Sleep and Neuroimaging / 대한핵의학회잡지

We spend about one-third of our lives either sleeping or attempting to sleep. Therefore, the socioeconomic implications of sleepdisorders may be higher than expected. However, the fundamental mechanisms and functions of sleep are not yet fully understood.Neuroimaging has been utilized to reveal the connectivity between sleep and the brain, which is associated with thephysiology of sleep. Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imagingstudies have become increasingly common in sleep research. Recently, significant progress has been made in understanding thephysiology of sleep through neuroimaging and the use of various radiopharmaceuticals, as the sleep–wake cycle is regulated bymultiple neurotransmitters, including dopamine, adenosine, glutamate, and others. In addition, the characteristics of rapid eye andnon-rapid eye movement sleep have been investigated by measuring cerebral glucose metabolism. The physiology of sleep hasbeen investigated using PET to study glymphatic function as a means to clear the amyloid burden. However, the basic mechanismsand functions of sleep are not yet fully understood. Further studies are needed to investigate the effects and consequencesof chronic sleep deprivation, and the relevance of sleep to other diseases.

Effect of Single-Nucleotide Polymorphisms on Decline of Dopamine Transporter Availability in Parkinson's Disease

BACKGROUND AND PURPOSE: We aimed to determine the association between the annual changes in dopamine transporter (DAT) availability as measured by 123I-ioflupane (123I-FP-CIT) single-photon-emission computed tomography and single-nucleotide polymorphisms (SNPs) known to be risk factors in Parkinson's disease (PD). METHODS: In total, 150 PD patients were included from the Parkinson's Progression Markers Initiative database. Specific SNPs that are associated with PD were selected for genotyping. SNPs that were not in Hardy-Weinberg equilibrium or whose minor allele frequency was less than 0.05 were excluded. Twenty-three SNPs met the inclusion criteria for this study. The Kruskal-Wallis test was used to compare annual percentage changes in DAT availability for three subgroups of SNP. RESULTS: None of the 23 SNPs exerted a statistically significant effect (p < 0.0022) on the decline of DAT availability in PD patients. However, we observed trends of association (p < 0.05) between three SNPs of two genes with the annual percentage change in DAT availability: 1) rs199347 on the putamen (p=0.0138), 2) rs356181 on the caudate nucleus (p=0.0105), and 3) rs3910105 on the caudate nucleus (p=0.0374). A post-hoc analysis revealed that DAT availability was reduced the most for 1) the putamen in the CC genotype of rs199347 (vs. CT, p=0.0199; vs. TT, p=0.0164), 2) the caudate nucleus in the TT genotype of rs356181 (vs. CC, p=0.0081), and 3) the caudate nucleus in the CC genotype of rs3910105 (vs. TT, p=0.0317). CONCLUSIONS: Significant trends in the associations between three SNPs and decline of DAT availability in PD patients have been discovered.

Effects of Thyrotropin Suppression on Bone Health in Menopausal Women with Total Thyroidectomy

BACKGROUND: This study examined the change in the trabecular bone score (TBS), areal bone mineral density (aBMD), and osteoporosis in postmenopausal women who underwent thyrotropin (TSH)-suppressive therapy for treating papillary thyroid cancer after a total thyroidectomy procedure. METHODS: We evaluated 36 postmenopausal women who received a total thyroidectomy for papillary thyroid cancer and were undergoing TSH suppressive therapy with levothyroxine. Postmenopausal women (n=94) matched for age and body mass index were recruited as healthy controls. The aBMD and TBS of the lumbar spine were compared between dual energy X-ray absorptiometry (DXA) at baseline and at follow-up after an average of 4.92 years. RESULTS: There was no significant difference in the rate of diagnoses of osteoporosis, osteopenia, or normal bone status between the 2 groups during the baseline DXA evaluation. However, the TBS was significantly lower whereas aBMD did not show significant difference at the time of baseline DXA measurement (1st DXA, 1.343±0.098 vs. 1.372±0.06317, P < 0.001; 2nd DXA, 1.342±0.095 vs. 1.370±0.062, P < 0.001). The TBS and aBMD did not differ significantly between the initial and follow-up DXA images in both groups of TSH suppressive patients and controls. CONCLUSIONS: The average value of TBS and aBMD did not significantly change during the follow-up period. The TSH suppressive therapy was revealed as not a significant factor for the progressive deterioration of bone status during long term follow-up.

