In vivo imaging of dopamine D1 receptor and activated microglia in attention-deficit/hyperactivity disorder: a positron emission tomography study.

Alterations in the cortical dopamine system and microglial activation have been implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD), one of neurodevelopmental disorders that can be conventionally treated with a dopamine enhancer (methylphenidate) albeit unsatisfactorily. Here, we investigated the contributions of the dopamine D1 receptor (D1R) and activated microglia and their interactions to the clinical severities in ADHD individuals using positron emission tomography (PET). Twenty-four psychotropic-naïve ADHD individuals and 24 age- and sex-matched typically developing (TD) subjects underwent PET measurements with [11C]SCH23390 for the D1R and [11C](R)PK11195 for activated microglia as well as assessments of clinical symptoms and cognitive functions. The ADHD individuals showed decreased D1R in the anterior cingulate cortex (ACC) and increased activated microglia in the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) compared with the TD subjects. The decreased D1R in the ACC was associated with severe hyperactivity in the participants with ADHD. Microglial activation in the DLPFC were associated with deficits in processing speed and attentional ability, and that in the OFC was correlated with lower processing speed in the ADHD individuals. Furthermore, positive correlations between the D1R and activated microglia in both the DLPFC and the OFC were found to be significantly specific to the ADHD group and not to the TD group. The current findings suggest that microglial activation and the D1R reduction as well as their aberrant interactions underpin the neurophysiological mechanism of ADHD and indicate these biomolecular changes as a novel therapeutic target.

Neural correlates of head restraint: Unsolicited neuronal activation and dopamine release.

To minimize motion-related distortion of reconstructed images, conventional positron emission tomography (PET) measurements of the brain inevitably require a firm and tight head restraint. While such a restraint is now a routine procedure in brain imaging, the physiological and psychological consequences resulting from the restraint have not been elucidated. To address this problem, we developed a restraint-free brain PET system and conducted PET scans under both restrained and non-restrained conditions. We examined whether head restraint during PET scans could alter brain activities such as regional cerebral blood flow (rCBF) and dopamine release along with psychological stress related to head restraint. Under both conditions, 20 healthy male participants underwent [15O]H2O and [11C]Raclopride PET scans during working memory tasks with the same PET system. Before, during, and after each PET scan, we measured physiological and psychological stress responses, including the State-Trait Anxiety Inventory (STAI) scores. Analysis of the [15O]H2O-PET data revealed higher rCBF in regions such as the parahippocampus in the restrained condition. We found the binding potential (BPND) of [11C]Raclopride in the putamen was significantly reduced in the restrained condition, which reflects an increase in dopamine release. Moreover, the restraint-induced change in BPND was correlated with a shift in the state anxiety score of the STAI, indicating that less anxiety accompanied smaller dopamine release. These results suggest that the stress from head restraint could cause unsolicited responses in brain physiology and emotional states. The restraint-free imaging system may thus be a key enabling technology for the natural depiction of the mind.

Alterations in α4ß2 nicotinic receptors in cognitive decline in Alzheimer's aetiopathology.

