• The Korean Journal of Nuclear Medicine
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• v.34 no.6
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• pp.445-455
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• 2000

Purpose: We evaluated the distribution of hypoperfusion in patients with traumatic brain injury (TBI) and the relationship of thalamic hypoperfusion to severity of cognitive and behavioral sequelae. Materials and Methods: Tc-99m ECD SPECT and MRI were performed in 103 patients (M/F=81/22, mean age $34.7{\pm}15.4$ yrs) from 0.5 to 55 months (mean 10.3 months) after TBI. The patients were divided into three groups showing no abnormalities (G1), focal (G2) and diffuse injury (G3) on MRI. Psychometric tests assessed 11 cognitive or behavioral items. In all patients, we evaluated the distribution of hypoperfused areas in SPECT, and in 57/103 patients, neuropsychological (NP) abnormalities in patients with thalamic hypoperfusion were compared with those of patients without thalamic hypoperfusion. Results: The perfusion deficits were most frequently located in the frontal lobe (G1, 42.3%: G2 34.5%: G3 33.3%), temporal lobe ($24{\sim}26%$) thalami ($21{\sim}22.4%$), parietal and occipital lobe (${\leq}10%$). Numbers of NP abnormalities in the cases of cortical hypoperfusion with or without concomitant thalamic hypoperfusion were following: the former $4.7{\pm}1.5$ and the latter $3.2{\pm}1.4\;in\;G1,\;5.0{\pm}1.1\;and\;4.8{\pm}1.2\;in\;G2,\;6.8{\pm}1.8\;and\;6.3{\pm}1.1\;in\;G3$, respectively. This difference according to thalamic hypoperfusion was significant in G1 (p=0.002), but was not significant in G2 or G3. Conclusion: SPECT in patients with TBI had demonstrated hypoperfusion mostly involving the frontal, temporal and thalami. In normal group on MRI, frontal hypoperfusion was more prominent than that of any other group, Furthermore in this group, SPECT could predict severity of NP outcome by concomitant thalamic hypoperfusion with cerebral cortical abnormalities.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.1
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• pp.9-15
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• 2007

Purpose: Repetitive transcranial magnetic stimulation (rTMS) has recently been clinically applied in the treatment of drug resistant depressed patients. There are mixed findings about the efficacy of rTMS on depression. Furthermore, the influence of rTMS on the physiology of the brain is not clear. We prospectively evaluated changes of regional cerebral blood flow (rCBF) between pre- and post-rTMS treatment in patients with drug resistant depression. Materials and Methods: Twelve patients with drug-resistant depression (7 male, 5 female; age range: $19{\sim}52$ years; mean age: $29.3{\pm}9.3$ years) were given rTMS on right prefrontal lobe with low frequency (1 Hz) and on left prefrontal lobe with high frequency (20 Hz), with 20-minute-duration each day for 3 weeks. Tc-99m ECD brain perfusion SPECT was obtained before and after rTMS treatment. The changes of cerebral perfusion were analyzed using statistical parametric mapping (SPM; t=3.14, uncorrected p<0.01, voxel=100). Results: Following areas showed significant increase in rCBF after 3 weeks rTMS treatment: the cingulate gyrus, fusiform gyrus of right temporal lobe, precuneus, and left lateral globus pallidus. Significant decrement was noted in: the precental and middle frontal gyrus of right frontal lobe, and fusiform gyrus of left occipital lobe. Conclusion: Low-frequency rTMS on the right prefrontal cortex and high-frequency rTMS on the left prefrontal cortex for 3 weeks as an add-on regimen have increased and decreased rCBF in the specific brain regions in drug-resistant depressed patients. Further analyses correlating clinical characteristics and treatment paradigm with functional imaging data may be helpful in clarifying the pathophysiology of drug-resistant depressed patients.

