Hiroshi Fukuda

Tohoku University, Sendai-shi, Miyagi, Japan

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Publications (273)868.11 Total impact

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    ABSTRACT: Background The neuropsychological features and neuropathological progression patterns associated with rapidly evolving cognitive decline or dementia in Parkinson's disease (PD) remain to be elucidated. Methods Fifty-three PD patients without dementia were recruited to participate in a 3-year longitudinal cohort study. The patients were grouped according to the Clinical Dementia Rating (CDR). Group-wise comparisons were made with regard to demographic characteristics, motor symptoms, neuropsychological performances and 18F-fluorodeoxyglucose positron emission tomography. Results Patients who had memory-plus cognitive impairment (patients whose CDR was 0 at baseline and 0.5 in memory and other domains at follow-up, and those whose baseline CDR was 0.5 in memory and other domains) exhibited higher age at onset, visuoperceptual impairment, non-tremor-dominant motor disturbance, rapid symptomatic progression and posterior neocortical hypometabolism. In patients who were cognitively unimpaired and those who had memory-dominant cognitive impairment (patients whose CDR was 0 at baseline and 0.5 only in memory domain at follow-up, and those whose baseline CDR was 0.5 only in memory domain), the posterior neocortex was relatively unaffected until a later stage of the disease. Conclusions These results suggest that visuoperceptual impairment and the early involvement of the posterior neocortex may be risk factors for rapid symptomatic progression and dementia in PD.
    No preview · Article · Oct 2014 · PLoS ONE
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    ABSTRACT: Two methods are commonly used in brain image voxel-based analyses widely used for dementia work-ups: 3-dimensional stereotactic surface projections (3D-SSP) and statistical parametric mapping (SPM). The methods calculate the Z-scores of the cortical voxels that represent the significance of differences compared to a database of brain images with normal findings, and visualize them as surface brain maps. The methods are considered useful in amyloid positron emission tomography (PET) analyses to detect small amounts of amyloid-β deposits in early-stage Alzheimer's disease (AD), but are not fully validated. We analyzed the (11)C-labeled 2-(2-[2-dimethylaminothiazol-5-yl]ethenyl)-6-(2-[fluoro]ethoxy)benzoxazole (BF-227) amyloid PET imaging of 56 subjects (20 individuals with mild cognitive impairment [MCI], 19 AD patients, and 17 non-demented [ND] volunteers) with 3D-SSP and the easy Z-score imaging system (eZIS) that is an SPM-based method. To clarify these methods' limitations, we visually compared Z-score maps output from the two methods and investigated the causes of discrepancies between them. Discrepancies were found in 27 subjects (9 MCI, 13 AD, and 5 ND). Relatively high white matter uptake was considered to cause higher Z-scores on 3D-SSP in 4 subjects (1 MCI and 3 ND). Meanwhile, in 17 subjects (6 MCI, 9 AD, and 2 ND), Z-score overestimation on eZIS corresponded with high skull uptake and disappeared after removing the skull uptake ("scalping"). Our results suggest that non-specific uptakes in the white matter and skull account for errors in voxel-based amyloid PET analyses. Thus, diagnoses based on 3D-SSP data require checking white matter uptake, and "scalping" is recommended before eZIS analysis.
