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Background About 40–50% of patients with amnestic mild cognitive impairment (MCI) are found to have no significant Alzheimer’s pathology based on amyloid PET positivity. Notably, conversion to dementia in this population is known to occur... more
Background About 40–50% of patients with amnestic mild cognitive impairment (MCI) are found to have no significant Alzheimer’s pathology based on amyloid PET positivity. Notably, conversion to dementia in this population is known to occur much less often than in amyloid-positive MCI. However, the relationship between MCI and brain amyloid deposition remains largely unknown. Therefore, we investigated the influence of subthreshold levels of amyloid deposition on conversion to dementia in amnestic MCI patients with negative amyloid PET scans. Methods This study was a retrospective cohort study of patients with amyloid-negative amnestic MCI who visited the memory clinic of Asan Medical Center. All participants underwent detailed neuropsychological testing, brain magnetic resonance imaging, and [18F]-florbetaben (FBB) positron emission tomography scan (PET). Conversion to dementia was determined by a neurologist based on a clinical interview with a detailed neuropsychological test or a ...
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Objectives We aimed to evaluate the diagnostic ability for the prediction of histologic grades and prognostic values on recurrence and death of pretreatment 2-[ 18 F]FDG PET/CT in patients with resectable thymic epithelial tumours (TETs).... more
Objectives We aimed to evaluate the diagnostic ability for the prediction of histologic grades and prognostic values on recurrence and death of pretreatment 2-[ 18 F]FDG PET/CT in patients with resectable thymic epithelial tumours (TETs). Methods One hundred and fourteen patients with TETs who underwent pretreatment 2-[ 18 F]FDG PET/CT between 2012 and 2018 were retrospectively evaluated. TETs were classified into three histologic subtypes: low-risk thymoma (LRT, WHO classification A/AB/B1), high-risk thymoma (HRT, B2/B3), and thymic carcinoma (TC). Area under the receiver operating characteristics curve (AUC) was used to assess the diagnostic performance of PET/CT variables (maximum standardised uptake value [SUVmax], metabolic tumour volume [MTV], total lesion glycolysis [TLG], maximum diameter). Cox proportional hazards models were built using PET/CT and clinical variables. Results The tumours included 52 LRT, 33 HRT, and 29 TC. SUVmax showed good diagnostic ability for differentiating HRT/TC from LRT (AUC 0.84, 95% confidence interval [CI] 0.76 − 0.92) and excellent ability for differentiating TC from LRT/HRT (AUC 0.94, 95% CI 0.90 − 0.98), with significantly higher values than MTV, TLG, and maximum diameter. With an optimal cut-off value of 6.4, the sensitivity, specificity, and accuracy for differentiating TC from LRT/HRT were 69%, 96%, and 89%, respectively. In the multivariable Cox proportional hazards analyses for freedom-from-recurrence, SUVmax was an independent prognostic factor ( p < 0.001), whereas MTV and TLG were not. SUVmax was a significant predictor for overall survival in conjunction with clinical stage and resection margin. Conclusion SUVmax showed excellent diagnostic performance for prediction of TC and significant prognostic value in terms of recurrence and survival. Key Points • Maximum standardised uptake value (SUVmax) shows excellent performance in the differentiation of thymic carcinoma from low- and high-risk thymoma. • SUVmax is an independent prognostic factor for freedom-from-recurrence in the multivariable Cox proportional hazard model and a significant predictor for overall survival. • 2-[ 18 F]FDG PET/CT can provide a useful diagnostic and prognostic imaging biomarker in conjunction with histologic classification and stage and help choose appropriate management for thymic epithelial tumours.
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Tau and amyloid β (Aβ), 2 key pathogenic proteins in Alzheimer’s disease (AD), reportedly spread throughout the brain as the disease progresses. Models of how these pathogenic proteins spread from affected to unaffected areas had been... more
Tau and amyloid β (Aβ), 2 key pathogenic proteins in Alzheimer’s disease (AD), reportedly spread throughout the brain as the disease progresses. Models of how these pathogenic proteins spread from affected to unaffected areas had been proposed based on the observation that these proteins could transmit to other regions either through neural fibers (transneuronal spread model) or through extracellular space (local spread model). In this study, we modeled the spread of tau and Aβ using a graph theoretical approach based on resting-state functional magnetic resonance imaging. We tested whether these models predict the distribution of tau and Aβ in the brains of AD spectrum patients. To assess the models’ performance, we calculated spatial correlation between the model-predicted map and the actual map from tau and amyloid positron emission tomography. The transneuronal spread model predicted the distribution of tau and Aβ deposition with significantly higher accuracy than the local spre...
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PURPOSE 4-(3S)-3-[5-(2-[18F]-fluoroethoxy)pyridin-3-yl]-3-[({(3R)-1-[3-(piperidin-4-yl)propanoyl]-piperidin-3-yl}carbonyl)amino]propanoic acid ([18F]GP1) is a radiotracer developed for targeted imaging of activated platelet glycoprotein... more
PURPOSE 4-(3S)-3-[5-(2-[18F]-fluoroethoxy)pyridin-3-yl]-3-[({(3R)-1-[3-(piperidin-4-yl)propanoyl]-piperidin-3-yl}carbonyl)amino]propanoic acid ([18F]GP1) is a radiotracer developed for targeted imaging of activated platelet glycoprotein IIb/IIIa receptors with positron emission tomography/computed tomography (PET/CT) in acute thromboembolism. We evaluated here radiation dosimetry of [18F]GP1 in humans. PROCEDURES We studied 30 subjects (10 with deep vein thrombosis, 10 with pulmonary embolism, and 10 with arterial thromboembolism) who had signs or symptoms of acute thromboembolism, and were confirmed to have thromboembolic foci by imaging studies. Dynamic whole-body PET/CT images were acquired for up to 140 min after injection of 250 MBq of [18F]GP1. Radiation absorbed dose and effective dose were calculated using the OLINDA/EXM software. RESULTS [18F]GP1 PET images showed high initial uptake of the tracer in the heart, spleen, kidney, and liver. [18F]GP1 activity was cleared by hepatobiliary and urinary excretion. The organ receiving the highest radiation absorbed dose (mGy/MBq) was the urinary bladder (0.0884 ± 0.0458), followed by upper large intestine (0.0498 ± 0.0189), small intestine (0.0454 ± 0.0166), and kidneys (0.0350 ± 0.0231). The effective dose (mSv/MBq) was 0.0212 ± 0.0027 (ICRP 103). ED was not significantly different between the three disease groups (p = 0.94). A 45-minute voiding reduced the urinary bladder wall radiation dose to 0.0495 ± 0.0140 mGy/MBq, and effective dose (ICRP 103) to 0.0186 ± 0.0030. CONCLUSIONS [18F]GP1 has favorable radiation dosimetry profile for clinical PET/CT imaging. The ED is comparable to commonly used 18F PET tracers.
