Adenosine A1 receptors measured with 11 C-MPDX PET in early Parkinson's disease.

Adenosine A1 receptors (A1 Rs) interact negatively with dopamine D1 receptors (D1 Rs) in neurons of the basal ganglia's direct pathway, while adenosine A2A receptors (A2A Rs) negatively interact with dopamine D2 receptors (D2 Rs) in indirect-pathway neurons. The aim of this study was to investigate the cerebral density of A1 Rs in Parkinson's disease (PD) in its early stages, using PET scans with the radioligand 8-dicyclopropylmethyl-1-11 C-methyl-3-propylxanthine (11 C-MPDX). We studied 10 drug-naïve patients with early PD. Each patient was also examined for dopamine transporters (DATs) and D2 Rs by PET using 11 C-2-ß-carbomethoxy-3-ß-(4-fluorophenyl)-tropane (11 C-CFT) and 11 C-raclopride (11 C-RAC), respectively. Ten elderly, healthy volunteers were recruited as controls for 11 C-MPDX PET scanning and eight elderly volunteers were recruited as controls for 11 C-CFT and 11 C-RAC PET scanning. The PET scans revealed a decrease in the uptake ratio index (URI) of 11 C-CFT and an increase in the URI of 11 C-RAC in patients. In the temporal lobe, the binding potential for 11 C-MPDX was higher in the patient group than in healthy subjects, but not in the other regions examined, including the striatum. In patients, we observed motor-symptom asymmetry and a relationship between parkinsonism and the striatal density of DATs, but not A1 R density. In the putamen of early PD, asymmetrical down-regulation of A2A Rs is likely a compensatory mechanism in response to a decrease in dopamine. However, our study suggests that A1 Rs are unaltered in the putamen of early PD.

Effects of exercise on brain activity during walking in older adults: a randomized controlled trial.

BACKGROUND: Physical activity may preserve neuronal plasticity, increase synapse formation, and cause the release of hormonal factors that promote neurogenesis and neuronal function. Previous studies have reported enhanced neurocognitive function following exercise training. However, the specific cortical regions activated during exercise training remain largely undefined. In this study, we quantitatively and objectively evaluated the effects of exercise on brain activity during walking in healthy older adults. METHODS: A total of 24 elderly women (75-83 years old) were randomly allocated to either an intervention group or a control group. Those in the intervention group attended 3 months of biweekly 90-min sessions focused on aerobic exercise, strength training, and physical therapy. We monitored changes in regional cerebral glucose metabolism during walking in both groups using positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG). RESULTS: All subjects completed the 3-month experiment and the adherence to the exercise program was 100%. Compared with the control group, the intervention group showed a significantly greater step length in the right foot after 3 months of physical activity. The FDG-PET assessment revealed a significant post-intervention increase in regional glucose metabolism in the left posterior entorhinal cortex, left superior temporal gyrus, and right superior temporopolar area in the intervention group. Interestingly, the control group showed a relative increase in regional glucose metabolism in the left premotor and supplemental motor areas, left and right somatosensory association cortex, and right primary visual cortex after the 3-month period. We found no significant differences in FDG uptake between the intervention and control groups before vs. after the intervention. CONCLUSION: Exercise training increased activity in specific brain regions, such as the precuneus and entorhinal cortices, which play an important role in episodic and spatial memory. Further investigation is required to confirm whether alterations in glucose metabolism within these regions during walking directly promote physical and cognitive performance. TRIAL REGISTRATION: UMIN-CTR ( UMIN000021829 ). Retrospectively registered 10 April 2016.

Central µ-Opioidergic System Activation Evoked by Heavy and Severe-Intensity Cycling Exercise in Humans: a Pilot Study Using Positron Emission Tomography with 11C-Carfentanil.