    No preview · Article · Oct 2014 · The Tohoku Journal of Experimental Medicine
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    ABSTRACT: To investigate whether personality traits affect the rate of decline of gray matter volume, we analyzed the relationships between personality traits and the annual rate of changes of gray matter volume in 274 healthy community dwelling subjects with a large age range by applying a longitudinal design over 6 years, using brain magnetic resonance images (MRI) and the Revised NEO Personality Inventory (NEO-PI-R) at baseline. Brain MRI data were processed using voxel-based morphometry with a custom template by applying the DARTEL diffeomorphic registration tool. For each subject, we used NEO-PI-R to evaluate the five major personality traits, including neuroticism, extraversion, openness, agreeableness, and conscientiousness. The results show that the annual rate of change in regional gray matter volume in the right inferior parietal lobule was correlated significantly and negatively with a personality of openness, which is known to be related to intellect, intellectual curiosity, and creativity adjusting for age, gender, and intracranial volume. This result indicates that subjects with a personality trait of less openness have an accelerated loss of gray matter volume in the right inferior parietal lobule, compared with subjects with a personality trait of more openness. Because the right inferior parietal lobule is involved in higher cognitive function such as working memory and creativity, a personality trait of openness is thought to be important for preserving gray matter volume and cognitive function of the right inferior parietal lobule in healthy adults. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
    Full-text · Article · Dec 2013 · Human Brain Mapping
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    Kentaro Inoue · Ryoi Goto · Hideo Shimomura · Hiroshi Fukuda
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    ABSTRACT: Sarcoidosis or sarcoid reactions, which appear as FDG-avid lesions in oncologic patients, need to be differentiated from disseminated malignancies. We aimed to promote awareness of development of sarcoidosis or sarcoid reactions after antineoplastic therapy to avoid diagnostic errors with FDG-PET/CT findings and assess the utility of FDG-PET/CT for follow-up. We retrospectively reviewed radiological reports of FDG-PET/CT scans performed between January 2009 and December 2011. Among oncologic patients with more than 2 FDG-PET/CT scans, those with nearly symmetrical increases in FDG uptake in the hilar or mediastinal lymph nodes were identified, and those with known sarcoidosis, concurrent diagnoses of sarcoidosis with malignancy, or histopathologically proven malignancies were excluded. Then, only those cases were selected for which sarcoidosis or sarcoid reactions were diagnosed. Four of 376 oncologic cases met the criteria. At 9 months to 6 years after antineoplastic therapy, abnormal FDG uptakes were observed in the hilar, mediastinal, abdominal, pelvic, and inguinal nodes, and/or spleen and lung parenchyma with SUVmax up to 17.7. On the basis of these findings, 1 patient received anticancer chemotherapy because of tumor recurrence suspicion. A gradual decrease in FDG uptake was observed on subsequent PET/CT scans. Sarcoidosis or sarcoid reactions should be considered in differential diagnosis of oncologic patients who have developed FDG-avid lesions any time after antineoplastic therapy. FDG-PET/CT can be used for follow-up in nondiagnostic situations to detect decreases in FDG uptake due to presence of sarcoidal granulomas.
    Preview · Article · Dec 2013 · SpringerPlus
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    ABSTRACT: Although elevated serum high-sensitivity C-reactive protein (hsCRP) is related to atherosclerosis, brain infarction, and cognitive decline, it has not been clarified whether increased hsCRP is associated with the decline in brain gray matter volume. Therefore, the purpose of this study was to determine the relationship between hsCRP levels and brain regional gray matter volume using brain magnetic resonance imaging (MRI) data from 109 community-dwelling healthy elderly subjects. Brain MRIs were processed with voxel-based morphometry using a custom template by applying diffeomorphic anatomical registration using the exponentiated lie algebra (DARTEL) procedure. We found a significant negative correlation between regional gray matter volume of the posterior and lateral aspects of the left temporal cortex and hsCRP level after adjusting for age, gender, and intracranial volume. Our results suggest that subjects who have mild inflammation related to arteriosclerosis have decreased regional gray matter volume in the posterior and lateral aspects of the left temporal cortex. Thus, preventing the progression of arteriosclerosis may be important for preventing a decrease in gray matter volume in healthy elderly subjects. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