• The Korean Journal of Nuclear Medicine
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• v.36 no.4
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• pp.244-254
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• 2002

Purpose: This study investigated the differences between technetium-99m ethyl cysteinate dimer (Tc-99m ECD) and technetium-99m hexamethylpropylene amine oxime (Tc-99m HMPAO) uptake in the normal brain by means of statistical parametric mapping (SPM) analysis. Materials and Methods: We retrospectively analyzed age and sex matched 53 cases of normal brain SPECT. Thirty-two cases were obtained with Tc-99m ECD and 21 cases with Tc-99m HMPAO. There were no abnormal findings on brain MRIs. All of the SPECT images were spatially transformed to standard space, smoothed and globally normalized. The differences between the Tc-99m ECD and Tc-99m HMPAO SPECT images were statistically analyzed using statistical parametric mapping (SPM'99) software. The differences bgetween the two groups were considered significant ant a threshold of corrected P values less than 0.05. Results: SPM analysis revealed significantly different uptakes of Tc-99m ECD and Tc-99m HMPAO in the normal brains. On the Tc-99m ECD SPECT images, relatively higher uptake was observed in the frontal, parietal and occipital lobes, in the basal ganglia and thalamus, and in the superior region of the cerebellum. On the Tc-99m HMPAO SPECT images, relatively higher uptakes was observed in subcortical areas of the frontal region, temporal lobe, and posterior portion of inferior cerebellum. Conclusion: Uptake of Tc-99m ECD and Tc-99m HMPO in the normallooking brain was significantly different on SPM analysis. The selective use of Tc-99m ECD of Tc-99m HMPAO in brain SPECT imaging appears especially valuable for the interpretation of cerebral perfusion. Further investigation is necessary to determine which tracer is more accurate for diagnosing different clinical conditions.

• 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.31 no.3
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• pp.330-338
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• 1997

This study investigated the method to adjust acquisition time(a) and injection dose (i) to make the best basal and subtraction images in consecutive SPECT. Image quality was assumed to be mainly affected by signal to noise ratio(S/N). Basal image was subtracted from the second image consecutively acquired at the same position. We calculated S/N ratio in basal SPECT images($S_1/N_1$) and subtraction SPECT images(Ss/Ns) to find a(time) and i(dose) to maximize S/N of both images at the same time. From phantom images, we drew the relation of image counts and a(time) and i(dose) in our system using fanbeam-high-resolution collimated triple head SPECT. Noise by imaging process depended on Poisson distribution. We took maximum tolerable duration of consecutive acquisition as 30 minutes and maximum injectible dose as 1,850MBq(50 mCi)(sum of two injections) per study. Counts of second-acquired image($S_2$), counts($S_s$) and noise($N_s$) of subtraction SPECT were as follows. $C_1$ was the coefficient of measurement with our system. $$S_2=S_1{\cdot}(\frac{30-a}{a})+background{\cdot}(1-\frac{30-a}{a})+C_1{\cdot}(30-a){\cdot}{\epsilon}{\cdot}(50-i)$$ $$Ss=S_2-\{S_1{\cdot}(\frac{30-a}{a})+background{\cdot}(1-\frac{(30-a)}{a})\}$$ $$Ns={\sqrt{N_2^2+N_1^2{\cdot}\frac{(30-a)^2}{a^2}}={\sqrt{S_2+S_1{\cdot}\frac{(30-a)^2}{a^2}}$$ In case of rest/acetazolamide study, effect(${\epsilon}$) of acetazolamide to increase global brain uptake of Tc-99m-HMPAO could be 1.5 or less. Varying ${\epsilon}$ from 1 to 1.5, a(time) and i(dose) pair to maximize both $S_1/N_l$ and Ss/Ns was determined. 15 mCi/17 min and 35mCi/13min was the best a(time) and i(dose) pair for rest/acetazolamide study(when ${\epsilon}$ were 1.2) and came to be used for our clinical routine after this study. We developed simple method to maximize S/N ratios of basal and subtraction SPECT from consecutive acquisition. This method could be applied to ECD/HMPAO and brain activation studies as well as rest/acetazolamide studies.

• The Korean Journal of Nuclear Medicine
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• v.35 no.1
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• pp.23-32
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• 2001

