Publications by authors named "Minyoung Oh"

58 Publications

FDG-PET patterns associated with ideomotor apraxia and imitation apraxia in patients with corticobasal syndrome.

Parkinsonism Relat Disord 2021 Jul 16;88:96-101. Epub 2021 Jun 16.

Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address:

Introduction: Apraxia is a core clinical feature of corticobasal syndrome (CBS). Among the subtypes of apraxia, ideomotor and imitation apraxia are frequently found in CBS. However, little is known about the brain networks that are characteristic of each apraxia subtype or their clinical implication. In this study, we used F-fluorodeoxyglucose positron emission tomography (FDG-PET) to explore the specific patterns of glucose hypometabolism that are characteristic of apraxia subtypes by focusing on ideomotor and imitation apraxia.

Methods: We compared the areas of glucose hypometabolism in the brains of 52 patients with CBS and 13 healthy controls, both as a whole and according to apraxia subtypes. In addition, we investigated the relationship between the apraxia subtypes and the clinical phenotype of CBS.

Results: In patients with CBS, common hypometabolism was observed in the frontal gyrus, precentral gyrus and caudate regardless of apraxia subtypes. In particular, ideomotor apraxia was associated with hypometabolism in the angular gyrus, while imitation apraxia was associated with hypometabolism in the posterior part including the postcentral gyrus, precuneus, and posterior cingulate gyrus. Patients who showed both ideomotor and imitation apraxia were more likely to show the typical features of CBS and progressive supranuclear palsy compared with patients showing only one type of apraxia.

Conclusion: Group comparison analysis using FDG-PET revealed distinct pathways of ideomotor and imitation apraxia in CBS. These findings add to our understanding of the brain networks underlying apraxia in association with the clinical features of CBS.
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http://dx.doi.org/10.1016/j.parkreldis.2021.06.006DOI Listing
July 2021

Crossed Hemispheric Accumulation of β-Amyloid and Tau Protein in a Patient With Typical Alzheimer Disease.

Alzheimer Dis Assoc Disord 2021 Jun 16. Epub 2021 Jun 16.

Departments of Neurology Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Amyloid (Aβ) and tau proteins are pathologic hallmarks of Alzheimer disease (AD). It is well known that there is spatial disparity between Aβ and tau protein deposition but, crossed hemispheric accumulation of these 2 proteins has not been reported. Here we report the case of a 76-year-old woman with typical AD who underwent amyloid positron emission tomography (PET) ([18F]-florbetaben) and tau PET scans ([18F]PI-2620), revealing crossed accumulation of Aβ and tau in the cerebral hemisphere. A neuropsychological assessment showed impairment in memory with spared activities of daily living. In the PET analysis, amyloid deposition was observed only in the left side of the cerebral hemisphere and tau only in the right side. Neuroimaging follow-up indicated that the spatial pattern of these protein accumulations had not changed. This case suggests the possibility of independent Aβ and tau pathogenic pathways in AD.
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http://dx.doi.org/10.1097/WAD.0000000000000460DOI Listing
June 2021

The Characteristics of Women with Subsequent Distal Radius Fracture after Initial Distal Radius Fracture.

J Bone Metab 2021 May 31;28(2):123-129. Epub 2021 May 31.

Department of Orthopedic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: The purpose of this study was to investigate the characteristics of women with subsequent distal radius fracture (DRF) and to compare bone fragility variables in women with initial and subsequent DRF.

Methods: We enrolled 227 women who experienced DRF (203 women with initial DRF and 24 women with subsequent DRF) between September 2016 and April 2019. We compared demographic characteristics and bone fragility variables, including bone mineral density, trabecular bone score, hip geometry, bicortical thickness of the distal radius, and fracture risk assessment tool (FRAX) scores between the 2 groups. To reduce bias, patients with subsequent DRF were propensity score-matched in a 1:2 manner with patients affected by initial DRF, and additional comparisons were performed.

Results: Patients in the subsequent DRF group were older than those in the initial DRF group, but this difference was not significant (P=0.091). The proportion of patients receiving treatment with osteoporosis medication was significantly higher in the subsequent DRF group (41.7% vs. 19.2%, P=0.011). Bone fragility variables did not differ significantly between the 2 groups. However, the ten-year probability of major osteoporotic fractures based on FRAX scores was significantly higher in patients with subsequent DRF (7.5% vs. 10.8%, P<0.001). Similar results were observed when comparing the propensity score-matched initial and subsequent DRF groups.

Conclusions: These findings suggest that the occurrence of subsequent DRF after initial DRF can be attributed to multiple factors rather than bone fragility alone. Systematic and multidisciplinary management would be helpful in preventing the occurrence of subsequent DRF after the initial DRF.
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http://dx.doi.org/10.11005/jbm.2021.28.2.123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206611PMC
May 2021

Combination of automated brain volumetry on MRI and quantitative tau deposition on THK-5351 PET to support diagnosis of Alzheimer's disease.

Sci Rep 2021 May 14;11(1):10343. Epub 2021 May 14.

Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-Gu, Seoul, 05505, South Korea.