Nicotinic acetylcholine receptor subtype α4ß2 is considered important in the regulation of attention and memory, and cholinergic degeneration is known as one pathophysiology of Alzheimer's disease. Brain amyloid-ß protein deposition is also a key pathological marker of Alzheimer's disease. Recent amyloid-ß imaging has shown many cognitively normal subjects with amyloid-ß deposits, indicating a missing link between amyloid-ß deposition and cognitive decline. To date, the relationship between the α4ß2 nicotinic acetylcholine receptor and amyloid-ß burden has not been elucidated in vivo. In this study we investigated the relation between α4ß2 nicotinic acetylcholine receptor availability in the brain, cognitive functions and amyloid-ß burden in 20 non-smoking patients with Alzheimer's disease at an early stage and 25 age-matched non-smoking healthy elderly adults by measuring levels of α4ß2 nicotinic acetylcholine receptor binding estimated from a simplified ratio method (BPRI) and Logan plot-based amyloid-ß accumulation (BPND) using positron emission tomography with α4ß2 nicotinic acetylcholine receptor tracer (18)F-2FA-85380 and (11)C-Pittsburgh compound B. The levels of tracer binding were compared with clinical measures for various brain functions (general cognition, episodic and spatial memory, execution, judgement, emotion) using regions of interest and statistical parametric mapping analyses. Between-group statistical parametric mapping analysis showed a significant reduction in (18)F-2FA-85380 BPRI in the cholinergic projection region in patients with Alzheimer's disease with a variety of (11)C-Pittsburgh compound B accumulation. Spearman rank correlation analyses showed positive correlations of (18)F-2FA-85380 BPRI values in the medial frontal cortex and nucleus basalis magnocellularis region with scores of the Frontal Assessment Battery (a test battery for executive functions and judgement) in the Alzheimer's disease group (P < 0.05 corrected for multiple comparison), and also positive correlations of the prefrontal and superior parietal (18)F-2FA-85380 BPRI values with the Frontal Assessment Battery score in the normal group (P < 0.05 corrected for multiple comparison). These positive correlations indicated an in vivo α4ß2 nicotinic acetylcholine receptor role in those specific functions that may be different from memory. Both region of interest-based and voxelwise regression analyses showed a negative correlation between frontal (11)C-Pittsburgh compound B BPND and (18)F-2FA-85380 BPRI values in the medial frontal cortex and nucleus basalis magnocellularis region in patients with Alzheimer's disease (P < 0.05 corrected for multiple comparison). These findings suggest that an impairment of the cholinergic α4ß2 nicotinic acetylcholine receptor system with the greater amount of amyloid deposition in the system plays an important role in the pathophysiology of Alzheimer's disease.

Neural correlates of standing imagery and execution in Parkinsonian patients: The relevance to striatal dopamine dysfunction.

It has been reported that the cerebellar vermis is equally involved in both motor imagery about axial movement and the actual execution of postural balance in healthy human subjects, but this finding is yet to be explored in Parkinson's disease (PD). We therefore investigated the neuronal responses during observation of standing posture, imagination of standing and the assumption of an upright posture in ten drug-naïve PD patients using positron emission tomography (PET) with [15O]H2O and evaluated dopamine dysfunction by measuring the level of dopamine transporter binding of [11C]CFT. Within-group statistical parametric mapping (SPM) analysis showed similar cerebellar activation during imagination of standing and its real execution between the PD and control groups (12 healthy subjects); i.e., increases in regional cerebral blood flow (rCBF) were observed in the anterior cerebellar vermis during motor imagination and the posterior vermis during standing. A comparison between the groups showed that the motor execution of standing significantly activated the superior part of the posterior vermis (declive VI) and the paracentral sulcus region in the PD patients, while the prefrontal cortices were deactivated during standing (p<0.001 uncorrected). Correlation analysis within the PD group revealed that the postural rCBF increases in the cerebellar vermis (pyramis) were negatively correlated with putaminal [11C]CFT binding (p<0.01, r = 0.94) and that the postural rCBF reductions in the orbitofrontal cortex were positively correlated with caudate [11C]CFT binding (p<0.05, r = 0.70). These results suggest that while the neural circuits for postural imagery and execution are intact in PD, standing performance, which requires more recruitment of dopaminergic control, may result in compensatory overstimulation of the cerebellar vermis and paracentral foot area in PD patients. Hyperactivity in these areas along with mesocortical hypofunction may be pathophysiological aspects of postural control in PD patients. Hence, our findings would help understand the modifications observed within the neural networks in relationship with postural performance, and possible compensatory mechanisms in PD.

In vivo mitochondrial and glycolytic impairments in patients with Alzheimer disease.

