H Fukuda

Tohoku University, Sendai, Kagoshima-ken, Japan

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Publications (457)1123.93 Total impact

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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.
    SpringerPlus 12/2013; 2(1):113.
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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.
    Journal of Nuclear Medicine 07/2013; · 5.77 Impact Factor
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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.
    Neuroradiology 02/2013; · 2.70 Impact Factor
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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.
    BMJ Open 01/2013; 3(3). · 1.58 Impact Factor
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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.
    Frontiers in Human Neuroscience 01/2013; 7:113. · 2.91 Impact Factor
  • 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.
    The Tohoku Journal of Experimental Medicine 01/2013; 230(3):155-69. · 1.37 Impact Factor
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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.
    PLoS ONE 01/2013; 8(2):e55347. · 3.53 Impact Factor
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    ABSTRACT: OBJECTIVE: The aim of this study was to survey the 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) cancer screening program conducted in Japan. METHODS: The "FDG-PET cancer screening program" included both FDG-PET and positron emission tomography with computed tomography (PET/CT) with or without other combined screening tests that were performed for cancer screening in asymptomatic subjects. A total of 155,456 subjects who underwent the FDG-PET cancer screening program during 2006-2009 were analyzed. RESULTS: Of the 155,456 subjects, positive findings suggesting possible cancer were noted in 16,955 (10.9 %). The number of cases with detected cancer was 1,912 (1.23 % of the total screened cases, annual range 1.14-1.30 %). Of the 1,912 cases of detected cancer, positive findings on FDG-PET were present in 1,491 cases (0.96 % of the total number of screened cases). According to the results of further examinations, the true positive rate for subjects with suggested possible cancer (positive predictive value) was 32.3 % with FDG-PET. Cancers of the colon/rectum, thyroid, lung, and breast were most frequently found (396, 353, 319, and 163 cases, respectively) with high PET sensitivity (85.9, 90.7, 86.8, 84.0 %, respectively). Prostate cancer and gastric cancer (165 and 124 cases, respectively) had low PET sensitivity (37.0 and 37.9 %, respectively). The Union for International Cancer Control (UICC) clinical stage of cancer found with the FDG-PET cancer screening program was mainly Stage I. CONCLUSIONS: The FDG-PET screening program in Japan has detected a variety of cancers at an early stage. However, several cancers were found in repeated FDG-PET cancer screening program, indicating the limitation of a one-time FDG-PET cancer screening program. The value of the FDG-PET cancer screening program is left to the judgment of individuals with regard to its potentials and limitations.
    Annals of Nuclear Medicine 10/2012; · 1.41 Impact Factor
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    ABSTRACT: Orally administered I-labeled 15-(4-iodophenyl)-3(R,S)-methylpentadecanoic acid (BMIPP), a fatty acid analog, is absorbed from the intestine and ascends to the venous angle through the thoracic duct (TD). The objective of this study was to evaluate the clinical feasibility of 3-dimensional (3D) TD scintigraphy using SPECT/CT and BMIPP for the detection of anatomical anomalies of TD. This study included 35 consecutive patients with esophageal cancer who underwent tumor resection after TD scintigraphy. For scintigraphy, 111 MBq of BMIPP was orally administered, and static images and SPECT/CT images were obtained. On the basis of the SPECT/CT fusion images, TD was divided into the following 4 segments: cervical, upper thoracic, middle thoracic, and lower thoracic. The TD visualization was categorized into 5 grades, from grade 1 (poor) to 5 (excellent). In addition, the diagnostic accuracy of 3D TD scintigraphy for the detection of anatomical anomalies of TD was calculated using the intraoperative finding as a criterion standard. The TD visualization grades for the cervical, upper, middle, and lower thoracic segments were 4.4 ± 0.6, 3.7 ± 1.0, 3.1 ± 0.8, and 2.1 ± 0.9, respectively. The TD scintigraphy demonstrated an uncommon accumulation including that in the right- or bilateral-sided mediastinum or venous angle in 6 (17%) of the 35 patients. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of 3D TD scintigraphy for the detection of anatomical anomalies of TD were 0.75, 0.90, 0.5, 0.97, and 0.89, respectively. Three-dimensional TD scintigraphy by BMIPP is a simple and minimally invasive method for imaging the anatomical configuration of the TD and for detecting any anatomical anomalies, except in the lower thoracic segment.
    Clinical nuclear medicine 09/2012; 37(11):1047-51. · 3.92 Impact Factor
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    ABSTRACT: Background: Prader-Willi syndrome (PWS) is a genetically determined neurodevelopmental disorder and is generally regarded as a genetic model of obesity. Individuals with PWS exhibit behavioral symptoms including temper tantrums, rigid thinking, and compulsive behavior. The most striking feature of PWS is abnormal eating behavior, including hyperphagia, intense preoccupation with food, and incessant food seeking. To explore brain regions associated with the behavioral symptoms of PWS, we investigated differences in resting-state regional cerebral blood flow (rCBF) between individuals with PWS and healthy controls. Correlation analyses were also performed to examine the relationship between rCBF and altered eating behavior in PWS individuals. Methods: Twelve adults with PWS and 13 age- and gender-matched controls underwent resting-state single photon emission computerized tomography (SPECT) with N-isopropyl-p-[(123)I] iodoamphetamine (IMP). The rCBF data were analyzed on a voxel-by-voxel basis using SPM5 software. Results: The results demonstrated that compared with controls, individuals with PWS had significantly lower rCBF in the right thalamus, left insular cortex, bilateral lingual gyrus, and bilateral cerebellum. They had significantly higher rCBF in the right inferior frontal gyrus, left middle/inferior frontal gyrus (anterior and posterior clusters), and bilateral angular gyrus. Additionally, rCBF in the left insula, which was significantly lower in PWS individuals, was negatively correlated with the eating behavior severity score. Conclusions: These results suggest that specific brain regions, particularly the left insula, may be partly responsible for the behavioral symptoms in PWS.
    Brain & development 08/2012; · 1.74 Impact Factor
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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.
    Human Brain Mapping 07/2012; · 6.88 Impact Factor
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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.