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 incorporating automated volumes of selected brain regions on MRI (cingulate isthmus, inferior parietal lobule, hippocampus) and SUVRs of Braak ROIs on [18F] THK-5351 PET showed higher performance than SUVRs of Braak ROIs on [18F] THK-5351 PET in discriminating AD from HC (0.98 vs 0.88, P = 0.033) but not in discriminating AD from MCI (0.85 vs 0.79, P = 0.178). The combined model showed comparable performance to automated volumes of selected brain regions on MRI in discriminating AD from HC (0.98 vs 0.94, P = 0.094) and MCI (0.85 vs 0.78; P = 0.065).
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http://dx.doi.org/10.1038/s41598-021-89797-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121780PMC
May 2021

A 4-Year Follow-Up of Subjects with Visually Equivocal Amyloid Positron Emission Tomography Findings from the Alzheimer's Disease Neuroimaging Initiative Cohort.

Nucl Med Mol Imaging 2021 Apr 4;55(2):71-78. Epub 2021 Mar 4.

Department of Nuclear Medicine, Asan Medical Center, Seoul, Korea.

Background: To date, the clinical significance of visually equivocal amyloid positron emission tomography (PET) has not been well established.

Objective: We studied the clinical significance of equivocal amyloid PET images from the Alzheimer's Disease Neuroimaging Initiative (ADNI).

Methods: 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.

Results: 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 ( <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%, <0.001) and positive (3.13 ± 4.38%, <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.

Conclusion: 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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http://dx.doi.org/10.1007/s13139-021-00690-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053637PMC
April 2021

F-THK-5351, Fluorodeoxyglucose, and Florbetaben PET Images in Atypical Alzheimer's Disease: A Pictorial Insight into Disease Pathophysiology.

Brain Sci 2021 Apr 6;11(4). Epub 2021 Apr 6.

Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

The recent advance of positron emission tomography (PET) tracers as biomarkers in Alzheimer's disease (AD) provides more insight into pathophysiology, preclinical diagnosis, and further therapeutic strategies. However, synergistic processes or interactions between amyloid and tau deposits are still poorly understood. To better understand their relationship in focal brain changes with clinical phenotypes, we focused on region-specific or atypical AD characterized by focal clinical presentations: Posterior cortical atrophy (PCA) and logopenic variant of primary progressive aphasia (lpvPPA). We compared three different PET images with F-THK-5351 (tau), F-Florbetaben (amyloid beta, Aβ), and F-Fluorodeoxyglucose (glucose metabolism) to investigate potential interactions among pathologies and clinical findings. Whereas the amyloid accumulations were widespread throughout the neocortex, tau retentions and glucose hypometabolism showed focal changes corresponding to the clinical features. The distinctly localized patterns were more prominent in tau PET imaging. These findings suggest that tau pathology correlates more closely to the clinical symptoms and the neurodegenerative processes than Aβ pathology in AD.
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http://dx.doi.org/10.3390/brainsci11040465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067517PMC
April 2021

Statin/ezetimibe combination therapy vs statin monotherapy for carotid atherosclerotic plaque inflammation.

Medicine (Baltimore) 2021 Mar;100(10):e25114

Department of Medicine.

Abstract: It remains uncertain whether statin/ezetimibe combination therapy serves as a useful and equivalent alternative to statin monotherapy for reducing atherosclerotic plaque inflammation. The aim of the present study was to compare the effects of statin/ezetimibe combination therapy and statin monotherapy on carotid atherosclerotic plaque inflammation using 18F-fluorodeoxyglucose (18FDG) positron emission tomography (PET)/computed tomography (CT) imaging. Data were pooled from 2 clinical trials that used serial 18FDG PET/CT examination to investigate the effects of cholesterol-lowering therapy on carotid atherosclerotic plaque inflammation. The primary outcome was the percent change in the target-to-background ratio (TBR) of the index vessel in the most diseased segment (MDS) at 6-month follow-up. Baseline characteristics were largely similar between the 2 groups. At the 6-month follow-up, the MDS TBR of the index vessel significantly decreased in both groups. The percent change in the MDS TBR of the index vessel (primary outcome) did not differ significantly between the 2 groups (-8.41 ± 15.9% vs -8.08 ± 17.0%, respectively, P = .936). Likewise, the percent change in the whole vessel TBR of the index vessel did not differ significantly between the 2 groups. There were significant decreases in total and LDL cholesterol levels in both groups at follow-up (P < .001). There were no significant correlations between the percent changes in MDS TBR of the index vessel, changes in the lipid, and high-sensitive C-reactive protein levels. The reduction in carotid atherosclerotic plaque inflammation by statin/ezetimibe combination therapy was equivalent to that by the statin monotherapy.
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http://dx.doi.org/10.1097/MD.0000000000025114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969286PMC
March 2021

Test-retest reproducibility of dopamine transporter density measured with [F]FP-CIT PET in patients with essential tremor and Parkinson's disease.

Ann Nucl Med 2021 Mar 2;35(3):299-306. Epub 2021 Jan 2.

Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Objective: F-labeled fluoropropyl-carbomethoxylodopropyl-nor-ß-tropane ([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 [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 [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: [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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http://dx.doi.org/10.1007/s12149-020-01561-9DOI Listing
March 2021

Quantitative Proteomic Analysis of Primitive Neural Stem Cells from LRRK2 G2019S-Associated Parkinson's Disease Patient-Derived iPSCs.

Life (Basel) 2020 Dec 7;10(12). Epub 2020 Dec 7.

Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea.