OBJECTIVE: In vivo glycolysis-related glucose metabolism and electron transport chain-related mitochondrial activity may be different regionally in the brains of patients with Alzheimer disease (AD). To test this hypothesis regarding AD pathophysiology, we measured the availability of mitochondrial complex-I (MC-I) with the novel PET probe [18F]2-tert- butyl-4-chloro-5-2H- pyridazin-3-one ([18F]BCPP-EF), which binds to MC-I, and compared [18F]BCPP-EF uptake with 18F-fluorodeoxyglucose ([18F]FDG) uptake in the living AD brain. METHODS: First, the total distribution volume (VT) of [18F]BCPP-EF from 10 normal controls (NCs) was quantified using arterial blood samples and then tested to observe whether VT could substitute for the standard uptake value relative to the global count (SUVRg). Eighteen NCs and 14 different NCs underwent PET with [18F]BCPP-EF or [18F]FDG, respectively. Second, 32 patients with AD were scanned semiquantitatively with double PET tracers. Interparticipant and intraparticipant comparisons of the levels of MC-I activity ([18F]BCPP-EF) and glucose metabolism ([18F]FDG) were performed. RESULTS: The [18F]BCPP-EF VT was positively correlated with the [18F]BCPP-EF SUVRg, indicating that the use of the SUVRg was sufficient for semiquantitative evaluation. The [18F]BCPP-EF SUVRg, but not the [18F]FDG SUVRg, was significantly lower in the parahippocampus in patients with AD, highlighting the prominence of oxidative metabolic failure in the medial temporal cortex. Robust positive correlations between the [18F]BCPP-EF SUVRg and [18F]FDG SUVRg were observed in several brain regions, except the parahippocampus, in early-stage AD. CONCLUSIONS: Mitochondrial dysfunction in the parahippocampus was shown in early-stage AD. Mitochondria-related energy failure may precede glycolysis-related hypometabolism in regions with pathologically confirmed early neurodegeneration in AD.

Altered brain serotonin transporter and associated glucose metabolism in Alzheimer disease.

UNLABELLED: Whether preclinical depression is one of the pathophysiologic features of Alzheimer disease (AD) has been under debate. In vivo molecular imaging helps clarify this kind of issue. Here, we examined in vivo changes in the brain serotoninergic system and glucose metabolism by scanning early- to moderate-stage AD patients with and without depression using PET with a radiotracer for the serotonin transporter, (11)C-3-amino-4-(2-dimethylaminomethylphenylsulfanyl) benzonitrile (DASB), and a metabolic marker, (18)F-FDG. METHODS: Fifteen AD patients (8 nondepressed and 7 depressed) and 10 healthy subjects participated. All participants underwent 3-dimensional MRI and quantitative (11)C-DASB PET measurements, followed by (18)F-FDG PET scans in the AD group. Region-of-interest analysis was used to examine changes in (11)C-DASB binding potential estimated quantitatively by the Logan plot method in the serotonergic projection region. In addition, statistical parametric mapping was used to examine whether glucose metabolism in any brain region correlated with levels of (11)C-DASB binding in the dense serotonergic projection region (striatum) in AD. RESULTS: Psychologic evaluation showed that general cognitive function (Mini-Mental State Examination) was similar between the 2 AD subgroups. Striatal (11)C-DASB binding was significantly lower in AD patients, irrespective of depression, than in healthy controls (P < 0.05, corrected), and (11)C-DASB binding in other dense projection areas decreased significantly in the depressive group, compared with the control group. The (11)C-DASB binding potential levels in the subcortical serotonergic projection region correlated negatively with depression score (Spearman correlation, P < 0.01) but not with dementia score. Statistical parametric mapping correlation analysis showed that glucose metabolism in the right dorsolateral prefrontal cortex was positively associated with the level of striatal (11)C-DASB binding in AD. CONCLUSION: The significant reduction in (11)C-DASB binding in nondepressed AD patients suggests that presynaptic serotonergic function is altered before the development of psychiatric problems such as depression in AD. The depressive AD group showed greater and broader reductions in binding, suggesting that a greater loss of serotonergic function relates to more severe psychiatric symptoms in the disease. This serotonergic dysfunction may affect the activity of the right dorsolateral prefrontal cortex, a higher center of cognition and emotion in AD.

