4T MR动脉自旋标记成像对早期Alzheimer病的脑灌注研究
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摘要
研究背景及目的:Alzheimer病(Alzheimer's disease, AD)是以认知功能障碍、情感障碍及行为异常为主要表现的神经退行性病变,是造成痴呆最常见的原因。组织学上以老年斑、神经元纤维缠结、神经元丧失和淀粉样血管病变的出现为特点。最初的神经病理学改变位于内侧颞叶,晚期可扩展至颞顶叶和额叶等相关皮层,初级感觉中枢和运动中枢一般不受累。功能神经影像学,能够在疾病亚临床期检测AD患者脑功能及血流动力学的改变,实现早期诊断,使患者能够获得及时有效的治疗,延缓病程,提高生活质量。本研究目的在于利用高场MR获得早期AD患者在静息态及记忆任务刺激下的脑血流动力学及功能异常。
     研究方法:研究对象为临床诊为早期AD的志愿者12人(平均年龄72.3±7.9岁)和年龄匹配的正常对照组12人(平均年龄73.7±5.5岁)。在4T MR采用动脉自旋标记(arterial spin labeling, ASL)灌注技术,对所有受试者在静息态下行MR灌注扫描,并采用ASL及血氧水平依赖(blood oxygenation level dependent, BOLD)对比分别在记忆编码及记忆提取任务下行功能成像。数据后处理应用FSL和SPM软件,统计学处理采用SPSS 19.0。
     结果:静息状态下,AD患者脑血流灌注主要分布于右侧额叶、左侧颞、枕叶及前扣带回。与对照组相比,AD组在双侧额叶、左顶叶楔回、右侧颞上回及后扣带回出现了散在的低灌注区,同时在双侧前额叶皮层(包括前额叶背外侧皮层和前额叶腹外侧皮层)、右顶叶及前扣带回出现了显著的灌注增高区。执行记忆编码和提取任务时,AD组除在双侧额叶和运动区出现低灌注/激活区外,在双侧前额叶皮层(包括双侧前额叶背外侧皮层、前额叶腹外侧皮层、额极)和前扣带回可见显著的高灌注/激活区。
     结论:4TMR下,早期AD患者在静息态及认知状态下,脑内均存在一定的灌注损伤。同时,双侧前额叶皮层均出现了神经代偿反应。ASL和BOLD两种成像方式在检测AD静息态及认知状态下的脑血流灌注及功能活动方面具有可比性。
Background and objective:Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive impairments and is the most common reason for dementia. The histological changes are characterized by senile plaque, neurofibrillary tangles, neuron loss and granulovacuolar degeneration. Brain damage begins in the medial temporal lobe in the early stage of AD and extends gradually to the entire neocortex. Neuroimaging techniques have played an important role in diagnosing AD, especially in finding functional abnormalities in early stage of the disease. The purpose of this study was to detect brain hemodynamic and functional changes in subjects with AD at both resting state and during cognitive tasks.
     Methods:Twelve subjects with early AD (mean age=72.3±7.9 yrs, females=5) and 12 age-matched cognitively normal (CN, mean age=73.7±5.5yrs, females=9) subjects were recruited for this study. Perfusion-weighted imaging with arterial spin labeling (ASL) was employed to study the hemodynamic abnormalities in AD at resting state. ASL-based fMRI was used to investigate brain functional changes during cognitive states including both encoding and retrieval tasks in AD. Blood oxygenation level dependent (BOLD)-functional MRI (fMRI) was also conducted for comparison. Data post-processing was performed with SPM and FSL software package. SPSS versoin19.0 was used for statistics.
     Results:During the resting state, brain perfusion was located in AD in the right frontal lobe, left temporal and occipital lobes, and anterior cingulate cortex (ACC). In comparison with the CN group, hypoperfusion occurred in AD in the bilateral prefrontal cortex, left precuneus and posterior cingulate cortex. Hyperperfusion was also found in the bilateral prefrontal cortex (including the dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC) and ACC in subjects with AD. During the memory task performance, the AD group showed significantly greater perfusion/activation than the normal controls in bilateral prefrontal cortex (including the DLPFC and VLPFC), as well as the ACC under both encoding and retrieval tasks.
