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研究生: 彭馨蕾
Peng, Shin-Lei
論文名稱: 利用磁振造影研究因年齡而變化的血液動力學: 從動物模型到人類實驗
Investigation on the hemodynamic changes with age by MRI: from animal model to human study
指導教授: 王福年
Wang, Fu-Nien
口試委員: 鍾孝文
Chung, Hsiao-Wen
劉鶴齡
Liu, Ho-Ling
陸漢璋
Lu, Hanzhang
葉子成
Yeh, Tzu-Chen
吳文超
Wu, Wen-Chau
彭旭霞
Peng, Hsu-Hsia
學位類別: 博士
Doctor
系所名稱: 原子科學院 - 生醫工程與環境科學系
Department of Biomedical Engineering and Environmental Sciences
論文出版年: 2014
畢業學年度: 102
語文別: 英文
論文頁數: 114
中文關鍵詞: 功能性磁振造影電刺激大鼠血液含氧量腦血流腦部代謝
外文關鍵詞: functional MRI, electrical stimulation, rat, blood oxygenation, cerebral blood flow, cerebral metabolism
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  • 磁振造影的優點為高度的解像能力及非侵入性檢查。有鑑於此,利用磁振造影技術來研究隨著年齡而變化的血液動力特性已行之有年。能夠了解與年齡相關的腦部生理參數不僅僅能夠用於評估臨床病理的狀況,也能觀察正常的老化過程。此外,動物模型更是一項研究與年齡相關之神經科學研究的利器。
    在此論文中,我們將先探討在isoflurane的麻醉下,電刺激大鼠臉部肌肉區的功能性磁振造影之再現性。結果顯示在連續三周進行fMRI實驗下,活化區域皆可重複地出現在主要體感覺桶狀皮質區、次要體感覺皮質區以及主要體感覺頷皮質區。一但檢驗過此動物模型的再現性之後,我們將著重在年齡對於大鼠的功能性磁振造影的影響。結果發現,不管在活化區大小、引起的訊號變化、血液動力延遲以及時態對比雜訊率方面,三個月大的老鼠以及十五個月大的老鼠其表現都沒有顯著差別。因此我們推斷,在進行功能性磁振造影實驗包含此一年齡範圍的大鼠時,將不用特別考慮年齡會造成的影響。
    論文的最後一部分將探討與年齡相關的總體腦部氧代謝率。此一研究包含118位健康受試者,其年齡分布為18-74歲。我們分別利用相位對比磁振造影技術來量測腦部血流量以及利用T2遲緩時間質子標記法來量測上矢狀竇的含氧濃度。結合這兩項技術,我們將可量測出總體腦部氧代謝率。結果顯示,腦部氧代謝率將會隨著年齡增加而增加,這暗示著老化的腦需要消耗更多的能量才能維持正常的功能。此外,和男性相比,女性的腦部氧代謝率受年齡影響較緩。這也暗示著,腦部氧代謝率隨時間的變化會因性別不同而展現出不同的時間模式。


    With the merit of high spatial resolution and non-invasive, investigations on the hemodynamic changes with age via magnetic resonance imaging (MRI) techniques have flourished for years. The understanding of normal age-associated values in brain would help evaluate not only clinical-pathologic conditions but also normal aging processes. In addition, animal studies provide approaches to better understanding in the field of age-related neuroscience research.
    This thesis first explores the reproducibility of rat fMRI study by employing electric mystacial pad stimulation under isoflurane anesthesia. Results showed that all rats exhibited reproducible activation in primary somatosensory barrel field cortex (S1BF), secondary somatosensory cortex (S2) and the primary somatosensory jaw region cortex (S1J) in all fMRI sessions in 3 successive weeks. Once the reproducibility was tested, we had examined age-related changes in the animal fMRI studies for the first time. In terms of the spatial extent of activation, induced signal change, hemodynamic delay and temporal contrast-to-noise ratio, there was no significantly different between 3-month-old and 15-month-old rats. These findings suggested the further age-related correlation is not needed in rodent fMRI studies composed of rats aging up to 15-month-old.
    The final part of this thesis is designed to assess age-related differences in global cerebral metabolic rate of oxygen (CMRO2) in a relatively large cohort (118 subjects) with a wide age range (18-74 years). Computation of CMRO2 is based on global cerebral blood flow (CBF) obtained from phase-contrast MRI and venous oxygen saturation (Yv) measurements in the superior sagittal sinus with a T2 relaxation experiment. The central finding is that CMRO2 increases with age, suggesting the aged brain may engage more energy to maintain the same functionality. In addition, women have a slower rate of CMRO2 change when compared to men (P<0.001 for interaction term), indicating a sex-difference in its temporal pattern.

