Ken Okada

Tohoku University, Japan

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Publications (25)76.57 Total impact

  • Nano-Biomedical Engineering 2012 - The Tohoku University Global Centre of Excellence Programme; 01/2012
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    ABSTRACT: Community structure is a universal and significant feature of many complex networks in biology, society, and economics. Community structure has also been revealed in human brain structural and functional networks in previous studies. However, communities overlap and share many edges and nodes. Uncovering the overlapping community structure of complex networks remains largely unknown in human brain networks. Here, using regional gray matter volume, we investigated the structural brain network among 90 brain regions (according to a predefined anatomical atlas) in 462 young, healthy individuals. Overlapped nodes between communities were defined by assuming that nodes (brain regions) can belong to more than one community. We demonstrated that 90 brain regions were organized into 5 overlapping communities associated with several well-known brain systems, such as the auditory/language, visuospatial, emotion, decision-making, social, control of action, memory/learning, and visual systems. The overlapped nodes were mostly involved in an inferior-posterior pattern and were primarily related to auditory and visual perception. The overlapped nodes were mainly attributed to brain regions with higher node degrees and nodal efficiency and played a pivotal role in the flow of information through the structural brain network. Our results revealed fuzzy boundaries between communities by identifying overlapped nodes and provided new insights into the understanding of the relationship between the structure and function of the human brain. This study provides the first report of the overlapping community structure of the structural network of the human brain.
    PLoS ONE 05/2011; 6(5):e19608. · 3.53 Impact Factor
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    ABSTRACT: The aim of this study was to examine structural brain networks using regional gray matter volume, as well as to investigate changes in small-world and modular organization with normal aging. We constructed structural brain networks composed of 90 regions in young, middle, and old age groups. We randomly selected 350 healthy subjects for each group from a Japanese magnetic resonance image database. Structural brain networks in three age groups showed economical small-world properties, providing high global and local efficiency for parallel information processing at low connection cost. The small-world efficiency and node betweenness varied significantly and revealed a U- or inverted U-curve model tendency among three age groups. Results also demonstrated that structural brain networks exhibited a modular organization in which the connections between regions are much denser within modules than between them. The modular organization of structural brain networks was similar between the young and middle age groups, but quite different from the old group. In particular, the old group showed a notable decrease in the connector ratio and the intermodule connections. Combining the results of small-world efficiency, node betweenness and modular organization, we concluded that the brain network changed slightly, developing into a more distributed organization from young to middle age. The organization eventually altered greatly, shifting to a more localized organization in old age. Our findings provided quantitative insights into topological principles of structural brain networks and changes related to normal aging.
    Human Brain Mapping 03/2011; 33(3):552-68. · 6.92 Impact Factor
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    ABSTRACT: In clinical positron emission tomography (PET) studies for oncology, it is occasionally required to differentiate a diffuse increase in bone marrow (BM) F-18 fluoro-2-deoxyglucose (FDG) uptake due to the involvement of malignancy or hematopoietic disease and that due to the administration of hematopoietic cytokines, an inflammation reaction, or stimulation by some types of malignancy. The objectives of this study were to clarify the relationships between BM F-18 FDG uptake and blood parameters as well as age, and also to determine the degree of F-18 FDG accumulation that constitutes an abnormal level referring to blood parameters. Records of 65 patients, 32 with benign diseases and 33 with malignancies without metastasis in bone and liver until a half year after the PET examination, were analyzed retrospectively. Regions of interest were placed on the liver and the lower thoracic and lumbar vertebrae to measure the standardized uptake value (SUV), and vertebral SUVs were averaged as the BM SUV(mean). The BM SUV(mean) was divided by the liver SUV to calculate the BM/liver ratio. The relationships among the BM SUV(mean), or BM/liver ratio, and blood parameters and age were tested using multiple regression analysis. In both patients with and without malignancy, a multiple regression model using the BM/liver ratio showed a higher coefficient of determination value than that using the BM SUV(mean), indicating that the correction by the liver SUV reduced the interindividual variation in the BM SUV(mean). The BM/liver ratio was negatively correlated with age (beta = -0.41 and -0.43, respectively) and positively correlated with serum C-reactive protein (CRP) level (beta = 0.39 and 0.46, respectively) in both groups of patients. Every patient with benign disease who had a ratio greater than or equal to 1 had an increased CRP level. The BM F-18 FDG uptake depends on the patient's age and serum CRP level, both with and without malignancy. A BM F-18 FDG uptake greater than or equal to that of the liver may indicate BM activation.
