The neuromodulatory role of dopamine in improved reaction time by acute cardiovascular exercise.

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

The quantification of muscle activities during arm elevation following reverse shoulder arthroplasty or superior capsular reconstruction for irreparable rotator cuff tears using positron emission tomography.

BACKGROUND: Reverse shoulder arthroplasty (RSA) and superior capsular reconstruction (SCR) are recognized as surgical options for an irreparable rotator cuff tear. However, the postoperative changes of the muscle activity patterns remain unclear. The purpose of this study was to investigate the quantified muscle activities on shoulder elevation in patients treated with RSA or SCR using fluorine-18-labelled fluorodeoxyglucose-positron emission tomography. METHODS: Asymptomatic shoulders that underwent RSA or SCR and those without a rotator cuff tear were analyzed as the RSA, SCR, and control groups. All subjects underwent shoulder elevation exercise, followed by a fluorine-18-labelled fluorodeoxyglucose-positron emission tomography examination. Using previously established methods to quantify the uptake of each muscle on positron emission tomography images, the standard uptake values (SUVs) for 16 portions of the deltoid, rotator cuff, and periscapular muscles were obtained to compare the muscle activity patterns among 3 groups. RESULTS: The deltoid muscle showed the most characteristic differences according to the surgeries. The mean SUVs of the anterior, middle, and posterior deltoid were 3.3, 3.7, and 1.5 for the RSA group; 2.7, 4.2, and 1.5 for the SCR group; and 1.3, 2.0, and 0.9 for the control group, respectively. In comparison to the control group, both the RSA and SCR groups showed significantly increased SUVs at all portions of the deltoid muscle. The RSA group showed similar SUVs for the anterior and middle deltoid, whereas the SCR and control groups showed greatest SUVs at the middle deltoid. In addition, the serratus anterior, levator scapulae, and upper portion of the trapezius in the RSA group showed greater SUVs than in the control group. CONCLUSION: The deltoid muscle showed increased activity in the RSA and SCR groups. The middle deltoid was mainly used in the SCR group, whereas the anterior and middle deltoid, as well as the upward rotator muscles of the scapula, were mainly used in the RSA group.

Muscle activities during shoulder internal rotation differ in arm position: a preliminary quantitative analysis using positron emission tomography.

OBJECTIVE: To investigate the muscle activity patterns of the glenohumeral joint during internal rotation both with the arm at 0° and 90° of abduction using 2-deoxy-2-[18F] fluoro-D-glucose (FDG) positron emission tomography (PET) and magnetic resonance imaging (MRI). MATERIALS AND METHODS: Six healthy male volunteers underwent PET examination after performing active glenohumeral internal rotation exercise using an elastic band both with the arm at 0° and 90° of abduction. As a control, PET scan under resting condition was also performed. The exercise was performed before and after 18 fluorodeoxyglucose injection. Each PET image was fused to the corresponding MRI to identify each muscle. The standardized uptake value (SUV) of each muscle was compared between the two arm positions. RESULTS: With the arm at 0° of abduction, the SUV increased significantly after exercise both in the middle and inferior 1/3 of the subscapularis, which were significantly higher than that of the superior 1/3 of the subscapularis (P < 0.05). The SUV of the inferior 1/3 of the subscapularis was significantly higher at 90° of abduction than at 0° of abduction and was significantly higher than that of the superior 1/3 at 90° of abduction (P < 0.01). The SUV after exercise in the inferior infraspinatus and teres minor increased. CONCLUSIONS: The middle and inferior parts of the subscapularis are the main shoulder internal rotators in 0° of abduction, whereas the inferior part of the subscapularis is the main internal rotator in 90° of abduction.

Effects of levocetirizine and diphenhydramine on regional glucose metabolic changes and hemodynamic responses in the human prefrontal cortex during cognitive tasks.