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The cingulum bundle (CB) connects gray matter structures of the limbic system and as such has been implicated in the etiology of schizophrenia. There is growing evidence to suggest that the CB is actually comprised of a conglomeration of... more
The cingulum bundle (CB) connects gray matter structures of the limbic system and as such has been implicated in the etiology of schizophrenia. There is growing evidence to suggest that the CB is actually comprised of a conglomeration of discrete sub-connections. The present study aimed to use Diffusion Tensor tractography to subdivide the CB into its constituent sub-connections, and to investigate the structural integrity of these sub-connections in patients with schizophrenia and matched healthy controls. Diffusion Tensor Imaging scans were acquired from 24 patients diagnosed with chronic schizophrenia and 26 matched healthy controls. Deterministic tractography was used in conjunction with FreeSurfer-based regions-of-interest to subdivide the CB into 5 sub-connections (I1 to I5). The patients with schizophrenia exhibited subnormal levels of FA in two cingulum sub-connections, specifically the fibers connecting the rostral and caudal anterior cingulate gyrus (I1) and the fibers con...
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Objective 18 F-labeled fluoropropyl-carbomethoxylodopropyl-nor-ß-tropane ([ 18 F]FP-CIT) positron emission tomography (PET) is a useful tool for evaluating disease progression in Parkinson’s disease (PD) patients. We evaluated the... more
Objective 18 F-labeled fluoropropyl-carbomethoxylodopropyl-nor-ß-tropane ([ 18 F]FP-CIT) positron emission tomography (PET) is a useful tool for evaluating disease progression in Parkinson’s disease (PD) patients. We evaluated the test–retest reproducibility of [ 18 F]FP-CIT PET measures in essential tremor (ET) and PD patients. Methods Fifteen ET (68.9 ± 6.6 years) and 10 PD patients (70.5 ± 6.3 years; Hoehn and Yahr stage, 2.3 ± 0.8) underwent two [ 18 F]FP-CIT PET/CT scans with an interval of 48 ± 7 day. For both the test and retest studies, standardized uptake value ratios were estimated for 90-min and 3-h acquisitions for the caudate, anterior putamen, and posterior putamen using T1-MRI-based normalization (automatic) and fixed-VOI (manual) methods, with the occipital lobe as a reference. Reproducibility was evaluated by the bias, variability, percent test–retest, within-subject coefficient of variation, repeatability coefficient, and intraclass correlation coefficient (ICC). Results Reproducibility was excellent, with low variability (ET: 6.99–8.02%, PD: 3.51–6.94%) and high reliability (ICC; ET: 0.88–0.96, PD: 0.98–0.99). The ET group showed higher variability and lower ICCs than the PD group. The variability in the 90-min images (ET: 7.85–8.59%, PD: 1.52–2.75%) was comparable to that in the 3-h images (ET: 6.99–8.02%, PD: 3.51–6.94%). There were no differences in variability among the subregions in the ET group. In the PD group, the variability was high in the posterior putamen (automatic method: 6.94%, manual method: 11.80%). The test–retest variability and ICCs were similar for the manual and automatic methods. Conclusion [ 18 F]FP-CIT PET is reproducible for the quantitative measurement of DAT binding in both ET and PD individuals, independent of the acquisition time or analysis method. Also, the automatic method is more suitable for evaluating early loss of DAT binding in patients with PD
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Background Individuals at ultra-high risk (UHR) for psychosis have self-disturbances and deficits in social cognition and functioning. Midline default network areas, including the medial prefrontal cortex and posterior cingulate cortex,... more
Background Individuals at ultra-high risk (UHR) for psychosis have self-disturbances and deficits in social cognition and functioning. Midline default network areas, including the medial prefrontal cortex and posterior cingulate cortex, are implicated in self-referential and social cognitive tasks. Thus, the neural substrates within the default mode network (DMN) have the potential to mediate self-referential and social cognitive information processing in UHR subjects. Methods This study utilized functional magnetic resonance imaging (fMRI) to investigate resting-state DMN and task-related network (TRN) functional connectivity in 19 UHR subjects and 20 matched healthy controls. The bilateral posterior cingulate cortex was selected as a seed region, and the intrinsic organization for all subjects was reconstructed on the basis of fMRI time series correlation. Results Default mode areas included the posterior/anterior cingulate cortices, the medial prefrontal cortex, the lateral parie...
