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Imaging Neuroreceptors in the Living Human Brain

  • Wagner Jr Henry N.;Dannals Robert F.;Frost J. James;Wong Dean F.;Ravert Hayden T.;Wilson Alan A.;Links Jonathan M.;Burns H. Donald;Kuhar Michael J.;Snyder Solomon H.
    • The Korean Journal of Nuclear Medicine
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    • v.18 no.2
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    • pp.17-23
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    • 1984
  • For nearly a century it has been known that chemical activity accompanies mental activity, but only recently has it been possible to begin to examine its exact nature. Positron-emitting radioactive tracers have made it possible to study the chemistry of the human mind in health and disease, using chiefly cyclotron-produced radionuclides, carbon-11, fluorine-18 and oxygen-15. It is now well established that measurable increases in regional cerebral blood flow, glucose and oxygen metabolism accompany the mental functions of perception, cognition, emotion and motion. On May 25, 1983 the first imaging of a neuroreceptor in the human brain was accomplished with carbon-11 methyl spiperone, a ligand that binds preferentially to dopamine-2 receptors, 80% of which are located in the caudate nucleus and putamen. Quantitative imaging of serotonin-2, opiate, benzodiazapine and muscarinic cholinergic receptors has subsequently been accomplished. In studies of normal men and women, it has been found that dopamine and serotonin receptor activity decreases dramatically with age, such a decrease being more pronounced in men than in women and greater in the case of dopamine receptors than serotonin-2 receptors. Preliminary studies in patients with neuropsychiatric disorders suggests that dopamine-2 receptor activity is diminished in the caudate nucleus of patients with Huntington's disease. Positron tomography permits quantitative assay of picomolar quantities of neuro-receptors within the living human brain. Studies of patients with Parkinson's disease, Alzheimer's disease, depression, anxiety, schizophrenia, acute and chronic pain states and drug addiction are now in progress. The growth of any scientific field is based on a paradigm or set of ideas that the community of scientists accepts. The unifying principle of nuclear medicine is the tracer principle applied to the study of human disease. Nineteen hundred and sixty-three was a landmark year in which technetium-99m and the Anger camera combined to move the field from its latent stage into a second stage characterized by exponential growth within the framework of the paradigm. The third stage, characterized by gradually declining growth, began in 1973. Faced with competing advances, such as computed tomography and ultrasonography, proponents and participants in the field of nuclear medicine began to search for greener pastures or to pursue narrow sub-specialties. Research became characterized by refinements of existing techniques. In 1983 nuclear medicine experienced what could be a profound change. A new paradigm was born when it was demonstrated that, despite their extremely low chemical concentrations, in the picomolar range, it was possible to image and quantify the distribution of receptors in the human body. Thus, nuclear medicine was able to move beyond physiology into biochemistry and pharmacology. Fundamental to the science of pharmacology is the concept that many drugs and endogenous substances, such as neurotransmitters, react with specific macromolecules that mediate their pharmacologic actions. Such receptors are usually identified in the study of excised tissues, cells or cell membranes, or in autoradiographic studies in animals. The first imaging and quantification of a neuroreceptor in a living human being was performed on May 25, 1983 and reported in the September 23, 1983 issue of SCIENCE. The study involved the development and use of carbon-11 N-methyl spiperone (NMSP), a drug with a high affinity for dopamine receptors. Since then, studies of dopamine and serotonin receptors have been carried out in over 100 normal persons or patients with various neuropsychiatric disorders. Exactly one year later, the first imaging of opitate receptors in a living human being was performed [1].

