• Journal of The Korean Society of Inherited Metabolic disease
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• v.5 no.1
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• pp.33-43
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• 2005

Purpose: X-linked adrenoleukodystrophy(ALD) is a rare disorder that shows a great deal of phenotypic variability. We subdivided chidhood X-linked ALD patients into several phenotypes by the age at onset, the sites of most severe clinical involvement and the rate of progression of neurologic symptoms. Methods: Thirteen patients who had been diagnosed as X-linked ALD and followed up for at least one year were enrolled from 1996 to 2003. Results: 1. Ten had childhood cerebral ALD, who showed first neurologic symptoms at 7.02 years and progressed rapidly: interval between first symptoms and vegetative state was 1.35 years, and interval from initial symptoms to death was 3.35 years. Treatment with Lorenzo's oil did not prevent neurologic progression. Two patients who underwent umbilical cord blood transplantation died. 2. Two had adolescent cerebral ALD. They had first symptoms at 11.5 years, and showed tendency to progress less rapidly than childhood cerebral form patients. 3. One "Addison only" patient who had adrenal insufficiency without nervous system involvement remained asymptomatic during Lorenzo's oil treatment. 4. All cerebral form patients except one showed the lesions in both parieto-ocipital white matter in brain magnetic resonance imaging. Conclusion: The cerebral ALD was the most common form in childhood and was asoociated with a serious prognosis.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.23 no.1
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• pp.25-30
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• 2023

Leigh syndrome is a rare progressive neurodegenerative mitochondrial disorder with clinical and genetic heterogeneity. Recently, balletic IARS2 variants have been identified in a number of patients presenting broad clinical phenotypes from Leigh and West syndrome to a rare syndrome CAGSSS characterized by cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia syndrome (OMIM#616007). We describe a child with Korean Leigh syndrome with urologic manifestations resulting from a compound heterozygote mutation in IARS2. A 5-year-old girl visited the emergency room with a complaint of abdominal pain accompanied by abdominal distension. Abdominal-pelvic CT showed a markedly distended urinary bladder without definite obstructive lesions. She was diagnosed with neurogenic bladder dysfunction based on a urodynamic study. She had global delayed development due to neurologic regression after 6 months of age and a history of bilateral cataract surgery at the age of 2 years. Her brain magnetic resonance imaging showed symmetrically increased signal intensities in the bilateral putamen and caudate nuclei with diffuse cerebral atrophy. No gene variants were identified through whole-mitochondrial genome analysis. Whole exome sequencing was performed for diagnosis, and compound heterozygous pathogenic variants were identified in IARS2: c.2446C>T (p. Arg816Ter) and c.2450G>A (p. Arg817His). To the best of our knowledge, this is the first case report of bladder dysfunction manifestation in a patient with IARS2-related Leigh syndrome. Thus, it broadens the clinical and genetic spectrum of IARS2-associated diseases.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.1
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• pp.23-27
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• 2006

Purpose: There are a few case reports on asymmetric vocal cord uptake on FDG-PET in patients with unilateral vocal cord paralysis, which could be a potential pitfall in the interpretation of FDG-PET images. We evaluated the metabolic activity of laryngeal muscles of patients with unilateral vocal cord paralysis in comparison to normal controls during both speech and silence. Methods: Eleven patients with unilateral vocal cord palsy (thyroldectomy=7, lung cancer=1, others=3) and 12 normal controls underwent FDG-PET with usual protocol. They were divided into two groups respectively; one group read books aloud for 20 minutes (phonation group) and the other kept silence (non-phonation groups) after FDG injection. Recent neck CT scan were co-registered with FDG-PET to produce PET-CT fusion images to elaborate small laryngeal muscles. Results: In patients with unilateral vocal cord palsy, contralateral non-paralyzed vocal cord showed hypermetabolism mainly on thyroarytenoid muscle, more intensely with phonation group ($SUV=5.88{\pm}2.65$) than with non-phonation group ($SUV=2.30{\pm}0.39$). Normal control subjects showed hypermetabolism ($3.68{\pm}0.96$) in interarytenoid muscle and symmetric mild hypermetabolism in both lateral cricoarytenoid muscles in only phonation group. Conclusion: FDG-PET with fusion images using CT scan in patients with unilateral vocal cord paralysis showed hypermetabolism of contralateral non-paralyzed thyroarytenoid muscle, suggesting compensatory action during phonation. Phonation durung FDG PET study enhanced FDG uptake on different laryngeal muscles between patients with unilateral vocal cord paralysis and normal subjects.