Research Interests: Psychology, Cognitive Science, Anterior Cingulate, Magnetic Resonance Imaging, Information Processing, and 15 moreFunctional Connectivity, Brain, Humans, Default Mode Network, Female, Male, Parietal Cortex, Adult, Behavioral, Neural pathways, Inferior Parietal Lobule, Neurosciences, Medial Prefrontal Cortex, Dorsolateral Prefrontal Cortex, and Magnetic resonance image
Although skull-stripping and brain region segmentation are essential for precise quantitative analysis of positron emission tomography (PET) of mouse brains, deep learning (DL)-based unified solutions, particularly for spatial... more
Although skull-stripping and brain region segmentation are essential for precise quantitative analysis of positron emission tomography (PET) of mouse brains, deep learning (DL)-based unified solutions, particularly for spatial normalization (SN), have posed a challenging problem in DL-based image processing. In this study, we propose an approach based on DL to resolve these issues. We generated both skull-stripping masks and individual brain-specific volumes-of-interest (VOIs—cortex, hippocampus, striatum, thalamus, and cerebellum) based on inverse spatial normalization (iSN) and deep convolutional neural network (deep CNN) models. We applied the proposed methods to mutated amyloid precursor protein and presenilin-1 mouse model of Alzheimer’s disease. Eighteen mice underwent T2-weighted MRI and 18F FDG PET scans two times, before and after the administration of human immunoglobulin or antibody-based treatments. For training the CNN, manually traced brain masks and iSN-based target V...
Imaging biomarkers support the diagnosis of Alzheimer’s disease (AD). We aimed to determine whether combining automated brain volumetry on MRI and quantitative measurement of tau deposition on [18F] THK-5351 PET can aid discrimination of... more
Imaging biomarkers support the diagnosis of Alzheimer’s disease (AD). We aimed to determine whether combining automated brain volumetry on MRI and quantitative measurement of tau deposition on [18F] THK-5351 PET can aid discrimination of AD spectrum. From a prospective database in an IRB-approved multicenter study (NCT02656498), 113 subjects (32 healthy control, 55 mild cognitive impairment, and 26 Alzheimer disease) with baseline structural MRI and [18F] THK-5351 PET were included. Cortical volumes were quantified from FDA-approved software for automated volumetric MRI analysis (NeuroQuant). Standardized uptake value ratio (SUVR) was calculated from tau PET images for 6 composite FreeSurfer-derived regions-of-interests approximating in vivo Braak stage (Braak ROIs). On volumetric MRI analysis, stepwise logistic regression analyses identified the cingulate isthmus and inferior parietal lobule as significant regions in discriminating AD from HC and MCI. The combined model incorporati...
To date, the clinical significance of visually equivocal amyloid positron emission tomography (PET) has not been well established. We studied the clinical significance of equivocal amyloid PET images from the Alzheimer’s Disease... more
To date, the clinical significance of visually equivocal amyloid positron emission tomography (PET) has not been well established. We studied the clinical significance of equivocal amyloid PET images from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Subjects with F-18 florbetapir PET scans at baseline who were followed up for 4 years were selected. Clinical characteristics, imaging biomarkers, cognitive function, and rate of conversion to AD were compared in subjects with visually equivocal findings. Of 249 subjects who completed the follow-up, 153 (61.4%), 20 (8.0%), and 129 (30.5%) were F-18 florbetapir-negative, -equivocal, and -positive, respectively. The mean standardized uptake value ratios (SUVR) of F-18 florbetapir PET were 0.75 ± 0.04, 0.85 ± 0.10, and 1.00 ± 0.09 for each group (p <0.001 between groups), and 15.0%, 70.0%, and 98.7% of patients were quantitatively above the positive threshold. The change in the SUVR of F-18 florbetapir PET was higher in the equivocal (6.09 ± 3.61%, p <0.001) and positive (3.13 ± 4.38%, p <0.001) groups than the negative group (0.88 ± 4.28%). Among the subjects with normal or subjective memory impairment and mild cognitive impairment, 5.3% with negative amyloid PET and 37.5% with positive amyloid PET converted to AD over the 4-year period. None of the equivocal amyloid PET subjects converted to AD during this period. Approximately 8% of subjects from the ADNI cohort showed visually equivocal amyloid PET scans with intermediate load and rapid accumulation of amyloid, but did not convert to AD during the 4-year follow-up.
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Catatonia is one of the main symptoms of anti-N-Methyl-D-aspartate receptor (NMDAR) encephalitis. However, it is unknown whether metabolic changes observed with (18)F-Fluorodeoxyglucose positron-emission tomography (FDG-PET) are... more
Catatonia is one of the main symptoms of anti-N-Methyl-D-aspartate receptor (NMDAR) encephalitis. However, it is unknown whether metabolic changes observed with (18)F-Fluorodeoxyglucose positron-emission tomography (FDG-PET) are correlated with the severity of the catatonic symptoms and clinical course. Three patients with anti-NMDAR encephalitis showing variable degrees of catatonia were performed with FDG-PET scans during the acute and recovery phase. PET findings showed hypermetabolism in the frontotemporoparietal regions and bilateral basal ganglia in the patient with mild catatonia, but more widespread hypermetabolic regions including the thalamus and brainstem were observed in the patients with more severe catatonia. Follow-up PET scans in one patient showed mild hypermetabolism in the right basal ganglia that correlated with mild rigidity and tonic posturing in the left extremities. Extent of cerebral metabolic changes correlates with the severity of catatonia accompanied by ...