The central opioid receptor system likely contributes to the mechanism underlying the changes in affect elicited by exercise. Our aim was to use positron emission tomography (PET) to test whether exercise intensity influences activation of the µ-opioid receptor system in the brain, and whether changes in opioid receptor activation correlate with exercise-induced changes in affect. 7 healthy young male subjects (23±2 years) performed 20-min constant-load cycling exercises at heavy (ExH) and severe-intensity (ExS), and PET was performed using [11C]carfentanil as a tracer before and after each exercise. Exercise elicited the µ-opioidergic system activation in the large areas of the limbic system, particularly in the insular cortex, and cerebellum. Of note, deactivation of the µ-opioidergic system in the pituitary gland was identified as a specific finding in ExS, which evoked a distinctive sensation of fatigue. Within these brain areas, µ-opioid receptor activation correlated positively with increased positive affect (R2=0.67-0.95) in ExH and negative affect (R2=0.63-0.77) in ExS. These findings suggest that central µ-opioidergic neurotransmission evoked by continuous exercise is discriminated by work intensity. Notably, we also observed a possible contribution of the central µ-opioidergic system to the development of the sensation of fatigue during exhaustive exercise.

Improvement of Glucose Metabolism in the Visual Cortex Accompanies Visual Field Recovery in a Patient with Hemianopia.

Damage to the visual cortex or the geniculostriatal pathways could cause homonymous visual field (VF) defects at the contralateral side of the lesion. In clinical practice, it is known that the VF defects are gradually recovered over months on the cases. We report a case with recovered homonymous hemianopia following an infarction in the visual cortex by positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) and (11)C-flumazenil (FMZ). A 58-year-old man experienced defect of left VF, and magnetic resonance imaging (MRI) revealed a localized infarction in the right occipital lobe. Goldmann VF perimetry revealed left homonymous hemianopia, but central VF was intact. Three months after the onset of infarction, we measured cerebral glucose metabolism with FDG and FMZ binding using PET. FMZ binding reflects the density of surviving neurons. Moreover, eight months after the onset, FDG-PET scan was performed. Goldmann VF perimetry was also performed at the same times of PET examinations. Decrease of cerebral glucose metabolism in the right anterior striate cortex was observed at three months after onset, while FMZ binding in the same area did not decrease in the patient. At eight months after onset, we observed recovery of VF and improvement of cerebral glucose metabolism in the anterior striate cortex. We presented change of cerebral glucose metabolism using PET accompanying improvement of VF. Evaluation of cerebral glucose metabolism and FMZ binding in the striate cortex is useful for estimating the prognosis of hemianopia caused by organic brain damage.

Cerebral Functional Response during Eyelid Opening/Closing with Bell's Phenomenon and Volitional Vertical Eye Movements in Humans.

Bell's phenomenon is a physiological phenomenon wherein the eye ball involuntarily rolls upward during eyelid closing. Although this phenomenon occurs in healthy individuals, the neural mechanism related to Bell's phenomenon has not yet been identified. We aimed to investigate the brain regions relevant to Bell's phenomenon and volitional eye movement using [15O] H2O and positron emission tomography (PET). We measured regional cerebral blood flow (rCBF) in 8 normal subjects under 3 conditions: at rest with eyes closed, during opening and closing of the eyelids in response to sound stimuli (lid opening/closing), and during vertical movement of the eyes with lids closed in response to sound stimuli (volitional eye movement). The supplementary motor area (SMA) proper, right superior temporal gyrus, right insular cortex and left angular gyrus were activated during lid opening/closing. The right frontal eye field (FEF), pre-SMA, left primary motor area, right angular gyrus, and SMA proper were activated during volitional eye movement. The SMA proper was active during both tasks, while the FEF and pre-SMA were active during volitional eye movement, but not during eyelid opening/closing. A comparison of activation during volitional eye movements and lid opening/closing tasks revealed a relative increase in rCBF in the FEF. There were no areas that are activated in relation to Bell's phenomenon. In conclusion, activation in the FEF mainly occurs during volitional eye movement. Since Bell's phenomenon is a reflexive eye movement, the FEF is scarcely concerned in Bell's phenomenon.

Evaluation of a New Motion-correction Algorithm Using On-rigid Registration in Respiratory-gated PET/CT Images of Liver Tumors.