    Annals of Nuclear Medicine 08/2009; 23(7):643-9. · 1.41 Impact Factor
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    ABSTRACT: The dependent-density of computed tomography (CT) images of positron emission tomography (PET)/CT is sometimes difficult to distinguish from chronic interstitial lung disease (ILD) when it accompanies increased (18)F-fluorodeoxy-D: -glucose ((18)FDG) uptake. Though the possible utility of (18)FDG-PET for the diagnosis of active ILD has been reported, the clinical relevance of mild lung (18)FDG uptake in ILD cases without signs and symptoms suggesting acute progression has not been described. This study aimed to test relationships between (18)FDG uptake and lung density on CT using PET/CT in patients with normal lung as well as clinically stable chronic ILD. Thirty-six patients with normal lungs (controls) and 28 patients with chronic ILD (ILD cases) without acute exacerbation were retrospectively selected from (18)FDG-PET/CT scans performed in examination of malignant neoplasms. Elliptical regions of interest (ROIs) were placed on the lung. The relationships between CT density and (18)FDG uptake between the control and ILD cases were tested. The CT density and (18)FDG uptake had a linear correlation in both the controls and the ILD cases without a difference in their regression slopes, and they were overlapped between the controls and the ILD cases with higher mean values in the ILD cases. Lung (18)FDG uptake was considered to reflect a gravity-dependent tissue density in the normal lung. Though the lung (18)FDG uptake as well as the CT density tended to be higher in chronic ILD patients, it may be difficult to distinguish them in normal dependent regions from those related to chronic ILD in some cases.
    Annals of Nuclear Medicine 04/2009; 23(3):277-81. · 1.51 Impact Factor
  • Nano-Biomedical Engineering 2009 - The Tohoku University Global Centre of Excellence Programme; 01/2009
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    ABSTRACT: To investigate any correlation between BMI and brain gray matter volume, we analyzed 1,428 healthy Japanese subjects by applying volumetric analysis and voxel-based morphometry (VBM) using brain magnetic resonance (MR) imaging, which enables a global analysis of brain structure without a priori identification of a region of interest. We collected brain MR images from 690 men and 738 women, and their height, weight, and other clinical information. The collected images were automatically normalized into a common standard space for an objective assessment of neuroanatomical correlations in volumetric analysis and VBM with BMI. Volumetric analysis revealed a significant negative correlation in men (P < 0.001, adjusting for age, lifetime alcohol intake, history of hypertension, and diabetes mellitus), although not in women, between BMI and the gray matter ratio, which represents the percentage of gray matter volume in the intracranial volume. VBM revealed that, in men, the regional gray matter volume of the bilateral medial temporal lobes, anterior lobe of the cerebellum, occipital lobe, frontal lobe, precuneus, and midbrain showed significant negative correlations with BMI, while those of the bilateral inferior frontal gyri, posterior lobe of the cerebellum, frontal lobes, temporal lobes, thalami, and caudate heads showed significant positive correlations with BMI. Global loss and regional alterations in gray matter volume occur in obese male subjects, suggesting that male subjects with a high BMI are at greater risk for future declines in cognition or other brain functions.
    Obesity 02/2008; 16(1):119-24. · 4.39 Impact Factor
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    ABSTRACT: The serum tumor marker carbohydrate associated antigen 19-9 (CA19-9) has been used for screening for cancer, because its increase has been associated with many cancers. We aimed to evaluate the clinical value of positron emission tomography using F-18 fluorodeoxyglucose (18FDG-PET) that was prompted by increases of serum CA19-9 without findings on conventional imaging. Twenty-two patients were retrospectively selected. Eleven were without a history of cancer and eleven had a history of cancer and were treated with curative intent. All 18FDG-PET findings were compared with the findings of histopathology by surgery or biopsy, or clinical follow-up for at least 1 year. We found only two true positive cases, and eleven cases without a cancer history included 10 true negatives and one false positive. Increases in serum CA19-9 are caused by many benign conditions. Increases of CA19-9 without findings on conventional imaging do not justify 18FDG-PET examination, particularly in patients without a cancer history.