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Purpose : The purpose of this study was to implement a software to visualize tumor and its surrounding fiber tracts simultaneously using diffusion tensor imaging and examine the feasibility of our software for investigating the influence... more
Purpose : The purpose of this study was to implement a software to visualize tumor and its surrounding fiber tracts simultaneously using diffusion tensor imaging and examine the feasibility of our software for investigating the influence of tumor on its surrounding fiber connectivity. Material and Methods : MR examination including T1-weigted and diffusion tensor images of a patient with brain tumor was performed on a 3.0 T MRI unit. We used the skull-striped brain and segmented tumor images for volume/surface rendering and anatomical information from contrast-enhanced T1-weighted images. Diffusion tensor images for the white matter fiber-tractography were acquired using a SE-EPI with a diffusion scheme of 25 directions. Fiber-tractography was performed using the streamline and tensorline methods. To correct a spatial mismatch between T1-weighted and diffusion tensor images, they were coregistered using a SPM. Our software was implemented under window-based PC system. Results : We successfully implemented the integrated visualization of the fiber tracts with tube-like surfaces, cortical surface and the tumor with volume/surface renderings in a patient with brain tumor. Conclusion : Our result showed the feasibility of the integrated visualization of brain tumor and its surrounding fiber tracts. In addition, our implementation for integrated visualization can be utilized to navigate the brain for the quantitative analysis of fractional anisotropy to assess changes in the white matter tract integrity of edematic and peri-edematic regions in a number of tumor patients.
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Research Interests: Cognition, Diffusion Tensor Imaging, Adolescent, Attentional Control, Brain development, and 15 moreAnisotropy, Learning, Problem Solving, Brain, Humans, Female, Brain Plasticity, Neuroimage, Male, Neuronal Plasticity, Cognitive Process, Neural plasticity, Fractional Anisotropy, Neural pathways, and Medical and Health Sciences
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Catatonia is one of the main symptoms of anti-N-Methyl-D-aspartate receptor (NMDAR) encephalitis. However, it is unknown whether metabolic changes observed with 18F-Fluorodeoxyglucose positron-emission tomography (FDG-PET) are correlated... more
Catatonia is one of the main symptoms of anti-N-Methyl-D-aspartate receptor (NMDAR) encephalitis. However, it is unknown whether metabolic changes observed with 18F-Fluorodeoxyglucose positron-emission tomography (FDG-PET) are correlated with the severity of the catatonic symptoms and clinical course. Three patients with anti-NMDAR encephalitis showing variable degrees of catatonia were performed with FDG-PET scans during the acute and recovery phase. PET findings showed hyper-metabolism in the frontotemporoparietal regions and bilateral basal ganglia in the patient with mild catatonia, but more widespread hypermetabolic regions including the thalamus and brainstem were observed in the patients with more severe catatonia. Follow-up PET scans in one patient showed mild hypermetabolism in the right basal ganglia that correlated with mild rigidity and tonic posturing in the left extremities. Extent of cerebral metabolic changes correlates with the severity of catatonia accompanied by b...
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Abstract: Diffusion tensor imaging (DTI) and fiber tractography are useful tools for reconstructing white matter tracts (WMT) in the brain. Previous tractography studies have sought to segment reconstructed WMT into anatomical structures... more
Abstract: Diffusion tensor imaging (DTI) and fiber tractography are useful tools for reconstructing white matter tracts (WMT) in the brain. Previous tractography studies have sought to segment reconstructed WMT into anatomical structures using several approaches, but quantification has been limited to extracting mean values of diffusion indices. Delineating WMT in schizophrenia is of particular interest because schizophrenia has been hypothesized to be a disorder of disrupted connectivity, especially between frontal and temporal regions of the brain. In this study, we aim to differentiate diffusion properties of thalamo-frontal pathways in schizophrenia from normal controls. We present a quantitative group comparison method, which combines the strengths of both tractography-based and voxelbased studies. Our algorithm extracts white matter pathways using whole brain tractography. Functionally relevant bundles are selected and parsed from the resulting set of tracts, using an internal...
Research Interests: Cognitive Science, Schizophrenia, Adolescent, Anisotropy, Brain Mapping, and 15 moreHumans, Thalamus, Chronic Disease, United States, Female, Male, Young Adult, Middle Aged, Adult, Analysis of Variance, Human Brain Mapping, Neural pathways, Neurosciences, Frontal Lobe, and Diffusion magnetic resonance imaging
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Interests in human brain functionality and its connectivity have much frown up. DTI (Diffusion tensor imaging) has been known as a non-invasive MR) technique capable of providing information on water diffusion in tissues and the... more
Interests in human brain functionality and its connectivity have much frown up. DTI (Diffusion tensor imaging) has been known as a non-invasive MR) technique capable of providing information on water diffusion in tissues and the organization of white matter tract. Thus. It can provide us the information on the direction of brain fiber tract and the connectivity among many important cortical regions which can not be examined by other anatomical or functional MRI techniques. In this study. was used the 24 bit color coding scheme on the IDL platform in the windows environment to visualize the orientation of major fiber tracts of brain such as main association, projection, commissural fibers and corticospinal tracts. We additionally implemented a color coding scheme for each directional component and FA (fractional anisotropy), and used various color tables for them to be visualized more definitely. Consequently we implemented a fancy and basic technique to visualize the directional inf...
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Highlights • 18F-FDG PET/CT visualizes altered glucose metabolism which is underpinned by the alteration of specific genes and signaling pathways.• Our analysis of TCGA-HNSC data showed a positive correlation of FDG uptake with the total... more
Highlights • 18F-FDG PET/CT visualizes altered glucose metabolism which is underpinned by the alteration of specific genes and signaling pathways.• Our analysis of TCGA-HNSC data showed a positive correlation of FDG uptake with the total and non-silent mutation rates, genetic heterogeneity, and copy number alterations.• Significant higher FDG uptake was noted in patients with alterations in cell cycle (CDKN2A gene), or TP53 oncogenic signaling pathways (TP53 gene).