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Effects of Motion Correction for Dynamic $[^{11}C]Raclopride$ Brain PET Data on the Evaluation of Endogenous Dopamine Release in Striatum (동적 $[^{11}C]Raclopride$ 뇌 PET의 움직임 보정이 선조체 내인성 도파민 유리 정량화에 미치는 영향)

  • Lee, Jae-Sung;Kim, Yu-Kyeong;Cho, Sang-Soo;Choe, Yearn-Seong;Kang, Eun-Joo;Lee, Dong-Soo;Chung, June-Key;Lee, Myung-Chul;Kim, Sang-Eun
    • The Korean Journal of Nuclear Medicine
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    • v.39 no.6
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    • pp.413-420
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    • 2005
  • Purpose: Neuroreceptor PET studies require 60-120 minutes to complete and head motion of the subject during the PET scan increases the uncertainty in measured activity. In this study, we investigated the effects of the data-driven head mutton correction on the evaluation of endogenous dopamine release (DAR) in the striatum during the motor task which might have caused significant head motion artifact. Materials and Methods: $[^{11}C]raclopride$ PET scans on 4 normal volunteers acquired with bolus plus constant infusion protocol were retrospectively analyzed. Following the 50 min resting period, the participants played a video game with a monetary reward for 40 min. Dynamic frames acquired during the equilibrium condition (pre-task: 30-50 min, task: 70-90 min, post-task: 110-120 min) were realigned to the first frame in pre-task condition. Intra-condition registrations between the frames were performed, and average image for each condition was created and registered to the pre-task image (inter-condition registration). Pre-task PET image was then co-registered to own MRI of each participant and transformation parameters were reapplied to the others. Volumes of interest (VOI) for dorsal putamen (PU) and caudate (CA), ventral striatum (VS), and cerebellum were defined on the MRI. Binding potential (BP) was measured and DAR was calculated as the percent change of BP during and after the task. SPM analyses on the BP parametric images were also performed to explore the regional difference in the effects of head motion on BP and DAR estimation. Results: Changes in position and orientation of the striatum during the PET scans were observed before the head motion correction. BP values at pre-task condition were not changed significantly after the intra-condition registration. However, the BP values during and after the task and DAR were significantly changed after the correction. SPM analysis also showed that the extent and significance of the BP differences were significantly changed by the head motion correction and such changes were prominent in periphery of the striatum. Conclusion: The results suggest that misalignment of MRI-based VOI and the striatum in PET images and incorrect DAR estimation due to the head motion during the PET activation study were significant, but could be remedied by the data-driven head motion correction.

Anatomical studies on pattern of branches of portal veins in Korean native cattle (한우문맥(韓牛門脈)의 분지(分枝)에 관한 해부학적(解剖學的) 연구(硏究))

  • Kim, Chong-sup
    • Korean Journal of Veterinary Research
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    • v.29 no.2
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    • pp.1-9
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    • 1989
  • The distribution of portal veins within the liver in 30 Korean native cattle were observed. Vinylite solution was injected into portal veins of eighteen specimens for cast preparation. The angiography was prepared in twelve specimens by injecting 30% barium sulfate solution into portal veins, and then radiographed on a X-ray apparatus(Shimadzu 800MA 120Kvp). The results were summarized as follow: 1. The Vena portae was divided immediately upon entering the liver into a very short Truncus dexter venae portae($14.75{\pm}4.86$ : 6.9~23.1mm) and a long Truncus sinister venae portae($94.16{\pm}9.62$ : 110~150mm). 2. The Truncus sinister venae portae runs of first in the long axis of the liver from the Porta hepatis toward the left lobe. At the boundary between the quadrate and left lobes it bends sharply 50 to 80 degrees toward the Incisura ligamentum teretis, and after a course of 36. 5 to 54.mm between the quadrate and left lobes, ends abruptly. The Truncus sinister venae portae is divided for description into the Pars transversa, from the Porta hepatis to the flexure, and the Pars umbilicalis, from the flexure to the end. 3. The branches of Venae portae were Ramus ventralis lobi sinistri, Ramus intermedius lobi sinistri, Ramus dorsalis lobi sinistri, Ramus lobi quadratii, Ramus ventralis lobi dextri, Ramus intermedius lobi dextri, Ramus dorsalis lobi dextri, Rami processus caudatorum and Rami processus papillarum. 4. The Ramus intermedius lobi sinistri was arised from the left surface of the Pars umbilicalis, and was origined on the common trunk with Ramus dorsalis lobi sinistri(3 cases, 10%) or Ramus ventralis lobi sinistri(3 cases, 10%). 5. The Rami lobi quadratii consisted of the vein(15 cases, 50%) or two veins(15 cases, 50%), and was observed on the arched-shaped at 2 cases (6.6%) of the liver. 6. The Rami processus caudatorum consisted of one vein(28 cases, 93.3%) or two veins(2 cases, 6.6%). The former were formed common trunk with R, dorsalis lobi dextri(7 cases, 23.3%) or R. ventralis lobi dextri (2 cases, 6.6%). 7. The Rami processus papillarum were arised from the dorsal border of Pars transversa, and also gave off many small branches supplied papillary process of the caudate lobe. 8. The anastomosis on the branches of Vena portae was observed in the intralobar and interlobar areas. 9. The Truncus dexter venae portae and Truncus sinister venae were ramified many secondary branches that were radiated within the liver. 10. On the diaphragmatic surface, small vessels of the portal veins were observed, while there were big ones on the visceral surface. 11. The ramified angles at Ramus dorsalis lobi dextri, Rami processus papillarum, Ramus dorsalis lobi sinistri, Ramus intermedius lobi sinistri, Ramus ventralis lobi sinistri, Rami lobi quadratii, Rami processus caudatorum, Ramus ventralis lobi dextri and Ramus intermedius were 10~50, 70~110, 100~150, 140~170, 185~220, 270~330, 240~300, 270~320 and 340~10 degrees, respectively.