     Conclus i on:Hypoperfusion occurred in multiple areas in AD at both resting state and under memory tasks, reflecting perfusion damage in early AD. Meanwhile, hyperperfusion/hyperactivation was also found in bilateral prefrontal cortex in subjects with AD in both resting state and under task performance, suggesting the neurocompensatory response in these areas. ASL and BOLD are comparable in detecting brain hemodynamic changes in AD with 4T MR.
引文
1. Alzheimer's Association.2009 Alzheimer's disease facts and figures. Alzheimer's and Dementia,2009,5(3):234-270.
    2. Viswanathan A, Rocca WA, Tzourio C. Vascular risk factors and dementia:how to move forward? Neurology,2009,72(4):368-374.
    3. de la Torre JC. Cerebrovascular and cardiovascular pathology in Alzheimer's disease. Int Rev Neurobiol,2009,84:35-48.
    4. Braak H, Braak E. Neuropathological staging of Alzheimer-related changes. Acta Neuropathol,1991,82(4):239-259.
    5. Kodama N, Shimada T, Fukumoto I. Image-based diagnosis of Alzheimer-type dementia:measurements of hippocampal and ventricular areas in MR images. Magn Reson Med Sci,2002,1(1):14-20.
    6. Jack CR Jr, Petersen RC, Xu YC, Waring SC et al. Medial temporal atrophy on MRI in normal aging and very mild Alzheimer's disease. Neurology,1997,49(3): 786-794.
    7. Jack CR Jr, Petersen RC, Xu Y, O'Brien PC, et al. Rate of medial temporal lobe atrophy in typical aging and Alzheimer's disease. Neurology,1998,51(4): 993-999.
    8. Rodriguez G, Vitali P, Calvini P, Bordoni C, et al. Hippocampal perfusion in mild Alzheimer's disease. Psychiatry Res,2000,100(2):65-74.
    9. Waragai M, Mizumura S, Yamada T, Matsuda H. Differentiation of early-stage Alzheimer's disease from other types of dementia using brain perfusion single photon emission computed tomography with easy Z-score imaging system analysis. Dement Geriatr Cogn Disord,2008,26(6):547-55.
    10. Tohgi H, Yonezawa H, Takahashi S, Sato N, et al. Cerebral blood flow and oxygen metabolism in senile dementia of Alzheimer's type and vascular dementia with deep white matter changes. Neuroradiology,1998; 40(3):131-137.
    11. Festa EK, Insler RZ, Salmon DP, Paxton J, et al. Neocortical disconnectivity disrupts sensory integration in Alzheimer's disease. Neuropsychology,2005,19(6): 728-738.
    12. Sperling RA, Bates JF, Chua EF, Cocchiarella AJ, et al. fMRI studies of associative encoding in young and elderly controls and mild Alzheimer's disease. J Neurol Neurosurg Psychiatry,2003,74(1):44-50.
    13. Machulda MM, Ward HA, Borowski B, Gunter JL, et al. Comparison of memory fMRI response among normal, MCI, and Alzheimer's patients. Neurology,2003, 61(4):500-506.
    14. Rombouts SA, Barkhof F, Goekoop R, Stam CJ, et al. Altered resting state networks in mild cognitive impairment and mild Alzheimer's disease:an fMRI study. Hum Brain Mapp,2005,26(4):231-239.
    15. Dickerson BC, Salat DH, Greve DN, Chua EF, et al. Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD. Neurology,2005,65(3):404-411.
    16. Sperling R. Functional MRI studies of associative encoding in normal aging, mild cognitive impairment, and Alzheimer's disease. Ann N Y Acad Sci,2007,1097: 146-155.
    17. Grossman M, Koenig P, Glosser G, DeVita C, et al. Neural basis for semantic memory difficulty in Alzheimer's disease:an fMRI study. Brain,2003,126 (Pt 2): 292-311.
    18. Schwindt GC, Black SE. Functional imaging studies of episodic memory in Alzheimer's disease:a quantitative meta-analysis. Neuroimage,2009,45(1): 181-190.
    19. Sperling R, Chua E, Cocchiarella A, Rand-Giovannetti E, et al. Putting names to faces:successful encoding of associative memories activates the anterior hippocampal formation. Neuroimage,2003,20(2):1400-1410.
    20. Grady CL, McIntosh AR, Beig S, Keightley ML, et al. Evidence from functional neuroimaging of a compensatory prefrontal network in Alzheimer's disease. J Neurosci,2003,23(3):986-993.
