Investigative Magnetic Resonance Imaging

Korean Society of Magnetic Resonance in Medicine (대한자기공명의과학회)
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Pharmacological Functional Magnetic Resonance Imaging of Cloropidol on Motor Task

운동과제에 대한 클로피도그렐의 약리적 뇌자기공명영상

  • Chang, Yong-Min (Department of Molecular Medicine, Kyungpook National University College of Medicine)
  • 장용민 (경북대학교 의학전문대학원 분자의학교실)
  • Received : 2012.06.21
  • Accepted : 2012.08.08
  • Published : 2012.08.31
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Abstract

Purpose : To investigate the pharmacologic modulation of motor task-dependent physiologic responses by antiplatelet agent, clopidogrel, during hand motor tasks in healthy subjects. Materials and Methods: Ten healthy, right-handed subjects underwent three functional magnetic resonance (fMRI) sessions: one before drug administration, one after high dose drug administration and one after reaching drug steady state. For the motor task fMRI, finger flexion-extension movements were performed. Blood oxygenation level dependent (BOLD) contrast was collected for each subject using a 3.0 T VHi (GE Healthcare, Milwaukee, USA) scanner. $T2^*$-weighted echo planar imaging was used for fMRI acquisition. The fMRI data processing and statistical analyses were carried out using SPM2. Results: Second-level analysis revealed significant increases in the extent of activation in the contralateral motor cortex including primary motor area (M1) after drug administration. The number of activated voxels in motor cortex was 173 without drug administration and the number increased to 1049 for high dose condition and 673 for steady-state condition respectively. However, there was no significant difference in the magnitude of BOLD signal change in terms of peak T value. Conclusion: The current results suggest that cerebral motor activity can be modulated by clopidogrel in healthy subjects and that fMRI is highly senstive to evidence such changes.

목적: 정상인에서 항혈소판제제인 클로피도그렐이 손운동기능 과제를 수행하는 동안 운동기능의 생리학적 반응에 대한 약리적 조절효과를 알아보고자 하였다. 대상과 방법: 10명의 오른손잡이 정상인을 대상으로 클로피도그렐 사용전, 최대 복용량 복용후, 정상상태 유지시로 세번에 걸쳐 뇌기능 자기공명영상 데이터를 획득하였다. 운동과제로는 주먹을 쥐었다 폈다하는 운동을 시행하였고 3.0 테슬라 자기공명영상기기에서 혈액산소의존성(BOLD) 대조도를 획득하였으며 이를 위하여 $T2^*$ 강조 EPI 영상기법을 사용하였다. 뇌기능 자기공명영상 데이터의 영상전처리 및 통계분석은 SPM2를 사용하였다. 결과: 이차수준 분석에서 주운동영역을 포함하는 편측 감각운동중추의 활성화가 나타났다. 클로피도그렐 사용전의 활성화 화소수는 173, 최대 복용량 복용후 활성화 화소수는 1049, 정상상태 유지시 활성화 화소수는 673 이었다. 최대 T값을 기준으로 측정한 BOLD 신호의 강도변화는 관찰되지 않았다. 결론: 본 연구결과는 클로피도그렐에 의해 대뇌 운동 활성이 조절된다는 사실과 또한 뇌기능 자기공명영상이 이러한 변화를 감지할수 있을만큼 높은 민감성을 가진다는 사실을 제안하고 있다.

Keywords

References

  1. Kimberg D, Aguirre G, Lease J, D'Esposito M. Cortical effects of bromocriptine, a D-2 dopamine receptor agonist, in human subjects, revealed by fMRI. Hum Brain Mapp 2001;12:246-257
  2. Honey G, Bullmore E, Soni W, Varatheesan M, Williams S, Sharma T. Differences in frontal cortical activation by a working memory task after substitution of risperidone for typical antipsychotic drugs in patients with schizophrenia. Proc Natl Acad Sci USA 1999;96:13432-13437
  3. Braus D, Ende G, Weber-Fahr W, et al. Antipsychotic drug effects on motor activation measured by functional magnetic resonance imaging in schizophrenic patients. Schizophr Res 1999;39:19-29
  4. Loubinoux I, Boulanouar K, Ranjeva J-P, et al. Cerebral functional magnetic resonance imaging activation modulated by a single dose of the monoamine neurotransmission enhancers fluoxetine and fenozolone during hand motor tasks. J Cereb Blood Flow Metab 1999;19:1365-1375
  5. Goldstein L, Coviello A, Miller G, Davis J. Norepinephrine depletion impairs motor recovery following sensorimotor cortex injury in the rat. Restor Neurol Neurosci 1991;3:41-47
  6. Goldstein L. Common drugs may influence motor recovery after stroke. Neurology 1995;45:865-871
  7. Gubitz G, Sandercock P, Counsell C. Antiplatelet therapy for acute ischemic stroke. In: The Cochrane Library, Issue 1, 2000. Oxford
  8. Tokumaru S, Yoshikai T, Uchino A, Matsui M, Kuroda Y, Kudo S. Technetium-99m-ECD SPECT in antiphospholipid antibody syndrome: a drastic improvement in brain perfusion by antiplatelet therapy. Eur Radiol 2001;11:2611-2615
  9. Chan F, Ching J, Hung L, et al. Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding. New Engl J Med 2005;352:238-244
  10. Herbert JM, Savi P. P2Y12, a new platelet ADP receptor, target of clopidogrel. Semin Vasc Med 2003;3:113-122
  11. Friston K, Holmes A, Worsley K, Poline J, Frith C, Frackowiak R. Statistical parametric paps in functional imaging: a general linear approach. Hum Brain Mapp 1995;2:189-210
  12. Evans A, Collins D, Mills S, Brown E, Kelly R, Peters T. 3D statistical neuroanatomical models from 305 MRI volumes. Proc. IEEE-Nucl. Sci. Symp. Med. Imaging 1993;1813-1817
  13. Talairach J, Tournoux P. Co-Planar Stereotaxic Atlas of the Human Brain. Thieme, 1988, New York
  14. Hochberg Y, Tamhane A. Multiple comparisons procedures. Wiley, 1987, New York
  15. Worsley K, Marrett S, Neelin P, Vandal A, Friston K, Evans A. A unified statistical approach for determining significant voxels in images of cerebral activation. Hum Brain Mapp 1996;4:58-73
  16. Mintzer M, Griffiths R.R. Acute dose-effects of scopolamine on false recognition. Psychopharmacology 2001;153:425-433
  17. Bozzali M, MacPherson SE, Dolan RJ, Shallice T. Left prefrontal cortex control of novel occurrences during recollection: a psychopharmacological study using scopolamine and eventrelated fMRI. Neuroimage 2006;33:286-295
  18. Hasbroucq T, Rihet P, Blin O, Possamai C. Serotonin and human information processing: fluvoxamine can improve reaction time performance. Neurosci Lett 1997;229:204-208
  19. Weisskoff R, Zuo C, Boxerman J, Rosen B. Microscopic susceptibility variation and transverse relaxation: theory and experiment. Magn Reson Med 1994;31:601-610
  20. Lee S-P, Silva A, Ugurbil K, Kim S-G. Diffusion-weighted spinecho fMRI at 9.4T: microvascular/tissue contribution to BOLD signal change. Magn Reson Med 1999;42:919-928