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Effect of Trachelospermi Caulis Herbal-acupuncture on the Collagen-induced Arthritis in Rats (낙석등(絡石藤)약침이 Collagen 유발 관절염에 미치는 영향)

  • Lee, Tae-Ho;Lee, Eun-Young
    • Journal of Acupuncture Research
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    • v.26 no.6
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    • pp.51-65
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    • 2009
  • Objectives : This study was built to investigate the effect of Trachelospermi Caulis herbal-acupuncture on the Collagen-induced arthritis(CIA) in rats. Methods : Arthritis was induced by intradermal injection of Bovine type II collagen solution into base of tail. Experimental group were divided into 5 groups ; Normal(N) group, Control(C) group, Trachelospermi Caulis high(TH) group, Trachelospermi Caulis low(TL) group, Saline(S) group(n=7 for each group). Normal group was had no management. Control group was injected with Bovine type II collagen solution and taken no treatment. Trachelospermi Caulis high group was injected with Bovine type II collagen solution and taken high-intensity(10mg/kg) herbal-acupuncture treatment on $ST_{36}$. Trachelospermi Caulis low group was injected with Bovine type II collagen solution and taken low-intensity(5mg/kg) herbal-acupuncture treatment on $ST_{36}$. Saline group was injected with Bovine type II collagen solution and taken saline injection on $ST_{36}$. Body weight, paw edema volume and ankle joint thickness were measured during experimental day. On the last experimental day, we analyzed WBC count, TNF-$\alpha$ & IL-$1{\beta}$ concentration, c-fos immunohistochemistry and NADPH-d histochemistry for evaluating the effect of Trachelospermi Caulis herbal-acupuncture. Results : The results were as follows ; 1. In the change of paw edema volume, TH group only has significant difference compared with C group. 2. In the change of ankle joint thickness, TH group only has significant difference compared with C group. 3. In WBC count of serum, TH, TL groups have significant decrease compared with C group. 4. In TNF-$\alpha$ concentration of effusion, TH, TL groups have significant decrease compared with C group. and TH group has significant decrease compared with TL group. 5. In IL-$1{\beta}$ concentration of effusion, TH, TL groups have significant decrease compared with C group. and TH group has significant decrease compared with TL group. 6. In c-fos positive neurons of S1S2(cortex) region, TH, TL, S groups have significant decrease compared with C group. 7. In NADPH-d positive neurons of CPu(caudate putamen) region, TH, TL groups have significant decrease compared with C group. 8. In NADPH-d positive neurons of Tfp(transverse fibers of pons) region, TH, TL, S groups have significant decrease compared with C group. and TH group has significant decrease compared with S group. Conclusions : According to above results, we hope that Trachelospermi Caulis herbal-acupuncture may have the effect that decreases progression and development of CIA. And it can be suggested that Trachelospermi Caulis herbal-acupuncture may reduce the expression of c-fos and NOS.