OBJECTIVE: Antihistamines often have sedative side effects. This was the first study to measure regional cerebral glucose (energy) consumption and hemodynamic responses in young adults during cognitive tests after antihistamine administration. METHODS: In this double-blind, placebo-controlled, three-way crossover study, 18 healthy young Japanese men received single doses of levocetirizine 5 mg and diphenhydramine 50 mg at intervals of at least six days. Subjective feeling, task performances, and brain activity were evaluated during three cognitive tests (word fluency, two-back, and Stroop). Regional cerebral glucose consumption changes were measured using positron emission tomography with [18 F]fluorodeoxyglucose. Regional hemodynamic responses were measured using near-infrared spectroscopy. RESULTS: Energy consumption in prefrontal regions was significantly increased after antihistamine administration, especially diphenhydramine, whereas prefrontal hemodynamic responses, evaluated with oxygenated hemoglobin levels, were significantly lower with diphenhydramine treatment. Stroop test accuracy was significantly impaired by diphenhydramine, but not by levocetirizine. There was no significant difference in subjective sleepiness. CONCLUSIONS: Physiological "coupling" between metabolism and perfusion in the healthy human brain may not be maintained under pharmacological influence due to antihistamines. This uncoupling may be caused by a combination of increased energy demands in the prefrontal regions and suppression of vascular permeability in brain capillaries after antihistamine treatment. Further research is needed to validate this hypothesis.

[(18)F]THK-5117 PET for assessing neurofibrillary pathology in Alzheimer's disease.

PURPOSE: Visualization of the spatial distribution of neurofibrillary tangles would help in the diagnosis, prevention and treatment of dementia. The purpose of the study was to evaluate the clinical utility of [(18)F]THK-5117 as a highly selective tau imaging radiotracer. METHODS: We initially evaluated in vitro binding of [(3)H]THK-5117 in post-mortem brain tissues from patients with Alzheimer's disease (AD). In clinical PET studies, [(18)F]THK-5117 retention in eight patients with AD was compared with that in six healthy elderly controls. Ten subjects underwent an additional [(11)C]PiB PET scan within 2 weeks. RESULTS: In post-mortem brain samples, THK-5117 bound selectively to neurofibrillary deposits, which differed from the binding target of PiB. In clinical PET studies, [(18)F]THK-5117 binding in the temporal lobe clearly distinguished patients with AD from healthy elderly subjects. Compared with [(11)C]PiB, [(18)F]THK-5117 retention was higher in the medial temporal cortex. CONCLUSION: These findings suggest that [(18)F]THK-5117 provides regional information on neurofibrillary pathology in living subjects.

Rhodium-catalysed arylative annulation of 1,4-enynes with arylboronic acids.

The rhodium(I)-catalysed arylative annulation of 1,4-enynes with arylboronic acids was investigated. The reaction was found to proceed via an addition-1,4-rhodium migration-addition sequence, affording the corresponding 1,1-disubstituted 3-(arylmethylene)indanes.

Muscle activity pattern of the shoulder external rotators differs in adduction and abduction: an analysis using positron emission tomography.

BACKGROUND: The muscle activity pattern during shoulder external rotation has not been fully clarified. This study aimed to determine the activities involved in external rotation in the adducted and abducted positions using positron emission tomography (PET). METHODS: Seven healthy volunteers underwent PET examinations after performing external rotation using an elastic band at both 0° and 90° of shoulder abduction in the frontal plane. External rotation exercise was performed before and after injection of fluorine 18 fluorodeoxyglucose, which was followed by PET examination. The protocols for external rotation exercise were identical between the 2 shoulder positions. To obtain control data, PET examination was also performed under resting conditions. The order of these 3 PET examinations was randomized, and they were performed at intervals of 1 week or greater. Each PET image was fused to the corresponding magnetic resonance image to identify each shoulder muscle. After this, the standardized uptake value was calculated in each muscle and was compared between the 2 shoulder positions. RESULTS: The infraspinatus showed the greatest muscle activity during external rotation at 0° of abduction, whereas the teres minor showed the greatest activity at 90° of abduction. The teres minor-infraspinatus ratio at 90° of abduction (mean ± SD, 1.21 ± 0.23) was significantly higher than that at 0° of abduction (0.84 ± 0.15) (P < .01). CONCLUSION: The infraspinatus and teres minor are the main shoulder external rotators. The teres minor is more important as an external rotator in abduction than in adduction.

Cerebral metabolic changes in men after chiropractic spinal manipulation for neck pain.