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Purpose PET is a useful tool for detecting the presence and extent of brain tau accumulation. However, most first-generation tau PET tracers are limited for high off-target binding and detection of tau in non-Alzheimer disease (AD). This... more
Purpose PET is a useful tool for detecting the presence and extent of brain tau accumulation. However, most first-generation tau PET tracers are limited for high off-target binding and detection of tau in non-Alzheimer disease (AD). This study evaluated potential clinical applications of 18F-PI-2620 as a novel PET tracer with a high binding affinity for tau deposition in AD and non-AD tauopathies. Methods Twenty-six participants diagnosed with either mild cognitive impairment, probable AD, frontotemporal dementia, or parkinsonism, as well as healthy controls underwent a 60- to 90-minute brain PET scan after 7 mci (259 MBq) injection of 18F-PI-2620. Some participants had previous PET scans using 18F-THK-5351 or 18F-FP-CIT for dopamine transporter imaging. Results All participants showed no increase in off-target binding in basal ganglia on 18F-PI-2620 PET images, as noted for first-generation tau tracers. Aβ+ mild cognitive impairment or AD patients showed diverse cortical 18F-PI-2620 uptake in frontotemporoparietal cortex that correlated with Mini-Mental Status Examination (ρ = −0.692, P = 0.013). Aβ+ Parkinson disease with dementia and (Aβ unknown) primary progressive aphasia patients also showed increased 18F-PI-2620 uptakes in the frontotemporoparietal cortex. Patients with parkinsonism showed increased uptakes in the pallidum compared with Aβ− healthy controls (left: 1.41 ± 0.14 vs 1.04 ± 0.13, P = 0.014; right: 1.18 ± 0.16 vs 0.95 ± 0.07, P = 0.014). Conclusions 18F-PI-2620 PET might be a sensitive tool to detect cortical tau deposits in patients with Aβ+ AD and Aβ+ non-AD tauopathies. Furthermore, this study showed that “off-target” binding in the basal ganglia does not affect 18F-PI-2620.
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PURPOSE OF THE REPORT Oxidative stress is a leading factor in the pathogenesis of idiopathic Parkinson disease (IPD). Two intrinsic antioxidative molecules, bilirubin and uric acid, are known to protect dopaminergic neurons from oxidative... more
PURPOSE OF THE REPORT Oxidative stress is a leading factor in the pathogenesis of idiopathic Parkinson disease (IPD). Two intrinsic antioxidative molecules, bilirubin and uric acid, are known to protect dopaminergic neurons from oxidative stress in IPD. The objective of this study was to determine the relationship between basal serum levels of 2 molecules and dopaminergic deficit assessed by dopamine transporter imaging with F-fluorinated-N-3-fluoropropyl-2-β-carboxymethoxy-3-β-(4-iodophenyl)nortropane ([F]FP-CIT) PET/CT in patients with early-stage drug-naive IPD. METHODS Cases of IPD patients who possess the levels of uric acid and bilirubin within a month from [F]FP-CIT PET/CT from January 2011 to December 2016 were retrospectively reviewed. As a control, the same criteria applied to patients with essential tremor (ET). PET images were analyzed using volume-of-interest templates for 12 striatal subregions and 1 occipital area, and the specific-to-nonspecific binding ratio (SNBR) was calculated. RESULTS One hundred five patients with drug-naive, early-stage IPD and 62 patients with ET were finally included. Levels of bilirubin were significantly higher in the IPD group than in controls (P = 0.026), and bilirubin level was the factor showing the most correlations with SNBR in IPD (P < 0.001), whereas uric acid showed no such difference or relationship. Furthermore, levels of bilirubin showed a positive correlation with SNBR in more affected posterior putamen in the IPD group (Pearson correlation coefficient, ρ = 0.456; P < 0.001), but a negative one in the ET group (ρ = -0.440, P < 0.001). CONCLUSIONS Bilirubin, not uric acid, was the most significant antioxidant marker for dopaminergic deficit in early-stage drug-naive IPD assessed by [F]FP-CIT PET/CT.
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BACKGROUND The severity of parkinsonism and response to levodopa vary in patients with multiple system atrophy (MSA) because of the heterogeneity of nigrostriatal neuropathology. OBJECTIVE To investigate the difference in clinical... more
BACKGROUND The severity of parkinsonism and response to levodopa vary in patients with multiple system atrophy (MSA) because of the heterogeneity of nigrostriatal neuropathology. OBJECTIVE To investigate the difference in clinical features between MSA patients with predominantly pre-synaptic nigrostriatal dysfunction and those with trans-synaptic nigrostriatal dysfunction. METHODS We retrospectively analyzed clinical data of 61 patients with MSA who underwent both [18F]FP-CIT-PET and [18F]FDG-PET within 3 months of clinical evaluation, and who had ≤3 years of disease duration. Tracer uptake of the striatum on [18F]FP-CIT-PET and glucose metabolism of the striatum on [18F]FDG-PET were analyzed using eight striatal subregional volumes-of-interest templates. The patients were classified into two subgroups according to the predominant pre-synaptic tracer uptake loss of the posterior putamen on [18F]FP-CIT-PET (MSA-SNpc, n = 21) and trans-synaptic dopaminergic dysfunction reflected by both [18F]FP-CIT-PET and [18F]FDG-PET (MSA-STR, n = 40). RESULTS Parkinsonian features were significantly more severe in the MSA-STR group than in the MSA-SNpc group (P = .005) and cerebellar ataxia was significantly more severe in the MSA-SNpc group (P = .036). The cerebellar type of MSA was significantly more common in the MSA-SNpc group (P = .001). There was no difference in age at onset, disease duration at the time of study, or Mini-Mental Status Examination scores between the groups. CONCLUSIONS Patients with MSA showed distinct clinical features depending on whether the pattern of nigrostriatal dysfunction was predominantly pre-synaptic or trans-synaptic.