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Manganese Distribution in Brains of Sprague Dawley Rats after 60 Days of Stainless Steel Welding-Fume Exposure

  • Yu, Il-Je;Park, Jung-Duck;Park, Eon-Sub;Song, Kyung-Seuk;Han, Kuy-Tae;Han, Jeong-Hee;Chung, Yong-Hyun;Choi, Byung-Sun;Chung, Kyu-Hyuck;Cho, Myung-Haeng
    • Environmental Mutagens and Carcinogens
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    • v.23 no.3
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    • pp.85-93
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    • 2003
  • Welders working in a confined space, like in the shipbuilding industry, are at risk of being exposed to high concentrations of welding fumes and developing pneumoconiosis or other welding-fume exposure related diseases. Among such diseases, manganism resulting from welding-fume exposure remains a controversial issue, as the movement of manganese into specific brain regions has not been clearly established. Accordingly, to investigate the distribution of manganese in the brain after welding-fume exposure, male Sprague Dawley rats were exposed to welding fumes generated from manual metal arc stainless steel (MMA-SS) at concentrations of $63.6{\pm}4.1$ $mg/m^3$ (low dose, containing 1.6 $mg/m^3$ Mn) and $107.1{\pm}6.3$ $mg/m^3$ (high dose, containing 3.5 $mg/m^3$ Mn) total suspended particulates for 2 hrs per day, in an inhalation chamber over a 60-day period. Blood, brain, lungs and liver samples were collected after 2 hr, 15, 30, and 60 days of exposure and the tissues analyzed for their manganese concentrations using an atomic absorption spectrophotometer. Although dose- and time-dependent increases in the manganese concentrations were found in the lungs and livers of the rats exposed for 60 days, only slight manganese increases were observed in the blood during this period. Major statistically significant increases in the brain manganese concentrations were detected in the cerebellum after 15 days of exposure and up until 60 days. Slight increases in the manganese concentrations were also found in the substantia nigra, basal ganglia (caudate nucleus, putamen, and globus pallidus), temporal cortex, and frontal cortex, thereby indicating that the pharmacokinetics and distribution of manganese inhaled from welding fumes would appear to be different from those resulting from manganese-only exposure.

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A Case of Glutaric Aciduria Type I with Macrocephaly (Glutaric Aciduria Type I 1례)

  • Shin, Woo Jong;Moon, Yeo Ok;Yoon, Hye Ran;Dong, Eun Sil;Ahn, Young Min
    • Clinical and Experimental Pediatrics
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    • v.46 no.3
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    • pp.295-301
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    • 2003
  • Glutaric aciduria type 1(GA1) is an autosomal recessive disorder of the lysine, hydroxylysine and tryptophan metabolism caused by the deficiency of mitochondrial glutaryl-CoA dehydrogenase. This disease is characterized by macrocephaly at birth or shortly after birth and various neurologic symptoms. Between the first weeks and the 4-5th year of life, intercurrent illness such as viral infections, gastroenteritis, or even routine immunizations can trigger acute encephalopathy, causing injury to caudate nucleus and putamen. But intellectual functions are well preserved until late in the disease course. We report a one-month-old male infant with macrocephaly and hypotonia. In brain MRI, there was frontotemporal atrophy(widening of sylvian cistern). In metabolic investigation, there were high glutarylcarnitine level in tandem mass spectrometry and high glutarate in urine organic acid analysis, GA1 was confirmed by absent glutaryl-CoA dehydrogenase activity in fibroblast culture. He was managed with lysine free milk and carnitine and riboflavin. He developed well without a metabolic crisis. If there is macrocephaly in an infant with neuroradiologic sign of frontotemporal atrophy, GA1 should have a high priority in the differential diagnosis. Because current therapy can prevent brain degeneration in more than 90% of affected infants who are treated prospectively, recognition of this disorder before the brain has been injured is essential for treatment.