    Human Brain Mapping 04/2012; · 6.88 Impact Factor
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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.
    Human Brain Mapping 03/2012; · 6.88 Impact Factor
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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.
    Human Brain Mapping 03/2012; · 6.88 Impact Factor
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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.
    Human Brain Mapping 03/2012; · 6.88 Impact Factor
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    ABSTRACT: The Clinical Dementia Rating (CDR) is an assessment of dementia severity based on observations of activities of daily living, and a CDR of 0.5 (CDR 0.5) represents questionable dementia. A combination of the Cognitive Abilities Screening Instrument (CASI) and the Trail Making Test (TMT) scores discriminated CDR 0.5 subjects from healthy participants with a high degree of accuracy. We investigated the neurological background of CDR 0.5 subjects by correlating CASI and TMT scores with regional cerebral blood flow (rCBF) as measured by single photon emission computed tomography (SPECT). From a community-based cohort, 22 CDR 0.5 participants were recruited. CASI and TMT scores, rCBF measure using [(123) I]-N-isopropyl-p-iodoamphetamine and SPECT were obtained. We evaluated the relationships between the CASI domain scores, between TMT scores and rCBF in a regions-of-interest-based analysis, and voxel-based analysis using Statistical Parametric Mapping 5 software. We found that lower rCBF in the left medial temporal cortex correlated with a decreased CASI domain recent memory score both in the regions-of-interest and statistical parametric mapping analysis. In both the regions-of-interest and statistical parametric mapping analysis, the rCBF in the left prefrontal cortex correlated with CASI domain remote memory and mental manipulation and concentration. Our results indicate that some CDR 0.5 subjects have functional impairments in the medial temporal lobe as well as in the prefrontal cortex, as reflected in the cognitive decline measured by CASI and TMT.
    Psychogeriatrics 03/2012; 12(1):27-33. · 1.26 Impact Factor
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    ABSTRACT: The attentional set-shifting deficit that has been observed in Parkinson's disease (PD) has long been considered neuropsychological evidence of the involvement of meso-prefrontal and prefrontal-striatal circuits in cognitive flexibility. However, recent studies have suggested that non-dopaminergic, posterior cortical pathologies may also contribute to this deficit. Although several neuroimaging studies have addressed this issue, the results of these studies were confounded by the use of tasks that required other cognitive processes in addition to set-shifting, such as rule learning and working memory. In this study, we attempted to identify the neural correlates of the attentional set-shifting deficit in PD using a compound letter task and 18F-fluoro-deoxy-glucose (FDG) positron emission tomography during rest. Shift cost, which is a measure of attentional set-shifting ability, was significantly correlated with hypometabolism in the right dorsolateral prefrontal cortex, including the putative human frontal eye field. Our results provide direct evidence that dysfunction in the dorsolateral prefrontal cortex makes a primary contribution to the attentional set-shifting deficit that has been observed in PD patients.
    PLoS ONE 01/2012; 7(6):e38498. · 3.53 Impact Factor
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    ABSTRACT: Dementia is one of the most debilitating symptoms of Parkinson's disease. A recent longitudinal study suggests that up to 80% of patients with Parkinson's disease will eventually develop dementia. Despite its clinical importance, the development of dementia is still difficult to predict at early stages. We previously identified olfactory dysfunction as one of the most important indicators of cortical hypometabolism in Parkinson's disease. In this study, we investigated the possible associations between olfactory dysfunction and the risk of developing dementia within a 3-year observation period. Forty-four patients with Parkinson's disease without dementia underwent the odour stick identification test for Japanese, memory and visuoperceptual assessments, (18)F-fluorodeoxyglucose positron emission tomography scans and magnetic resonance imaging scans at baseline and 3 years later. A subgroup of patients with Parkinson's disease who exhibited severe hyposmia at baseline showed more pronounced cognitive decline at the follow-up survey. By the end of the study, 10 of 44 patients with Parkinson's disease had developed dementia, all of whom had severe hyposmia at baseline. The multivariate logistic analysis identified severe hyposmia and visuoperceptual impairment as independent risk factors for subsequent dementia within 3 years. The patients with severe hyposmia had an 18.7-fold increase in their risk of dementia for each 1 SD (2.8) decrease in the score of odour stick identification test for Japanese. We also found an association between severe hyposmia and a characteristic distribution of cerebral metabolic decline, which was identical to that of dementia associated with Parkinson's disease. Furthermore, volumetric magnetic resonance imaging analyses demonstrated close relationships between olfactory dysfunction and the atrophy of focal brain structures, including the amygdala and other limbic structures. Together, our findings suggest that brain regions related to olfactory function are closely associated with cognitive decline and that severe hyposmia is a prominent clinical feature that predicts the subsequent development of Parkinson's disease dementia.
    Brain 01/2012; 135(Pt 1):161-9. · 9.92 Impact Factor
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    ABSTRACT: Sleep is essential for living beings, and sleep loss has been shown to affect hippocampal structure and function in rats by inhibiting cell proliferation and neurogenesis in this region of the brain. We aimed to analyze the correlation between sleep duration and the hippocampal volume using brain magnetic resonance images of 290 healthy children aged 5-18 years. We examined the volume of gray matter, white matter, and the cerebrospinal fluid (CSF) space in the brain using a fully automated and established neuroimaging technique, voxel-based morphometry, which enabled global analysis of brain structure without bias towards any specific brain region while permitting the identification of potential differences or abnormalities in brain structures. We found that the regional gray matter volume of the bilateral hippocampal body was significantly positively correlated with sleep duration during weekdays after adjusting for age, sex, and intracranial volume. Our results indicated that sleep duration affects the hippocampal regional gray matter volume of healthy children. These findings advance our understanding of the importance of sleep habits in the daily lives of healthy children.
    NeuroImage 12/2011; 60(1):471-5. · 6.25 Impact Factor