    Hepato-gastroenterology 01/2008; 55(81):46-9. · 0.91 Impact Factor
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    ABSTRACT: The correct estimation of the portosystemic shunt (PSS) ratio prior to surgery for patent ductus venosus is important. Until now, formulas using the lung and liver uptake for per-rectal portal scintigraphy using 123I-iodoamphetamine (IMP) have been mainly used for calculating the PSS ratio. However, these methods did not take radioactivity in the brain or changes in organ radioactivity over time into consideration. Here, we performed sequential whole-body scanning by per-sigmoid colon 123I-IMP scintigraphy, and evaluated the changes in radioactivity in the liver, lungs, and brain over time. The patient was 7-year-old boy with a patent ductus venosus. A 10 Fr. catheter was inserted into the sigmoid colon under fluoroscopic guidance, through which about 55.5 MBq of 123I-IMP was administered. Following the administration, the patient was placed in the supine position and sequential whole-body scanning (from head to thigh) was performed for up to about 80 min. Four regions of interest (ROIs) were placed on the whole brain, lungs, liver, and mediastinum. The PSS ratios were calculated using both the traditional formula (PSS index: brain uptake is not considered) and our original formula (new index: brain uptake is considered). Prior to surgery, the radioactivity could be seen clearly in the brain and lungs just following the injection. The liver uptake was faint on the first and second scans (15 min/scan), and increased gradually over time. In contrast, almost no radioactivity was detected in the brain or lungs following surgery. The liver uptake could be seen clearly just following the injection. The new index was significantly higher than the PSS index. Both the new index and the PSS index showed changes over time especially prior to surgery. Distinct brain radioactivity was observed early following administration in a patient with PSS. The calculation of the PSS fraction should be performed taking the brain radioactivity into consideration. The timing of the scan should be fixed, but 30 min following administration may be too early to begin scanning.
    Annals of Nuclear Medicine 01/2008; 21(10):597-601. · 1.51 Impact Factor
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    ABSTRACT: The vertebral spine is frequently affected by the SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome. We report the collective imaging findings of hybrid F-18 fluorodeoxyglucose-positron emission tomography/computed tomography (18FDG-PET/CT), as well as bone scans and magnetic resonance imaging, in a patient who had suspected metastatic vertebral bone tumors. 18FDG-PET/CT can be utilized to exclude metastatic vertebral tumors, as well as identifying stable lesions, by demonstrating active inflammatory lesions with accurate anatomic localization through the convergence of the functional information from 18FDG uptake with the anatomic information of CT.
    Annals of Nuclear Medicine 11/2007; 21(8):477-80. · 1.51 Impact Factor
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    ABSTRACT: We compared the diagnostic accuracy achieved by a human observer (nuclear medicine physician) and a channelized Hotelling (CH) observer on the basis of receiver-operating characteristics (ROC) curve for the differential diagnosis of Alzheimer's disease (AD) from SPECT images. The I-123-IMP brain perfusion SPECT images of 42 subjects (21 AD patients and 21 healthy controls) were used for an interpretation study and those of 10 healthy subjects were for a normal database. SPECT images were processed into four types: original SPECT images, three-dimensional stereotactic surface projection (3DSSP) images derived from them, Z-scores of SPECT images, and Z-scores of 3DSSP images. Five nuclear medicine physicians evaluated the test dataset sequentially as to whether the presented images were those of AD patients, which were rated using five categories of certainty: definitely, possibly, equivocally, possibly not, and definitely not. The test statistics (lambda) of the dataset generated by the CH observer were rated for ROC analysis. The areas under the ROC curves (Az) for the four image types interpreted by the human and CH observers were estimated and compared. Among the four image types, the best performance based on Az obtained by both the CH and human observers was observed for the Z-score of 3DSSP images, and the lowest was for the original SPECT images. The performance of the CH observer was similar to that of the human observers, and both were dependent on the image type. This indicates that the CH observer may predict human performance in discriminating Alzheimer's dementia and can be useful for comparing and optimizing image processing methods of brain perfusion SPECT without human observers.
    Annals of Nuclear Medicine 12/2006; 20(9):605-13. · 1.51 Impact Factor
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    ABSTRACT: It is well known that hematopoietic cytokine stimulation can cause diffuse increase of FDG accumulation in bone marrow on PET imaging, which simulates that seen in patients with bone marrow metastases. However, diffuse bone marrow FDG uptake can be caused by other etiologies. We report 2 patients who did not have a history of hematopoietic cytokine stimulation. The FDG PET images showed diffuse bone marrow FDG uptake, and the patients were diagnosed as having myelodysplastic syndromes. These cases demonstrate that diffuse FDG uptake by bone marrow can suggest neoplastic disease of the hematopoietic tissues.