Diagnostic test accuracy: application and practice using R software / 한국역학회지

The objective of this paper is to describe general approaches of diagnostic test accuracy (DTA) that are available for the quantitative synthesis of data using R software. We conduct a DTA that summarizes statistics for univariate analysis and bivariate analysis. The package commands of R software were “metaprop” and “metabin” for sensitivity, specificity, and diagnostic odds ratio; forest for forest plot; reitsma of “mada” for a summarized receiver-operating characteristic (ROC) curve; and “metareg” for meta-regression analysis. The estimated total effect sizes, test for heterogeneity and moderator effect, and a summarized ROC curve are reported using R software. In particular, we focus on how to calculate the effect sizes of target studies in DTA. This study focuses on the practical methods of DTA rather than theoretical concepts for researchers whose fields of study were non-statistics related. By performing this study, we hope that many researchers will use R software to determine the DTA more easily, and that there will be greater interest in related research.

Intervention meta-analysis: application and practice using R software / 한국역학회지

The objective of this study was to describe general approaches for intervention meta-analysis available for quantitative data synthesis using the R software. We conducted an intervention meta-analysis using two types of data, continuous and binary, characterized by mean difference and odds ratio, respectively. The package commands for the R software were “metacont”, “metabin”, and “metagen” for the overall effect size, “forest” for forest plot, “metareg” for meta-regression analysis, and “funnel” and “metabias” for the publication bias. The estimated overall effect sizes, test for heterogeneity and moderator effect, and the publication bias were reported using the R software. In particular, the authors indicated methods for calculating the effect sizes of the target studies in intervention meta-analysis. This study focused on the practical methods of intervention meta-analysis, rather than the theoretical concepts, for researchers with no major in statistics. Through this study, the authors hope that many researchers will use the R software to more readily perform the intervention meta-analysis and that this will in turn generate further related research.

Network meta-analysis: application and practice using R software / 한국역학회지

The objective of this study is to describe the general approaches to network meta-analysis that are available for quantitative data synthesis using R software. We conducted a network meta-analysis using two approaches: Bayesian and frequentist methods. The corresponding R packages were “gemtc” for the Bayesian approach and “netmeta” for the frequentist approach. In estimating a network meta-analysis model using a Bayesian framework, the “rjags” package is a common tool. “rjags” implements Markov chain Monte Carlo simulation with a graphical output. The estimated overall effect sizes, test for heterogeneity, moderator effects, and publication bias were reported using R software. The authors focus on two flexible models, Bayesian and frequentist, to determine overall effect sizes in network meta-analysis. This study focused on the practical methods of network meta-analysis rather than theoretical concepts, making the material easy to understand for Korean researchers who did not major in statistics. The authors hope that this study will help many Korean researchers to perform network meta-analyses and conduct related research more easily with R software.

Diagnostic test accuracy: application and practice using R software / 한국역학회지

The objective of this paper is to describe general approaches of diagnostic test accuracy (DTA) that are available for the quantitative synthesis of data using R software. We conduct a DTA that summarizes statistics for univariate analysis and bivariate analysis. The package commands of R software were “metaprop” and “metabin” for sensitivity, specificity, and diagnostic odds ratio; forest for forest plot; reitsma of “mada” for a summarized receiver-operating characteristic (ROC) curve; and “metareg” for meta-regression analysis. The estimated total effect sizes, test for heterogeneity and moderator effect, and a summarized ROC curve are reported using R software. In particular, we focus on how to calculate the effect sizes of target studies in DTA. This study focuses on the practical methods of DTA rather than theoretical concepts for researchers whose fields of study were non-statistics related. By performing this study, we hope that many researchers will use R software to determine the DTA more easily, and that there will be greater interest in related research.