Prognostic value of 18F-FDG PET in patients with head and neck squamous cell cancer.

OBJECTIVE: This study was designed to assess whether tumor uptake of (18)F-FDG (FDG) expressed as the standardized uptake value (SUV) can be used to predict survival in patients with head and neck cancer. Furthermore, a prognostic maximum SUV was determined with univariate and bivariate analyses. CONCLUSION: Low SUVs ( 7.0). In the Cox proportional hazards model, tumor SUV was a significant and independent predictor of local control (p = 0.022) and disease-free survival (p = 0.019). In addition, in the group of high SUV, high T stage was more associated with poorer outcome than low T stage (p = 0.0502). Therefore, patients with higher tumor FDG uptake should be considered for a more aggressive treatment approach.

Alterations in serotonin transporter and body image-related cognition in anorexia nervosa.

The serotonin system has been implicated in the pathophysiology of anorexia nervosa (AN). A recent report proposed that body image distortion (BID), a core symptom of AN, may relate to abnormalities of the serotonin system, especially the serotonin transporter (5HTT). Positron emission tomography (PET) studies of underweight patients with active AN reported alterations in serotonin receptors, but not 5HTT. Here, we aimed to disclose the clinicopathophysiology of AN by focusing on 5HTT and cognitive functions, including BID, in groups with active AN. Twenty-two underweight female patients with AN (12 restricting-type AN (ANR); 10 binge-eating/purging-type AN (ANBP)) and 20 age-matched healthy female subjects underwent PET with a 5HTT radioligand [11C]DASB. The binding potential (BPND) of [11C]DASB was estimated semiquantitatively, and clinical data from Raven's colored progressive matrices for general intelligence, the Stroop test for focused attention, the Iowa gambling task for decision making and a dot-probe task designed for BID were compared with the levels of BPND in different groups. [11C]DASB BPND was significantly decreased in the medial parietal cortex in patients with AN and in the dorsal raphe in patients with ANR compared with healthy subjects (p < .05 corrected). Patients with ANR showed a significantly negative correlation between [11C]DASB BPND in the dorsal raphe and performance on the dot-probe task (p < .05 corrected). While reduced 5HTT in the medial parietal cortex (the somatosensory association area) is pathophysiologically important in AN in general, additional 5HTT reduction in the dorsal raphe as seen in ANR is implicated for the clinicopathophysiological relevance.

Neuroinflammation following disease modifying therapy in multiple sclerosis: A pilot positron emission tomography study.

INTRODUCTION: Chronic activation of microglia accelerates the neurodegenerative process in multiple sclerosis (MS). Although disease modifying therapy (DMT) is reportedly effective for neuroinflammatory responses in MS, the progression of neuroinflammation after DMT remains unclear. METHODS: We evaluated microglial activation in six clinically stable relapsing-remitting MS patients after DMT by quantifying changes in translocator protein (TSPO) density using PET with [11C]DPA713, a selective TSPO tracer for microglial activation. All patients underwent [11C]DPA713 PET scans twice, and the scans were conducted one year apart. The binding potential (BPND) of the tracer was estimated using a simplified reference tissue model. RESULTS: [11C]DPA713 BPND measured at 6months after DMT was significantly higher in the MS group than that in the control group. Compared with the first PET measurement, the one-year PET measurement revealed significantly elevated [11C]DPA713 BPND in broader brain regions covering the temporal and parietal cortices after one year of DMT. CONCLUSIONS: The current results indicate that microglial activation may proceed in the entire brain of clinically stable MS patients even after receiving DMT.

Brain serotonin transporter density and aggression in abstinent methamphetamine abusers.