    21. Pariente J, Cole S, Henson R, Clare L, et al. Alzheimer's patients engage an alternative network during a memory task. Ann Neurol,2005,58(6):870-879.
    22. Alsop DC, Casement M, de Bazelaire C, Fong T, et al. Hippocampal hyperperfusion in Alzheimer's disease. Neuroimage,2008; 42(4):1267-1274.
    23. Greicius MD, Srivastava G, Reiss AL, Menon V. Default-mode network activity distinguishes Alzheimer's disease from healthy aging:evidence from functional MRI. Proc Natl Acad Sci U S A,2004,101(13):4637-4642.
    24. Pihlajamaki M, Sperling RA. Functional MRI assessment of task-induced deactivation of the default mode network in Alzheimer's disease and at-risk older individuals. Behav Neurol,2009,21(1):77-91.
    25. Fleisher AS, Sherzai A, Taylor C, Langbaum JB, et al. Resting-state BOLD networks versus task-associated functional MRI for distinguishing Alzheimer's disease risk groups. Neuroimage,2009,47(4):1678-1690.
    26. Sheline YI, Raichle ME, Snyder AZ, Morris JC, et al. Amyloid plaques disrupt resting state default mode network connectivity in cognitively normal elderly. Biol Psychiatry,2010,67(6):584-587.
    27. Zhang HY, Wang SJ, Liu B, Ma ZL, et al. Resting brain connectivity:changes during the progress of Alzheimer disease. Radiology,2010,256(2):598-606.
    28. Wintermark M, Sesay M, Barbier E, Borbely K et al. Comparative overview of brain perfusion imaging techniques. Stroke,2005; 36(9):e83-99.
    29. Johnson NA, Jahng GH, Weiner MW, Miller BL et al. Pattern of cerebral hypoperfusion in Alzheimer disease and mild cognitive impairment measured with arterial spin-labeling MR imaging:initial experience. Radiology,2005; 234(3):851-9.
    30. Dai W, Lopez OL, Carmichael OT, Becker JT, et al. Mild cognitive impairment and Alzheimer disease:patterns of altered cerebral blood flow at MR imaging. Radiology,2009; 250(3):856-66.
    31. Bozzao A, Floris R, Baviera ME, Apruzzese A, et al. Diffusion and perfusion MR imaging in cases of Alzheimer's disease:correlations with cortical atrophy and lesion load. AJNR Am J Neuroradiol,2001; 22(6):1030-1036.
    32. Alsop DC, Detre JA, Grossman M. Assessment of cerebral blood flow in Alzheimer's disease by spin-labeled magnetic resonance imaging. Ann Neurol, 2000; 47(1):93-100.
    33. Asllani I, Habeck C, Scarmeas N, Borogovac A, et al. Multivariate and univariate analysis of continuous arterial spin labeling perfusion MRI in Alzheimer's disease. J Cereb Blood Flow Metab,2008; 28(4):725-736.
    34. Du AT, Jahng GH, Hayasaka S, Kramer JH, et al. Hypoperfusion in frontotemporal dementia and Alzheimer disease by arterial spin labeling MRI. Neurology,2006,67(7):1215-1220.
    35. Luckhaus C, Flub MO, Wittsack HJ, Grass-Kapanke B et al. Detection of changed regional cerebral blood flow in mild cognitive impairment and early Alzheimer's dementia by perfusion-weighted magnetic resonance imaging. Neuroimage,2008; 40(2):495-503.
    36. Yoshiura T, Hiwatashi A, Yamashita K, Ohyagi Y, et al. Simultaneous measurement of arterial transit time, arterial blood volume, and cerebral blood flow using arterial spin-labeling in patients with Alzheimer disease. AJNR Am J Neuroradiol,2009; 30(7):1388-1393.
    37. Garcia Santos JM, Gavrila D, Antunez C, Tormo MJ, et al. Magnetic resonance spectroscopy performance for detection of dementia, Alzheimer's disease and mild cognitive impairment in a community-based survey. Dement Geriatr Cogn Disord,2008; 26(1):15-25.
    38. Waldman AD, Rai GS. The relationship between cognitive impairment and in vivo metabolite ratios in patients with clinical Alzheimer's disease and vascular dementia:a proton magnetic resonance spectroscopy study. Neuroradiology,2003, 45(8):507-512.