BACKGROUND: Chiropractic spinal manipulation (CSM) is an alternative treatment for back pain. The autonomic nervous system is often involved in spinal dysfunction. Although studies on the effects of CSM have been performed, no chiropractic study has examined regional cerebral metabolism using positron emission tomography (PET). OBJECTIVE: The aim of the present study was to investigate the effects of CSM on brain responses in terms of cerebral glucose metabolic changes measured by [18F]fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS: Twelve male volunteers were recruited. Brain PET scanning was performed twice on each participant, at resting and after CSM. Questionnaires were used for subjective evaluations. A visual analogue scale (VAS) was rated by participants before and after chiropractic treatment, and muscle tone and salivary amylase were measured. RESULTS: Increased glucose metabolism was observed in the inferior prefrontal cortex, anterior cingulated cortex, and middle temporal gyrus, and decreased glucose metabolism was found in the cerebellar vermis and visual association cortex, in the treatment condition (P < .001). Comparisons of questionnaires indicated a lower stress level and better quality of life in the treatment condition. A significantly lower VAS was noted after CSM. Cervical muscle tone and salivary amylase were decreased after CSM. Conclusion The results of this study suggest that CSM affects regional cerebral glucose metabolism related to sympathetic relaxation and pain reduction.

18F-THK5351 Positron Emission Tomography Imaging in Neurodegenerative Tauopathies.

Introduction: We aimed to determine whether in vivo tau deposits and monoamine oxidase B (MAO-B) detection using 18F-THK5351 positron emission tomography (PET) can assist in the differential distribution in patients with corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), and Alzheimer's disease (AD) and whether 18F-THK5351 retention of lesion sites in CBS and PSP can correlate with clinical parameters. Methods: 18F-THK5351 PET was performed in 35 participants, including 7, 9, and 10 patients with CBS, PSP, and AD, respectively, and 9 age-matched normal controls. In CBS and PSP, cognitive and motor functions were assessed using the Montreal Cognitive Assessment, Addenbrooke's Cognitive Examination-Revised, and Frontal Assessment Battery, Unified Parkinson's Disease Rating Scale Motor Score, and PSP Rating Scale. Results: 18F-THK5351 retention was observed in sites susceptible to disease-related pathologies in CBS, PSP, and AD. 18F-THK5351 uptake in the precentral gyrus clearly differentiated patients with CBS from those with PSP and AD. Furthermore, 18F-THK5351 uptake in the inferior temporal gyrus clearly differentiated patients with AD from those with CBS and PSP. Regional 18F-THK5351 retention was associated with the cognitive function in CBS and PSP. Conclusion: Measurement of the tau deposits and MAO-B density in the brain using 18F-THK5351 may be helpful for the differential diagnosis of tauopathies and for understanding disease stages.

Function of the shoulder muscles during arm elevation: an assessment using positron emission tomography.

Although 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) positron emission tomography (PET) has been used for the assessment of skeletal muscle activities, its application to the shoulder muscles is only sparse. The purpose of this study was to investigate the activities of the shoulder muscles during arm elevation using PET. Six healthy volunteers performed an arm elevation exercise before and after FDG injection. The exercise consisted of 200 repetitions of arm elevation in the scapular plane with a 0.25-kg weight fixed to the wrist on both arms. PET examination was performed 50 min after FDG injection. For control data, PET scan was repeated for each subject on a separate day without any exercise. The volume of interest was established for each shoulder muscle. The subscapularis was divided into three portions (superior, middle, and inferior). The standardized uptake value (SUV) was calculated in each muscle to quantify its activity. The SUVs increased significantly after exercise in the deltoid, supraspinatus, and the superior portion of subscapularis. Among three divided portions of the subscapularis, the SUV of the superior one-third was significantly greater than the rest of the muscle after exercise. Our current study clearly indicated that there were two functionally different portions in the subscapularis muscle and the superior one-third played an important role during arm elevation in the scapular plane.

Error propagation analysis of seven partial volume correction algorithms for [18F]THK-5351 brain PET imaging.