Intervention meta-analysis: application and practice using R software / 한국역학회지

The objective of this study was to describe general approaches for intervention meta-analysis available for quantitative data synthesis using the R software. We conducted an intervention meta-analysis using two types of data, continuous and binary, characterized by mean difference and odds ratio, respectively. The package commands for the R software were “metacont”, “metabin”, and “metagen” for the overall effect size, “forest” for forest plot, “metareg” for meta-regression analysis, and “funnel” and “metabias” for the publication bias. The estimated overall effect sizes, test for heterogeneity and moderator effect, and the publication bias were reported using the R software. In particular, the authors indicated methods for calculating the effect sizes of the target studies in intervention meta-analysis. This study focused on the practical methods of intervention meta-analysis, rather than the theoretical concepts, for researchers with no major in statistics. Through this study, the authors hope that many researchers will use the R software to more readily perform the intervention meta-analysis and that this will in turn generate further related research.

Network meta-analysis: application and practice using R software / 한국역학회지

The objective of this study is to describe the general approaches to network meta-analysis that are available for quantitative data synthesis using R software. We conducted a network meta-analysis using two approaches: Bayesian and frequentist methods. The corresponding R packages were “gemtc” for the Bayesian approach and “netmeta” for the frequentist approach. In estimating a network meta-analysis model using a Bayesian framework, the “rjags” package is a common tool. “rjags” implements Markov chain Monte Carlo simulation with a graphical output. The estimated overall effect sizes, test for heterogeneity, moderator effects, and publication bias were reported using R software. The authors focus on two flexible models, Bayesian and frequentist, to determine overall effect sizes in network meta-analysis. This study focused on the practical methods of network meta-analysis rather than theoretical concepts, making the material easy to understand for Korean researchers who did not major in statistics. The authors hope that this study will help many Korean researchers to perform network meta-analyses and conduct related research more easily with R software.

Diagnostic test accuracy: application and practice using R software / 한국역학회지

The objective of this paper is to describe general approaches of diagnostic test accuracy (DTA) that are available for the quantitative synthesis of data using R software. We conduct a DTA that summarizes statistics for univariate analysis and bivariate analysis. The package commands of R software were “metaprop” and “metabin” for sensitivity, specificity, and diagnostic odds ratio; forest for forest plot; reitsma of “mada” for a summarized receiver-operating characteristic (ROC) curve; and “metareg” for meta-regression analysis. The estimated total effect sizes, test for heterogeneity and moderator effect, and a summarized ROC curve are reported using R software. In particular, we focus on how to calculate the effect sizes of target studies in DTA. This study focuses on the practical methods of DTA rather than theoretical concepts for researchers whose fields of study were non-statistics related. By performing this study, we hope that many researchers will use R software to determine the DTA more easily, and that there will be greater interest in related research.

Intervention meta-analysis: application and practice using R software / 한국역학회지

The objective of this study was to describe general approaches for intervention meta-analysis available for quantitative data synthesis using the R software. We conducted an intervention meta-analysis using two types of data, continuous and binary, characterized by mean difference and odds ratio, respectively. The package commands for the R software were “metacont”, “metabin”, and “metagen” for the overall effect size, “forest” for forest plot, “metareg” for meta-regression analysis, and “funnel” and “metabias” for the publication bias. The estimated overall effect sizes, test for heterogeneity and moderator effect, and the publication bias were reported using the R software. In particular, the authors indicated methods for calculating the effect sizes of the target studies in intervention meta-analysis. This study focused on the practical methods of intervention meta-analysis, rather than the theoretical concepts, for researchers with no major in statistics. Through this study, the authors hope that many researchers will use the R software to more readily perform the intervention meta-analysis and that this will in turn generate further related research.

