frontal gyrus, superior parietal lobule, lingual gyrus and left cerebellar hemisphere in the i.v. group than in the oral group. Metabolically active areas were found in the superior, middle and inferior temporal gyrus, parahippocampal gyrus, amygdaloid nucleus, pons and cerebellum in the oral group when compared with the i.v. group. These differences were presumably induced by differences between FDG kinetics and/or time-weighted behavioral effects in the two studies. This study suggests the need for extreme caution when selecting a pooled control population for designated activation studies.