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pathological forms of tau with sufficient sensitivity, specificity and practicality. In these neurodegenerative diseases tau accumulates in self-seeding filaments. For example, Pick disease (PiD) is associated with frontotemporal... more
pathological forms of tau with sufficient sensitivity, specificity and practicality. In these neurodegenerative diseases tau accumulates in self-seeding filaments. For example, Pick disease (PiD) is associated with frontotemporal degeneration and accumulation of 3-repeat (3R) tau isoforms in filaments constituting Pick bodies. Here we describe a real time quaking-induced conversion (RTQuIC) assay, called tau RT-QuIC, for disease-associated tau seeding activity. Methods: Tau RT-QuIC measures the capacity of tau aggregates to seed the polymerization of recombinant tau constructs into amyloid fibrils in a 96-well plate format with fluorescence detection. Our initial assay uses a 3R tau fragment as a substrate, and has been optimized for the detection of the predominantly 3R tau deposits in PiD. Results:Tau RT-QuIC detected tau seeds in 2 ml aliquots of PiD brain dilutions down to 10-10. PiD seeding activities were 100-fold higher in frontal and temporal lobes compared to cerebellar cortex. Strikingly, this test was 10to 10-fold less responsive when seeded with brain containing predominant 4-repeat (4R) tau aggregates from cases of corticobasal degeneration, argyrophilic grain disease, and progressive supranuclear palsy. Alzheimer disease brain, with 3R+4R tau deposits, also gave much weaker responses than PiD brain. When applied to cerebrospinal fluid samples (5 ml), tau RT-QuIC analyses clearly discriminated PiD from non-PiD cases. Conclusions:These findings demonstrate that abnormal tau aggregates can be detected with high sensitivity and disease-specificity in crude tissue and fluid samples. Accordingly, this tau RT-QuIC assay exemplifies a new approach to diagnosing tauopathies and monitoring therapeutic trials using aggregated tau itself as a biomarker.
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years of education, being 59.0% female underwent 3 Tesla MRI scans with 3DT1 acquisition. From the whole sample, 45 had dementia, 26 had cognitive impairment no-dementia and 112 were cognitively healthy. The images were processed in SPM... more
years of education, being 59.0% female underwent 3 Tesla MRI scans with 3DT1 acquisition. From the whole sample, 45 had dementia, 26 had cognitive impairment no-dementia and 112 were cognitively healthy. The images were processed in SPM 12. Hippocampi volumes were extracted, along with other brain cortical areas important to memory using the Neuromorphometrics atlas. Multivariate linear regression was conducted with the verbal-visual episodic memory test (the delayed recall task of the Brief Cognitive Battery) as a dependent variable and the left hippocampal volume as the predictor valuable, controlling for age, the test’s learning task, the Mini-Mental State Examination (MMSE) and the sum of the other cortical regions. The same analysis was conducted after splitting the sample in low education (<4 years of education) and relatively high education (>1⁄44 years) groups. Results:The multivariate regression model explained 68.2% of the variation on the performance on the memory test, and the left hippocampus was significantly associated, along with the learning phase of the test, the MMSE and education. The model explained 60.2% in the low educated group and 74.0% in the high educated. Furthermore, the left hippocampus was significantly more associated with the performance on memory on the high educated group. Conclusions:Education can modulate the role of the left hippocampus on episodic memory performance, even at low levels (>1⁄44 years). Further studies with brain structural connectivity can clarify if these findings reflect different structural patterns of network organization related to episodic memory processing.
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Research Interests: Magnetic Resonance Imaging, Mild Cognitive Impairment, Neurobiology, Medicine, Humans, and 15 moreCerebral Cortex, Female, Male, Clinical Sciences, Aged, Middle Aged, Entorhinal Cortex, Atrophy, Analysis of Variance, Degeneration, Fractional Anisotropy, Chi Square Distribution, Alzheimer Disease, Cognition disorders, and Neuropsychological Tests
Research Interests: Magnetic Resonance Imaging, Mild Cognitive Impairment, Neurobiology, Medicine, Humans, and 15 moreCerebral Cortex, Female, Male, Clinical Sciences, Aged, Middle Aged, Entorhinal Cortex, Atrophy, Analysis of Variance, Degeneration, Fractional Anisotropy, Chi Square Distribution, Alzheimer Disease, Cognition disorders, and Neuropsychological Tests
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Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) may be a promising modality for treating medial temporal lobe epilepsy. (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a noninvasive method for... more
Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) may be a promising modality for treating medial temporal lobe epilepsy. (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a noninvasive method for monitoring in vivo glucose metabolism. We evaluated the efficacy of hUCB-MSCs transplantation in chronic epileptic rats using FDG-PET. Rats with recurrent seizures were randomly assigned into three groups: the stem cell treatment (SCT) group received hUCB-MSCs transplantation into the right hippocampus, the sham control (ShC) group received same procedure with saline, and the positive control (PC) group consisted of treatment-negative epileptic rats. Normal rats received hUCB-MSCs transplantation acted as the negative control (NC). FDG-PET was performed at pre-treatment baseline and 1- and 8-week posttreatment. Hippocampal volume was evaluated and histological examination was done. In the SCT group, bilateral hippocampi at 8-week after transplantation s...
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A substantial amount of amyloid-beta (Aβ) accumulates in the occipital cortices; however, it draws less attention. We investigated the clinical implications of Aβ accumulation in the occipital lobes in the Alzheimer’s disease (AD)... more
A substantial amount of amyloid-beta (Aβ) accumulates in the occipital cortices; however, it draws less attention. We investigated the clinical implications of Aβ accumulation in the occipital lobes in the Alzheimer’s disease (AD) continuum. [18F]-Florbetaben amyloid PET scans were performed in a total of 121 AD or amnestic mild cognitive impairment (aMCI) patients. Of the 121 patients, 74 Aβ positive patients were divided into occipital Aβ positive (OCC+) and occipital Aβ negative (OCC−) groups based on Aβ accumulation in the bilateral occipital lobes. The OCC+ group (41/74, 55.4%) was younger and had a younger age at onset than the OCC− group. The OCC+ group also had an increased standard uptake value ratio in the occipital lobes and greater cortical thinning in relevant areas. The OCC+ group had a higher global deterioration scale, lower performance for the copy, immediate recall, delayed recall, and recognition in Rey–Osterrieth Complex Figure tests than the OCC- group, although...