Network meta-analysis: application and practice using R software / 한국역학회지

The objective of this study is to describe the general approaches to network meta-analysis that are available for quantitative data synthesis using R software. We conducted a network meta-analysis using two approaches: Bayesian and frequentist methods. The corresponding R packages were “gemtc” for the Bayesian approach and “netmeta” for the frequentist approach. In estimating a network meta-analysis model using a Bayesian framework, the “rjags” package is a common tool. “rjags” implements Markov chain Monte Carlo simulation with a graphical output. The estimated overall effect sizes, test for heterogeneity, moderator effects, and publication bias were reported using R software. The authors focus on two flexible models, Bayesian and frequentist, to determine overall effect sizes in network meta-analysis. This study focused on the practical methods of network meta-analysis rather than theoretical concepts, making the material easy to understand for Korean researchers who did not major in statistics. The authors hope that this study will help many Korean researchers to perform network meta-analyses and conduct related research more easily with R software.

mRNA Expression of SLC5A5 and SLC2A Family Genes in Papillary Thyroid Cancer: An Analysis of The Cancer Genome Atlas

PURPOSE: The present study investigated the dynamics and prognostic role of messenger RNA (mRNA) expression responsible for 18F-fluorodeoxyglucose (FDG) uptake in FDG positron emission tomography (PET) and radioactive iodine (131I) uptake in whole-body radioactive iodine scans (WBS) in papillary thyroid cancer (PTC) patients. MATERIALS AND METHODS: The primary and processed data were downloaded from the Genomic Data Commons Data Portal. Expression data for sodium/iodide symporter (solute carrier family 5 member 5, SLC5A5), hexokinase (HK1–3), glucose-6-phosphate dehydrogenase (G6PD), and glucose transporter (solute carrier family 2, SLC2A1–4) mRNA were collected. RESULTS: Expression of SLC5A5 mRNA were negatively correlated with SLC2A1 mRNA and positively correlated with SLC2A4 mRNA. In PTC with BRAF mutations, expressions of SLC2A1, SLC2A3, HK2, and HK3 mRNA were higher than those in PTC without BRAF mutations. Expression of SLC5A5, SLC2A4, HK1, and G6PD mRNA was lower in PTC without BRAF mutation. PTCs with higher expression of SLC5A5 mRNA had more favorable disease-free survival, but no association with overall survival. CONCLUSION: Expression of SLC5A5 mRNA was negatively correlated with SLC2A1 mRNA. This finding provides a molecular basis for the management of PTC with negative WBS using 18F-FDG PET scans. In addition, higher expression of SLC5A5 mRNA was associated with less PTC recurrence, but not with deaths.

Effect of rs3910105 in the Synuclein Gene on Dopamine Transporter Availability in Healthy Subjects

PURPOSE: The present study investigated associations between dopamine transporter (DAT) availability and α-synuclein levels in cerebrospinal fluid, as well as synuclein gene (SNCA) transcripts, and the effect of single nucleotide polymorphism of SNCA on DAT availability in healthy subjects. MATERIALS AND METHODS: The study population comprised healthy controls who underwent 123I-FP-CIT single-photon emission computed tomography screening. Five SNCA probes were used to target the boundaries of exon 3 and exon 4 (SNCA-E3E4), transcripts with a long 3′UTR region (SNCA-3UTR-1, SNCA-3UTR-2), transcripts that skip exon 5 (SNCA-E4E6), and the rare short transcript isoforms that comprise exons 1–4 (SNCA-007). RESULTS: In total, 123 healthy subjects (male 75, female 48) were included in this study. DAT availability in the caudate nucleus (p=0.0661) and putamen (p=0.0739) tended to differ according to rs3910105 genotype. In post-hoc analysis, DAT availability in the putamen was lower in subjects of TT genotype than those of CC/CT (p=0.0317). DAT availability in the caudate nucleus also showed a trend similar to that in the putamen (p=0.0597). Subjects of CT genotype with rs3910105 showed negative correlations with DAT availability in the putamen with SNCA-E3E4 (p=0.037, rho=−0.277), and SNCA-E4E6 (p=0.042, rho=−0.270), but not those of CC/TT genotypes. CONCLUSION: This is the first study to investigate the association of rs3910105 in SNCA with DAT availability. rs3910105 had an effect on DAT availability, and the correlation between DAT availability and SNCA transcripts were significant in CT genotypes of rs3910105.