Parkinson's disease (PD) is a common neurodegenerative disease, causing movement defects. The incidence of PD is constantly increasing and this disease is still incurable. Thus, understanding PD pathophysiology would be pivotal for the development of PD therapy, and various PD models have thus been already developed. Through recent advances in reprogramming techniques, a primitive neural stem cell (pNSC) derived from PD patient induced pluripotent stem cells (iPSCs) could be potentially used as a reproducible and reliable experimental system to analyze the effect of the leucine-rich repeat kinase 2 mutation (LK2GS) in neural cells. Here, we investigated the advantages of such a model system through quantitative proteomic analysis of pNSCs from normal control iPSCs and familial PD patient iPSCs harboring LK2GS. We confirmed that the expression of molecules known to be involved in PD pathogenesis, such as oxidative stress-, cell adhesion-, and cytoskeleton-related proteins, were altered in the LK2GS pNSC. In addition, we showed that down-regulation of Ku80, which was found in the proteomic analysis with LK2GS pNSCs, resulted in apoptosis induced by DNA damage response. Taken together, we suggest that pNSCs from PD iPSCs could provide a reliable and useful model system to study PD. Moreover, the highly expandable pNSC is suitable for multi-omics approaches to understand PD pathologies and discover therapeutic targets for PD.
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http://dx.doi.org/10.3390/life10120331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762312PMC
December 2020

Comparative Characterization of Two Homologs in : Genomic, Transcriptional and Functional Analyses.

Biomolecules 2020 09 28;10(10). Epub 2020 Sep 28.

Department of Marine Life Sciences & Fish Vaccine Research Center, Jeju National University, Jeju Self-Governing Province 63243, Korea.

CXCL8 (interleukin-8, IL-8) is a CXC family chemokine that recruits specific target cells and mediates inflammation and wound healing. This study reports the identification and characterization of two homologs from rock bream, . Investigation of molecular signature, homology, phylogeny, and gene structure suggested that they belonged to lineages 1 (L1) and 3 (L3), and designated and . While and revealed quadripartite and tripartite organization, in place of the mammalian ELR (Glu-Leu-Arg) motif, their peptides harbored EMH (Glu-Met-His) and NSH (Asn-Ser-His) motifs, respectively. Transcripts of s were constitutively detected by Quantitative Real-Time PCR (qPCR) in 11 tissues examined, however, at different levels. transcript robustly responded to treatments with stimulants, such as flagellin, concanavalin A, lipopolysaccharide, and poly(I:C), and pathogens, including , , and rock bream iridovirus, when compared with mRNA. The differences in the putative promoter features may partly explain the differential transcriptional modulation of s. Purified recombinant OfCXCL8 (rOfCXCL8) proteins were used in in vitro chemotaxis and proliferation assays. Despite the lack of ELR motif, both rOfCXCL8s exhibited leukocyte chemotactic and proliferative functions, where the potency of rOfCXCL8-L1 was robust and significant compared to that of rOfCXCL8-L3. The results, taken together, are indicative of the crucial importance of s in inflammatory responses and immunoregulatory roles in rock bream immunity.
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http://dx.doi.org/10.3390/biom10101382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601086PMC
September 2020

Clinical Evaluation of 18F-PI-2620 as a Potent PET Radiotracer Imaging Tau Protein in Alzheimer Disease and Other Neurodegenerative Diseases Compared With 18F-THK-5351.

Clin Nucl Med 2020 Nov;45(11):841-847

From the Departments of Nuclear Medicine.

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 F-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 F-PI-2620. Some participants had previous PET scans using F-THK-5351 or F-FP-CIT for dopamine transporter imaging.

Results: All participants showed no increase in off-target binding in basal ganglia on F-PI-2620 PET images, as noted for first-generation tau tracers. Aβ+ mild cognitive impairment or AD patients showed diverse cortical F-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 F-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: F-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 F-PI-2620.
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http://dx.doi.org/10.1097/RLU.0000000000003261DOI Listing
November 2020

Comparison of High-Dose Rosuvastatin Versus Low-Dose Rosuvastatin Plus Ezetimibe on Carotid Atherosclerotic Plaque Inflammation in Patients with Acute Coronary Syndrome.

J Cardiovasc Transl Res 2020 12 4;13(6):900-907. Epub 2020 May 4.

Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

We compared the effects of ezetimibe/rosuvastatin 10/5 mg versus rosuvastatin 20 mg on carotid atherosclerotic plaque inflammation measured by FDG PET/CT. Fifty patients with acute coronary syndrome (ACS) were randomly assigned to the ezetimibe/rosuvastatin 10/5 mg and rosuvastatin 20 mg groups. The primary outcome was the percent change in the target-to-background ratio (TBR) of the index vessel in the most diseased segment (MDS), as assessed by FDG PET/CT at baseline and at 6 months. Forty-eight patients completed follow-up PET/CT. MDS TBR was - 6.2 ± 13.9% for patients in the ezetimibe/rosuvastatin group and - 10.8 ± 17.7% for those in the rosuvastatin group (difference, 4.6 percentage points; upper limitation of one-sided confidence interval = 13.8; p = 0.60 for noninferiority). In conclusion, combination therapy with ezetimibe 10 mg and rosuvastatin 5 mg compared with rosuvastatin 20 mg did not meet the criterion for non-inferiority for primary outcome, and the present study was not conclusive on whether the former was non-inferior to the latter. Graphical Abstract.
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http://dx.doi.org/10.1007/s12265-020-10009-4DOI Listing
December 2020

First Draft Genome Assembly of Redlip Mullet () From Family Mugilidae.