    No preview · Article · Oct 2013 · Human Brain Mapping
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    ABSTRACT: The aim of this study was to analyze correlations among the annual rate of gray matter volume change, age, gender, and cerebrovascular risk factors in 381 healthy community-dwelling subjects with a large age range by applying a longitudinal design over 6 years using brain magnetic resonance images (MRIs). Brain MRI data were processed with voxel-based morphometry using a custom template by applying diffeomorphic anatomical registration using the exponentiated lie algebra procedure. The annual rate of regional gray matter volume change showed significant positive correlations with age in several regions, including the bilateral temporal pole, caudate nucleus, ventral and dorsolateral prefrontal cortices, insula, hippocampus, and temporoparietal cortex, whereas significant negative correlations with age were observed in several regions including the bilateral cingulate gyri and anterior lobe of the cerebellum. Additionally, a significant age-by-gender interaction was found for the annual rate of regional gray matter volume change in the bilateral hippocampus. No significant correlations were observed between the annual rate of regional gray matter volume change and body mass index or systolic blood pressure. A significant positive correlation between the annual rate of gray matter volume change and age indicates that the region shows not linear but accelerated gray matter loss with age. Therefore, evaluating the annual rate of the gray matter volume change with age in healthy subjects is important in understanding how gray matter volume changes with aging in each brain region and in anticipating what cognitive functions are likely to show accelerated decline with aging. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
    No preview · Article · Sep 2013 · Human Brain Mapping
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    ABSTRACT: We examined linear and curvilinear correlations of gray matter volume and density in cortical and subcortical gray matter with age using magnetic resonance images (MRI) in a large number of healthy children. We applied voxel-based morphometry (VBM) and region-of-interest (ROI) analyses with the Akaike information criterion (AIC), which was used to determine the best-fit model by selecting which predictor terms should be included. We collected data on brain structural MRI in 291 healthy children aged 5-18 years. Structural MRI data were segmented and normalized using a custom template by applying the diffeomorphic anatomical registration using exponentiated lie algebra (DARTEL) procedure. Next, we analyzed the correlations of gray matter volume and density with age in VBM with AIC by estimating linear, quadratic, and cubic polynomial functions. Several regions such as the prefrontal cortex, the precentral gyrus, and cerebellum showed significant linear or curvilinear correlations between gray matter volume and age on an increasing trajectory, and between gray matter density and age on a decreasing trajectory in VBM and ROI analyses with AIC. Because the trajectory of gray matter volume and density with age suggests the progress of brain maturation, our results may contribute to clarifying brain maturation in healthy children from the viewpoint of brain structure. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
    No preview · Article · Aug 2013 · Human Brain Mapping
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    ABSTRACT: In this study, we examined linear and curvilinear correlations of fractional anisotropy (FA), mean diffusivity (MD), and white matter volume with age by using brain structural and diffusion-tensor magnetic resonance imaging (MRI) in a large number of healthy children and voxel-based morphometry (VBM) and region-of-interest (ROI) analyses. We collected data by brain structural MRI in 246 healthy children, aged 5-18 years. FA and MD images were normalized using the normalization parameter of the corresponding structural MRI. Next, we analyzed the correlations between FA and age and between MD and age by estimating linear and logarithmic functions. We also analyzed the correlation between white matter volume and age by linear, quadratic, and cubic functions. Correlations between FA and age and between MD and age showed exponential trajectories in most ROIs in boys and girls, except for several fibers, such as the corpus callosum connecting the bilateral rectal gyri in boys. The correlation between white matter volume and age showed significant positive linear trajectories in most ROIs in boys and girls, except for a few fibers, such as the bilateral uncinate fasciculus. Additionally, maturational rates differed among major fibers, and in girls, the left superior longitudinal fasciculus, which connects the frontal and temporal lobes, showed a slower rate of maturation than other fibers. Our results may help to clarify the mechanisms of normal brain maturation from the viewpoint of brain white matter. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