CONTEXT: In animals, methamphetamine is known to have a neurotoxic effect on serotonin neurons, which have been implicated in the regulation of mood, anxiety, and aggression. It remains unknown whether methamphetamine damages serotonin neurons in humans. OBJECTIVE: To investigate the status of brain serotonin neurons and their possible relationship with clinical characteristics in currently abstinent methamphetamine abusers. DESIGN: Case-control analysis. SETTING: A hospital research center. PARTICIPANTS: Twelve currently abstinent former methamphetamine abusers (5 women and 7 men) and 12 age-, sex-, and education-matched control subjects recruited from the community. INTERVENTIONS: The brain regional density of the serotonin transporter, a structural component of serotonin neurons, was estimated using positron emission tomography and trans-1,2,3,5,6,10-beta-hexahydro-6-[4-(methylthio)phenyl]pyrrolo-[2,1-a]isoquinoline ([(11)C](+)McN-5652). Estimates were derived from region-of-interest and statistical parametric mapping methods, followed by within-case analysis using the measures of clinical variables. MAIN OUTCOME MEASURES: The duration of methamphetamine use, the magnitude of aggression and depressive symptoms, and changes in serotonin transporter density represented by the [(11)C](+)McN-5652 distribution volume. RESULTS: Methamphetamine abusers showed increased levels of aggression compared with controls. Region-of-interest and statistical parametric mapping analyses revealed that the serotonin transporter density in global brain regions (eg, the midbrain, thalamus, caudate, putamen, cerebral cortex, and cerebellum) was significantly lower in methamphetamine abusers than in control subjects, and this reduction was significantly inversely correlated with the duration of methamphetamine use. Furthermore, statistical parametric mapping analyses indicated that the density in the orbitofrontal, temporal, and anterior cingulate areas was closely associated with the magnitude of aggression in methamphetamine abusers. CONCLUSIONS: Protracted abuse of methamphetamine may reduce the density of the serotonin transporter in the brain, leading to elevated aggression, even in currently abstinent abusers.

Depiction of microglial activation in aging and dementia: Positron emission tomography with [11C]DPA713 versus [11C]( R)PK11195.

The presence of activated microglia in the brains of healthy elderly people is a matter of debate. We aimed to clarify the degree of microglial activation in aging and dementia as revealed by different tracers by comparing the binding potential (BPND) in various brain regions using a first-generation translocator protein (TSPO) tracer [11C]( R)PK11195 and a second-generation tracer [11C]DPA713. The BPND levels, estimated using simplified reference tissue models, were compared among healthy young and elderly individuals and patients with Alzheimer's disease (AD) and were correlated with clinical scores. An analysis of variance showed category-dependent elevation in levels of [11C]DPA713 BPND in all brain regions and showed a significant increase in the AD group, whereas no significant changes among groups were found when [11C]( R)PK11195 BPND was used. Cognito-mnemonic scores were significantly correlated with [11C]DPA713 BPND levels in many brain regions, whereas [11C]( R)PK11195 BPND failed to correlate with the scores. As mentioned elsewhere, the present results confirmed that the second-generation TSPO tracer [11C]DPA713 has a greater sensitivity to TSPO in both aging and neuronal degeneration than [11C]( R)PK11195. Positron emission tomography with [11C]DPA713 is suitable for the delineation of in vivo microglial activation occurring globally over the cerebral cortex irrespective of aging and degeneration.

[Measurement of radiation exposure to a PET institution driver from patients injected with FDG].

With the recent increase in FDG-PET examinations, concern has mounted regarding radiation exposure to hospital staff and the general public from patients injected with FDG. Because our PET institution is located 15 km from the hospital that provides these examinations, a driver has been designated to transport patients injected with FDG. This study was designed to measure the radiation dose to the driver from these patients (n=28) and to compare it with the estimated dose. A pocket dosimeter was used to measure radiation exposure to the driver. When the distances between the driver and patient were 1.1 m and 1.9 m, mean measured doses were 7.31 microSv and 2.26 microSv, respectively, while mean estimated doses were 8.61 microSv and 2.82 microSv, respectively, per trip. It was presumed that maximum radiation exposure per year was between 3.02 mSv (1.1 m) and 0.92 mSv (1.9 m). According to our data, the measured dose was 20% lower than the estimated dose. This discrepancy may be due to the difference between the volume source (measured dose) and point source (estimated dose).

Extrastriatal spreading of microglial activation in Parkinson's disease: a positron emission tomography study.