• The Journal of the Korea Contents Association
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• v.14 no.11
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• pp.558-574
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• 2014

The number of fatty liver patients is sharply growing due to the rapid increase in the incidence of metabolic syndrome, which can lead to diseases such as abdominal obesity, hypertension, diabetes, and hyperlipidemia. Early diagnosis requires examinations using magnetic resonance imaging (MRI), wherein quantitative analyses are implemented through a professional water-fat separation method in many cases, as the intensity values of the areas of interest and non-interest are considerably similar or the same. However, such separation method generates inaccurate results in high magnetic fields, where the inhomogeneity of the fields increases. To overcome the limits of such conventional fat quantification methods, this paper proposes a field map estimation method that is effective in high magnetic fields. This method generates field maps through echo images that are obtained using the existing IDEAL sequences, and considers the wrapping degree of the field maps. Then clustering is performed to separate calibration areas, the least square fits based on the region growing method schema of the separated calibration areas, and the histograms are adjusted to separate the water from the fats. In experiment results, our proposed method had a superior fat detection rate of an average of 86.4%, compared to the ideal method with an average of 61.5% and Yu's method with an average of 62.6%. In addition, it was confirmed that the proposed method had a more accurate water detection rate of 98.4% on the average than the 88.6% average of the fat saturation method.

• Investigative Magnetic Resonance Imaging
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• v.4 no.2
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• pp.94-99
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• 2000

Purpose : With the use of localized, water-suppressed in vivo $^1H$ magnetic resonance spectroscopy (MRS), we evaluated the proton metabolic alterations in patients with chronic alcoholism and healthy normal controls. Material and Methods : Patients with chronic alcoholism (N = 10) and normal control subjects (N = 10) underwent MRS examinations using a stimulated echo acquisition mode (STEAM) pulse sequence with $2{\times}2{\times}2{\;}\textrm{cm}^3$ volume of interest (VOI) in the left cerebellum and basal ganglia. Proton metabolite ratios relative to creative (Cr) were obtained using a Marquart algorithm. Results : The specific feature in patients with chronic alcoholism was a significant decrease of N-acetylaspartate (NAA)/Cr ratio in the left cerebellum, compared with normal controls. No clear correlation of other metabolite ratios such as choline (Cho)/Cr and inositols (Ins)/Cr was established. Conclusion : Our preliminary study suggests that the reduction of NAA/Cr ratio may indicate neuronal loss in patients with chronic alcoholism. Thus, in vivo 1H MRS may be a useful modality in the clinical evaluation of patients with chronic alcoholism based on the proton metabolite ratios.

• The Korean Journal of Nuclear Medicine
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• v.28 no.3
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• pp.377-383
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• 1994

Objective : We retrospectively analysed $^{99m}Tc$-MDP bone and $^{67}Ga$ scans to evaluate therapeutic response of bone lymphoma among patients with complete remission. Subjects and Methods : We reviewed 35 cases with an increased uptake finding $^{99m}Tc$-MDP bone scans and 16 $^{67}Ga$ scans that were follow-up studies during and after therapy. The $^{99m}Tc$-MDP bone and $^{67}Ga$ scans were graded visually from 1 to 4 in which grade 3 means same uptake density as that of normal sacroiliac articulation in bone scan and normal liver in $^{67}Ga$ scan, respectively. Results: The improvement findings during and after therapy were found in 66.0% (19/ 29) and 72.7% (24/33) with $^{99m}Tc$-MDP bone scan, 84.6% (l1/13) and 86.7% (13/15) with $^{67}Ga$ scan, respectively. The mean grades of the uptake density in $^{99m}Tc$-MDP bone scan were 3.06 before, 2.34 during, 1.75 after therapy. Those in the $^{67}Ga$ scan were 3.22 before, 1.42 during 1.30 after therapy. Conclusion. $^{67}Ga$ scans appeared more sensitive than bone scans in evaluating therapeutic response of bone lymphoma.