BACKGROUND: Novel partial volume correction (PVC) algorithms have been validated by assuming ideal conditions of image processing; however, in real clinical PET studies, the input datasets include error sources which cause error propagation to the corrected outcome. METHODS: We aimed to evaluate error propagations of seven PVCs algorithms for brain PET imaging with [18F]THK-5351 and to discuss the reliability of those algorithms for clinical applications. In order to mimic brain PET imaging of [18F]THK-5351, pseudo-observed SUVR images for one healthy adult and one adult with Alzheimer's disease were simulated from individual PET and MR images. The partial volume effect of pseudo-observed PET images were corrected by using Müller-Gärtner (MG), the geometric transfer matrix (GTM), Labbé (LABBE), regional voxel-based (RBV), iterative Yang (IY), structural functional synergy for resolution recovery (SFS-RR), and modified SFS-RR algorithms with incorporation of error sources in the datasets for PVC processing. Assumed error sources were mismatched FWHM, inaccurate image-registration, and incorrectly segmented anatomical volume. The degree of error propagations in ROI values was evaluated by percent differences (%diff) of PV-corrected SUVR against true SUVR. RESULTS: Uncorrected SUVRs were underestimated against true SUVRs (- 15.7 and - 53.7% in hippocampus for HC and AD conditions), and application of each PVC algorithm reduced the %diff. Larger FWHM mismatch led to larger %diff of PVC-SUVRs against true SUVRs for all algorithms. Inaccurate image registration showed systematic propagation for most algorithms except for SFS-RR and modified SFS-RR. Incorrect segmentation of the anatomical volume only resulted in error propagations in limited local regions. CONCLUSIONS: We demonstrated error propagation by numerical simulation of THK-PET imaging. Error propagations of 7 PVC algorithms for brain PET imaging with [18F]THK-5351 were significant. Robust algorithms for clinical applications must be carefully selected according to the study design of clinical PET data.

Quantitative analysis of donepezil binding to acetylcholinesterase using positron emission tomography and [5-(11)C-methoxy]donepezil.

The aim of this study was to establish kinetic analysis of [5-(11)C-methoxy]donepezil ([(11)C]donepezil), which was developed for the in-vivo visualization of donepezil binding to acetylcholinesterase (AChE) using positron emission tomography (PET). Donepezil is an AChE inhibitor that is widely prescribed to ameliorate the cognitive impairment of patients with dementia. Six healthy subjects took part in a dynamic study involving a 60-min PET scan after intravenous injection of [(11)C]donepezil. The total distribution volume (tDV) of [(11)C]donepezil was quantified by compartmental kinetic analysis and Logan graphical analysis. A one-tissue compartment model (1TCM) and a two-tissue compartment model (2TCM) were applied in the kinetic analysis. Goodness of fit was assessed with chi(2) criterion and Akaike's Information Criterion (AIC). Compared with a 1TCM, goodness of fit was significantly improved by a 2TCM. The tDVs provided by Logan graphical analysis were slightly lower than those provided by a 2TCM. The rank order of the mean tDVs in 10 regions was in line with the AChE activity reported in a previous post-mortem study. Logan graphical analysis generated voxel-wise images of tDV, revealing the overall distribution pattern of AChE in individual brains. Significant correlation was observed between tDVs calculated with and without metabolite correction for plasma time-activity curves, indicating that metabolite correction could be omitted. In conclusion, this method enables quantitative analysis of AChE and direct investigation of the pharmacokinetics of donepezil in the human brain.

Evaluation of individual skeletal muscle activity by glucose uptake during pedaling exercise at different workloads using positron emission tomography.

Skeletal muscle glucose uptake closely reflects muscle activity at exercise intensity levels <55% of maximal oxygen consumption (VO2max). Our purpose was to evaluate individual skeletal muscle activity from glucose uptake in humans during pedaling exercise at different workloads by using [18F]fluorodeoxyglucose (FDG) and positron emission tomography (PET). Twenty healthy male subjects were divided into two groups (7 exercise subjects and 13 control subjects). Exercise subjects were studied during 35 min of pedaling exercise at 40 and 55% VO2max exercise intensities. FDG was injected 10 min after the start of exercise or after 20 min of rest. PET scanning of the whole body was conducted after completion of the exercise or rest period. In exercise subjects, mean FDG uptake [standardized uptake ratio (SUR)] of the iliacus muscle and muscles of the anterior part of the thigh was significantly greater than uptake in muscles of control subjects. At 55% VO2max exercise, SURs of the iliacus muscle and thigh muscles, except for the rectus femoris, increased significantly compared with SURs at 40% VO2max exercise. Our results are the first to clarify that the iliacus muscle, as well as the muscles of the anterior thigh, is the prime muscle used during pedaling exercise. In addition, the iliacus muscle and all muscles in the thigh, except for the rectus femoris, contribute when the workload of the pedaling exercise increases from 40 to 55% VO2max.