    39. Kantarci K, Jack CR Jr, Xu YC, Campeau NG, et al. Mild cognitive impairment and Alzheimer disease:regional diffusivity of water. Radiology,2001,219(1): 101-107.
    40. Kantarci K, Petersen RC, Boeve BF, Knopman DS, et al. DWI predicts future progression to Alzheimer disease in amnestic mild cognitive impairment. Neurology,2005,64(5):902-904.
    41. Bozzali M, Falini A, Franceschi M, Cercignani M, et al. White matter damage in Alzheimer's disease assessed in vivo using diffusion tensor magnetic resonance imaging.J Neurol Neurosurg Psychiatry,2002,72(6):742-746.
    42. Sugihara S, Kinoshita T, Matsusue E, Fujii S et al. Usefulness of diffusion tensor imaging of white matter in Alzheimer disease and vascular dementia. Acta Radiol, 2004,45(6):658-663.
    43. Fellgiebel A, Wille P, MuIler MJ, Winterer G, et al. Ultrastructural hippocampal and white matter alterations in mild cognitive impairment:a diffusion tensor imaging study. Dement Geriatr Cogn Disord,2004,18(1):101-108.
    44. Naggara O, Oppenheim C, Rieu D, Raoux N, et al. Diffusion tensor imaging in early Alzheimer's disease. Psychiatry Res,2006,146(3):243-249.
    45. Detre JA, Leigh JS, Williams DS, Koretsky AP. Perfusion imaging. Magn Reson Med,1992; 23(1):37-45.
    46. Roberts DA, Detre JA, Bolinger L, Insko EK, et al. Quantitative magnetic resonance imaging of human brain perfusion at 1.5 T using steady-state inversion of arterial water. Proc Natl Acad Sci USA,1994,91(1):33-37.
    47. Kim HS, Kim SY, Kim JM. Underestimation of cerebral perfusion on flow-sensitive alternating inversion recovery image:semi quantitative evaluation with time-to-peak values. AJNR Am J Neuroradiol,2007,28(10):2008-2013.
    48. Kim SG. Quantification of relative cerebral blood flow change by flow-sensitive alternating inversion recovery (FAIR) technique:application to functional mapping. Magn Reson Med,1995,34(3):293-301.
    49. Kim SG, Tsekos NV. Perfusion imaging by a flow-sensitive alternating inversion recovery (FAIR) technique:application to functional brain imaging. Magn Reson Med,1997,37(3):425-435.
    50. Detre JA, Wang J. Technical aspects and utility of fMRI using BOLD and ASL Clin Neurophysiol,2002,113(5):621-634.
    51. Guedj E, Barbeau EJ, Didic M, Felician O, et al. Effects of medial temporal lobe degeneration on brain perfusion in amnestic MCI of AD type:deafferentation and functional compensation? Eur J Nucl Med Mol Imaging,2009,36(7):1101-1112.
    52. Gould RL, Arroyo B, Brown RG, Owen AM, et al. Brain mechanisms of successful compensation during learning in Alzheimer disease. Neurology, 2006,67(6):1011-1017.
    53. Buckner RL, Andrews-Hanna JR, Schacter DL. The brain's default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci,2008,1124:1-38.
    54. Buckner RL. Memory and executive function in aging and AD:multiple factors that cause decline and reserve factors that compensate. Neuron,2004,44(1): 195-208.
    55. Arnsten AF Toward a new understanding of attention-deficit hyperactivity disorder pathophysiology:an important role for prefrontal cortex dysfunction. CNS Drugs,2009,23 Suppl 1:33-41.
    56. Harris GJ, Lewis RF, Satlin A, English CD, et al. Dynamic susceptibility contrast MRI of regional cerebral blood volume in Alzheimer's disease. Am J Psychiatry, 1996,153(5):721-724.
    57. Maas LC, Harris GJ, Satlin A, English CD, et al. Regional cerebral blood volume measured by dynamic susceptibility contrast MR imaging in Alzheimer's disease: a principal components analysis. J Magn Reson Imaging,1997,7(1):215-219.
    58. Harris GJ, Lewis RF, Satlin A, English CD, Scott TM, Yurgelun-Todd DA, et al. Dynamic susceptibility contrast MR imaging of regional cerebral blood volume in Alzheimer disease:a promising alternative to nuclear medicine. AJNR Am J Neuroradiol,1998,19(9):1727-1732.