    Full-text · Article · Aug 2013 · Human Brain Mapping
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    ABSTRACT: 2-Deoxy-2-(18)F-fluoro-d-mannose ((18)F-FDM) is an (18)F-labeled mannose derivative and a stereoisomer of (18)F-FDG. Our preliminary study demonstrated that (18)F-FDM accumulated in tumors to the same extent as (18)F-FDG, with less uptake in the brain and faster clearance from the blood. However, detailed studies on the uptake of (18)F-FDM in tumors have not been conducted. We undertook this study to establish a practical method of (18)F-FDM synthesis based on an (18)F-nucleophilic substitution (SN2) reaction and to advance the biologic characterization of (18)F-FDM for potential application as a tumor-imaging agent. We synthesized 4,6-O-benzylidene-3-O-ethoxymethyl-1-O-methyl-2-O-trifluoromethanesulfonyl-β-d-glucopyranoside as a precursor for the nucleophilic synthesis of (18)F-FDM. The precursor was radiofluorinated with (18)F-KF/Kryptofix222, followed by removal of the protecting groups with an acid. (18)F-FDM was purified by preparative high-performance liquid chromatography and then subjected to in vitro evaluation regarding phosphorylation by hexokinase as well as uptake and metabolism in AH109A tumor cells. The in vivo properties of (18)F-FDM were examined in Donryu rats bearing AH109A tumor cells by biodistribution studies and imaging with a small-animal PET system. We radiosynthesized (18)F-FDM in sufficient radiochemical yields (50%-68%) with excellent purities (97.6%-98.7%). (18)F-FDM was phosphorylated rapidly by hexokinase, resulting in 98% conversion into (18)F-FDG-6-phosphate within 30 min. Tumor cells showed significant uptake of (18)F-FDM with time in vitro, and uptake was dose-dependently inhibited by d-glucose. (18)F-FDM injected into tumor-bearing rats showed greater uptake in tumors (2.17 ± 0.32 percentage injected dose per gram [%ID/g]) than in the brain (1.42 ± 0.10 %ID/g) at 60 min after injection. PET studies also revealed the tumor uptake of (18)F-FDM (quasi-standardized uptake value, 2.83 ± 0.22) to be the same as that of (18)F-FDG (2.40 ± 0.30), but the brain uptake of (18)F-FDM (1.89 ± 0.13) was ≈30% lower than that of (18)F-FDG (2.63 ± 0.26). We prepared (18)F-FDM with good radiochemical yield and purity by an SN2 reaction. We demonstrated that (18)F-FDM had adequate tumor cell uptake by a metabolic trapping mechanism and can afford high-contrast tumor images with less uptake in the brain, indicating that (18)F-FDM has almost the same potential as (18)F-FDG for PET tumor imaging, with better advantages with regard to the imaging of brain tumors.
    No preview · Article · Jul 2013 · Journal of Nuclear Medicine
  • Hiroshi Fukuda · Kazuo Kubota · Taiju Matsuzawa
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    ABSTRACT: Positron emission tomography (PET) with (18)F-fluorodeoxyglucose ((18)F-FDG), a glucose analog, is widely used throughout the world as an indispensable imaging modality for the management of cancer treatment. This article reviews the pioneering achievements of PET in oncology with a focus on the development of PET that occurred from 1980 through the early-1990s. (18)F-FDG was first applied for imaging of animal tumors in 1980 and for brain tumor imaging clinically in 1982. (18)F-FDG enabled to visualize liver metastasis as clear positive image that could not be obtained by conventional nuclear imaging. Subsequently, (18)F-FDG was used for imaging various cancers, such as lung, pancreas, colorectal and hepatoma. (11)C-L-methionine ((11)C-MET) that reflects amino acid transport of cancers has an advantage that its uptake is lower in the brain and inflammatory tissue compared to (18)F-FDG, and was first applied for imaging lung cancer and brain tumor. (18)F-FDG and (11)C-MET were proved to be sensitive tracers that can be used to objectively evaluate the effectiveness of cancer treatment. The diagnostic accuracy of PET, which is critical in clinical practice, was evaluated for the differential diagnosis of malignant and benign lung nodules using (18)F-FDG or (11)C-MET. In addition to (18)F-FDG and (11)C-MET, many radiopharmaceuticals were developed, such as (18)F-labled thymidine analogs for evaluating proliferative activity, (18)F-fluoromisonidazole for imaging of hypoxia, and (18)F-fluorodeoxygalactose for evaluating liver-specific galactose metabolism and for imaging of hepatoma that retains galactose metabolic activity. These early efforts and achievements have greatly contributed to the development and clinical application of (18)F-FDG PET in oncology.