• The Korean Journal of Nuclear Medicine
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• v.36 no.1
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• pp.1-7
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• 2002

Positron Emission Tomography (PET) is a nuclear medicine imaging modality that consists of systemic administration to a subject of a radiopharmaceutical labeled with a positron-emitting radionuclide. Following administration, its distribution in the organ or structure under study can be assessed as a function of time and space by (1) defecting the annihilation radiation resulting from the interaction of the positrons with matter, and (2) reconstructing the distribution of the radioactivity from a series of that used in computed tomography (CT). The nuclides most generally exhibit chemical properties that render them particularly desirable in physiological studies. The radionuclides most widely used in PET are F-18, C-11, O-15 and N-13. Regarding to the number of the current PET Centers worldwide (based on ICP data), more than 300 PET Centers were in operation in 2000. The use of PET technology grew rapidly compared to that in 1992 and 1996, particularly in the USA, which demonstrates a three-fold rise in PET installations. In 2001, 194 PET Centers were operating in the USA. In 1994, two clinical and research-oriented PET Centers at Seoul National University Hospital and Samsung Medical Center, was established as the first dedicated PET and Cyclotron machines in Korea, followed by two more PET facilities at the Korea Cancer Center Hospital, Ajou Medical Center, Yonsei University Medical Center, National Cancer Center and established their PET Center. Catholic Medical School and Pusan National University Hospital have finalized a plan to install PET machine in 2002, which results in total of nine PET Centers in Korea. Considering annual trends of PET application in four major PET centers in Korea in Asan Medical Center recent six years (from 1995 to 2000), a total of 11,564 patients have been studied every year and the number of PET studies has shown steep growth year upon year. We had 1,020 PET patients in 1995. This number increased to 1,196, 1,756, 2,379, 3,015 and 4,414 in 1996,1997,1998,1999 and 2000, respectively. The application in cardiac disorders is minimal, and among various neuropsychiatric diseases, patients with epilepsy or dementia can benefit from PET studios. Recently, we investigated brain mapping and neuroreceptor works. PET is not a key application for evaluation of the cardiac patients in Korea because of the relatively low incidence of cardiac disease and less costly procedures such as SPECT can now be performed. The changes in the application of PET studios indicate that, initially, brain PET occupied almost 60% in 1995, followed by a gradual decrease in brain application. However, overall PET use in the diagnosis and management of patients with cancer was up to 63% in 2000. The current medicare coverage policy in the USA is very important because reimbursement policy is critical for the promotion of PET. In May 1995, the Health Care Financing Administration (HCFA) began covering the PET perfusion study using Rubidium-82, evaluation of a solitary pulmonary nodule and pathologically proven non-small cell lung cancer. As of July 1999, Medicare's coverage policy expanded to include additional indications: evaluation of recurrent colorectal cancer with a rising CEA level, staging of lymphoma and detection of recurrent or metastatic melanoma. In December of 2001, National Coverage decided to expand Medicare reimbursement for broad use in 6 cancers: lung, colorecctal, lymphoma, melanoma, head and neck, and esophageal cancers; for determining revascularization in heart diseases; and for identifying epilepsy patients. In addition, PET coverage is expected to further expand to diseases affecting women, such as breast, ovarian, uterine and vaginal cancers as well as diseases like prostate cancer and Alzheimer's disease.

• The Korean Journal of Nuclear Medicine
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• v.34 no.4
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• pp.303-311
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• 2000

Purpose: Thallium behaves similarly to potassium in vivo. Potassium channel opener (K-opener) opens ATP-sensitive $K^+$-channel located at cell membrane, resulting in potassium efflux from cytosol. We have previously reported that K-opener can alter biokinetics of Tl-201 in cultured cells and in vivo. Malignant tumor cells have high Na-K ATPase activity due to increased metabolic activities and dedifferentiation, and differential delineation of malignant tumor can be possible with Tl-201 imaging. K-opener may affect tumoral uptake of Tl-201 in vivo. To investigate the effects of pinacidil (one of the potent K-openers) on the localization of the tumor with Tl-201 chloride, we evaluated the changes in biodistribution of Tl-201 with pinacidil treatment in tumor-bearing mice. Materials and Methods: Baltic mice received subcutaneous implantation of murine breast cancer cells in the thigh and were used for biodistribution study 3 weeks later. $100{\mu}g$ of pinacidil dissolved in $200{\mu}l$ DMSO/PBS solution was injected intravenously via tail vein at 10 min after 185 KBq ($5{\mu}Ci$) Tl-201 injection. Percentage organ uptake and whole body retention ratio of Tl-201 were measured at various periods after injection, and values were compared between control and pinacidil-treated mice. Results: Pinacidil treatment resulted in mild decrease in blood levels of Tl-201, but renal uptakes were markedly decreased at 30-min, 1- and 2-hour, compared to control group. Hepatic, intestinal and muscular uptake were not different. Absolute percentage uptake and tumor to blood ratios of Tl-201 were lower in pinacidil treated mice than in the control group at all time points measured. Whole body retention ratio of Tl-201 was lower in pinacidil treated mice ($58{\pm}4%$ ), than in the control group ($67{\pm}3%$) at 24 hours after with injection of $100{\mu}g$ pinacidil. Conclusion: K-opener did not enhance, but rather decreased absolute tumoral uptake and tumor-to-blood ratios of Tl-201. Decreased whole body retention ratio and renal uptake were observed with pinacidil treatment in tumor-bearing mice.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.5
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• pp.263-270
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• 2006