Front Genet 2019 3;10:1246. Epub 2019 Dec 3.

Department of Marine Life Sciences and Fish Vaccine Research Center, Jeju National University, Jeju-si, South Korea.

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http://dx.doi.org/10.3389/fgene.2019.01246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902644PMC
December 2019

Intra-individual correlations between quantitative THK-5351 PET and MRI-derived cortical volume in Alzheimer's disease differ according to disease severity and amyloid positivity.

PLoS One 2019 13;14(12):e0226265. Epub 2019 Dec 13.

Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Purpose: To assess the in vivo whole-brain relationship between uptake of [18F]THK-5351 on PET and cortical atrophy on structural MRI according to the presence and severity of Alzheimer's disease (AD).

Materials And Methods: Sixty-five participants (21 normal controls, 32 mild cognitive impairment [MCI] subjects, and 12 AD patients) were enrolled from a prospective multicenter clinical trial (NCT02656498). Structural MRI and [18F]THK-5351 PET were performed within a 2-month interval. Cortical volume and standardized uptake value ratios (SUVR) were calculated from MRI and PET images, respectively, for 35 FreeSurfer-derived cortical regions. Pearson's correlation coefficients between SUVR and cortical volume were calculated for the same regions, and correlated regions were compared according to disease severity and β-amyloid PET positivity.

Results: No significantly correlated regions were found in the normal controls. Negative correlations between SUVR and cortical volume were found in the MCI and AD groups, mainly in limbic locations in MCI and isocortical locations in AD. The AD group exhibited stronger correlations (r = -0.576-0.781) than the MCI group (r = 0.368-0.571). Hippocampal atrophy did not show any correlation with SUVR in the β-amyloid PET-negative group, but negatively correlated with SUVR (r = -0.494, P = .012) in the β-amyloid PET-positive group.

Conclusions: Regional THK-5351 uptake correlated more strongly with cortical atrophy in AD compared with MCI, thereby demonstrating a close relationship between the neuro-pathologic process and cortical atrophy. Hippocampal atrophy was associated with both β-amyloid and THK-5351 uptake, possibly reflecting an interaction between β-amyloid and tau deposition in the neurodegeneration process.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226265PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910674PMC
April 2020

The clinical feasibility of deep learning-based classification of amyloid PET images in visually equivocal cases.

Eur J Nucl Med Mol Imaging 2020 02 6;47(2):332-341. Epub 2019 Dec 6.

Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

Purpose: Although most deep learning (DL) studies have reported excellent classification accuracy, these studies usually target typical Alzheimer's disease (AD) and normal cognition (NC) for which conventional visual assessment performs well. A clinically relevant issue is the selection of high-risk subjects who need active surveillance among equivocal cases. We validated the clinical feasibility of DL compared with visual rating or quantitative measurement for assessing the diagnosis and prognosis of subjects with equivocal amyloid scans.

Methods: F-florbetaben scans of 430 cases (85 NC, 233 mild cognitive impairment, and 112 AD) were assessed through visual rating-based, quantification-based, and DL-based methods. DL was trained using 280 two-dimensional PET images (80%) and tested by randomly assigning the remaining (70 cases, 20%) cases and a clinical validation set of 54 equivocal cases. In the equivocal cases, we assessed the agreement among the visual rating, quantification, and DL and compared the clinical outcome according to each modality-based amyloid status.

Results: The visual reading was positive in 175 cases, equivocal in 54 cases, and negative in 201 cases. The composite SUVR cutoff value was 1.32 (AUC 0.99). The subject-level performance of DL using the test set was 100%. Among the 54 equivocal cases, 37 cases were classified as positive (Eq(deep+)) by DL, 40 cases were classified by a second-round visual assessment, and 40 cases were classified by quantification. The DL- and quantification-based classifications showed good agreement (83%, κ = 0.59). The composite SUVRs differed between Eq(deep+) (1.47 [0.13]) and Eq(deep-) (1.29 [0.10]; P < 0.001). DL, but not the visual rating, showed a significant difference in the Mini-Mental Status Examination score change during the follow-up between Eq(deep+) (- 4.21 [0.57]) and Eq(deep-) (- 1.74 [0.76]; P = 0.023) (mean duration, 1.76 years).

Conclusions: In visually equivocal scans, DL was more related to quantification than to visual assessment, and the negative cases selected by DL showed no decline in cognitive outcome. DL is useful for clinical diagnosis and prognosis assessment in subjects with visually equivocal amyloid scans.
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http://dx.doi.org/10.1007/s00259-019-04595-yDOI Listing
February 2020

False-negative Hepatobiliary Scintigraphy for Biliary Atresia.

Nucl Med Mol Imaging 2019 Oct 21;53(5):356-360. Epub 2019 Aug 21.

1Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

We present the case of a patient with biliary and duodenal atresia who showed false-negative hepatobiliary scintigraphy results. The patient was born at 37 weeks and 2 days of gestation. Her mother had undergone amnioreduction after detection of a double-bubble ultrasound sign in the fetal abdomen. At 2 days of age, total serum bilirubin level was elevated. On hepatobiliary scintigraphy 4 days later, the gallbladder was visualized from 30 min and it showed duodeno-gastric reflux at 240 min. After 24 h, the radiotracer was almost washed out in the hepatic parenchyma, but there was retention in the gastroduodenal junction. Because the biliary to duodenal transit was visible, biliary atresia seemed unlikely. Abdominal ultrasonography at 7 days of age showed a small dysmorphic gallbladder, but triangular cord sign was not definite. Magnetic resonance cholangiography revealed atretic gallbladder. Although cystic and common bile ducts were visible, the proximal common hepatic bile duct was not visible. The next day, serum total bilirubin levels remained elevated (17.1 mg/dl) with direct bilirubin level of 1.2 mg/dl. Kasai portoenterostomy with duodeno-duodenostomy was performed at 10 days of age. Histopathological evaluation showed a fibrous obliteration of the common bile duct, consistent with that of biliary atresia.
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http://dx.doi.org/10.1007/s13139-019-00606-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821929PMC
October 2019

Association of striatal dopaminergic neuronal integrity with cognitive dysfunction and cerebral cortical metabolism in Parkinson's disease with mild cognitive impairment.

Nucl Med Commun 2019 Dec;40(12):1216-1223

Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul.

Objectives: Cognitive impairment is a common non-motor feature of Parkinson's disease (PD). However, the underlying pathophysiology of cognitive decline is unclear. We investigated the association of striatal dopamine transporter (DAT) loss with cognitive function and cerebral cortical metabolism in PD.

Methods: Twenty-eight patients (63.1 ± 7.1 yrs, M:F = 15:13) with advanced stage of PD were enrolled, including 15 (53.6%) diagnosed with mild cognitive impairment (MCI). All patients underwent FP-CIT PET/CT, neuropsychological tests, and FDG PET/CT within a 2-week interval. We calculated the specific to non-specific binding ratio on FP-CIT PET images in 12 striatal subregional VOIs, using one occipital VOI template as a reference. Age-adjusted normalized specific to non-specific binding ratios (%BRs) of striatal subregions were compared in two groups: PD with MCI versus PD (without cognitive impairment).

Results: There were no statistical differences in age, age at onset, disease duration, motor symptoms, or level of education between the two groups. The PD with MCI had lower %BRs in all striatal subregions (P < 0.05) except the posterior putamen, compared with the PD. Striatal DAT availability correlated with frontal/executive function (r = 0.567, P = 0.003) and visuospatial function (r = 0.614, P = 0.001) but not with memory function. Dopamine transporter binding of striatal subregions also correlated with posterior cortical metabolism.

Conclusion: This study suggest that DAT loss in the striatum, except in the posterior putamen, is associated with cognitive dysfunction, specifically frontal/executive function and visuospatial function in PD subjects.
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http://dx.doi.org/10.1097/MNM.0000000000001098DOI Listing
December 2019

Bilirubin-Related Differential Striatal [18F]FP-CIT Uptake in Parkinson Disease.

Clin Nucl Med 2019 Nov;44(11):855-859

From the Departments of Nuclear Medicine.

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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http://dx.doi.org/10.1097/RLU.0000000000002749DOI Listing
November 2019

THK5351 and flortaucipir PET with pathological correlation in a Creutzfeldt-Jakob disease patient: a case report.

BMC Neurol 2019 Aug 29;19(1):211. Epub 2019 Aug 29.

Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea.

Background: THK5351 and flortaucipir tau ligands have high affinity for paired helical filament tau, yet diverse off-target bindings have been reported. Recent data support the hypothesis that THK5351 binds to monoamine oxidase B (MAO-B) expressed from reactive astrocytes and that flortaucipir has an affinity toward MAO-A and B; however, pathological evidence is lacking. We performed a head-to-head comparison of the two tau ligands in a sporadic Creutzfeldt-Jakob disease (CJD) patient and performed an imaging-pathological correlation study.

Case Presentation: A 67-year-old man visited our clinic a history of 6 months of rapidly progressive dementia, visual disturbance, and akinetic mutism. Diffusion-weighted imaging showed cortical diffusion restrictions in the left temporo-parieto-occipital regions. F-THK5351 PET, but not F-flortaucipir PET showed high uptake in the left temporo-parieto-occipital regions, largely overlapping with the diffusion restricted areas. Cerebrospinal fluid analysis was weakly positive for 14-3-3 protein and pathogenic prion protein was found. The patient showed rapid cognitive decline along with myoclonic seizures and died 13 months after his first visit. A post-mortem study revealed immunoreactivity for PrP, no evidence of neurofibrillary tangles, and abundant astrocytosis which was reactive for MAO-B antibody.

Conclusions: Our findings add pathological evidence that increased THK5351 uptake in sporadic CJD patients might be caused by an off-target binding driven by its high affinity for MAO-B.
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http://dx.doi.org/10.1186/s12883-019-1434-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714095PMC
August 2019

Effects of ezetimibe/simvastatin 10/10 mg versus Rosuvastatin 10 mg on carotid atherosclerotic plaque inflammation.

BMC Cardiovasc Disord 2019 08 19;19(1):201. Epub 2019 Aug 19.