BACKGROUND: The neuroinflammatory glial response contributes to the degenerative process in Parkinson's disease (PD). However, the pattern of microglial progression remains unclear. METHODS: We evaluated microglial activation in early stage PD patients by quantifying changes in neuroinflammation using PET with [(11)C]DPA713, a selective PET tracer for microglial activation. Eleven PD patients (Hoehn and Yahr stages 1-2) without dementia underwent the [(11)C]DPA713 PET scan two times with 1 year apart. The binding potential (BPND) was estimated with the simplified reference tissue model. Voxelwise and regions of interest analyses were used to compare the regional BPND among groups. RESULTS: Significant increase in [(11)C]DPA713 BPND was found extrastriatally in the occipital, temporal and parietal cortex in PD patients, and the degree of BPND became much higher over the brain regions predominantly in the temporal and occipital cortex 1 year later. CONCLUSION: The current results indicated that an extrastriatal spreading of microglial activation reflects one of PD pathophysiology occurring at an early stage.

Neural substrates in judgment process while playing go: a comparison of amateurs with professionals.

A professional go player shows incomparable ability in judgment during go game. Positron emission tomography (PET) was used to investigate the neural substrates of professional go player's judgment process. Eight professional go players and six amateur players were instructed to think over silently in the opening-stage game (fuseki, territorial planning) problems and the life-or-death (tsume, checkmate judgment) problems presented on the monitor in front of them for 60 s of H2 15O PET scans and to state the answer afterwards. We found that in the territorial planning problems the parietal activation was equally observed in both groups with the additional prefrontal activation in the amateur group, and in the checkmate-decision problems the precuneus and cerebellum were activated in professionals while the premotor and parietooccipital cortices (visuospatial processing region) were extensively activated in amateurs. The comparison of the two groups showed stronger activations in the precuneus and cerebellum in the professionals in contrast to the premotor activation in amateurs during checkmate judgment. In addition, the cerebellum was remarkably activated in the higher ranking professional players. These findings suggested the cerebellum and precuneus play important roles in processing of accurate judgment by visual imagery and nonmotor learning memory processes in professional go players.

Effect of simple motor performance on regional dopamine release in the striatum in Parkinson disease patients and healthy subjects: a positron emission tomography study.

To investigate changes in dopamine release in the striatum during motor exercise in human subjects with and without striatal dopamine denervation, eight healthy subjects and eight patients with Parkinson disease (PD) were measured during unilateral foot extension/flexion movement using positron emission tomography with [11C]raclopride. Five subjects in each group were later scanned in the resting condition. Estimation of binding potential (k3/k4) of [11C]raclopride was based on Logan plot method. Significant reductions in [11C]raclopride k3/k4 were found in the dorsal putamen contralateral to the exercise side in the healthy group and ipsilaterally in the PD group. Spearman rank correlation analysis showed that [11C]raclopride k3/k4 correlated inversely with the decrease in performance (velocity and motion range) in the dorsal putamen contralaterally in the healthy group and ipsilaterally in the PD group. These results suggest that simple but laborious motor exercise (motor stimulation) generates significant dopamine release in the dorsal striatum contralateral to the motor execution in humans. Lack of the crossed pattern and ipsilateral increase in dopamine release in the dorsal striatum during the unilateral limb movement may reflect the pathophysiology for hypokinetic and insufficient coordinating movement in PD.

Association of dopamine transporter loss in the orbitofrontal and dorsolateral prefrontal cortices with methamphetamine-related psychiatric symptoms.