Purpose: Cortical dysplasia (CD) designates a diverse group of malformations resulting from one or more abnormalities in the development of the cerebral cortex. We investigated the findings of interictal SPECT and the diagnostic usefulness of interical and ictal SFECT according to pathological grading (PG) in comparison with MRI. Materials and Methods: This study included 16 patients (M:F=9:7, age: $19.9{\pm}11.8$ yrs) with pathologically proven CD. Tc-99m ECD SPECT was performed in all patients: interictal 11, interictal and ictal 3, ictal 2. MRI were obtained in all patients and image analysis was done blindly as to the result of SPECT. Pathologic findings of CD were classified into grade 1 G1, dyslamination), grade 2 (G2, dysplastic neurons) and grade 3 (G3, balloon cells). We compared SFECT with MRI in lesions-to-lesions and analyzed the result according to PG. Results: In SFECT and MRI. 38 and 27 lesions were visually recognized. In 14 interictal SPECT, variable findings in 35 lesions were demonstrated: 25 were hypoperfusion, 7 hyperperfusion, 2 heterotopic perfusion in the white matter. By comparison between two studios, missed lesions were founded: SPECT were 1 lesion, MRI 12. Review of missed 12 lesions of MRI were followed according to PG: G1 patients were 16.7% (4/19), G2 40.0% (6/15), and G3 50% (2/4). Conclusion: Interictal SFECT in CD showed variable findings such as hypoperfusion, hyperperfusion or heterotopic perfusion. However, for detection of missed CD on MRI, SFECT may help to detect a functional abnormality of the lesion with high PG.

• The Korean Journal of Pharmacology
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• v.21 no.1
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• pp.49-61
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• 1985

In view of the facts that dopamine (DA) when given directly into a lateral ventricle (i.c.v.) of the rabbit brain induces antidiuresis and that haloperidol, a non-specific antagonist of DA receptors, produces anti-diuresis in smaller doses and diuresis and natriuresis in larger doses, the present study was undertaken to delineate the roles of various DA receptors involved in the center-mediated regulation of renal function. Bromocriptine (BRC), a relatively specific agonist of D-2 receptors and at the same time a D-,1 antagonist, elicited natriuresis and diuresis when given i.c.v. in doses ranging from 20 to 600 {\mu}g/kg$, roughly in dose-related fashion, while the renal perfusion and glomerular filtration progressively decreased with doses, indicating that the diuretic, natriuretic action resides in the tubules, not related to the hemodynamic effects. These diuresis and natriuresis were most marked with 200 ${\mu}g/kg$, with the fractional sodium excretion reaching about 10%. With 600 ${\mu}g/kg$, however, the diuretic, natriuretic action was preceded by a transient oliguria resulting from severe reduction of renal perfusion, concomitant with marked but transient hypertension. When given intravenously, however, BRC produced antidiuresis and antinatriuresis along with decreases in renal hemodynamics associated with systemic hypotension, thus indicating that the renal effects produced by i.c.v. BRC is not caused by a direct renal effects of the agent which might have reached the systemic circulation. In experiments in which DA was given i.c.v. prior to BRC, 150 ${\mu}g/kg$ DA did not affect the effects of BRC (200 ${\mu}g/kg$), while 500 ${\mu}g/kg$ DA abolished the BRC effect. In rabbits treated with reserpine, 1 mg/kg i.v.,24 h prior to the experiment, i.c.v. BRC could unfold its renal effects not only undiminished but rather exaggerated and more promptly. In preparations in which one kidney is deprived of nervous connection, the denervated kidney responded with marked diuresis and natriuresis, whereas the innervated, control kidney exhibited antidiuresis. These observations suggest that i.c.v. BRC influences the renal function through release of some humoral natriuretic factor as well as by increasing sympathetic tone, and that various DA receptors might be involved with differential roles in the center-mediated regulation of the renal function.

• Radiation Oncology Journal
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• v.22 no.4
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• pp.288-297
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• 2004

Puporse: The aims of this study were to evaluate the change of $[^18F]fluoromisonidazole$($[^18F]FMISO$) uptake in C3H mouse squamous cell carcinoma-VII (SCC-VII) treated with mild hyperthermia ($42^{circ}C$) and nicotinamide and to assess the biodistribution of the markers in normal tissues under similar conditions. Methods and Materials: $[^18F]FMISO$ was producedby our hospital. Female C3H mice with a C3H SCC-VII tumor grown on their extremities were used. Tumors were size matched. Non-anaesthetized, tumor-bearing mice underwent control or mild hyperthermia at $42^{circ}C$ for 60 min with nicotinamide (50 mg/kg i.p. injected) and were examined by gamma counter, autoradiography and animal PET scan 3 hours after tracer i.v. injected with breathing room air, The biodistribution of these agents were obtained at 3 h after $[^18F]FMISO$ injection. Blood, tumor, muscle, heart, lung, liver, kidney, brain, bone, spleen, and intestine were removed, counted for radioactivity and weighed. The tumor and liver were frozen and cut with a cryomicrotome into 10- um sections. The spatial distribution of radioactivity from the tissue sections was determined with digital autoradiography. Results: The mild hyperthermia with nicotinamide treatment had only slight effects on the biodistribution of either marker in normal tissues. We observed that the whole tumor radioactivity uptake ratios were higher in the control mice than in the mild hyperthermia with nicotinamide treated mice for $[^18F]FMISO$ ($1.56{\pm}1.03$ vs. $0.67{\pm}0.30$; p=0.063). In addition, autoradiography and animal PET scan demonstrated that the area and intensity of $[^18F]FMISO$ uptake was significantly decreased. Conclusion: Mild hyperthermla and nicotinamide significantly improved tumor hypoxia using $[^18F]FMISO$ and this uptake reflected tumor hypoxic status.