Division of Cardiology, Heart Institute, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Background: Using F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) imaging, we examined the effects of ezetimibe/simvastatin 10/10 mg versus rosuvastatin 10 mg on carotid atherosclerotic plaque inflammation. Whether the combination therapy of ezetimibe with low-dose statin is as effective as potent statin monotherapy in attenuating carotid atherosclerotic plaque inflammation remains unclear.

Methods: In this 2-by-2 factorial trial, 50 patients with FDG uptake (target-to-background ratio [TBR] ≥1.6) in the carotid artery and acute coronary syndrome were randomized to receive either simvastatin/ezetimibe 10/10 mg or rosuvastatin 10 mg. FDG PET/CT examinations were performed at baseline and at 6 months. The percent change in the TBR of the index vessel at the most diseased segment (MDS) was the primary endpoint.

Results: Baseline characteristics of the two groups were largely similar. At 6-month follow-up, the MDS TBR of the index vessel and aorta significantly decreased in ezetimibe/simvastatin group and tended to decrease in rosuvastatin group. However, the percent change in the MDS TBR of the index vessel was similar between the 2 groups (- 10.22 ± 17.49% vs. -5.84 ± 15.78%, respectively, p = 0.357), as was the percent change in the whole vessel TBR of the index vessel. Likewise, the changes in the MDS TBR or whole vessel TBR of the aorta were similar in both groups. Total cholesterol and low-density lipoprotein cholesterol levels improved to a similar degree in both groups.

Conclusion: Treatment with ezetimibe/simvastatin versus rosuvastatin resulted in a similar improvement of carotid atherosclerotic plaque inflammation, suggesting their equivalent anti-inflammatory effects.

Trial Registration: The trial is registered at ClinicalTrials.gov : NCT02378064, 3-4-2015. /IRB No. 2015-0194.
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http://dx.doi.org/10.1186/s12872-019-1184-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700958PMC
August 2019

Distinct clinical features of predominant pre-synaptic and trans-synaptic nigrostriatal dysfunction in multiple system atrophy.

J Neurol Sci 2019 Jul 16;402:100-106. Epub 2019 May 16.

Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. Electronic address:

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 [F]FP-CIT-PET and [F]FDG-PET within 3 months of clinical evaluation, and who had ≤3 years of disease duration. Tracer uptake of the striatum on [F]FP-CIT-PET and glucose metabolism of the striatum on [F]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 [F]FP-CIT-PET (MSA-SNpc, n = 21) and trans-synaptic dopaminergic dysfunction reflected by both [F]FP-CIT-PET and [F]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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http://dx.doi.org/10.1016/j.jns.2019.05.017DOI Listing
July 2019

Comparison of Amyloid β and Tau Spread Models in Alzheimer's Disease.

Cereb Cortex 2019 09;29(10):4291-4302

Graduate School of Medical Science & Engineering, KAIST, Daejeon, Republic of Korea.

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 spread model. Compared with tau, the local spread model also predicted a comparable portion of Aβ deposition. These findings provide evidence of transneuronal spread of AD pathogenic proteins in a large-scale brain network and furthermore suggest different contributions of spread models for tau and Aβ in AD.
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http://dx.doi.org/10.1093/cercor/bhy311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963115PMC
September 2019

Comparison of fimasartan and amlodipine therapy on carotid atherosclerotic plaque inflammation.

Clin Cardiol 2019 Feb 20;42(2):241-246. Epub 2018 Dec 20.

Department of Medicine, University of Ulsan College of Medicine, Seoul, South Korea.

Background: The renin-angiotensin system plays an important role in promoting atherosclerotic plaque inflammation, which may be inhibited by angiotension-II receptor blockers.

Hypothesis: We investigated the effects of fimasartan and amlodipine therapy on carotid atherosclerotic plaque inflammation using F-fluorodeoxyglucose ( FDG) positron emission tomography (PET) imaging.

Methods: Fifty patients with acute coronary syndrome (ACS) and at least one lesion with FDG uptake in the carotid artery (target-to-background ratio [TBR] ≥ 1.6) were randomly assigned to receive either fimasartan (60 mg once a day) or amlodipine (5 mg once a day). FDG PET examinations were performed in all patients at baseline and 6 months. The primary endpoint was the percent change in the index vessel TBR for the most diseased segment (MDS TBR).

Results: The two groups had similar baseline characteristics. At the 6-month follow-up, index vessel and aorta MDS TBR significantly decreased in both groups. However, the percent change in index vessel MDS TBR was similar between the two groups (-9.33 ± 14.2% vs -7.73 ± 19.1%, respectively, P = 0.9). No significant difference was found for the percent change in the whole vessel TBR for the index vessel between the two groups, with similar findings for changes in MDS TBR or whole vessel TBR for the aorta. Total cholesterol, low-density lipoprotein cholesterol levels, and blood pressure improved to a similar degree in both groups.

Conclusions: Fimasartan and amlodipine reduce carotid atherosclerotic plaque inflammation similarly in patients with ACS, offering the same level of effectiveness.
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http://dx.doi.org/10.1002/clc.23133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712325PMC
February 2019

Neural substrates of cognitive reserve in Alzheimer's disease spectrum and normal aging.

Neuroimage 2019 02 29;186:690-702. Epub 2018 Nov 29.

Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea; KI for Health Science and Technology, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea; Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea. Electronic address:

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'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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http://dx.doi.org/10.1016/j.neuroimage.2018.11.053DOI Listing
February 2019

Molecular characterization and expression analysis of big-belly seahorse (Hippocampus abdominalis) interleukin-10 and analysis of its potent anti-inflammatory properties in LPS-induced murine macrophage RAW 264.7 cells.

Gene 2019 Feb 25;685:1-11. Epub 2018 Oct 25.

Department of Marine Life Sciences & Fish Vaccine Research Center, Jeju National University, Jeju Self-Governing Province 63243, Republic of Korea; Marine Science Institute, Jeju National University, Jeju Self-Governing Province 63333, Republic of Korea. Electronic address:

Interleukin-10 (IL-10) is a pleiotropic cytokine involved in the regulation of innate and adaptive immunity. In this study, IL-10 from big-belly seahorse (Hippocampus abdominalis) (HaIL-10) was characterized based on its molecular and functional aspects. The coding sequence of HaIL-10 is 570 bp in length and encodes a 189-amino acid residue protein (calculated molecular weight, 21.89 kDa). The deduced amino acid sequence comprises a typical signal peptide and a mature peptide domain sequence carrying four conserved Cys residues and two additional Cys residues specific to fish. Phylogenetic analysis indicated an evolutionary relationship between HaIL-10 and its counterparts in other vertebrates, with close clustering to the fish-specific homologs. Recombinant HaIL-10 (rHaIL-10) significantly reduced nitric oxide (NO) production by lipopolysaccharide (LPS)-induced murine macrophage RAW 264.7 cells in a concentration-dependent manner but had no effect on cell viability, suggestive of its involvement in immune response. The protein expressions of iNOS and COX-2 were significantly reduced by rHaIL-10 in LPS-induced murine macrophages RAW 264.7 cells. HaIL-10 mRNA expression was observed in all analyzed tissues, with the maximum expression being noted in the kidney and ovary. However, transcriptional levels of HaIL-10 were significantly higher in the blood, gill, and intestine upon in vivo induction with LPS, polyinosinic:polycytidylic acid [poly (I:C)], and Streptococcus iniae. To summarize, our findings help in the improved understanding of the biological functions of HaIL-10 and modulation of HaIL-10 mRNA expression in response to immune stress.
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http://dx.doi.org/10.1016/j.gene.2018.10.053DOI Listing
February 2019

Differences in gray and white matter F-THK5351 uptake between behavioral-variant frontotemporal dementia and other dementias.

Eur J Nucl Med Mol Imaging 2019 02 14;46(2):357-366. Epub 2018 Aug 14.

Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

Purpose: 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).

Methods: 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.

Results: 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, regardless of lobar region. In AD, memory function correlated with parietal GM (ρ = -0.74, p < 0.001) and WM (ρ = -0.53, p < 0.001) SUVR. In SD, language function correlated with temporal GM SUVR (ρ = -0.69, p = 0.006). The frontal WM SUVR was higher in bvFTD than in AD (p = 0.003) or SD (p = 0.017). The frontal WM/GM ratio was higher in bvFTD than in AD (p < 0.001). In bvFTD, the WM/GM ratio increased more prominently than the GM SUVR only in the frontal lobe (R = 0.026). In bvFTD, executive function correlated with frontal WM SUVR (ρ = -0.64, p = 0.014).

Conclusions: Frontal WM F-THK5351 uptake was higher in bvFTD than in other dementias. The increase in frontal WM uptake was greater than the increase in GM uptake and correlated with executive function. This suggests that frontal lobe WM F-THK5351 uptake reflects neuropathological differences between bvFTD and other dementias.
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http://dx.doi.org/10.1007/s00259-018-4125-xDOI Listing
February 2019

Amide proton transfer imaging seems to provide higher diagnostic performance in post-treatment high-grade gliomas than methionine positron emission tomography.

Eur Radiol 2018 Aug 27;28(8):3285-3295. Epub 2018 Feb 27.

Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Objectives: To compare the diagnostic performance of amide proton transfer (APT) imaging and 11-C methionine positron emission tomography (MET-PET) for in vivo molecular imaging of protein metabolism in post-treatment gliomas.

Materials And Methods: This study included 43 patients (12 low and 31 high grade) with post-treatment gliomas who underwent both APT and MET-PET imaging within 3 weeks. APT-weighted voxel values and semi-quantitative tumour-to-normal ratios (TNR) were obtained from tumour portions. The voxel-wise relationships between TNR and APT were assessed. The diagnostic performance for recurrence of high-grade gliomas was calculated, using the area under the receiver operating characteristic curve (AUC) with maximum (TNR and APT) and 90% histogram values (TNR90 and APT90).

Results: A moderate positive correlation between TNR and APT was found in low-grade recurrences (r = 0.47, p < 0.001), but not in high-grade ones (r = -0.24, p < 0.001). For distinguishing recurrence in post-treatment high-grade gliomas, APT (AUC, 0.88) and APT90 (AUC, 0.78-0.83) had a similar to better diagnostic performance than TNR (AUC, 0.71, p = 0.08) or TNR90 (AUC, 0.53-0.59, p = 0.01-0.05).

Conclusions: In post-treatment high-grade gliomas, APT provides different regional information to MET-PET and provides higher diagnostic performance. This difference needs to be considered when using APT or MET-PET as a surrogate marker for tumour protein metabolism.