    59. Johnson NA, Jahng GH, Weiner MW, Miller BL, et al. Pattern of cerebral hypoperfusion in Alzheimer disease and mild cognitive impairment measured with arterial spin-labeling MR imaging:initial experience. Radiology,2005, 234(3):851-859.
    60. Wang J, Alsop DC, Li L, Listerud J, et al. Comparison of quantitative perfusion imaging using arterial spin labeling at 1.5 and 4.0 Tesla. Magn Reson Med, 2002,48(2):242-254.
    61. Nestor PJ, Fryer TD, Ikeda M, Hodges JR. Retrosplenial cortex (BA 29/30) hypometabolism in mild cognitive impairment (prodromal Alzheimer's disease). Eur J Neurosci,2003,18(9):2663-2667.
    62. Ishii K, Sasaki M, Yamaji S, Sakamoto S, et al. Paradoxical hippocampus perfusion in mild-to-moderate Alzheimer's disease. J Nucl Med,1998,39(2): 293-298.
    63. Chetelat G, Desgranges B, Landeau B, Mezenge F, et al. Direct voxel-based comparison between grey matter hypometabolism and atrophy in Alzheimer's disease. Brain,2008,131(pt 1):60-71.
    64. Baron JC, Chetelat G, Desgranges B, Perchey G, et al. In vivo mapping of gray matter loss with voxel-based morphometry in mild Alzheimer's disease. Neuroimage,2001,14(2):298-309.
    65. Chetelat G, Desgranges B, De La Sayette V, Viader F, et al Mapping gray matter loss with voxel-based morphometry in mild cognitive impairment. Neuroreport, 2002,13(15):1939-1943.
    66. Grady CL, McIntosh AR, Horwitz B, Maisog JM, et al. Age-related reductions in human recognition memory due to impaired encoding. Science,1995,269(5221): 218-221.
    67. Cabeza R, Nyberg L. Neural bases of learning and memory:functional neuroimaging evidence. Curr Opin Neurol,2000,13(4):415-421.
    68. Golay X, Petersen ET. Arterial spin labeling:benefits and pitfalls of high magnetic field. Neuroimaging Clin N Am,2006,16(2):259-268.
    69. Lamar M, Resnick SM, Zonderman AB. Longitudinal changes in verbal memory in older adults:distinguishing the effects of age from repeat testing. Neurology, 2003,60(1):82-86.
    70. Smith E E, Jonides J. Storage and executive processes in the frontal lobes. Science,1999,283(3):1657-1661.
    71. Kelley WM, Miezin FM, McDermott KB, Buckner RL, et al. Hemispheric specialization in human dorsal frontal cortex and medial temporal lobe for verbal and nonverbal memory encoding. Neuron,1998,20(5):927-936.
    72. Myers CE, Shohamy D, Gluck MA, Grossman S, et al. Dissociating hippocampal versus basal ganglia contributions to learning and transfer. J Cogn Neurosci, 2003,15(2):185-193.
    73. Shu SY, Wu YM, Bao XM, Wen ZB, et al. A new area in the human brain associated with learning and memory:immunohistochemical and functional MRI analysis. Mol Psychiatry,2002,7(9):1018-1022.
    74. Poldrack RA, Clark J, Pare-Blagoev EJ, Shohamy D, et al. Interactive memory systems in the human brain. Nature,2001,414(6863):546-550.
    75. Braver TS, Barch DM, Kelley WM, Buckner RL, et al. Direct comparison of prefrontal cortex regions engaged by working and long-term memory tasks. Neuroimage,2001,14(1 Pt 1):48-59.
    76. Rossi S, Miniussi C, Pasqualetti P, Babiloni C, et al. Age-related functional changes of prefrontal cortex in long-term memory:a repetitive transcranial magnetic stimulation study. J Neurosci,2004,24(36):7939-7944.
    77. Tulving E, Markowitsch HJ, Kapur S, Habib R, et al. Novelty encoding networks in the human brain:positron emission tomography data. Neuroreport,1994,5(18): 2525-2528.