Purpose: Several radioisotope-labeled thymidine derivatives such as $[^{11}C]$thymidine was developed to demonstrate cell proliferation in tumor. But it is difficult to track metabolism with $[^{11}C]$thymidine due to rapid in vivo degradation and its short physical half-life. 3'-$[^{18}F]$fluoro-3'-deoxythymidine ($[^{18}F]$FLT) was reported to have the longer half life of fluorine-18 and the lack of metabolic degradation in vivo. Here, we described the synthesis of the 3'-$[^{18}F]$fluoro-3'-deoxythymidine ($[^{18}F]$FLT) and compared with $([^{18}F]FET)\;and\;([^{18}F]FDG)$ in cultured 9L cell and obtained the biodistribution and PET image in 9L tumor hearing rats. Material and Methods: For the synthesis of $[^{18}F]$FLT, 3-N-tert-butoxycarbonyl-(5'-O-(4,4'-dimet hoxytriphenylmethyl)-2'-deoxy-3'-O-(4-nitrobenzenesulfonyl)-${\beta}$-D-threopentofuranosyl)thymine was used as a FLT precursor, on which the tert-butyloxycarbonyl group was introduced to protect N3-position and nitrobenzenesulfonyl group. Radiolabeling of nosyl substitued precursor with $^{18}F$ was performed in acetonitrile at $120^{\circ}C$ and deproteced with 0.5 N HCI. The cell uptake was measured in cultured 9L glioma cell. The biodistribution was evaluated in 9L tumor bearing rats after intravenous injection at 10 min, 30 min, 60 min and 120 min and obtained PET image 60 minutes after injection. Results: The radiochemical yield was about 20-30% and radiochemical purity was more than 95% after HPLC purification. Cellular uptake of $[^{18}F]$FLT was increased as time elapsed. At 120 min post-injection, the ratios of tumor/blood, tumor/muscle and tumor/brain were $1.61{\pm}0.34,\;1.70{\pm}0.30\;and\;9.33{\pm}2.22$, respectively. The 9L tumor was well visualized at 60 min post injection in PET image. Conclusion: The uptake of $[^{18}F]$FLT in tumor was higher than in normal brain and PET image of $[^{18}F]$FLT was acceptable. These results suggest the possibility of $[^{18}F]$FLT at an imaging agent for brain tumor.

• The Korean Journal of Nuclear Medicine
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• v.37 no.6
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• pp.374-381
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• 2003

Purpose: Determining an appropriate thresholding is crucial for PDG PET analysis since strong control of Type I error could fail to find pathological differences between eariy Alzheimer' disease (AD) patients and healthy normal controls. We compared the SPM results on FDG PET imaging of early AD using uncorrected p-value, random-field based corrected p-value and false discovery rate (FDR) control. Materials and Methods: Twenty-eight patients ($66{\pm}7$ years old) with early AD and 18 age-matched normal controls ($68{\pm}6$ years old) underwent FDG brain PET. To identify brain regions with hypo-metabolism in group or individual patient compared to normal controls, group images or each patient's image was compared with normal controls usingthe same fixed p-value of 0.001 on uncorrected thresholding, random-field based corrected thresholding and FDR control. Results: The number of hypo-metabolic voxels was smallest in corrected p-value method, largest in uncorrected p-value method and intermediate in FDG thresholding in group analysis. Three types of result pattern were found. The first was that corrected p-value did not yield any voxel positive but FDR gave a few significantly hypometabolic voxels (8/28, 29%). The second was that both corrected p-value and FDR did not yield any positive region but numerous positive voxels were found with the threshold of uncorrected p-values (6/28, 21%). The last was that FDR was detected as many positive voxels as uncorrected p-value method (14/28, 50%). Conclusions FDR control could identify hypo-metaboiic areas in group or individual patients with early AD. We recommend FDR control instead of uncorrected or random-field corrected thresholding method to find the areas showing hypometabolism especially in small group or individual analysis of FDG PET.