    ABSTRACT I DEDICATION V CONTENTS VI LIST OF FIGURES IX LIST OF TABLES X INTRODUCTION 1 CHAPTER 1 BACKGROUND AND SIGNIFICANCE 4 1.1 BOLD-fMRI in animal studies 4 1.2 Measurement of Cerebral Metabolic Rate of Oxygen (CMRO2) in human 8 1.3 Goal and hypothesis of this dissertation 12 1.4 References 13 CHAPTER 2 LONGITUDINAL fMRI STUDY ON RAT MYSTACIAL PAD STIMULATION UNDER ISOFLURANE ANESTHESIA 22 2.1 Introduction 22 2.2 Materials and Methods 25 2.2.1 Reproducibility of fMRI study on rat mystacial pad stimulation under ISO anesthesia 26 2.2.1.1 Somatosensory stimulation paradigm 26 2.2.1.2 MRI image acquisition 27 2.2.1.3 Data analysis 28 2.2.2 On the age effect of the BOLD signal in rat fMRI using electrical mystacial stimulation 32 2.2.2.1 Somatosensory stimulation paradigm 32 2.2.2.2 MRI image acquisition 33 2.2.2.3 Data analysis 33 2.3 Results 36 2.3.1 Reproducibility of fMRI study on rat mystacial pad stimulation under ISO anesthesia 37 2.3.2 On the age effect of the BOLD signal in rat fMRI using electrical mystacial stimulation 48 2.4 Discussions 54 2.5 Conclusion 61 2.6 Application 62 2.7 References 65 CHAPTER 3 AGE-RELATED HYPERMETABOLISM IN THE HUMAN BRAIN 72 3.1 Introduction 72 3.2 Materials and Methods 76 3.2.1 Participants 77 3.2.2 Experimental procedures 78 3.2.3 Measurement of global CMRO2 79 3.2.4 Statistical analysis 83 3.3 Results 85 3.4 Discussion 91 3.5 Conclusion 100 3.6 References 101 CHAPTER 4 SUMMARIES AND FUTURE WORKS 110 4.1 Summaries 110 4.2 Future works 112 4.2.1 Further investigation on the mechanism of reorganization 113 4.2.2 Investigation on the potential applications for the CMRO2 technique .114

    1. http://www.nia.nih.gov/research/publication/longer-lives-and-disability/burden-dementia.
    2. Ge, Y., et al., Age-related total gray matter and white matter changes in normal adult brain. Part I: volumetric MR imaging analysis. AJNR Am J Neuroradiol, 2002. 23(8): p. 1327-33.
    3. Lim, K.O., et al., Decreased gray matter in normal aging: an in vivo magnetic resonance study. J Gerontol, 1992. 47(1): p. B26-30.
    4. Pfefferbaum, A., et al., A quantitative magnetic resonance imaging study of changes in brain morphology from infancy to late adulthood. Arch Neurol, 1994. 51(9): p. 874-87.
    5. Taki, Y., et al., Correlations among brain gray matter volumes, age, gender, and hemisphere in healthy individuals. PLoS One, 2011. 6(7): p. e22734.
    6. Guttmann, C.R., et al., White matter changes with normal aging. Neurology, 1998. 50(4): p. 972-8.
    7. Resnick, S.M., et al., One-year age changes in MRI brain volumes in older adults. Cereb Cortex, 2000. 10(5): p. 464-72.
    8. Liu, Y., et al., Arterial spin labeling MRI study of age and gender effects on brain perfusion hemodynamics. Magn Reson Med, 2012. 68(3): p. 912-22.
    9. Lu, H., et al., Alterations in cerebral metabolic rate and blood supply across the adult lifespan. Cereb Cortex, 2011. 21(6): p. 1426-34.
    10. Cabeza, R., et al., Task-independent and task-specific age effects on brain activity during working memory, visual attention and episodic retrieval. Cerebral Cortex, 2004. 14(4): p. 364-375.
    11. Daselaar, S.M., et al., Neuroanatomical correlates of episodic encoding and retrieval in young and elderly subjects. Brain, 2003. 126: p. 43-56.
    12. Park, D.C., et al., Working memory for complex scenes: Age differences in frontal and hippocampal activations. Journal of Cognitive Neuroscience, 2003. 15(8): p. 1122-1134.
    13. Williams, D.S., et al., Magnetic resonance imaging of perfusion using spin inversion of arterial water. Proc Natl Acad Sci U S A, 1992. 89(1): p. 212-6.
    14. Ogawa S, L.T.M., Kay A.R, Tank D.W, Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proceedings of the National Academy of Sciences, 1990. 87: p. 9868-9872.
    15. Mandeville, J.B., et al., Dynamic functional imaging of relative cerebral blood volume during rat forepaw stimulation. Magn Reson Med, 1998. 39(4): p. 615-24.