Key Points: • APT and TNR values in low-grade recurrence showed a moderate voxel-wise correlation. • APT and TNR demonstrated regional differences in post-treatment high-grade gliomas. • APT90 showed better diagnostic performance than TNR90 in high-grade recurrence.
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http://dx.doi.org/10.1007/s00330-018-5341-2DOI Listing
August 2018

Clinical significance of visually equivocal amyloid PET findings from the Alzheimer's Disease Neuroimaging Initiative cohort.

Neuroreport 2018 05;29(7):553-558

Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine.

To evaluate the clinical and imaging characteristics of patients with visually equivocal amyloid PET images, patients from the Alzheimer's Disease Neuroimaging Initiative cohort who had fluorine-18-florbetapir PET scans both at baseline and 24 months were selected. Five nuclear medicine physicians visually assessed the PET images and classified them as either positive or negative. Images not reaching a majority agreement were classified as equivocal. Among a total of 379 patients, the number of patients in each fluorine-18-florbetapir PET negative/equivocal/positive categories was 218 (57.5%), 32 (8.4%), and 129 (34.0%). Eight to 9% of patients with normal cognition (N=12/141), mild cognitive impairment (N=20/214), and no Alzheimer's disease (N=0/24) showed equivocal PET finding for each. In negative/equivocal/positive groups, positive cerebrospinal fluid Aβ1-42 was observed in 25.7, 81.5, and 98.3%, respectively. Baseline standardized uptake value ratios of fluorine-18-florbetapir PET were 0.75±0.05, 0.86±0.09, and 1.01±0.09, respectively [F(2, 376)=603.547; P<0.001]. After 24 months of follow-up, the standardized uptake value ratios increased by 0.81±2.62, 2.81±2.90, and 2.17±3.66%, respectively [F(2, 376)=7.905, P<0.05 vs. the negative group]. Among mild cognitive impairment patients, the equivocal group showed a more rapid decline in glucose metabolism than the negative group [5.52±5.36 vs. 0.67±4.45; F(2, 122)=9.028, P<0.01]. 8.4% of the patients in this study showed a visually equivocal result of amyloid PET. These patients showed a moderate amount of amyloid accumulation and a rapid rate of accumulation.
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http://dx.doi.org/10.1097/WNR.0000000000000986DOI Listing
May 2018

Altered Biodistribution of Tc-DPD on Bone Scan After Intravenous Iron Supplement.

Nucl Med Mol Imaging 2017 Dec 25;51(4):347-349. Epub 2017 Jul 25.

Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505 Korea.

We report a case with altered biodistribution of Tc-dicarboxypropane diphosphonate (Tc-DPD) on whole body bone scan after intravenous iron supplement therapy. A 47-year-old male patient who had recently been detected with a hepatic mass suggestive of hepatocellular carcinoma underwent bone scan as staging work-up before surgery. Bone scan images at 3 h after injection of Tc-DPD demonstrated unusually increased blood pool activities in the heart, liver, and spleen with usual skeletal uptakes. The patient had been treated for severe anemia from hemorrhoid with two intravenous administration of ferric hydroxide carboxymaltose complex at approximately 22 h and 2 h prior to the Tc-DPD injection, which we consider as the most probable cause of altered biodistribution of Tc-DPD.
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http://dx.doi.org/10.1007/s13139-017-0486-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5721091PMC
December 2017

Longitudinal Decline of Striatal Subregional [F]FP-CIT Uptake in Parkinson's Disease.

Nucl Med Mol Imaging 2017 Dec 6;51(4):304-313. Epub 2017 Apr 6.

Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympicro 43-gil, Songpa-gu, Seoul, 05505 South Korea.

Purpose: Dopamine transporter imaging is suggested to be a useful imaging biomarker for Parkinson's disease (PD) progression and monitoring drug effects. We investigated the longitudinal decline characteristics of striatal [F]FP-CIT uptake in PD.

Methods: We retrospectively reviewed 35 PD patients and 9 non-PD patients. All patients underwent [F]FP-CIT PET at the initial diagnosis and follow-up. PET images were spatially normalized and analyzed with eight striatal and one occipital VOI templates. We measured the specific to non-specific binding ratio (SNBR) of the striatal subregions and calculated the absolute annual reduction (AAR) and relative annual reduction (%RAR) of the SNBRs.

Results: Total striatal SNBRs in PD patients were significantly lower than those in non-PD patients, with the most significant difference in the posterior putamen. Both AAR (0.26 ± 0.14 vs. 0.09 ± 0.19,  < 0.05) and %RAR (6.9 ± 3.5 vs. 1.2 ± 2.7,  < 0.001) of total striatal SNBRs were significantly greater in PD than non-PD patients. There were no significant differences in the AAR and %RAR of total striatal SNBRs between elderly and young onset PD. The AARs of the posterior putamen were higher in early PD than in advanced PD. Conversely, the %RARs were not significantly different between early and more advanced PD. The disease duration was significantly negatively correlated with the AAR but not with the %RAR of the posterior putamen.

Conclusions: The longitudinal decline of striatal [F]FP-CIT uptake in PD was nonlinear and significantly faster than that in non-PD, with a different rate of decline among the striatal subregions.
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http://dx.doi.org/10.1007/s13139-017-0481-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5721089PMC
December 2017
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