OBJECTIVE: The present study aimed to determine the qualitative and quantitative accuracy of the Q.Freeze algorithm in PET/CT images of liver tumors. METHODS: A body phantom and hot spheres representing liver tumors contained 5.3 and 21.2 kBq/mL of a solution containing 18F radioactivity, respectively. The phantoms were moved in the superior-inferior direction at a motion displacement of 20 mm. Conventional respiratory-gated (RG) and Q.Freeze images were sorted into 6, 10, and 13 phase-groups. The SUVave was calculated from the background of the body phantom, and the SUVmax was determined from the hot spheres of the liver tumors. Three patients with four liver tumors were also clinically assessed by whole-body and RG PET. The RG and Q.Freeze images derived from the clinical study were also sorted into 6, 10 and 13 phase-groups. Liver signal-to-noise ratio (SNR) and SUVmax were determined from the RG and Q.Freeze clinical images. RESULTS: The SUVave of Q.Freeze images was the same as those derived from the body phantom using RG. The liver SNR improved with Q.Freeze, and the SUVsmax was not overestimated when Q.Freeze was applied in both the phantom and clinical studies. Q.Freeze did not degrade the liver SNR and SUVmax even though the phase number was larger. CONCLUSIONS: Q.Freeze delivered qualitative and quantitative motion correction than conventional RG imaging even in 10-phase groups.

Dedicated phantom tools using traceable 68Ge/68Ga point-like sources for dedicated-breast PET and positron emission mammography scanners.

Since the early 2000s, many types of positron emission tomography (PET) scanners dedicated to breast imaging for the diagnosis of breast cancer have been introduced. However, conventional performance evaluation methods developed for whole-body PET scanners cannot be used for such devices. In this study, we developed phantom tools for evaluating the quantitative accuracy of positron emission mammography (PEM) and dedicated-breast PET (dbPET) scanners using novel traceable point-like 68Ge/68 Ga sources. The PEM phantom consisted of an acrylic cube (100 × 100 × 40 mm) and three point-like sources. The dbPET phantom comprised an acrylic cylinder (ø100 × 100 mm) and five point-like sources. These phantoms were used for evaluating the fundamental responses of clinical PEM and dbPET scanners to point-like inputs in a medium. The results showed that reasonable recovery values were obtained based on region-of-interest analyses of the reconstructed images. The developed phantoms using traceable 68Ge/68 Ga point-like sources were useful for evaluating the physical characteristics of PEM and dbPET scanners. Thus, they offer a practical, reliable, and universal measurement scheme for evaluating various types of PET scanners using common sets of sealed sources.

Differential effects of age on human striatal adenosine A1 and A(2A) receptors.

The aim of this study was to investigate the effect of age on the distribution of adenosine A1 receptors (A1Rs) and adenosine A(2A) receptors (A(2A)Rs) in the striatum of healthy subjects using PET imaging with 8-dicyclopropylmethyl-1-[¹¹C]methyl-3-propylxanthine ([¹¹C]MPDX) and [7-methyl-¹¹C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([¹¹C]TMSX), respectively. We recruited 8 young (22.0 ± 1.7 years) and 10 elderly (65.4 ± 7.6 years) volunteers to undergo [¹¹C]MPDX PET scanning, and 11 young (22.7 ± 2.7 years) and six elderly (60.7 ± 8.5 years) volunteers to undergo [¹¹C]TMSX PET scanning. A dynamic series of decay-corrected PET scans was performed for 60 min following injection of [¹¹C]MPDX or [¹¹C]TMSX. We calculated the binding potential (BP(ND) ) of [¹¹C]MPDX and distribution volume ratio (DVR) of [¹¹C]TMSX in the striatum. The BP(ND) of [¹¹C]MPDX was significantly lower in elderly than in young subjects, both in the putamen and head of the caudate nucleus. The BP(ND) was negatively correlated with age in both the putamen and the head of the caudate nucleus. However, no difference was found between the DVR of [¹¹C]TMSX in the striata of young and elderly subjects, nor was there a correlation between age and the DVR of [¹¹C]TMSX. The effect of age on the distribution of A1Rs in the human striatum described herein is similar to previous reports of age-related decreases in dopamine D1 and D2 receptors. Unlike A1Rs, however, this study suggests that the distribution of A(2A) Rs does not change with age.