    78. Cabeza R. Hemispheric asymmetry reduction in old adults:the HAROLD Model. Psychol Aging 2002; 17:85-100.
    79. Stebbins GT, Carrillo MC, Dorman J, et al. Aging effects on memory encoding in the frontal lobes. Psychol Aging 2002;17:44-55.
    80. Dolcos F, Rice HJ, Cabeza R. Hemispheric asymmetry and aging:right hemisphere decline or asymmetry reduction. Neurosci Biobehav Rev,2002,26(7): 819-825.
    81. Dennis NA, Hayes SM, Prince SE, Madden DJ, et al. Effects of aging on the neural correlates of successful item and source memory encoding. J Exp Psychol Learn Mem Cogn,2008,34(4):791-808.
    82. Xu G, Antuono PG, Jones J, Xu Y, et al. Perfusion fMRI detects deficits in regional CBF during memory-encoding tasks in MCI subjects. Neurology,2007, 69:1650-6165.
    83. Bateman GA, Levi CR, Schofield P, Wang Y, et al. Quantitative measurement of cerebral haemodynamics in early vascular dementia and Alzheimer's disease. J Clin Neurosci,2006,13(5):563-568.
    84. Girouard H, Iadecola C. Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease. J Appl Physiol,2006,100(1): 328-335.
    85. Iadecola C. Neurovascular regulation in the normal brain and in Alzheimer's disease. Nat Rev Neurosci,2004,5(5):347-360.
    1. Alzheimer's Association.2009 Alzheimer's disease facts and figures. Alzheimer's and Dementia 2009;5:234-70.
    2. Braak H, Braak E. Neuropathological staging of Alzheimer-related changes. Acta Neuropathol 1991;82:239-59.
    3. Mattsson N, Blennow K, Zetterberg H. CSF biomarkers:pinpointing Alzheimer pathogenesis. Ann N YAcad Sci 2009;1180:28-35.
    4. Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease:progress and problems on the road to therapeutics. Science 2002;297:353-6.
    5. Rocchi A, Orsucci D, Tognoni G, Ceravolo R, et al. The role of vascular factors in late-onset sporadic Alzheimer's disease. Genetic and molecular aspects. Curr Alzheimer Res 2009;6:224-37.
    6. Hachinski V, Munoz DG. Cerebrovascular pathology in Alzheimer's disease: cause, effect or epiphenomenon? Ann NY Acad Sci 1997;826:1-6.
    7. Morovic S, Jurasic MJ, Martinic Popovic I, Seric V, et al. Vascular characteristics of patients with dementia. J Neurol Sci 2009;283:41-3.
    8. Viswanathan A, Rocca WA, Tzourio C. Vascular risk factors and dementia: how to move forward? Neurology 2009;72:368-74.
    9. de la Torre JC. Cerebrovascular and cardiovascular pathology in Alzheimer's disease. Int Rev Neurobiol 2009;84:35-48.
    10. Skoog I, Gustafson D. Hypertension, hypertension-clustering factors and Alzheimer's disease. Neurol Res 2003;25:675-80.
    11. Dubois B, Feldman HH, Jacova C, Dekosky ST, et al. Research criteria for the diagnosis of Alzheimer's disease:revising the NINCDS-ADRDA criteria. Lancet Neurol 2007;6:734-46.
    12. Scheltens P. Imaging in Alzheimer's disease. Dialogues Clin Neurosci 2009; 11: 191-9.
    13. Smith CD. Neuroimaging through the course of Alzheimer's disease. J Alzheimers Dis 2010; 19:273-90.
    14. Zimny A, Sasiadek M, Leszek J, Czarnecka A, et al. Does perfusion CT enable differentiating Alzheimer's disease from vascular dementia and mixed dementia? A preliminary report. J Neurol Sci 2007;257:114-120.
    15. Stefani A, Sancesario G, Pierantozzi M, Leone G, et al. CSF biomarkers, impairment of cerebral hemodynamics and degree of cognitive decline in Alzheimer's and mixed dementia. J Neurol Sci 2009;283:109-15.
    16. Wintermark M, Sesay M, Barbier E, Borbely K, et al. Comparative overview of brain perfusion imaging techniques. Stroke 2005;36:e83-99.
    17. Holman BL, Tumeh SS. Single-photon emission computed tomography (SPECT). Applications and potential. JAMA 1990;263(4):561-4.