Analysis of Working Memory for Attention Deficit Hyperactivity Disorder (ADHD) Children using fMRI (주의력결핍 과잉행동성장애(ADHD) 아동의 작업기억 과제 수행 시 fMRI 분석)

  • Lee, Yong-Ki;Ahn, Sung-Min
    • The Journal of the Korea Contents Association
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    • v.14 no.12
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    • pp.854-862
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    • 2014
  • Attention deficit hyperactivity disorder (ADHD) students' intellctual defects, learning problems, and poor academic achievements seem to be due to significantly lower intelligence compared to the normal students, but rather the characteristic of inability to pay attention at a given time can be seen as the more attributing reason. In this study, a comparison between the ADHD students and the normal students will be performed using a fMRI analysis in order to differentiate the brain function between the two groups during a working memory task performance and to assess the difference in the activated regions of the brain. Clinical survey examinations and fMRI measurements were performed for a group of 26 elementary students from the Incheon area. The stimulus of fMRI was a working memory. Cartography statistically analyzed parameters and the Statistical Package of Social Sciences using single-sample t-test, two-sample t-test, were analyzed by multiple regression analysis, the statistical significance level was p<0.05 in, respectively. The disproportionate developments could be seen in the ADHD students group such as the frontal cortex, parietal cortex, thalamus, and caudate nucleus, among others. In addition, as some students felt the increase in the difficulty of working memory task performance, the orbitofrontal cortex and the hippocampus were activated, which seems to be the result of an effort for looking for an answer. More types of ADHD students needs to be secured as research subjects, and more stimulations for fMRI experiments should be considered as it would be useful in the overall evaluation of brain function.

Activation Differences of Superior Parietal Lobule and Cerebellum Areas While Inferring Geometrical Figures per Intellectual Category in Adolescents (도형 과제 수행 때 나타나는 청소년의 지능별 대뇌 및 소뇌의 활성도 차이 분석)

  • Kim, Ye Rim
    • Journal of Gifted/Talented Education
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    • v.23 no.5
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    • pp.637-648
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    • 2013
  • The relationship between the cerebral cortex and human intelligence has been studied using various methods, and related brain areas involved in intellectual manifestation have been discovered individually. Such studies have also shown the cerebellum is closely involved in various cognitive functions such as language, memory, and information processing. However, studies showing an activity difference between the cerebral cortex and cerebellum when performing specific tasks are hard to find. This study searched and analyzed the active regions of the cerebral cortex and cerebellum seen while performing the inference of geometrical figures. A WAIS intelligence test was conducted using 81 healthy boys (16.3 years of age on average), and five categories were classified. While performing the inference of shapes, their brain images were taken using functional magnetic resonance imaging (fMRI). As a result, the activity in 12 brain regions was observed, including in the cerebral cortex, the bilateral inferior parietal, the visual cortex, bilateral superior parietal, frontal-Inf-Tri-R, and bilateral caudate, while activities in 5 discrete areas were seen in the cerebellum. In particular, the higher the intelligence (IQ) of the subject, the stronger their activity. Among those with the most superior intelligence, subjects with an IQ of 140-147 showed significantly higher activity compared to the other groups. Such results seem to represent a very high utilization of intelligence in a highly gifted group, and we can expect to use this to determine the super gifted.