New standards for phantom image quality and SUV harmonization range for multicenter oncology PET studies.

Not only visual interpretation for lesion detection, staging, and characterization, but also quantitative treatment response assessment are key roles for 18F-FDG PET in oncology. In multicenter oncology PET studies, image quality standardization and SUV harmonization are essential to obtain reliable study outcomes. Standards for image quality and SUV harmonization range should be regularly updated according to progress in scanner performance. Accordingly, the first aim of this study was to propose new image quality reference levels to ensure small lesion detectability. The second aim was to propose a new SUV harmonization range and an image noise criterion to minimize the inter-scanner and intra-scanner SUV variabilities. We collected a total of 37 patterns of images from 23 recent PET/CT scanner models using the NEMA NU2 image quality phantom. PET images with various acquisition durations of 30-300 s and 1800 s were analyzed visually and quantitatively to derive visual detectability scores of the 10-mm-diameter hot sphere, noise-equivalent count (NECphantom), 10-mm sphere contrast (QH,10 mm), background variability (N10 mm), contrast-to-noise ratio (QH,10 mm/N10 mm), image noise level (CVBG), and SUVmax and SUVpeak for hot spheres (10-37 mm diameters). We calculated a reference level for each image quality metric, so that the 10-mm sphere can be visually detected. The SUV harmonization range and the image noise criterion were proposed with consideration of overshoot due to point-spread function (PSF) reconstruction. We proposed image quality reference levels as follows: QH,10 mm/N10 mm ≥ 2.5 and CVBG ≤ 14.1%. The 10th-90th percentiles in the SUV distributions were defined as the new SUV harmonization range. CVBG ≤ 10% was proposed as the image noise criterion, because the intra-scanner SUV variability significantly depended on CVBG. We proposed new image quality reference levels to ensure small lesion detectability. A new SUV harmonization range (in which PSF reconstruction is applicable) and the image noise criterion were also proposed for minimizing the SUV variabilities. Our proposed new standards will facilitate image quality standardization and SUV harmonization of multicenter oncology PET studies. The reliability of multicenter oncology PET studies will be improved by satisfying the new standards.

Clinical practice guidelines for high-resolution breast PET, 2019 edition.

Breast positron emission tomography (PET) has had insurance coverage when performed with conventional whole-body PET in Japan since 2013. Together with whole-body PET, accurate examination of breast cancer and diagnosis of metastatic disease are possible, and are expected to contribute significantly to its treatment planning. To facilitate a safer, smoother, and more appropriate examination, the Japanese Society of Nuclear Medicine published the first edition of practice guidelines for high-resolution breast PET in 2013. Subsequently, new types of breast PET have been developed and their clinical usefulness clarified. Therefore, the guidelines for breast PET were revised in 2019. This article updates readers as to what is new in the second edition. This edition supports two different types of breast PET depending on the placement of the detector: the opposite-type (positron emission mammography; PEM) and the ring-shaped type (dedicated breast PET; dbPET), providing an overview of these scanners and appropriate imaging methods, their clinical applications, and future prospects. The name "dedicated breast PET" from the first edition is widely used to refer to ring-shaped type breast PET. In this edition, "breast PET" has been defined as a term that refers to both opposite- and ring-shaped devices. Up-to-date breast PET practice guidelines would help provide useful information for evidence-based breast imaging.

Validation of cardiac (123)I-MIBG scintigraphy in patients with Parkinson's disease who were diagnosed with dopamine PET.