Application of positron emission tomography to neuroimaging in sports sciences.

To investigate exercise-induced regional metabolic and perfusion changes in the human brain, various methods are available, such as positron emission tomography (PET), functional magnetic resonance imaging (fMRI), near-infrared spectroscopy (NIRS) and electroencephalography (EEG). In this paper, details of methods of metabolic measurement using PET, [(18)F]fluorodeoxyglucose ([(18)F]FDG) and [(15)O]radio-labelled water ([(15)O]H(2)O) will be explained. Functional neuroimaging in the field of neuroscience was started in the 1970s using an autoradiography technique on experimental animals. The first human functional neuroimaging exercise study was conducted in 1987 using a rough measurement system known as (133)Xe inhalation. Although the data was useful, more detailed and exact functional neuroimaging, especially with respect to spatial resolution, was achieved by positron emission tomography. Early studies measured the cerebral blood flow changes during exercise. Recently, PET was made more applicable to exercise physiology and psychology by the use of the tracer [(18)F]FDG. This technique allowed subjects to be scanned after an exercise task is completed but still obtain data from the exercise itself, which is similar to autoradiography studies. In this report, methodological information is provided with respect to the recommended protocol design, the selection of the scanning mode, how to evaluate the cerebral glucose metabolism and how to interpret the regional brain activity using voxel-by-voxel analysis and regions of interest techniques (ROI). Considering the important role of exercise in health promotion, further efforts in this line of research should be encouraged in order to better understand health behavior. Although the number of research papers is still limited, recent work has indicated that the [(18)F]FDG-PET technique is a useful tool to understand brain activity during exercise.

Dose dependency of brain histamine H(1) receptor occupancy following oral administration of cetirizine hydrochloride measured using PET with [11C]doxepin.

AIMS: The strength of sedation due to antihistamines can be evaluated using positron emission tomography (PET). The purpose of the present study is to measure histamine H(1) receptor (H(1)R) occupancy following oral administration of cetirizine (10 and 20 mg) in order to examine dose dependency. METHODS: Fifteen healthy male volunteers (age range, 20-35 years) were divided into 3 subgroups and were studied following single oral administration of cetirizine at 10 mg (n = 5) and 20 mg (n = 5) or hydroxyzine at 30 mg (n = 5) using PET with 11C-doxepin. Each subject was scanned also following the administration of placebo. Binding potential and H(1)RO values were calculated in the prefrontal and anterior cingulate cortices. Subjective sleepiness was also measured, and the correlation to H(1)RO was examined for each antihistamine. RESULTS: The averaged H(1)ROs of cetirizine 10 mg, 20 mg, and hydroxyzine 30 mg in the prefrontal and cingulate cortices was 12.6%, 25.2%, and 67.6%, respectively. The H(1)RO of hydroxyzine 30 mg correlated well with subjective sleepiness (p < 0.001); however, those of cetirizine 10 and 20 mg showed no correlation with subjective sleepiness. CONCLUSION: It was demonstrated that the brain penetration of orally administered cetirizine was dose-dependent. Cetirizine 10 mg, with its low H(1)RO and thus minimal sedation, could be more safely used than cetirizine 20 mg for the treatment of various allergic disorders.

Redistribution of whole-body energy metabolism by exercise: a positron emission tomography study.