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To investigate the effect of diabetes mellitus (DM) on the clinicoradiological features in patients with Parkinson's disease (PD). 671 patients with de novo PD were classified into two groups according to the presence of DM (106 with... more
To investigate the effect of diabetes mellitus (DM) on the clinicoradiological features in patients with Parkinson's disease (PD). 671 patients with de novo PD were classified into two groups according to the presence of DM (106 with DM and 565 without). We performed inter-group comparative analyses of the striatal dopamine transporter (DAT) availability in all patients and level of cognitive performances in 312 patients (58 with DM and 254 without). Neuroimaging analyses of cortical thickness were performed in 42 patients with DM and 42 matched patients without DM. We assessed the longitudinal changes in the levodopa-equivalent dose (LED) across time in 549 patients who were treated for at least two years (86 with DM and 463 without) using a linear mixed model. The PD patients with DM were older at the onset of parkinsonism and had more severely decreased baseline DAT availability in the caudate and ventral striatum than those without DM. The PD group with DM showed poorer perf...
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The concept of cognitive reserve (CR) originated from discrepancies between the degree of brain pathology and the severity of clinical manifestations. CR has been characterized through CR proxies, such as education and occupation... more
The concept of cognitive reserve (CR) originated from discrepancies between the degree of brain pathology and the severity of clinical manifestations. CR has been characterized through CR proxies, such as education and occupation complexity; however, such approaches have inherent limitations. Although several methods have been developed to overcome these limitations, they fail to reflect the entire Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (AD) pathology. Meanwhile, graph theory analysis, one of most powerful and flexible approaches, have established remarkable network properties of the brain. The functional and structural brain networks are damaged in neurodegenerative diseases. Therefore, network analysis has been applied to clarify the characteristics of the disease or give insight. Here, using multimodal neuroimaging, we propose an intuitive model to estimate CR based on its original definition, and explore the neural substrates of CR from the perspective of networks and functional connectivity. A total of 87 subjects (21 AD, 32 mild cognitive impairment, and 34 normal aging) underwent tau and amyloid PET, 3D T1-weighted MR, and resting-state fMRI. We hypothesized CR as a residual of actual cognitive performance and expected performance to be related to quantitative factors, such as AD pathology, demographics, and a genetic factor. Then, we correlated this marker using education and occupation complexity as conventional CR proxies. We validated this marker by testing whether it would modulate the effect of brain pathology on memory function. To examine the neural substrates associated with CR, we performed graph analysis to investigate the association between the CR marker and network measures at different granularities in total subjects, AD spectrum and normal aging, respectively. The CR marker from our model was well associated with education and occupation complexity. More directly, the CR marker was revealed to modify the relationship between brain pathology and memory function among AD spectrum. The CR marker was correlated with the global efficiency of the entire network, nodal clustering coefficient, and local efficiency of the right middle-temporal pole. In connectivity analysis, one cluster of edges centered on right middle-temporal pole was significantly correlated with the CR marker. In subgroup analysis, the network measures of right middle-temporal pole still correlated with the CR marker among AD spectrum. However, right precentral gyrus was revealed to be associated with the CR marker in normal aging. This study demonstrates that our intuitive model using multimodal neuroimaging and network perspective adequately and comprehensively captures CR. From a network perspective, CR is associated with the capacity to process information efficiently in the brain. The right middle-temporal pole was revealed to be a pivotal neural substrate of CR in AD spectrum. These findings foster understanding of AD and will be useful to help identify individuals with vulnerability or resistance to AD pathology, and characterize patients for intervention or drug trials.
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High-grade salivary gland carcinoma (SGC) shows a high rate of metastasis and post-treatment recurrence, resulting in poor patient survival. Therefore, we evaluated the utility of pre-treatment F-FDG PET/CT parameters in predicting... more
High-grade salivary gland carcinoma (SGC) shows a high rate of metastasis and post-treatment recurrence, resulting in poor patient survival. Therefore, we evaluated the utility of pre-treatment F-FDG PET/CT parameters in predicting metastasis, tumor progression, and survival of high-grade SGC patients. This observational study included 75 patients with previously untreated high-grade SGC who underwent pre-treatment F-FDG PET/CT scanning and subsequent treatment. Standardized uptake values (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured on pre-treatment F-FDG PET/CT. Logistic regression analysis was used to identify the relationship of these factors with metastasis. Cox proportional hazard regression analyses were used to identify associations between PET parameters and both progression-free survival (PFS) and overall survival (OS). A total of 36 (48%) patients had neck or distant metastases at initial staging. After controlling for clinical factors, MTV (&amp;amp;gt; 8.8 mL) was an independent factor for initial metastasis (adjusted odds ratio 4.80, 95% confidence interval 1.09-21.20; P = 0.039). All PET parameters of SUV (&amp;amp;gt; 4.3), SUV (&amp;amp;gt; 3.0), SUV (3.9), MTV (&amp;amp;gt; 8.8 mL), and TLG (&amp;amp;gt; 31.1 g) were significant variables for PFS (all P &amp;amp;lt; 0.05), while MTV and TLG were significant factors for OS. After controlling for clinicopathological factors, MTV (adjusted hazard ratio 4.36, 95% confidence interval 1.69-11.26; P = 0.002) and TLG (3.41, 1.47-7.91; P = 0.004) were significantly associated with PFS, but not OS. MTV is useful among quantitative PET measurements for predicting initial metastasis and PFS in patients with high-grade SGC.