PURPOSE: The aim of this study was to evaluate the diagnostic potential of cardiac (123)I-labelled metaiodobenzylguanidine ((123)I-MIBG) scintigraphy in idiopathic Parkinson's disease (PD). The diagnosis was confirmed by positron emission tomography (PET) imaging with (11)C-labelled 2beta-carbomethoxy-3beta-(4-fluorophenyl)-tropane ((11)C-CFT) and (11)C-raclopride (together designated as dopamine PET). METHODS: Cardiac (123)I-MIBG scintigraphy and dopamine PET were performed for 39 parkinsonian patients. To estimate the cardiac (123)I-MIBG uptake, heart to mediastinum (H/M) ratios in early and delayed images were calculated. On the basis of established clinical criteria and our dopamine PET findings, 24 patients were classified into the PD group and 15 into the non-PD (NPD) group. RESULTS: Both early and delayed images showed that the H/M ratios were significantly lower in the PD group than in the NPD group. When the optimal cut-off levels of the H/M ratio were set at 1.95 and 1.60 in the early and delayed images, respectively, by receiver-operating characteristic analysis, the sensitivity of cardiac (123)I-MIBG scintigraphy for the diagnosis of PD was 79.2 and 70.8% and the specificity was 93.3 and 93.3% in the early and delayed images, respectively. In the Hoehn and Yahr 1 and 2 PD patients, the sensitivity decreased by 69.2 and 53.8% in the early and delayed images, respectively. CONCLUSION: In early PD cases, cardiac (123)I-MIBG scintigraphy is of limited value in the diagnosis, because of its relatively lower sensitivity. However, because of its high specificity for the overall cases, cardiac (123)I-MIBG scintigraphy may assist in the diagnosis of PD in a complementary role with the dopaminergic neuroimaging.

Photophobia in essential blepharospasm--a positron emission tomographic study.

To localize regional alterations in cerebral glucose metabolism in essential blepharospasm (EB) patients with photophobia. We have studied 22 EB patients by performing positron emission tomography and [(18)F]-fluorodeoxyglucose analysis. The patients were classified into two subgroups, namely, EB with photophobia (P group) and EB without photophobia (NP group), and compared with a healthy control group (n = 44). There were no significant differences between the two patient groups with respect to the severity of motor symptoms or the duration for which the condition persisted. The FDG-PET images were analyzed using the statistical parametric mapping software. As compared to the control group, the P group exhibited significant hypermetabolism in the thalamus (P = 0.002), while the NP group exhibited significant hypometabolism in the dorsal midbrain, especially, in the superior colliculus (P = 0.005). The P group exhibited significant hypermetabolism in the thalamus and the dorsal midbrain as compared to the NP group (P < 0.001). These findings suggest that photophobia in EB patients may be associated with abnormal hyperactivity in the thalamus. Either hyperactivity of the thalamus or hypoactivity of the superior colliculus, or both may be associated with excessive blinking in these patients.

High occupancy of sigma1 receptors in the human brain after single oral administration of donepezil: a positron emission tomography study using [11C]SA4503.

The acetylcholinesterase (AChE) inhibitor donepezil is also a sigma1 receptor agonist. We examined whether donepezil binds to sigma1 receptors in the living human brain after a single oral administration. Dynamic positron emission tomography (PET) data acquisition using the selective sigma1 receptor ligand [11C]SA4503 was performed to evaluate quantitatively the binding of [11C]SA4503 to sigma1 receptors in eight healthy male volunteers. Each subject had a PET scan before and after receiving a single dose of donepezil (5 or 10 mg). The binding potential of [11C]SA4503 was calculated. Doses of 5 mg and 10 mg donepezil bound to sigma1 receptors in the human brain with occupancies of approximately 60% and approximately 75%, respectively, in a dose-dependent manner. This study demonstrated that donepezil binds to sigma1 receptors in the living human brain at therapeutic doses. Therefore, sigma1 receptors may be implicated in the pharmacological mechanism of donepezil in the human brain.

Regional analysis of age-related decline in dopamine transporters and dopamine D2-like receptors in human striatum.