Publication Stats

6k Citations
1,123.93 Total Impact Points

Institutions

  • 1982–2013
    • Tohoku University
      • • Institute of Development, Aging and Cancer
      • • Department of Diagnostic Radiology
      • • Department of Neurology
      • • Department of Pharmaceutical Chemistry
      • • Cyclotron and Radioisotope Center (CYRIC)
      Sendai, Kagoshima-ken, Japan
  • 2012
    • National Center for Global Health and Medicine in Japan
      • Division of Nuclear Medicine
      Edo, Tōkyō, Japan
    • National Rehabilitation Center for Persons with Disabilities
      Tokorozawa, Saitama, Japan
  • 2011
    • National Cancer Center, Japan
      • Research Center for Cancer Prevention and Screening
      Edo, Tōkyō, Japan
    • University Hospital Medical Information Network
      Edo, Tōkyō, Japan
  • 2009
    • Yamagata University
      • Department of Clinical Neuroscience
      Ямагата, Yamagata, Japan
  • 2007
    • Yokohama City University
      • Department of Radiology (YCUH)
      Yokohama, Kanagawa, Japan
  • 2006
    • Miyagi University of Education
      Japan
  • 1988–2006
    • National Institute of Radiological Sciences
      • Molecular Imagining Center
      Tiba, Chiba, Japan
    • Università Degli Studi Roma Tre
      • Department of Geological Science
      Roma, Latium, Italy
  • 1994–2005
    • Research Institute for Brain and Blood Vessels-Akita
      Akita, Akita, Japan
    • National Institute of Mental Health and Neuro Sciences
      Bengalūru, Karnātaka, India
  • 2004
    • Hokuriku Central Hospital
      Nanto-shi, Toyama, Japan
  • 2003
    • National Institute of Advanced Industrial Science and Technology
      Tsukuba, Ibaraki, Japan
    • University College London
      • Institute of Cognitive Neuroscience
      London, ENG, United Kingdom
  • 1999
    • Iwate Medical University
      Morioka, Iwate, Japan
    • Nihon Fukushi University
      Japan
  • 1996–1999
    • Kyoto University
      • Primate Research Institute
      Kyoto, Kyoto-fu, Japan
  • 1998
    • Sendai University
      Sendai, Kagoshima, Japan
  • 1991
    • Chiba University
      • Department of Neurology
      Chiba-shi, Chiba-ken, Japan
    • Chiba Cancer Center
      Tiba, Chiba, Japan