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Idiopathic pulmonary fibrosis (IPF) is associated with an increased incidence of lung cancer, but patients with IPF often have poor pulmonary function and are vulnerable to pneumothorax and so using an invasive procedure to diagnose a... more
Idiopathic pulmonary fibrosis (IPF) is associated with an increased incidence of lung cancer, but patients with IPF often have poor pulmonary function and are vulnerable to pneumothorax and so using an invasive procedure to diagnose a single nodule detected on chest CT risks a critical adverse outcome. F-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) is recognized to be useful for differentiating between benign and malignant solitary pulmonary nodules (SPN) in patients without IPF, but its diagnostic accuracy has not been investigated in patients with IPF. In this study, therefore, we investigated whether F-FDG PET/CT is useful for the differential diagnosis of SPNs in patients with IPF. From the IPF patient cohort of our institution, we retrospectively reviewed 55 patients (54 men, 1 woman; age 67.8 ± 7.6 years) with an SPN sized 8-30 mm (mean 18.5 ± 5.7 mm) who underwent chest CT followed by F-FDG PET/CT between April 2004 and March 2016. The ...
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Patients with Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (PD) present a variety of non-motor symptoms. However, it remains unclear whether dopamine depletion is related to non-motor symptoms, and which non-motor... more
Patients with Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (PD) present a variety of non-motor symptoms. However, it remains unclear whether dopamine depletion is related to non-motor symptoms, and which non-motor symptoms are significantly dependent on dopaminergic deficit. Forty-one patients with PD who underwent positron emission tomography imaging of dopamine transporters (DATs) were recruited for this study. The striatum was divided into 12 subregions, and DAT activity, as striatal dopaminergic concentration, was calculated in each subregion. In addition to measuring motor symptoms using the Unified Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Disease Rating Scale-part III (UPDRS-III), various non-motor symptoms were assessed using the Montreal cognitive assessment, frontal assessment battery, Beck depression inventory (BDI), Beck anxiety inventory, PD sleep scale (PDSS), PD fatigue scale, and non-motor symptoms scale (NMSS) for PD. For simple linear regression analyses, dopaminergic depletion in all striatal subregions was negatively correlated with the UPDRS-III score. The most relevant non-motor symptom assessment related to dopaminergic loss in the 12 subregions was NMSS, followed by BDI and PDSS. However, following multiple linear regression analyses, dopaminergic depletion in the 12 striatal subregions was not related with any of the non-motor symptoms. Conversely, dopaminergic deficit in the right anterior and posterior putamen was associated with the UPDRS-III score. Striatal dopaminergic depletion was not significantly correlated with any of the various non-motor symptoms in PD. Our findings suggest that non-dopaminergic systems are significantly implicated in the pathogenesis of non-motor symptoms in patients with PD.
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Depression frequently accompanies Parkinson's disease and often precedes the onset of motor symptoms. This study aimed to evaluate the impact of depression on motor compensation in patients with de novo Parkinson's disease. This... more
Depression frequently accompanies Parkinson's disease and often precedes the onset of motor symptoms. This study aimed to evaluate the impact of depression on motor compensation in patients with de novo Parkinson's disease. This retrospective cohort study analyzed data from 474 non-demented patients with de novo Parkinson's disease (mean age, 64.6±9.8 years; 242 men) who underwent both dopamine transporter PET scan and depression assessment using the Beck Depression Inventory at baseline. Patients were classified into tertiles by Beck Depression Inventory score. At baseline, high-tertile group (Beck Depression Inventory score ≥15, n = 157) showed more severe motor deficits and lower cognitive function than low-tertile group (Beck Depression Inventory score ≤7, n = 158, P = 0.034 and P = 0.008, respectively). Greater motor deficits in high-tertile group than low-tertile group remained significant after controlling for dopamine transporter binding in the posterior putamen,...
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To investigate whether the patterns of striatal dopamine depletion could provide prognostic information on the clinical profiles of early-stage Parkinson disease (PD). Approximately 634 patients with drug-naive PD who underwent F-FP-CIT... more
To investigate whether the patterns of striatal dopamine depletion could provide prognostic information on the clinical profiles of early-stage Parkinson disease (PD). Approximately 634 patients with drug-naive PD who underwent F-FP-CIT PET scans were followed up for at least 2 years. After quantifying dopamine transporter (DAT) availability in each striatal subregion, the patterns of striatal dopamine depletion of each patient were assessed based on (1) the degree of dopamine loss in the other striatal subregions compared to the posterior putamen (inter-subregional ratio [ISR]) and (2) the interhemispheric asymmetry of dopamine loss in the posterior putamen (asymmetry index [AI]). According to their patterns, we assessed the longitudinal changes in L-dopa-equivalent doses and L-dopa-induced dyskinesia (LID)-free times using the linear mixed model and Cox regression model, respectively. There was no significant correlation between the ISR and AI values (Pearson correlation coefficie...
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We investigated the regional distribution of F-THK5351 uptake in gray (GM) and white matter (WM) in patients with behavioral-variant frontotemporal dementia (bvFTD) and compared it with that in patients with Alzheimer's disease (AD)... more
We investigated the regional distribution of F-THK5351 uptake in gray (GM) and white matter (WM) in patients with behavioral-variant frontotemporal dementia (bvFTD) and compared it with that in patients with Alzheimer's disease (AD) or semantic dementia (SD). F-THK-5351 positron emission tomography (PET), F-florbetaben PET, magnetic resonance imaging, and neuropsychological testing were performed in 103 subjects including 30, 24, 9, and 8 patients with mild cognitive impairment, AD, bvFTD, and SD, respectively, and 32 normal subjects. Standardized uptake value ratios (SUVRs) of F-THK-5351 PET images were measured from six GM and WM regions using cerebellar GM as reference. GM and WM SUVRs and WM/GM ratios, the relationship between GM SUVR and WM/GM ratio, and correlation between SUVR and cognitive function were compared. In AD, both parietal GM (p < 0.001) and WM (p < 0.001) SUVRs were higher than in bvFTD. In AD and SD, the WM/GM ratio decreased as the GM SUVR increased, ...