    16. Kwong, K.K., et al., Dynamic Magnetic-Resonance-Imaging of Human Brain Activity during Primary Sensory Stimulation. Proceedings of the National Academy of Sciences of the United States of America, 1992. 89(12): p. 5675-5679.
    17. Ogawa, S., et al., Intrinsic Signal Changes Accompanying Sensory Stimulation - Functional Brain Mapping with Magnetic-Resonance-Imaging. Proceedings of the National Academy of Sciences of the United States of America, 1992. 89(13): p. 5951-5955.
    18. Peng, S.L., et al., Spatial-temporal clustering analysis in functional magnetic resonance imaging. Physics in Medicine and Biology, 2009. 54(24): p. 7301-7314.
    19. Liu, P.Y., et al., Age-related differences in memory-encoding fMRI responses after accounting for decline in vascular reactivity. Neuroimage, 2013. 78: p. 415-425.
    20. Lu, H., U.S. Yezhuvath, and G. Xiao, Improving fMRI sensitivity by normalization of basal physiologic state. Hum Brain Mapp, 2010. 31(1): p. 80-7.
    21. Stoewer, S., et al., An Analysis Approach for High-Field fMRI Data from Awake Non-Human Primates. Plos One, 2012. 7(1).
    22. Ma, M.X., et al., Setup and data analysis for functional magnetic resonance imaging of awake cat visual cortex. Neuroscience Bulletin, 2013. 29(5): p. 588-602.
    23. Fang, M.R., et al., FMRI Mapping of cortical centers following visual stimulation in postnatal pigs of different ages. Life Sciences, 2006. 78(11): p. 1197-1201.
    24. Spenger, C., et al., Functional MRI at 4.7 Tesla of the rat brain during electric stimulation of forepaw, hindpaw, or tail in single- and multislice experiments. Experimental Neurology, 2000. 166(2): p. 246-253.
    25. Ahrens, E.T. and D.J. Dubowitz, Peripheral somatosensory fMRI in mouse at 11.7 T. NMR in Biomedicine, 2001. 14(5): p. 318-324.
    26. Peeters, R.R., et al., Comparing BOLD fMRI signal changes in the awake and anesthetized rat during electrical forepaw stimulation. Magnetic Resonance Imaging, 2001. 19(6): p. 821-6.
    27. Young R Kim, I.J.H., Seong-Ryong Lee, Emiri Tejima, Joseph B Mandeville, Maurits PA van Meer, George Dai, Yong W Choi, Rick M Dijkhuizen, Eng H Lo, Bruce R Rosen, Measurements of BOLD/CBV ratio show altered fMRI hemodynamics during stroke recovery in rats. Journal of cerebral blood flow and metabloism, 2005. 25: p. 820-829.
    28. Li, R., et al., Cortical plasticity induced by different degrees of peripheral nerve injuries: a rat functional magnetic resonance imaging study under 9.4 Tesla. J Brachial Plex Peripher Nerve Inj, 2013. 8(1): p. 4.
    29. Gountouna, V.E., et al., Functional Magnetic Resonance Imaging (fMRI) reproducibility and variance components across visits and scanning sites with a finger tapping task. Neuroimage, 2010. 49(1): p. 552-60.
    30. Tegeler, C., et al., Reproducibility of BOLD-based functional MRI obtained at 4 T. Hum Brain Mapp, 1999. 7(4): p. 267-83.
    31. Wei, X., et al., Functional MRI of auditory verbal working memory: long-term reproducibility analysis. Neuroimage, 2004. 21(3): p. 1000-8.
    32. Yasuaki Nakao, Y.I., Tang-Yong Kuang, Michelle Cook, Jane Jehle, Louis Skoloff, Effects of anesthesia on functional activation of cerebral blood flow and metabolism. Proceedings of the National Academy of Sciences, 2001. 98: p. 7593-7598.
    33. Arfors, K.E., G. Arturson, and P. Malmberg, Effect of prolonged chloralose anesthesia on acid-base balance and cardiovascular functions in dogs. Acta Physiol Scand, 1971. 81(1): p. 47-53.
    34. Silverman, J. and W.W. Muir, 3rd, A review of laboratory animal anesthesia with chloral hydrate and chloralose. Lab Anim Sci, 1993. 43(3): p. 210-6.
    35. Steward, C.A., et al., Methodological considerations in rat brain BOLD contrast pharmacological MRI. Psychopharmacology (Berl), 2005. 180(4): p. 687-704.
    36. Zhaohui M. Liu, K.F.S., Kenneth M. Sicard, Timothy Q. Duong, Imaging oxygen consumption in forepaw somatosensory stimulation in rats under isoflurane anesthesia. Magnetic Resonance Imaging, 2004. 52: p. 277-285.