UNLABELLED: The purpose of this study was to evaluate the mechanisms of age-related decline of dopamine transporter (DAT) and dopamine D(2)-like receptor (D2R) densities in the human striatum by focusing on regional difference. METHODS: Positron emission tomography (PET) with [(11)C]CFT and [(11)C]raclopride for measuring DATs and D2Rs, respectively, was performed on 16 healthy volunteers ranging from 21 to 74 years in age. To evaluate in detail the regional difference within the striatum, in addition to the conventional region-of-interest-based analysis, we created a parametric image that enabled us to visualize the regional decline rate on a voxel-by-voxel basis, mapping the slope of the regression line between the age and uptake index of each tracer. RESULTS: The decreasing rates corresponded to 6.1, 5.5, and 5.6% per decade for DATs and 5.8, 4.9, and 4.8% per decade for D(2)Rs in the caudate nucleus, anterior putamen, and posterior putamen, respectively. The caudate nucleus for both DATs and D(2)Rs were the fastest among the striatum, and the regional difference of the decreasing rate for DATs was consistently associated with that for D2Rs. Meanwhile, previous histological studies have shown that age-related cell loss in the substantia nigra is likely to preferentially affect its dorsomedial part, which projects to the caudate nucleus. CONCLUSIONS: These results suggested that neuronal cell loss in the substantia nigra may be associated with the age-related DAT decline, and DAT decline may be associated functionally with age-related D2R decline.

A combination of unnatural phosphatidyl acceptor and tandem electrospray ionization mass spectrometry for tracing phospholipase D activity.

Phospholipase D (PLD) is a biocatalyst in the synthesis of bioactive compounds and a key enzyme in a variety of biological signal transductions. A combination of unnatural phosphatidyl acceptor, N,N,N-triethyl-N-2-hydroxyethylammonium bromide 6, as a substrate for PLD, and tandem electrospray ionization mass spectrometry (ESI MS) was found to provide information as to whether a given phospholipid serves as a substrate for the PLD-catalyzed reaction. Thus 2-(13'-hydroperoxy-octadecadienoyl)-1-palmitoylglycerophosphocholine 1, and its degradation products 2-(13'-oxo-octadecadienoyl)-1-palmitoylglycerophosphocholine 9 and 2-(13'-hydroxy-octadecadienoyl)-1-palmitoylglycerophosphocholine 11, in a mixture were found to be a substrate of the PLD-catalyzed transphosphatidylation. The sensitivity of this method was exemplified by the observation that PLD activity in cabbage leaves was detected using a small amount of crude crushed leaves with little pretreatment. This simple method can be used in screening for PLD activity and searching for inhibitors of the enzyme from various natural sources.

Preclinical and the first clinical studies on [11C]CHIBA-1001 for mapping alpha7 nicotinic receptors by positron emission tomography.

OBJECTIVE: 4-[(11)C]methylphenyl 2,5-diazabicyclo[3.2.2]nonane-2-carboxylate ([(11)C]CHIBA-1001), a 4-methyl-substituted derivative of the selective alpha7 nicotinic acetylcholine receptor (alpha7 nAChR) partial agonist 4-bromophenyl 1,4 diazabicyclo[3.2.2]nonane-4-carboxylate (SSR180711), is a potential radioligand for mapping alpha7 nAChRs in the brain by positron emission tomography (PET). In this study, we performed preclinical and first clinical PET studies using [(11)C]CHIBA-1001 for imaging alpha7 nAChRs in the human brain. METHODS: [(11)C]CHIBA-1001 was synthesized by methylation of the tributylstannyl precursor with [(11)C]CH(3)I in a palladium-promoted Stille cross-coupling reaction. The radiation absorbed-dose of [(11)C]CHIBA-1001 in humans was calculated from distribution data in mice. The acute toxicity of CHIBA-1001 at a dose of 3.20 mg/kg body weight, which is more than 41,000-fold the clinical equivalent dose of [(11)C]CHIBA-1001, was evaluated. The mutagenicity of CHIBA-1001 was studied by a reverse mutation test in Salmonella typhimurium (Ames test). Metabolite analysis in the mouse brain was carried out by high-performance liquid chromatography. The first clinical PET imaging of alpha7 nAChRs with [(11)C]CHIBA-1001 in a normal volunteer was also performed. RESULTS: A suitable preparation method for [(11)C]CHIBA-1001 injection was established. The radiation absorbed-dose by [(11)C]CHIBA-1001 in humans was low enough for clinical use, and no acute toxicity or mutagenicity of CHIBA-1001 was found. Most radioactivity in the mouse brain was detected as an unchanged form, although peripherally [(11)C]CHIBA-1001 was degraded. We successfully performed brain imaging by PET with [(11)C]CHIBA-1001 in a normal volunteer. A 90-min dynamic scan showed a rapid accumulation and gradual washout of radioactivity in the brain. The highest distribution volume of [(11)C]CHIBA-1001 was found in the thalamus; however, regional differences in brain radioactivity were small. Peripherally, [(11)C]CHIBA-1001 was stable in humans: >80% of the radioactivity in plasma was detected as the unchanged form for 60 min. CONCLUSIONS: These results demonstrate that [(11)C]CHIBA-1001 is a suitable radioligand to use in clinical trials for imaging alpha7 nAChRs in the human brain, providing acceptable dosimetry and pharmacological safety at the dose required for adequate PET imaging.