    No preview · Article · Jul 2013 · The Tohoku Journal of Experimental Medicine
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    Full-text · Dataset · May 2013
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    ABSTRACT: The aim of this study was to investigate age-related changes in the topological organization of structural brain networks by applying a longitudinal design over 6 years. Structural brain networks were derived from measurements of regional gray matter volume and were constructed in age-specific groups from baseline and follow-up scans. The structural brain networks showed economical small-world properties, providing high global and local efficiency for parallel information processing at low connection costs. In the analysis of the global network properties, the local and global efficiency of the baseline scan were significantly lower compared to the follow-up scan. Moreover, the annual rate of change in local and global efficiency showed a positive and negative quadratic correlation with the baseline age, respectively; both curvilinear correlations peaked at approximately the age of 50. In the analysis of the regional nodal properties, significant negative correlations between the annual rate of change in nodal strength and the baseline age were found in the brain regions primarily involved in the visual and motor/control systems, whereas significant positive quadratic correlations were found in the brain regions predominately associated with the default-mode, attention, and memory systems. The results of the longitudinal study are consistent with the findings of our previous cross-sectional study: the structural brain networks develop into a fast distribution from young to middle age (approximately 50 years old) and eventually became a fast localization in the old age. Our findings elucidate the network topology of structural brain networks and its longitudinal changes, thus enhancing the understanding of the underlying physiology of normal aging in the human brain.
    Full-text · Article · Apr 2013 · Frontiers in Human Neuroscience
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    ABSTRACT: Dysphagia is one of the cardinal symptoms of Parkinson's disease (PD). It is closely related to the quality of life and longevity of PD patients. The aim of the study is to clarify the pathophysiological mechanisms responsible for dysphagia in PD. A cross-sectional and longitudinal comparative study. Tohoku University Hospital. Eight patients with dysphagia, 15 patients without dysphagia and 10 normal control subjects. The time needed for swallowing initiation and changes in brain glucose metabolism at baseline and after a 3-year follow-up period. The time needed for swallowing initiation was significantly longer in the patients with dysphagia compared with the patients without dysphagia at baseline and after the 3-year follow-up period (p<0.05). The patients with dysphagia exhibited hypometabolism in the supplementary motor area (SMA) and the anterior cingulate cortex (ACC) compared with the 10 normal control subjects at baseline (uncorrected p<0.001). After the 3-year follow-up period, the number of brain areas showing hypometabolism increased, involving not only the SMA and the ACC but also the bilateral medial frontal lobes, middle cingulate cortex, thalamus and right superior, middle, inferior and orbital frontal gyri (uncorrected p<0.001). In contrast, the patients without dysphagia showed virtually no regional hypometabolism at baseline (uncorrected p<0.001) and only a small degree of hypometabolism in the SMA and ACC after the 3-year follow-up period (uncorrected p<0.001). These results suggest that dysphagia in PD patients is mainly related to a difficulty in swallowing initiation that is based on a combination of poor movement planning due to SMA dysfunction and impaired cognitive processing due to ACC dysfunction.