• Toxicological Research
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• v.17
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• pp.47-57
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• 2001

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, and its pathology is characterized by the presence of numerous numbers of senile plaques and neurofibrillary tangles. Several genetic and transgenic studies have indicated that excess amount of $\beta$-amyloid protein (A$\beta$) is produced by mutations of $\beta$TEX>$\beta$-amyloid precursor protein and causes learning impairment. Moreover, $A\beta$ has a toxic effect on cultured nerve cells. To prepare AD model animals, we have examined continuous (2 weeks) infusion of $A\beta$ into the cerebral ventricle of rats. Continuous infusion of $A\beta$ induces learning impairment in water maze and passive avoidance tasks, and decreases choline acetyltransferase activity in the frontal cortex and hippocampus. Immunohistochemical analysis revealed diffuse depositions of $A\beta$ in the cerebral cortex and hippocampus around the ventricle. Furthermore, the nicotine-evoked release of acetylcholine and dopamine in the frontal cortex/hippocampus and striatum, respectively, is decreased in the $A\beta$-infused group. Perfusion of nicotine (50 $\mu\textrm{M}$) reduced the amplitude of electrically evoked population spikes in the CA1 pyramidal cells of the control group, but not in those of the $A\beta$-infused group, suggesting the impairment of nicotinic signaling in the $A\beta$-infused group. In fact, Kd, but not Bmax, values for ［$^3H$］ cytisine binding in the hippocampus significantly increased in the $A\beta$-infused rats. suggesting the decrease in affinity of nicotinic acetylcholine receptors. Long-term potentiation (LTP) induced by tetanic stimulations in CA1 pyramidal cells, which is thought to be an essential mechanism underlying learning and memory, was readily observed in the control group, whereas it was impaired in the $A\beta$-infused group. Taken together, these results suggest that $A\beta$ infusion impairs the signal transduction mechanisms via nicotinic acetylcholine receptors. This dysfunction may be responsible, at least in part, for the impairment of LTP induction and may lead to learning and memory impairment. We also found the reduction of glutathione- and Mn-superoxide dismutase-like immunoreactivity in the brains of $A\beta$-infused rats. Administration of antioxidants or nootropics alleviated learning and memory impairment induced by $A\beta$ infusion. We believe that investigation of currently available transgenic and non-transgenic animal models for AD will help to clarify the pathogenic mechanisms and allow assessment of new therapeutic strategies.

• Microbiology and Biotechnology Letters
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• v.39 no.4
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• pp.364-373
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• 2011

Human embryonic stem cells have been highlighted as a valuable cellular source in the regenerative medicine field, due to their pluripotency. However, there is the challenge of the establishment of specific functional cell type forms of undifferentiated human embryonic stem cells (hESC). To establish and purify functional cell types from hESCs, we differentiated undifferentiated hESCs into vascular lineage cells and sorted the specific cell population from the whole cell population, depending on their cell volume, and compared them with the non-sorted cell population. We observed that about 10% of the PECAM positive population existed in the VEGF induced differentiating human embryoid body (hEB), and differentiated hEBs were made into single cells for cell transplantation. After making single cells, we performed cell sorting using a fluorescence-activated cell sorter (FACs), according to their cell volume on the basis of FSC region gating, and compared their therapeutic capacity with the non-sorted cell population through cell transplantation into hindlimb ischemic disease model mice. 4 Weeks after cell transplantation, the recovery rate of blood perfusion reached 54% and 17% in the FSC regions of sorted cells- and non-sorted cells, respectively. This result suggests that derivation of a functional cell population from hESCs can be performed through cell sorting on the basis of cell volume after preliminary differentiation induction. This approach may then greatly contribute to overcoming the limitations of marker sorting.