OBJECTIVE: Our aim was to evaluate changes in glucose metabolism of skeletal muscles and viscera induced by different workloads using (18)F-2-fluoro-2-deoxyglucose ([(18)F]FDG) and three-dimensional positron emission tomography (3-D PET). METHODS: Five male volunteers performed ergometer bicycle exercise for 40 min at 40% and 70% of the maximal O(2) consumption (VO(2max)). [(18)F]FDG was injected 10 min later following the exercise task. Wholebody 3-D PET was performed. Five other male volunteers were studied as a control to compare with the exercise group. The PET image data were analyzed using manually defined regions of interest to quantify the regional metabolic rate of glucose (rMRGlc). Group comparisons were made using analysis of variance, and significant differences (P < 0.05) were determined using Scheffe's test (post hoc analysis). RESULTS: Quantitative analysis demonstrated that rMRGlc increased (P < 0.05) in the skeletal muscles of the thigh at mild or moderate workloads when compared with the resting controls. For visceral organs such as the liver and brain, metabolic reduction was significant (P < 0.05) at mild and/or moderate exercise workload. CONCLUSIONS: The present study demonstrated linear increases or decreases in glucose uptake by skeletal muscles and viscera with mild and moderate exercise workloads, suggesting the presence of homeostatic energy metabolism. This result supports the finding that [(18)F]FDG-PET can be used as an index of organ energy metabolism for moderate exercise workloads (70% VO(2max)). The results of this investigation may contribute to sports medicine and rehabilitation science.

Error evaluation of the D-shuttle dosimeter technique in positron emission tomography study.

The D-shuttle dosimeter technique is a convenient approach for estimating the radiation dosimetry in a positron emission tomography (PET) study that employs multiple D-shuttle dosimeters attached to the body surface of a patient. To bring this technique into clinical usage, it is very important to evaluate its performance by investigating the bias associated with D-shuttle dosimeter positioning and by comparing the estimates with those of the whole-body dynamic PET imaging technique. The torso cavity and six spheres of the NEMA body phantom were filled with 18F-FDG solution, and then, the phantom was imaged for 1 h. We assumed the mislocated positioning of the D-shuttle dosimeters by shifting them in the z-direction (upper) in a range of 1-5 cm from the original positions. The cumulative radioactivities, absorbed doses, and effective dose were estimated using accurate and mislocated positions of the D-shuttle dosimeters. For comparison, the cumulative radioactivities were also estimated from the PET images, and then, the absorbed doses and effective dose were computed. The maximum bias of the average estimated cumulated radioactivities and the effective doses was - 15.0% and - 19.7% for the 1 cm shifted positions, respectively. The ratios of absorbed doses obtained from D-shuttle and PET measurement against the actual values were between 0.9 and 1.3, and 0.7 and 1.0, respectively. The bias associated with the D-shuttle dosimeter positions was significant and probably consistent, and both dosimetric techniques exhibited good performance in this phantom study.

Renal statistical map for positron emission tomography with [O-15] water.

Image statistics are frequently used for functional and molecular imaging research in which images from a patient group with a specific diagnosis are compared with images from a healthy control group who have been matched for demographic variables. The success of image statistics for brain imaging has encouraged us to develop a method for obtaining volumetrically normalized kidney to perform image statistics so that we can locally visualize the statistical significant difference comparing voxel by voxel between certain groups in terms kidney blood flow kinetic parameters. For the development of this evolutionary process, we first volumetrically normalized all subjects, which include healthy control (HC) and chronic renal failure (CRF) patients, 15O water PET image with respect to one HC subject's MRI image using affine transformation. Then 15O kinetic parametric images of normalized kidneys were obtained through the basis function method. Finally, the statistical map of these parametric images was produced using the threshold-free cluster enhancement based permutation method. Kinetic parameters of kidney namely, uptake rate constant (K1), clearance rate constant (k2) and blood volume (Va), were found to be notably lower in CRF than those of in HC and k2 parameter was found to be more stable compared to K1 and Va. The statistical map of these parametric images allowed us to visualize local significant differences statistically (P<0.05) between HC and CRF groups. Though PET and MRI techniques have enormous potentiality for functional and molecular imaging of kidney, these are, at best, in experimental level. It is speculated that statistical mapping of kidney could play a significant role in the successful implementation of functional and molecular kidney imaging. However, more research involving a larger sample size and improved normalization technique will be needed for the robustness of the process.

A systematic performance evaluation of head motion correction techniques for 3 commercial PET scanners using a reproducible experimental acquisition protocol.

