Keiichi Oda

Function of sigma1 receptors in Parkinson's disease

Objectiveu2002–u2002 The objective of this study was to investigate the mapping of sigma1 receptors in Parkinsons disease (PD) using [11C]SA4503 and positron emission tomography (PET), and to assess whether sigma1 receptors are involved in the damaged dopaminergic system in PD patients.

Striatal Distribution of Dopamine Transporters and Dopamine D2 Receptors at Different Stages of Parkinson's Disease A CFT and RAC PET Study

We investigated the alteration of dopaminergic system in striata of Parkinsons disease (PD) at different stages using positron emission tomography (PET), [11C]2β-carbomethoxy-3β-(4-fluorophenyl)tropane (CFT) for dopamine transporter (DAT), and [11C]raclopride (RAC) for dopamine D2 receptor (D2R). We studied eight elderly healthy volunteers (Group A), 13 drug naïve patients with PD (Group B), and seven advanced PD patients with mild dyskinesia (Group D). Six patients in Group B were re-examined after antiparkinsonian therapy (Group C). Regions of interest were drawn on the cerebellar hemisphere, head of the caudate nucleus (CN), and anterior (AP) and posterior putamen (PP) in the PET images. We calculated uptake ratio index (URI), asymmetry index (AI) and presynapse-to-postsynapse ratio (PPR) to evaluate dopaminergic function. DAT was smaller in the three PD groups than the Group A. URI of RAC in the PP was significantly larger in Group B than in Groups A and C. AI of CFT in the putamen was larger in the PD groups than in normal subjects, and AI of RAC in the PP was the largest in the Group B. PPRs in the AP and PP were smaller in the three PD groups than in Group A. DAT decreased with disease progression in patients with PD. Binding of RAC was largest in the putamen of drug-naïve PD patients, but the enhanced binding could not be detected in the therapeutic patients with PD because of weak D2R affinity of RAC.

Increased binding potential of brain adenosine A 1 receptor in chronic stages of patients with diffuse axonal injury measured with [1-methyl- 11 C] 8-dicyclopropylmethyl-1-methyl-3-propylxanthine PET imaging.

The positron emission tomography (PET) radioligand for adenosine A1 receptor (A1R) [1-methyl-11C] 8-dicyclopropylmethyl-1-methyl-3-propylxanthine (MPDX) has recently been developed for human brain imaging. In the present study, we evaluated the alteration of the A1R in patients with diffuse axonal injury (DAI) in chronic stage in vivo. Ten patients with DAI (7 men and 3 women) were included in this study. Three PET examinations were sequentially performed to measure A1R binding with 11C-MPDX, glucose metabolism with 18F-fluorodeoxyglucose (FDG), and central benzodiazepine receptor binding with 11C-flumazenil (FMZ), and decreases of 11C-FMZ uptake indicate neuronal loss. 11C- MPDX did not depict any lesion with significantly decreased nondisplaceable binding potential (BPND) in comparison to healthy controls (14 men) in region of interest (ROI) analysis. Instead, it showed a significant increase of BPND in the lower frontal and posterior cingulate cortexes and rolandic area (pu2009<u20090.05) in ROI analysis. In 18F-FDG PET, the standardized uptake values (SUVs) ratio to the whole brain were decreased in anterior and posterior cingulate gyrus compared to controls (14 men and 9 women; pu2009<u20090.01). In 11C-FMZ PET, the SUV ratio to the cerebellum was decreased in anterior cingulate gyrus in ROI analysis (controls, 9 men and 6 women; pu2009<u20090.01). The area with significantly increased 11C-MPDX binding, lower frontal cortex, rolandic area, and posterior cingulate gyrus, did not overlap with the areas of neuronal loss detected by decreased 11C-FMZ binding and did not completely overlap with area of reduced18F-FDG uptake. We obtained the first 11C-MPDX PET images reflecting the A1R BPND in human DAI brain in vivo. 11C-MPDX depicted increased A1R BPND in the areas surrounding the injured brain, whereas 18F-FDG demonstrated reduction throughout the brain. The results suggested that A1R might continuously confer neuroprotective or neuromodulatory effects in DAI even in the chronic stage.

Error and t Images Depend on ANOVA Design and Anatomical Standardization in PET Activation Analysis

In a positron emission tomography activation analysis with task replications within subject, a number of analysis of variance (ANOVA) designs are applicable with different definitions of t and error. The characteristics of t (and z) maps and error images and how they depend on the ANOVA design and on the anatomical standardization method have been investigated. Six subjects underwent measurement of regional cerebral blood flow with [15O]water under resting and while thinking of verbs associated with auditorily presented nouns, three times for each. The images were anatomically standardized with LINear, SPM95, or HBA. ANOVA was performed pixel by pixel to compute t statistics for the task main effect (verb vs rest) in four different ANOVA designs: (i) two way (subject and task) (2W), (ii) two way with interaction (2WI), (iii) two way with interaction, except that the “subject” was considered a random factor (2WI-RF), and (iv) three way (subject, task, and replication). The left frontal cortex extending from Brocas area to the premotor cortex was activated by the verb generation. The foci localization in the z images depended both on the anatomical standardization method and on the ANOVA design, and the variation ranged from 1 to 3 cm. SPM tended to present a higher peak z than LIN and HBA. The z images of 2W and 2WI looked alike, but 2WI-RF and 3W each presented a different z map within the activated area. The peak z score by 2WI-RF was lower than the others. The error images for 2W, 2WI, and 3W were heterogeneous, being high in gray and low in white.