OBJECTIVE: The authors examined dopamine transporter density in the orbitofrontal cortex, dorsolateral prefrontal cortex, and amygdala in methamphetamine users and assessed the relationship of these measures to the subjects' clinical characteristics. METHOD: Positron emission tomography with [(11)C]WIN 35,428 was used to examine the regions of interest in 11 methamphetamine users and nine healthy comparison subjects. Psychiatric symptoms were evaluated with the Brief Psychiatric Rating Scale. RESULTS: Dopamine transporter density in the three regions studied was significantly lower in the methamphetamine users than in the comparison subjects. The lower dopamine transporter density in the orbitofrontal and dorsolateral prefrontal cortex was significantly correlated with the duration of methamphetamine use and the severity of psychiatric symptoms. CONCLUSIONS: Chronic methamphetamine use may cause dopamine transporter reduction in the orbitofrontal cortex, dorsolateral prefrontal cortex, and amygdala in the brain. Psychiatric symptoms in methamphetamine users may be attributable to the decrease in dopamine transporter density in the orbitofrontal cortex and the dorsolateral prefrontal cortex.

Imaging of gynecologic tumors: comparison of (11)C-choline PET with (18)F-FDG PET.

UNLABELLED: This study was designed to compare the value of PET using (11)C-choline with that of PET using (18)F-FDG for the diagnosis of gynecologic tumors. METHODS: We examined 21 patients, including 18 patients with untreated primary tumors and 3 patients with suspected recurrence of ovarian cancer. (11)C-choline PET and (18)F-FDG PET were performed within 2 wk of each other on each patient. The patients fasted for at least 5 h before the PET examinations, and PET was performed 5 min ((11)C-choline) and 60 min ((18)F-FDG) after injection of each tracer. PET images were corrected for the transmission data, and the reconstructed images were visually analyzed. Then, the standardized uptake value (SUV) was calculated for quantitative assessment of tumor uptake. PET results were compared with surgical histology or >6 mo of clinical observations. RESULTS: Of 18 untreated patients, (11)C-choline PET correctly detected primary tumors in 16 patients, whereas (18)F-FDG PET detected them in 14 patients. In 1 patient with small uterine cervical cancer and 1 diabetic patient with uterine corpus cancer, only (11)C-choline PET was true-positive. Both tracers were false-negative for atypical hyperplasia of the endometrium in 1 patient and were false-positive for pelvic inflammatory disease in 1 patient. For the diagnosis of recurrent ovarian cancer (n = 3), (11)C-choline PET and (18)F-FDG PET were true-positive in 1 patient, whereas neither tracer could detect cystic recurrent tumor and microscopic peritoneal disease in the other 2 patients. In the 15 patients with true-positive results for both tracers, tumor SUVs were significantly higher for (18)F-FDG than for (11)C-choline (9.14 +/- 3.78 vs. 4.61 +/- 1.61, P < 0.0001). In 2 patients with uterine cervical cancer, parailiac lymph node metastases were clearly visible on (18)F-FDG PET but were obscured by physiologic bowel uptake on (11)C-choline PET. CONCLUSION: The use of (11)C-choline PET is feasible for imaging of gynecologic tumors. Unlike (18)F-FDG PET, interpretation of the primary tumor on (11)C-choline PET is not hampered by urinary radioactivity; however, variable background activity in the intestine may interfere with the interpretation.

Age-related changes in cerebral blood flow and glucose metabolism in conscious rhesus monkeys.

Regional cerebral blood flow (rCBF) and regional cerebral metabolic rate of glucose (rCMRglc) were measured in aged and young monkeys by positron emission tomography (PET). Our purpose was to examine whether the age-related changes observed in the human brain also occur in the monkey brain. Studies were performed on six aged and six young-adult male rhesus monkeys (Macaca mulatta). rCBF and the rCMRglc were serially measured using PET with [(15)O]H(2)O and 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG), respectively. In order to minimize the bias induced by anesthesia, the PET emission scans were performed in the conscious state. ROIs were taken for the cerebellum, hippocampus with adjacent cortex, striatum, occipital cortex, temporal cortex, frontal cortex and cingulate. Group differences and correlations between rCBF and rCMRglc in each group were determined. Aged monkeys had significantly lower rCBF in the cerebellum, hippocampus with the adjacent cortex, striatum, occipital cortex, temporal cortex, frontal cortex, and significantly lower rCMRglc in the cerebellum, hippocampus with the adjacent cortex, striatum, occipital cortex, temporal cortex, frontal cortex and cingulate, compared to young monkeys. There were significant correlations between rCBF and rCMRglc in both the aged and young groups, but no significant difference was found in relationship between the two groups. Age-related changes were observed not only in rCMRglc, but also in rCBF in aged monkeys, while the coupling between rCBF and rCMRglc was maintained even in aged monkeys. These results demonstrated the potential of aged monkeys to serve as an aged human model using PET.

