Keiichiro Yamaguchi

Assessment of radiotherapeutic effects on experimental tumors using 18F-2-fluoro-2-deoxy-D-glucose

The purpose of this study is to evaluation the effect of tumor volume and radiotherapy on the uptake of 18F-2-fluoro-2-deoxy-D-glucose (18FDG). The tumor models used were mouse mammary carcinoma MM48, FM3A, and rat hepatoma AH109A. Results were expressed as an 18FDG uptake ratio. This was the ratio of irradiated tumor uptake of 18FDG to unirradiated tumor uptake. The total tumor uptake was expressed as 18FDG uptake ratio multiplied by relative tumor volume. Following 20 Gy irradiation of the radioresistant tumor (MM48), the 18FDG uptake ratio was found to be unchanged, whereas in radiosensitive tumors (FM3A) the 18FDG uptake ratio was 0.37, the relative tumor volume was 0.31, and the calculated total tumor uptake was 0.11 on the eighth day after irradiation. The total tumor uptake was lower than the relative tumor volume. AH109A began to regrow after ten Gy irradiation, accompanied by elevated uptake of 18FDG on the seventh day. These results suggest that the 18FDG uptake by tumor is a good marker of radiotherapeutic effects as well as relapses of cancers and is more sensitive than morphological methods.

Decreased striatal D2 receptor density associated with severe behavioral abnormality in Alzheimer's disease.

Objectives: Since patients manifesting behavioral and psychological symptoms of dementia (BPSD) are a burden for their families and caregivers, the underlying neurobiological mechanism of this condition should be clarified. Using positron emission tomography (PET), we previously reported that wandering behavior in dementia was associated with a disturbed dopaminergic neuron system. We herein investigated the relationship between the severity of BPSD and the striatal D2 receptor density in Alzheimer’s disease (AD).Methods: Ten patients with probable AD as per the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the AD and Related Disorders Association (ADRDA) criteria and five normal subjects were examined with PET. The tracer used was [11C]raclopride (D2 antagonist). The uptake of [11C]raclopride was calculated as the estimation of binding potential (BP) of the striatum to the cerebellum. The D patients were institutionalized in multiple nursing homes, and their BPSD were evaluated by the Behavioral Pathology in AD Frequency Weighted Severity Scale (BEHAVE-AD-FW) scale (Reisberg).Results: There was a significant inverse Spearman’s correlation between BEHAVE-AD-FW score and the BP, especially between the score of the behavioral domain and the BP values. The BP was found to be lower in severer BPSD patients.Conclusions: Patients with AD who manifest severe BPSD may have some dysfunction of striatal dopamine metabolism compared with those without BPSD.

Neural correlates of context memory with real-world events

There has been little evidence for the difference in the retrieval processes of when and where something happened, one of the important factors in understanding episodic memory. We used positron emission tomography (PET) to identify the neural networks associated with temporal and spatial context memory of events experienced under experimental conditions similar to those of everyday life. Before PET, subjects experienced 36 events. The events were divided into four groups of nine each. The subjects experienced the first two groups of events before a 15-min recess and the other two after the recess; they experienced the first and last groups of events in one room, took a recess in another room, and experienced the second and third groups in a different room. During PET, the subjects were scanned under three different retrieval tasks: a time-retrieval task, a place-retrieval task, and a simple recognition task. The results showed that the retrieval of time and space, compared with the simple recognition, was associated with activity in substantially different regions as well as a common region: time retrieval with the posterior part of the right orbitofrontal cortex and left inferior parietal lobule, place retrieval with two regions in right parietal association cortex, right posterior cingulate gyrus, left precentral gyrus, and right cerebellum, and both with the right inferior frontal gyrus. These findings indicate that there are unique areas, in addition to a common area, for retrieving temporal and spatial context.

Functional brain mapping of actual car driving using [18F]FDG-PET

AimsThis study aims at identifying the brain activation during actual car-driving on the road, and at comparing the results to those of previous studies on simulated car-driving.MethodsThirty normal volunteers, aged 20 to 56 years, were divided into three subgroups, active driving, passive driving and control groups, for examination by positron emission tomography (PET) and [18F]2-deoxy-2-fluoro-D-glucose (FDG). The active driving subjects (n = 10) drove for 30 minutes on quiet normal roads with a few traffic signals. The passive driving subjects (n = 10) participated as passengers on the front seat. The control subjects (n = 10) remained seated in a lit room with their eyes open. Voxel-basedt-statistics were applied using SPM2 to search brain activation among the subgroups mentioned above.ResultsSignificant brain activation was detected during active driving in the primary and secondary visual cortices, primary sensorimotor areas, premotor area, parietal association area, cingulate gyrus, the parahippocampal gyrus as well as in thalamus and cerebellum. The passive driving manifested a similar-looking activation pattern, lacking activations in the premotor area, cingulate and parahippocampal gyri and thalamus. Direct comparison of the active and passive driving conditions revealed activation in the cerebellum.ConclusionThe result of actual driving looked similar to that of simulated driving, suggesting that visual perception and visuomotor coordination were the main brain functions while driving. In terms of attention and autonomic arousal, however, it seems there was a significant difference between simulated and actual driving possibly due to risk of accidents. Autonomic and emotional aspects of driving should be studied using an actual driving study-design.