    Clinical Nuclear Medicine 12/2006; 31(11):721-3. · 2.86 Impact Factor
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    ABSTRACT: Non-alcohol-dependent heavy drinkers, as well as alcohol-dependent individuals, show brain atrophy. The purpose of this study was to evaluate whether there are correlations between global and regional gray matter volumes and the lifetime alcohol intake using volumetric analysis and voxel-based morphometry (VBM) among Japanese non-alcohol-dependent male individuals. High-resolution three-dimensional magnetic resonance images were acquired from 405 Japanese non-alcohol-dependent male individuals. The collected images were normalized, segmented for volumetric analysis, and additionally smoothed for VBM. For volumetric analysis, the partial correlation coefficient was estimated between the gray matter ratio, which represents the percentage of gray matter volume in the intracranial volume, and the lifetime alcohol intake adjusted for the age of each subject. Multiple regression analysis was performed among regional gray matter volume, lifetime alcohol intake, and age using VBM. Volumetric analysis revealed that gray matter ratio showed a negative correlation with the lifetime alcohol intake adjusted for age (p=0.059, partial correlation coefficient=-0.091). The VBM revealed that the gray matter volumes of the bilateral middle frontal gyri showed a significant negative correlation with the lifetime alcohol intake adjusted for age and systolic blood pressure (left side, p=0.006, Z=4.77; right side, p=0.023, Z=4.45, and p=0.046, Z=4.27). Our study suggests that non-alcohol-dependent Japanese male individuals show that both global gray matter volume and regional gray matter volume have negative correlations with the lifetime alcohol intake. Our study may contribute to clarifying the mechanism underlying the brain structural changes because of alcohol influence in healthy non-alcohol-dependent individuals.
    Alcoholism Clinical and Experimental Research 07/2006; 30(6):1045-50. · 3.31 Impact Factor
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    ABSTRACT: Three accumulative tracers, iodine-123-labeled N-isopropyl-p-iodoamphetamine (I-123-IMP), technetium-99m-labeled hexamethylpropyleneamineoxime (Tc-99m-HMPAO), and technetium-99m-labeled ethyl cysteinate dimer (Tc-99m-ECD) are widely used to measure cerebral blood flow (CBF) in single-photon emission computed tomography (SPECT). In the present study, normal regional distribution of CBF measured with three different SPECT tracers was entered into a database and compared with regional distribution of CBF measured by positron emission tomography (PET) with H2(15)O. The regional distribution of tissue fractions of gray matter determined by voxel-based morphometry was also compared with SPECT and PET CBF distributions. SPECT studies with I-123-IMP, Tc-99m-HMPAO, and Tc-99m-ECD were performed on 11, 20, and 17 healthy subjects, respectively. PET studies were performed on 11 healthy subjects. Magnetic resonance (MR) imaging studies for voxel-based morphometry were performed on 43 of the 48 subjects who underwent SPECT study. All SPECT, PET, and MR images were transformed into the standard brain format with the SPM2 system. The voxel values of each SPECT and PET image were globally normalized to 50 ml/100 ml/min. Gray matter, white matter, and cerebrospinal fluid images were segmented and extracted from all transformed MR images by applying voxel-based morphometry methods with the SPM2 system. Regional distribution of all three SPECT tracers differed from that of H2150 in the pons, midbrain, thalamus, putamen, parahippocampal gyrus, posterior cingulate gyrus, temporal cortex, and occipital cortex. No significant correlations were observed between the tissue fraction of gray matter and CBF with any tracer. Differences in regional distribution of SPECT tracers were considered to be caused mainly by differences in the mechanism of retention of tracers in the brain. Regional distribution of CBF was independent of regional distribution of gray matter fractions, and consequently the blood flow per gray matter volume differed for each brain region.