    18. DeKosky ST, Shih WJ, Schmitt FA, Coupal J, et al. Assessing utility of single photon emission computed tomography (SPECT) scan in Alzheimer disease: correlation with cognitive severity. Alzheimer Dis Assoc Disord 1990;4:14-23.
    19. Ito H, Kanno I, Fukuda H. Human cerebral circulation:positron emission tomography studies. Ann Nucl Med 2005; 19:65-74.
    20. Alsop DC, Detre JA, Grossman M. Assessment of cerebral blood flow in Alzheimer's disease by spin-labeled magnetic resonance imaging. Ann Neurol 2000;47:93-100.
    21. Detre JA, Wang J, Wang Z, Rao H. Arterial spin-labeled perfusion MRI in basic and clinical neuroscience. Curr Opin Neurol 2009;22:348-55.
    22. Pollock JM, Tan H, Kraft RA, Whitlow CT, et al. Arterial spin-labeled MR perfusion imaging:clinical applications. Magn Reson Imaging Clin N Am 2009;17:315-38.
    23. Kim SG. Quantification of relative cerebral blood flow change by flow-sensitive alternating inversion recovery (FAIR) technique:application to functional mapping. Magn Reson Med 1995;34:293-301.
    24. Jahng GH, Zhu XP, Matson GB, Weiner MW, et al. Improved perfusion weighted MRI by a novel double inversion with proximal labeling of both tagged and control acquisitions. Magn Reson Med 2003;49:307-14.
    25. Tanabe JL, Yongbi M, Branch C, Hrabe J, et al. MR perfusion imaging in human brain using the UNFAIR technique. Un-inverted flow-sensitive alternating inversion recovery. J Magn Reson Imaging 1999;9:761-7.
    26. Liu TT, Brown GG. Measurement of cerebral perfusion with arterial spin labeling: part 1. methods. J Int Neuropsychol Soc 2007; 13:517-25.
    27. Aguirre GK, Detre JA, Zarahn E, Alsop DC. Experimental design and the relative sensitivity of BOLD and perfusion fMRI. Neuroimage 2002;15:488-500.
    28. Tjandra T, Brooks JC, Figueiredo P, Wise R, et al. Quantitative assessment of the reproducibility of functional activation measured with BOLD and MR perfusion imaging:implications for clinical trial design. Neuroimage 2005;27:393-401.
    29. Matsuda H. Role of neuroimaging in Alzheimer's disease, with emphasis on brain perfusion SPECT. J Nucl Med 2007;48:1289-300.
    30. Bradley KM, O'Sullivan VT, Soper ND, Nagy Z, et al. Cerebral perfusion SPET correlated with Braak pathological stage in Alzheimer's disease. Brain 2002; 125:1772-81.
    31. Kogure D, Matsuda H, Ohnishi T, Asada T, et al. Longitudinal evaluation of early Alzheimer's disease using brain perfusion SPECT. J Nucl Med 2000;41:1155-62.
    32. Hirao K, Ohnishi T, Hirata Y, Yamashita F, et al. The prediction of rapid conversion to Alzheimer's disease in mild cognitive impairment using regional cerebral blood flow SPECT. Neuroimage 2005; 28:1014-21.
    33. Wang H, Golob E, Bert A, Nie K, et al. Alterations in regional brain volume and individual MRI-guided perfusion in normal control, stable mild cognitive impairment, and MCI-AD converter. J Geriatr Psychiatry Neurol 2009;22:35-45.
    34. Guedj E, Barbeau EJ, Didic M, Felician O, et al. Effects of medial temporal lobe degeneration on brain perfusion in amnestic MCI of AD type:deafferentation and functional compensation? Eur J Nucl Med Mol Imaging 2009;36:1101-12.
    35. Hirao K, Ohnishi T, Matsuda H, Nemoto K, et al. Functional interactions between entorhinal cortex and posterior cingulate cortex at the very early stage of Alzheimer's disease using brain perfusion single-photon emission computed tomography. Nucl Med Commun 2006;27:151-6.
    36. O'Brien JT. Role of imaging techniques in the diagnosis of dementia. Br J Radiol 2007; 80:S71-7.
    37. Pasquier J, Michel BF, Brenot-Rossi I, Hassan-Sebbag N, et al. Value of (99m)Tc-ECD SPET for the diagnosis of dementia with Lewy bodies. Eur J Nucl Med Mol Imaging 2002;29:1342-8.