    37. Xin Yu, S.W., Der-yow Chen, Stephen Dodd, Artem Goloshevsky, Alan P Koretsky, 3D mapping of somatotopic reorganization with small animal functional MRI. Neuroimage, 2010. 49: p. 1667-1676.
    38. Pelled, G., et al., Functional MRI detection of bilateral cortical reorganization in the rodent brain following peripheral nerve deafferentation. Neuroimage, 2007. 37(1): p. 262-273.
    39. Luke Boorman, A.J.K., David Johnston, Myles Jones, Ying Zheng, Peter Redgrave, and Jason Berwick, Negative blood oxygen level dependence in the rat: a model for investigating the role of suppression in neurovascular coupling. The Journal of Neruoscience, 2010. 30: p. 4285-4294.
    40. Kety, S.S. and C.F. Schmidt, The Effects of Altered Arterial Tensions of Carbon Dioxide and Oxygen on Cerebral Blood Flow and Cerebral Oxygen Consumption of Normal Young Men. J Clin Invest, 1948. 27(4): p. 484-92.
    41. Iadecola, C., L. Park, and C. Capone, Threats to the Mind Aging, Amyloid, and Hypertension. Stroke, 2009. 40(3): p. S40-S44.
    42. Yamaguchi, T., et al., Reduction in regional cerebral metabolic rate of oxygen during human aging. Stroke, 1986. 17(6): p. 1220-8.
    43. Eustache, F., et al., Healthy aging, memory subsystems and regional cerebral oxygen consumption. Neuropsychologia, 1995. 33(7): p. 867-87.
    44. Ibaraki, M., et al., Interindividual variations of cerebral blood flow, oxygen delivery, and metabolism in relation to hemoglobin concentration measured by positron emission tomography in humans. J Cereb Blood Flow Metab, 2010. 30(7): p. 1296-305.
    45. Marchal, G., et al., Regional cerebral oxygen consumption, blood flow, and blood volume in healthy human aging. Arch Neurol, 1992. 49(10): p. 1013-20.
    46. Burns, A. and P. Tyrrell, Association of age with regional cerebral oxygen utilization: a positron emission tomography study. Age Ageing, 1992. 21(5): p. 316-20.
    47. Lassen, N.A., I. Feinberg, and M.H. Lane, Bilateral studies of cerebral oxygen uptake in young and aged normal subjects and in patients with organic dementia. J Clin Invest, 1960. 39: p. 491-500.
    48. Zaidi, Z.F., Gender differences in human brain: a review. The Open Anatomy Journal, 2010. 2: p. 37-55.
    49. Bolar, D.S., et al., QUantitative Imaging of eXtraction of oxygen and TIssue consumption (QUIXOTIC) using venular-targeted velocity-selective spin labeling. Magn Reson Med, 2011. 66(6): p. 1550-62.
    50. Xu, F., Y. Ge, and H. Lu, Noninvasive quantification of whole-brain cerebral metabolic rate of oxygen (CMRO2) by MRI. Magn Reson Med, 2009. 62(1): p. 141-8.
    51. Aslan, S., et al., Estimation of labeling efficiency in pseudocontinuous arterial spin labeling. Magn Reson Med, 2010. 63(3): p. 765-71.
    52. Lu, H. and Y. Ge, Quantitative evaluation of oxygenation in venous vessels using T2-Relaxation-Under-Spin-Tagging MRI. Magn Reson Med, 2008. 60(2): p. 357-63.
    53. Liu, P.Y., et al., Multi-site evaluations of a TRUST MRI technique to measure brain oxygenation. ISMRM, 2013.
    54. Liu, P., F. Xu, and H. Lu, Test-retest reproducibility of a rapid method to measure brain oxygen metabolism. Magn Reson Med, 2013. 69(3): p. 675-81.
    55. Ge, Y., et al., Characterizing brain oxygen metabolism in patients with multiple sclerosis with T2-relaxation-under-spin-tagging MRI. J Cereb Blood Flow Metab, 2012. 32(3): p. 403-12.
    56. Xu, F., et al., The influence of carbon dioxide on brain activity and metabolism in conscious humans. J Cereb Blood Flow Metab, 2011. 31(1): p. 58-67.
    57. Xu, F., et al., Effect of hypoxia and hyperoxia on cerebral blood flow, blood oxygenation, and oxidative metabolism. J Cereb Blood Flow Metab, 2012. 32(10): p. 1909-18.
    58. Thomas, B., et al., Characterization of CMRO2, resting CBF, and cerebrovascular reactivity in patients with very early stage of Alzheimer's Disease. ISMRM, 2013.
    59. Sheng, M., et al., Alterations in cerebral physiology in women suffering from anorexia nervosa. ISMRM, 2014.

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