Lu-177-Based Peptide Receptor Radionuclide Therapy for Advanced Neuroendocrine Tumors / 대한핵의학회잡지

Peptide receptor radionuclide therapy (PRRT) is a systemic cytotoxic radiation therapy using a compound of β-emitting radionuclide chelated to a peptide for the treatment of tumor with overexpressed specific cell receptor such as somatostatin receptor subtype 2 (SSTR2) of neuroendocrine tumor (NET). Surgical resection should be performed for the curative treatment for NETs when it is feasible; however, a multi-disciplinary approach is needed when locally advanced or metastasized disease. PRRT with lutetium-177 (Lu-177)-labeled somatostatin analogues, as a new treatment modality targeting metastatic or inoperable NETs expressing the SSTR2, have been developed and successfully used for the past two decades. As Lu-177 emits both β- and γ-radiation, it has the ability as a theragnostic agent for NETs compared with only β-emitting yttrium-90 labeled PRRT. Several recent studies reported that Lu-177 gave an overall positive response and improved the patients' quality of life. To fully exploit its potential, large comparative studies are needed for the assessment of distinct efficacies of Lu-177 labeled PRRT. Additionally, for extending the indications and developing new regimens of Lu-177-based PRRT, more dedicated clinical research is required.

Obesity and Brain Positron Emission Tomography / 대한핵의학회잡지

Obesity, an increasingly common problem in modern societies, results from energy intake chronically exceeding energy expenditure. This imbalance of energy can be triggered by the internal state of the caloric equation (homeostasis) and non-homeostatic factors, such as social, cultural, psychological, environmental factors or food itself. Nowadays, positron emission tomography (PET) radiopharmaceuticals have been examined to understand the cerebral control of food intake in humans. Using ¹⁵O–H₂ PET, changes in regional cerebral blood flow (rCBF) coupled to neuronal activity were reported in states of fasting, satiation after feeding, and sensory stimulation. In addition, rCBF in obese subjects showed a greater increase in insula, the primary gustatory cortex. ¹⁸F–fluorodeoxyglucose PET showed higher metabolic activity in postcentral gyrus of the parietal cortex and lower in prefrontal cortex and anterior cingulate cortex in obese subjects. In addition, dopamine receptor (DR) PET demonstrated lower DR availability in obese subjects, which might lead to overeating to compensate. Brain PET has been utilized to reveal the connectivity between obesity and brain. This could improve understanding of obesity and help develop a new treatment for obesity.

Lu-177-Based Peptide Receptor Radionuclide Therapy for Advanced Neuroendocrine Tumors / 대한핵의학회잡지

Peptide receptor radionuclide therapy (PRRT) is a systemic cytotoxic radiation therapy using a compound of β-emitting radionuclide chelated to a peptide for the treatment of tumor with overexpressed specific cell receptor such as somatostatin receptor subtype 2 (SSTR2) of neuroendocrine tumor (NET). Surgical resection should be performed for the curative treatment for NETs when it is feasible; however, a multi-disciplinary approach is needed when locally advanced or metastasized disease. PRRT with lutetium-177 (Lu-177)-labeled somatostatin analogues, as a new treatment modality targeting metastatic or inoperable NETs expressing the SSTR2, have been developed and successfully used for the past two decades. As Lu-177 emits both β- and γ-radiation, it has the ability as a theragnostic agent for NETs compared with only β-emitting yttrium-90 labeled PRRT. Several recent studies reported that Lu-177 gave an overall positive response and improved the patients' quality of life. To fully exploit its potential, large comparative studies are needed for the assessment of distinct efficacies of Lu-177 labeled PRRT. Additionally, for extending the indications and developing new regimens of Lu-177-based PRRT, more dedicated clinical research is required.