    Full-text · Article · Mar 2013 · BMJ Open
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    ABSTRACT: Introduction: Cigarette smoking decreases brain regional gray matter volume and is related to chronic obstructive lung disease (COPD). COPD leads to decreased pulmonary function, which is represented by forced expiratory volume in one second percentage (FEV1.0 %); however, it is unclear if decreased pulmonary function is directly related to brain gray matter volume decline. Because there is a link between COPD and cognitive decline, revealing a direct relationship between pulmonary function and brain structure is important to better understand how pulmonary function affects brain structure and cognitive function. Therefore, the purpose of this study was to analyze whether there were significant correlations between FEV1.0 % and brain regional gray and white matter volumes using brain magnetic resonance (MR) image data from 109 community-dwelling healthy elderly individuals. Methods: Brain MR images were processed with voxel-based morphometry using a custom template by applying diffeomorphic anatomical registration using the exponentiated lie algebra procedure. Results: We found a significant positive correlation between the regional white matter volume of the cerebellum and FEV1.0 % after adjusting for age, sex, and intracranial volume. Conclusion: Our results suggest that elderly individuals who have a lower FEV1.0 % have decreased regional white matter volume in the cerebellum. Therefore, preventing decreased pulmonary function is important for cerebellar white matter volume in the healthy elderly population.
    No preview · Article · Feb 2013 · Neuroradiology
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    Dataset: Table S2
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    ABSTRACT: Global hubs in functional brain networks using binary network analysis. (DOC)
    Preview · Dataset · Feb 2013
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    Dataset: Table S4
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    ABSTRACT: The effects of age, sex, and IQ on global network properties using weighted network analysis. (DOC)
    Preview · Dataset · Feb 2013
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    Dataset: Table S7
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    ABSTRACT: Age-by-sex interaction on regional nodal properties using weighted network analysis. (DOC)
    Preview · Dataset · Feb 2013
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    Dataset: Table S5
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    ABSTRACT: Effect of age on regional nodal properties using weighted network analysis. (DOC)
    Preview · Dataset · Feb 2013
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    Dataset: Table S6
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    ABSTRACT: Effect of sex on regional nodal properties using weighted network analysis. (DOC)
    Preview · Dataset · Feb 2013
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    ABSTRACT: Recent studies have demonstrated developmental changes of functional brain networks derived from functional connectivity using graph theoretical analysis, which has been rapidly translated to studies of brain network organization. However, little is known about sex- and IQ-related differences in the topological organization of functional brain networks during development. In this study, resting-state fMRI (rs-fMRI) was used to map the functional brain networks in 51 healthy children. We then investigated the effects of age, sex, and IQ on economic small-world properties and regional nodal properties of the functional brain networks. At a global level of whole networks, we found significant age-related increases in the small-worldness and local efficiency, significant higher values of the global efficiency in boys compared with girls, and no significant IQ-related difference. Age-related increases in the regional nodal properties were found predominately in the frontal brain regions, whereas the parietal, temporal, and occipital brain regions showed age-related decreases. Significant sex-related differences in the regional nodal properties were found in various brain regions, primarily related to the default mode, language, and vision systems. Positive correlations between IQ and the regional nodal properties were found in several brain regions related to the attention system, whereas negative correlations were found in various brain regions primarily involved in the default mode, emotion, and language systems. Together, our findings of the network topology of the functional brain networks in healthy children and its relationship with age, sex, and IQ bring new insights into the understanding of brain maturation and cognitive development during childhood and adolescence.
    Full-text · Article · Feb 2013 · PLoS ONE

Publication Stats

7k Citations
868.11 Total Impact Points

Institutions

  • 1982-2014
    • Tohoku University
      • • Institute of Development, Aging and Cancer
      • • Division of Brain Science
      • • Cyclotron and Radioisotope Center (CYRIC)
      • • Department of Pharmaceutical Chemistry
      Sendai-shi, Miyagi, Japan
  • 2009
    • Kyoto University
      Kioto, Kyoto, Japan
  • 2001
    • Tohoku Fukushi University
      Miyagi, Japan
  • 1999
    • Iwate Medical University
      Morioka, Iwate, Japan
  • 1986-1993
    • Research Institute of Tuberculosis
      Edo, Tōkyō, Japan
  • 1989
    • National Institute of Radiological Sciences
      Tiba, Chiba, Japan