Pre-discard estimation of radioactivated materials in positron emission tomography cyclotron systems and concrete walls of a cyclotron vault.

PURPOSE: The concrete vault, cyclotron body, and peripheral equipment in a cyclotron room become radioactivated by neutrons generated by operating an unshielded cyclotron. Radionuclides and the amounts of radioactivated materials must be identified before discarding a cyclotron system. The present study aimed to reduce the amounts of concrete from cyclotron vaults, as well as cyclotron components and peripheral equipment, that will be disposed of as radioactivated waste by clarifying the nature and quantity of radioactivated materials remaining in facilities after cyclotron operations have ceased. METHODS: Cylindrical concrete cores were bored into all four walls, ceiling, and floor of a room where a Cypris 370 cyclotron had been operated for 22.8 yr and then cooled for 40 months. The accelerated particles comprised protons and deuterons with constant energy of 18 and 10 MeV, respectively. The types and amounts of radionuclides in these cores, in 38 components of the cyclotron including the yoke, and in 13 pieces of equipment in the room, were determined by γ-ray spectrometry. Concentrations of radioactivity were also calculated using an updated version of Particle and Heavy Ion Transport System and DCHAIN-SP. Amounts of materials with both measured and calculated total radioactivity concentration (ΣD) of <0.1 Bq/g were identified as being nonradioactivated. RESULTS: The major radionuclides in the concrete were 60 Co and 152 Eu. The radioactivated concrete was distributed to a depth of <38 cm. Most cyclotron components and equipment were radioactivated by neutrons. The major radionuclides in cyclotron components and equipment were 54 Mn, 60 Co, and 65 Zn. A 33% volume of the yoke was regarded as nonradioactivated. CONCLUSIONS: The estimated amount of radioactivated waste in the concrete was about 70,000 kg (12.5% of the total concrete). Most components of the cyclotron except for the 33% volume of the yoke (20% of the cyclotron body), as well as most peripheral equipment in the room, were radioactivated. Part-by-part assessments of radioactive materials using measurements and calculations could distinguish nonradioactive from radioactive materials before they are discarded.

Presynaptic and postsynaptic nigrostriatal dopaminergic functions in multiple system atrophy.

A simultaneous evaluation of presynaptic and postsynaptic dopaminergic positron emission tomography markers, the dopamine transporters and the dopamine D2-like receptors, was performed in eight patients with parkinsonian phenotype of multiple system atrophy. Both presynaptic and postsynaptic markers were revealed to have declined in such a manner that they kept strong positive correlation throughout the striatum of all patients, suggesting that the degeneration process in the striatum may involve the entire structure of the dopaminergic synapse. In two L-3,4,dihydroxyphenyl-alanine-responsive cases, the balance of decline in two markers was relatively shifted to presynaptic dominant side. Correlative positron emission tomography study of presynaptic and postsynaptic dopaminergic function may be useful for the diagnosis of multiple system atrophy and to understand the mechanisms of its temporal L-3,4,dihydroxyphenyl-alanine responsiveness.