18F-FDG PET in the detection of extrahepatic metastases from hepatocellular carcinoma.

BACKGROUND: Positron emission tomography (PET) with 18F-fluoro-2-deoxy-D-glucose (18F-FDG) is useful in detecting distant metastases from a variety of malignancies. However, its efficiency in detecting distant metastases from hepatocellular carcinoma (HCC) has not been investigated. The aim of this study was to evaluate the usefulness of 18F-FDG PET for the detection of extrahepatic metastases from HCC. METHODS: Nineteen patients suspected of having extrahepatic HCC underwent 18F-FDG PET. Fourteen patients (group A) had extrahepatic lesions, which were detected by conventional studies. In five patients (group B), conventional imaging showed no extra- or intrahepatic lesions, but the tumor marker levels were elevated. The PET results were compared with those obtained by histopathology or by clinical follow-up. RESULTS: The detection rate of 18F-FDG PET was 83% (24 of 29 metastases) for extrahepatic metastases larger than 1 cm in greatest diameter and 13% (1 of 8 metastases) for lesions less than or equal to 1 cm. PET revealed two bone metastases not depicted by bone scan, and detected the nodal metastasis and intestinal metastases inconclusive on computed tomography. Extrahepatic lesions were resected in 5 patients of group A on the basis of PET findings. In all patients of group B, PET results were true negative for extrahepatic metastases, but HCCs were detected in the liver within 4 months in 4 patients. These were no false-positive lesions in either group. CONCLUSIONS: This preliminary study suggested that 18F-FDG PET could provide additional information and contribute to the management of HCC patients suspected of having extrahepatic metastases.

Microglial activation in young adults with autism spectrum disorder.

CONTEXT: A growing body of evidence suggests that aberrant immunologic systems underlie the pathophysiologic characteristics of autism spectrum disorder (ASD). However, to our knowledge, no information is available on the patterns of distribution of microglial activation in the brain in ASD. OBJECTIVES: To identify brain regions associated with excessively activated microglia in the whole brain, and to examine similarities in the pattern of distribution of activated microglia in subjects with ASD and control subjects. DESIGN: Case-control study using positron emission tomography and a radiotracer for microglia--[11C](R)-(1-[2-chrorophynyl]-N-methyl-N-[1-methylpropyl]-3 isoquinoline carboxamide) ([11C](R)-PK11195). SETTING: Subjects recruited from the community. PARTICIPANTS: Twenty men with ASD (age range, 18-31 years; mean [SD] IQ, 95.9 [16.7]) and 20 age- and IQ-matched healthy men as controls. Diagnosis of ASD was made in accordance with the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview-Revised. MAIN OUTCOME MEASURES: Regional brain [11C](R)-PK11195 binding potential as a representative measure of microglial activation. RESULTS: The [11C](R)-PK11195 binding potential values were significantly higher in multiple brain regions in young adults with ASD compared with those of controls (P < .05, corrected). Brain regions with increased binding potentials included the cerebellum, midbrain, pons, fusiform gyri, and the anterior cingulate and orbitofrontal cortices. The most prominent increase was observed in the cerebellum. The pattern of distribution of [11C](R)-PK11195 binding potential values in these brain regions of ASD and control subjects was similar, whereas the magnitude of the [11C](R)-PK11195 binding potential in the ASD group was greater than that of controls in all regions. CONCLUSIONS: Our results indicate excessive microglial activation in multiple brain regions in young adult subjects with ASD. The similar distribution pattern of regional microglial activity in the ASD and control groups may indicate augmented but not altered microglial activation in the brain in the subjects with ASD.