Obesity and Brain Positron Emission Tomography / 대한핵의학회잡지

Obesity, an increasingly common problem in modern societies, results from energy intake chronically exceeding energy expenditure. This imbalance of energy can be triggered by the internal state of the caloric equation (homeostasis) and non-homeostatic factors, such as social, cultural, psychological, environmental factors or food itself. Nowadays, positron emission tomography (PET) radiopharmaceuticals have been examined to understand the cerebral control of food intake in humans. Using ¹⁵O–H₂ PET, changes in regional cerebral blood flow (rCBF) coupled to neuronal activity were reported in states of fasting, satiation after feeding, and sensory stimulation. In addition, rCBF in obese subjects showed a greater increase in insula, the primary gustatory cortex. ¹⁸F–fluorodeoxyglucose PET showed higher metabolic activity in postcentral gyrus of the parietal cortex and lower in prefrontal cortex and anterior cingulate cortex in obese subjects. In addition, dopamine receptor (DR) PET demonstrated lower DR availability in obese subjects, which might lead to overeating to compensate. Brain PET has been utilized to reveal the connectivity between obesity and brain. This could improve understanding of obesity and help develop a new treatment for obesity.

What Do We Measure in Oncology PET? / 대한핵의학회잡지

Positron emission tomography (PET) has come to the practice of oncology. It is known that 18F-fluorodeoxyglucose (FDG) PET is more sensitive for the assessment of treatment response than conventional imaging. In addition, PET has an advantage in the use of quantitative analysis of the study. Nowadays, various PET parameters are adopted in clinical settings. In addition, a wide range of factors has been known to be associated with FDG uptake. Therefore, there has been a need for standardization and harmonization of protocols and PET parameters. We will introduce PET parameters and discuss major issues in this review.

Prognostic Value of Tumor-to-Blood Standardized Uptake Ratio in Patients with Resectable Non-Small-Cell Lung Cancer / 대한핵의학회잡지

OBJECTIVES: Previously published studies showed that the standard tumor-to-blood standardized uptake value (SUV) ratio (SUR) was a more accurate prognostic method than tumor maximum standardized uptake value (SUV(max)). This study evaluated and compared prognostic value of positron emission tomography (PET) parameters and normalized value of PET parameters by blood pool SUV in non-small-cell lung cancer (NSCLC) patients who received curative surgery.METHODS: Seventy-seven patients who underwent curative resection for NSCLC between January 2010 to December 2013 were enrolled in this study. ¹⁸Fluorine-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) was performed before surgery. The mean standardized uptake value (SUV(mean)), SUV(max), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of each lesion was measured, on the workstation. SUR(mean), SUR(max), and TLGSUR were calculated by dividing each of them by descending aorta SUV(mean). Cox proportional hazards regression was used to analyze the effect of age, sex, pathological parameters, and PET parameters on recurrence and death.RESULTS: In Cox regression analysis, N stage predicted for both recurrence (p < 0.0001) and death (p < 0.0001). SUR(max) predicted recurrence (p = 0.0014), not death. Area under the receiver operating characteristic curve of SUR(max) was 0.759 with cutoff value 4.004. However, SUV(max), SUV(mean), MTV, TLG, SUR(mean), and TLGSUR predicted neither recurrence nor death.CONCLUSIONS: Among PET parameters, SUR(max) was the independent predictor of recurrence in NSCLC patients who received curative surgery. N stage was the independent prognostic factor for both recurrence and death. Both parameters could be used to stratify the risk of NSCLC patients.