Measurement of the 11C-flumazenil binding in the visual cortex predicts the prognosis of hemianopia.

In order to determine whether functional neuroimaging studies can predict the prognosis of hemianopia due to organic cerebral disorders, we studied 8 patients (6 men and 2 women; age, 56.0+/-8.6 years) with homonymous hemianopia and compared them with 15 normal subjects (6 men and 9 women; age, 54.3+/-4.4 years). The cerebral glucose metabolism and 11C-flumazenil (FMZ) binding were measured by positron emission tomography, more than 1 month after the onset of the condition. Bilateral regions of interest (ROIs) were selected in the striate cortex, extrastriate cortex, cuneus and thalamus. Further, semi-quantitative data on the cerebral glucose metabolism and FMZ binding were obtained for the ROIs and compared with the data obtained for homologous regions in the contralateral hemisphere by calculating the ipsilateral/contralateral (I/C) ratio. The I/C ratios for the cerebral glucose metabolism and FMZ binding in the striate cortex were significantly low in the patients (glucose metabolism, P<0.0005; FMZ binding, P<0.005), while the ratio for the FMZ binding in the cuneus increased (P<0.0005). We observed that 5 patients, whose I/C ratio for the FMZ binding in the striate cortex was >0.850, experienced an improvement in their visual field, while that 3 patients with lower I/C ratios did not. The FMZ-PET may be useful to predict the prognosis of hemianopia in the chronic phase.

Influence of mild hyperglycemia on cerebral FDG distribution patterns calculated by statistical parametric mapping.

OBJECTIVE: In clinical cerebral 2-[(18)F]fluoro-2-deoxy-D: -glucose positron emission tomography (FDG-PET) studies, we sometimes encounter hyperglycemic patients with diabetes mellitus or patients who have not adhered to the fasting requirement. The objective of this study was to investigate the influence of mild hyperglycemia (plasma glucose range 110-160 mg/dl) on the cerebral FDG distribution patterns calculated by statistical parametric mapping (SPM). METHODS: We studied 19 healthy subjects (mean age 66.2 years). First, all the subjects underwent FDG-PET scans in the fasting condition. Then, 9 of the 19 subjects (mean age 64.3 years) underwent the second FDG-PET scans in the mild hyperglycemic condition. The alterations in the FDG-PET scans were investigated using SPM-and region of interest (ROI)-based analyses. We used three reference regions: (1) SPM global brain (SPMgb) used for SPM global mean calculation, (2) the gray and white matter region computed from magnetic resonance image (MRIgw), and (3) the cerebellar cortex (Cbll). RESULTS: The FDG uptake calculated as the standardized uptake value (average) in SPMgb, MRIgw, and Cbll regions in the mild hyperglycemic condition was 42.7%, 41.3%, and 40.0%, respectively, of that observed in the fasting condition. In SPM analysis, the mild hyperglycemia was found to affect the cerebral distribution patterns of FDG. The FDG uptake was relatively decreased in the gray matter, mainly in the frontal, temporal, and parietal association cortices, posterior cingulate, and precuneus in both SPMgb-and MRIgw-reference-based analyses. When Cbll was adopted as the reference region, those decrease patterns disappeared. The FDG uptake was relatively increased in the white matter, mainly in the centrum semiovale in all the reference-based analyses. CONCLUSIONS: It is noteworthy that the FDG distribution patterns were altered under mild hyperglycemia in SPM analysis. The decreased uptake patterns in SPMgb-(SPM default) and MRIgw-reference-based analyses resembled those observed in Alzheimer's disease. Under mild hyperglycemia, we can recommend Cbll as the reference region to detect decreased uptake patterns. We should pay special attention to controlling the diet condition, monitoring hyperglycemia, and optimizing the reference region in SPM analysis, particularly in the diagnosis of early Alzheimer's disease in clinical FDG-PET.