The Neural Correlates of Driving Performance Identified Using Positron Emission Tomography

Driving is a complex behavior involving multiple cognitive domains. To identify neural correlates of driving performance, [15O]H2O positron emission tomography was performed using a simulated driving task. Compared with the resting condition, simulated driving increased regional cerebral blood flow (rCBF) in the cerebellum, occipital, and parietal cortices. Correlations between rCBF and measurements of driving performance were evaluated during simulated driving. Interestingly, rCBF in the thalamus, midbrain, and cerebellum were positively correlated with time required to complete the course and rCBF in the posterior cingulate gyrus was positively correlated with number of crashes during the task. These brain regions may thus play roles in the maintenance of driving performance.

Risperidone is effective for wandering and disturbed sleep/wake patterns in Alzheimer's disease

Behavioral and psychological symptoms of dementia (BPSD), especially aggressiveness, wandering, and sleep disturbance, are a major burden for caregivers. Daily sleep/wake patterns and wandering of institutionalized patients with Alzheimer’s disease (AD) were visually monitored, and 34 patients who manifested wandering were selected and randomly classified into 2 groups: the risperidone group and the nonrisperidone group. After an administration of low-dose risperidone for the risperidone group, the BPSD were reassessed. The binding potentials of dopamine D2 receptor for preadministration and postadministration of risperidone were assessed using positron emission tomography (PET) for 1 case. After the use of risperidone, aggressiveness and wandering were reduced and the nighttime sleeping hours were increased. The PET revealed that the binding potential of dopamine receptor was increased after administration of the drug, associated with improved sleep/wake patterns and behavioral abnormality. Possible serotonergic modulation of dopaminergic function might explain the neurobiological basis of the effect of risperidone.

2-Deoxy-2-[18F]fluoro-d-galactose as an In Vivo tracer for imaging galactose metabolism in tumors with positron emission tomography

The feasibility of 2-deoxy-2-[18F]fluoro-D-galactose ([ 18F]FdGal) for imaging galactose metabolism in tumors with positron emission tomography (PET), was investigated using two hepatomas, Yoshida sarcoma, or glioma in rats, and mouse mammary carcinoma. In hepatoma-bearing rats the highest uptake of [18F]FdGal was observed in the liver followed by the kidney and tumor. The tumor uptake increased with time, and the high uptake ratios of tumor to organ were observed except for the liver and kidney. Tumor uptake was also measured in all tumors. As main metabolites in all tumors, [18F]FdGal 1-phosphate and UDP-[18F]FdGal were found by HPLC. Two hepatomas showed a slightly higher uptake and a larger percentage of UDP derivative than the other three tumors. By autoradiography the brain tumor was visualized clearly. These results indicate that [18F]FdGal has potential as a tracer for imaging galactose metabolism in tumors with PET.

Overall Activity of All Masticatory Muscles during Lateral Excursion

Quantification of the overall activity of every masticatory muscle is requisite for the analysis of stomatognathic function, which has not been accomplished by conventional electromyography. We used positron emission tomography and 18F-fluoro-deoxy-glucose to quantify the overall activity of every masticatory muscle during lateral excursion, and to evaluate the relative contribution of each masticatory muscle to lateral excursion. The present study suggested that lateral and medial pterygoid muscles are more responsible for lateral excursion than are masseter and temporal muscles. In particular, the contralateral lateral pterygoid muscle plays a major role, followed by the contralateral medial pterygoid muscle.

Impaired verbal description ability assessed by the Picture Description Task in Alzheimer's disease.

The language of patients with Alzheimers disease (AD) is globally non-informative and characterized by selective impairment of lexical-semantic processing as compared with a relative sparing of syntactic and phonological aspects. Verbal picture description is one of the most sensitive tests for detecting language disorders in AD. We assessed verbal description ability in AD and investigated its relation to regional cerebral blood flow (CBF). In part I of the study, 23 AD patients and 17 age-matched normal subjects performed the Picture Description Task, which yields six variables: (1) the amount of information, (2) the number of constituent parts of the picture, (3) the number of relevant and irrelevant descriptions, (4) efficiency of description, (5) appropriateness, and (6) sentence structure. In the study, variables 1, 3 and 4 were analyzed. In part II of the study, regional CBF of 14 of the above AD patients was measured using N-isopropyl-p-[(123)I]iodoamphetamine and single photon emission CT. In part I, there were significant difference between the groups for variables 1 and 4. In part II, there were significant correlations between variable 1 and rCBF in the bilateral occipital lobes and left thalamus. Variables 1 and 4 were useful in discriminating between AD patients and controls. Variable 1 was suggested to be related to the function of the left thalamus and the bilateral visual cortex.

Classical conditioned response of rectosigmoid motility and regional cerebral activity in humans

Abstract  The relationship between the central processes of classical conditioning and conditioned responses of the gastrointestinal function is incompletely understood in humans. We tested the hypothesis that the rectosigmoid motility becomes conditioned with anticipatory painful somatosensory stimulus and that characteristic brain areas become activated during anticipation. In nine right‐handed healthy male subjects, a loud buzzer (CS, conditional stimulus) was paired with painful transcutaneus electrical nerve stimulation to the right hand (unconditional stimulus). Rectosigmoid muscle tone measured by the barostat as the intrabag volume, phasic contractions of the bowel measured as the number of phasic volume events (PVEs), and regional cerebral blood flow assessed by positron emission tomography (PET), were measured before and after conditioning. Following conditional trials, the bag volume after CS alone did not show significant changes between before and after the stimulus, but the number of PVEs after 2‐minute interval of the CS alone was significantly greater than that before the stimulus (P < 0.05). The PET data showed the conditioning elicited significant cerebral activation of the prefrontal, anterior cingulate, parietal and insula cortices (P ≤ 0.001, uncorrected). Rectosigmoid motility can be conditioned with increase in phasic contractions in humans.