PURPOSES: Subject's motion during brain PET scan degrades spatial resolution and quantification of PET images. To suppress these effects, rigid-body motion correction systems have been installed in commercial PET scanners. In this study, we systematically compare the accuracy of motion correction among 3 commercial PET scanners using a reproducible experimental acquisition protocol. METHODS: A cylindrical phantom with two 22Na point sources was placed on a customized base to enable two types of motion, 5° yaw and 15° pitch rotations. Repetitive PET scans (5 min × 5 times) were performed at rest and under 2 motion conditions using 3 clinical PET scanners: the Eminence STARGATE G/L PET/CT (STARGATE) (Shimadzu Corp.), the SET-3000 B/X PET (SET-3000) (Shimadzu Corp.), and the Biograph mMR PET/MR (mMR) (Siemens Healthcare) systems. For STARGATE and SET-3000, the Polaris Vicra (Northern Digital Inc.) optical tracking system was used for frame-by-frame motion correction. For Biograph mMR, sequential MR images were simultaneously acquired with PET and used for LOR-based motion correction. All PET images were reconstructed by FBP algorithm with 1 × 1 mm pixel size. To evaluate the accuracy of motion correction, FWHMs and spherical ROI values were analyzed. RESULTS: The percent differences (%diff) in averaged FWHMs of point sources at 4 cm off-center between motion-corrected and static images were 0.77 ± 0.16 (STARGATE), 2.4 ± 0.34 (SET-3000), and 11 ± 1.0% (mMR) for a 5° yaw and 2.3 ± 0.37 (STARGATE) and 1.1 ± 0.60 (SET-3000) for a 15° pitch respectively. The averaged %diff between ROI values of motion-corrected images and static images were less than 2.0% for all conditions. CONCLUSIONS: In this study, we proposed a reproducible experimental framework to allow the systematic validation and comparison of multiple motion tracking and correction methodologies among different PET/CT and PET/MR commercial systems. Our proposed validation platform may be useful for future studies evaluating state-of-the-art motion correction strategies in clinical PET imaging.

Brain histamine H1 receptor occupancy of orally administered antihistamines, bepotastine and diphenhydramine, measured by PET with 11C-doxepin.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: 'Bepotastine besilate' is a novel second-generation antihistamine developed in Japan and its antiallergic effects have already been demonstrated by various studies. However, only a few clinical studies regarding its sedative property are available. In addition, histamine H(1) receptor occupancy (H(1)RO) of this new antihistamine has never been measured by positron emission tomography (PET). WHAT THIS STUDY ADDS: This paper provides the first measurement result of cerebral H(1)RO of bepotastine besilate (approximately 15%) as determined by PET. This result is in accordance with the clinical classification of bepotastine as a second-generation antihistamine. In addition, the relationship between subjective sleepiness and cerebral H(1)RO of this second-generation antihistamine is demonstrated for the first time using a placebo-controlled crossover study design. AIMS Antihistamines are frequently used for treating various allergic diseases, but often induce sedation. The degree of sedation can be evaluated by measuring histamine H(1) receptor occupancy (H(1)RO) in the brain using positron emission tomography (PET). The aim was to measure H(1)RO of bepotastine, a new second-generation antihistamine, and to compare it with that of diphenhydramine. METHODS: Eight healthy male volunteers (mean age +/- SD 24.4 +/- 3.3 years) were studied after single oral administration of bepotastine (10 mg), diphenhydramine (30 mg) or placebo, by PET imaging with (11)C-doxepin in a crossover study design. Binding potential ratio and H(1)ROs were calculated using placebo data and were compared between bepotastine and diphenhydramine in the anterior and posterior cingulate gyri (ACG and PCG, respectively), superior and inferior frontal cortices (SFC and IFC, respectively), orbitofrontal cortex (OFC), insular cortex (IC), lateral and medial temporal cortices (LTC and MTC, respectively), parietal cortex (PC), occipital cortex (OC) and sensorimotor cortex (SMC). Plasma concentration of each antihistamine was measured, and its correlation to H(1)RO was examined. RESULTS: H(1)RO after bepotastine treatment was significantly lower than that after diphenhydramine treatment in all cortical regions (P < 0.001). Mean H(1)ROs of bepotastine and diphenhydramine were 14.7% and 56.4%, respectively. H(1)ROs of both bepotastine and diphenhydramine correlated to their respective drug plasma concentration (P < 0.001). CONCLUSION: Oral bepotastine (10 mg), with its relatively low H(1)RO and thus minimal sedation, has the potential for use as a mildly or slightly sedative antihistamine in the treatment of various allergic disorders.