Learning-associated Reward and Penalty in Feedback Learning: an fMRI activation study (학습피드백으로서 보상과 처벌 관련 두뇌 활성화 연구)

  • Kim, Jinhee;Kan, Eunjoo
    • Korean Journal of Cognitive Science
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    • v.28 no.1
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    • pp.65-90
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    • 2017
  • Rewards or penalties become informative only when contingent on an immediately preceding response. Our goal was to determine if the brain responds differently to motivational events depending on whether they provide feedback with the contingencies effective for learning. Event-related fMRI data were obtained from 22 volunteers performing a visuomotor categorical task. In learning-condition trials, participants learned by trial and error to make left or right responses to letter cues (16 consonants). Monetary rewards (+500) or penalties (-500) were given as feedback (learning feedback). In random-condition trials, cues (4 vowels) appeared right or left of the display center, and participants were instructed to respond with the appropriate hand. However, rewards or penalties (random feedback) were given randomly (50/50%) regardless of the correctness of response. Feedback-associated BOLD responses were analyzed with ANOVA [trial type (learning vs. random) x feedback type (reward vs. penalty)] using SPM8 (voxel-wise FWE p < .001). The right caudate nucleus and right cerebellum showed activation, whereas the left parahippocampus and other regions as the default mode network showed deactivation, both greater for learning trials than random trials. Activations associated with reward feedback did not differ between the two trial types for any brain region. For penalty, both learning-penalty and random-penalty enhanced activity in the left insular cortex, but not the right. The left insula, however, as well as the left dorsolateral prefrontal cortex and dorsomedial prefrontal cortex/dorsal anterior cingulate cortex, showed much greater responses for learning-penalty than for random-penalty. These findings suggest that learning-penalty plays a critical role in learning, unlike rewards or random-penalty, probably not only due to its evoking of aversive emotional responses, but also because of error-detection processing, either of which might lead to changes in planning or strategy.

Manufacture of 3-Dimensional Image and Virtual Dissection Program of the Human Brain (사람 뇌의 3차원 영상과 가상해부 풀그림 만들기)

  • Chung, M.S.;Lee, J.M.;Park, S.K.;Kim, M.K.
    • Proceedings of the KOSOMBE Conference
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    • v.1998 no.11
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    • pp.57-59
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    • 1998
  • For medical students and doctors, knowledge of the three-dimensional (3D) structure of brain is very important in diagnosis and treatment of brain diseases. Two-dimensional (2D) tools (ex: anatomy book) or traditional 3D tools (ex: plastic model) are not sufficient to understand the complex structures of the brain. However, it is not always guaranteed to dissect the brain of cadaver when it is necessary. To overcome this problem, the virtual dissection programs of the brain have been developed. However, most programs include only 2D images that do not permit free dissection and free rotation. Many programs are made of radiographs that are not as realistic as sectioned cadaver because radiographs do not reveal true color and have limited resolution. It is also necessary to make the virtual dissection programs of each race and ethnic group. We attempted to make a virtual dissection program using a 3D image of the brain from a Korean cadaver. The purpose of this study is to present an educational tool for those interested in the anatomy of the brain. The procedures to make this program were as follows. A brain extracted from a 58-years old male Korean cadaver was embedded with gelatin solution, and serially sectioned into 1.4 mm-thickness using a meat slicer. 130 sectioned specimens were inputted to the computer using a scanner ($420\times456$ resolution, true color), and the 2D images were aligned on the alignment program composed using IDL language. Outlines of the brain components (cerebrum, cerebellum, brain stem, lentiform nucleus, caudate nucleus, thalamus, optic nerve, fornix, cerebral artery, and ventricle) were manually drawn from the 2D images on the CorelDRAW program. Multimedia data, including text and voice comments, were inputted to help the user to learn about the brain components. 3D images of the brain were reconstructed through the volume-based rendering of the 2D images. Using the 3D image of the brain as the main feature, virtual dissection program was composed using IDL language. Various dissection functions, such as dissecting 3D image of the brain at free angle to show its plane, presenting multimedia data of brain components, and rotating 3D image of the whole brain or selected brain components at free angle were established. This virtual dissection program is expected to become more advanced, and to be used widely through Internet or CD-title as an educational tool for medical students and doctors.

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