    Annals of Nuclear Medicine 03/2006; 20(2):131-8. · 1.51 Impact Factor
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    ABSTRACT: The limited spatial resolution of SPECT causes a partial volume effect (PVE) and can lead to the significant underestimation of regional tracer concentration in the small structures surrounded by a low tracer concentration, such as the cortical gray matter of an atrophied brain. The aim of the present study was to determine, using 123I-IMP and SPECT, normal CBF of elderly subjects with and without PVE correction (PVC), and to determine regional differences in the effect of PVC and their association with the regional tissue fraction of the brain. Quantitative CBF SPECT using 123I-IMP was performed in 33 healthy elderly subjects (18 males, 15 females, 54-74 years old) using the autoradiographic method. We corrected CBF for PVE using segmented MR images, and analyzed quantitative CBF and regional differences in the effect of PVC using tissue fractions of gray matter (GM) and white matter (WM) in regions of interest (ROIs) placed on the cortical and subcortical GM regions and deep WM regions. The mean CBF in GM-ROIs were 31.7 +/- 6.6 and 41.0 +/- 8.1 ml/100 g/min for males and females, and in WM-ROIs, 18.2 +/- 0.7 and 22.9 +/- 0.8 ml/100 g/min for males and females, respectively. The mean CBF in GM-ROIs after PVC were 50.9 +/- 12.8 and 65.8 +/- 16.1 ml/100 g/min for males and females, respectively. There were statistically significant differences in the effect of PVC among ROIs, but not between genders. The effect of PVC was small in the cerebellum and parahippocampal gyrus, and it was large in the superior frontal gyrus, superior parietal lobule and precentral gyrus. Quantitative CBF in GM recovered significantly, but did not reach values as high as those obtained by invasive methods or in the H2(15)O PET study that used PVC. There were significant regional differences in the effect of PVC, which were considered to result from regional differences in GM tissue fraction, which is more reduced in the frontoparietal regions in the atrophied brain of the elderly.
    Annals of Nuclear Medicine 03/2006; 20(2):139-46. · 1.51 Impact Factor
  • Future Medical Engineering Based on Bionanotechnology - The Final Symposium of the Tohoku University 21st Century Center of Excellence Program; 01/2006
  • Journal of Cerebral Blood Flow & Metabolism 08/2005; · 5.34 Impact Factor
  • Journal of Cerebral Blood Flow & Metabolism 08/2005; · 5.34 Impact Factor
  • Journal of Cerebral Blood Flow & Metabolism 08/2005; 25. · 5.34 Impact Factor
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    ABSTRACT: Single-photon emission computed tomography (SPECT) with iodine-123 (123I)-labeled N-isopropyl-p-iodoamphetamine (IMP) is widely used in measuring the cerebral blood flow (CBF) response to acetazolamide stress for assessment of cerebral vascular reserve. To quantitate CBF by means of SPECT with IMP, an autoradiographic (ARG) method has been developed and is widely used. Because the relation between the brain counts on the SPECT scan and CBF is not linear in the ARG method, a mixture of gray and white matter in a pixel causes errors in the calculation of CBF. In the present study, errors in the calculation of CBF and vascular response to acetazolamide stress by the ARG method due to tissue heterogeneity were estimated by simulation study. Correction for effects of tissue heterogeneity in SPECT data was also attempted. Images of gray and white matter fraction were obtained by voxel-based morphometry analysis of magnetic resonance (MR) imaging data set. Ideal CBF images, which were generated from gray and white matter fraction images with assumed blood flow values for gray and white matter, were compared to CBF images generated by the ARG method. Correction for effects of tissue heterogeneity in SPECT data was performed with gray and white matter fraction data obtained from MR images. Systematic underestimation of CBF due to tissue heterogeneity was observed in all brain regions. In the neocortical regions, underestimation by -21% to -16%, -26% to -20%, -31% to -24%, and -35% to -27% was observed for gray and white matter blood flow of 80 and 20, 100 and 25, 120 and 30, and 140 and 35 ml/100 ml/min, respectively. Vascular response was also systematically underestimated in most brain regions. Vascular responses in the neocortical regions ranged from 17% to 20%, from 31% to 37%, and from 42% to 52% when ideal vascular responses were 25%, 50%, and 75%, respectively. After correction for the effects of tissue heterogeneity, values of vascular response to acetazolamide stress ranged from 64% to 116% in the neocortical regions, whereas values obtained by the ARG method ranged from 48% to 52%. Underestimation of the vascular response to acetazolamide stress due to tissue heterogeneity should be considered in the estimation of cerebral vascular reserve.
    Annals of Nuclear Medicine 07/2005; 19(4):251-60. · 1.51 Impact Factor