    38. Kemp PM, Hoffmann SA, Holmes C, Bolt L, et al. The contribution of statistical parametric mapping in the assessment of precuneal and medial temporal lobe perfusion by 99mTc-HMPAO SPECT in mild Alzheimer's and Lewy body dementia. Nucl Med Commun 2005;26:1099-106.
    39. Minoshima S, Foster NL, Sima AA, Frey KA, et al. Alzheimer's disease versus dementia with Lewy bodies:cerebral metabolic distinction with autopsy confirmation. Ann Neurol 2001;50:358-65.
    40. Waragai M, Mizumura S, Yamada T, Matsuda H. Differentiation of early-stage Alzheimer's disease from other types of dementia using brain perfusion single photon emission computed tomography with easy Z-score imaging system analysis. Dement Geriatr Cogn Disord 2008;26:547-55.
    41. Ishii K, Sasaki M, Yamaji S, Sakamoto S, et al. Paradoxical hippocampus perfusion in mild-to-moderate Alzheimer's disease. JNucl Med 1998;39:293-8.
    42. Ishii K, Sasaki M, Yamaji S, Sakamoto S, et al. Demonstration of decreased posterior cingulate perfusion in mild Alzheimer's disease by means of H215O positron emission tomography. Eur JNucl Med 1997;24:670-3.
    43. Jagust WJ, Eberling JL, Reed BR, Mathis CA, et al. Clinical studies of cerebral blood flow in Alzheimer's disease. Ann N YAcad Sci 1997;826:254-62.
    44. Tohgi H, Yonezawa H, Takahashi S, Sato N, et al. Cerebral blood flow and oxygen metabolism in senile dementia of Alzheimer's type and vascular dementia with deep white matter changes. Neuroradiology 1998;40:131-7.
    45. Jeong Y, Cho SS, Park JM, Kang SJ, et al.18F-FDG PET findings in frontotemporal dementia:an SPM analysis of 29 patients. J Nucl Med 2005;46:233-9.
    46. Harris GJ, Lewis RF, Satlin A, English CD, et al. Dynamic susceptibility contrast MRI of regional cerebral blood volume in Alzheimer's disease. Am J Psychiatry 1996;153:721-4.
    47. Maas LC, Harris GJ, Satlin A, English CD, et al. Regional cerebral blood volume measured by dynamic susceptibility contrast MR imaging in Alzheimer's disease: a principal components analysis. J Magn Reson Imaging 1997;7:215-9.
    48. Harris GJ, Lewis RF, Satlin A, English CD, et al. Dynamic susceptibility contrast MR imaging of regional cerebral blood volume in Alzheimer disease:a promising alternative to nuclear medicine. AJNR Am J Neuroradiol 1998; 19:1727-32.
    49. Bozzao A, Floris R, Baviera ME, Apruzzese A, et al. Diffusion and perfusion MR imaging in cases of Alzheimer's disease:correlations with cortical atrophy and lesion load. AJNR Am J Neuroradiol 2001;22:1030-6.
    50. Luckhaus C, Flub MO, Wittsack HJ, Grass-Kapanke B, et al. Detection of changed regional cerebral blood flow in mild cognitive impairment and early Alzheimer's dementia by perfusion-weighted magnetic resonance imaging. Neuroimage 2008;40:495-503.
    51. Kubota T, Ushijima Y, Yamada K, Okuyama C, et al. Diagnosis of Alzheimer's disease using brain perfusion SPECT and MR imaging:which modality achieves better diagnostic accuracy? Eur JNucl Med Mol Imaging 2005;32:414-21.
    52. Cavallin L, Danielsson R, Oksengard AR, Wahlund LO, et al. Can dynamic susceptibility contrast magnetic resonance imaging replace single-photon emission computed tomography in the diagnosis of patients with Alzheimer's disease? A pilot study. Acta Radiol 2006;47:977-85.
    53. Yoshiura T, Mihara F, Kuwabara Y, Ogomori K, et al. MR relative cerebral blood flow mapping of Alzheimer disease:correlation with Tc-99m HMPAO SPECT. Acad Radiol 2002;9:1383-7.
    54. Mattia D, Babiloni F, Romigi A, Cincotti F, et al. Quantitative EEG and dynamic susceptibility contrast MRI in Alzheimer's disease:a correlative study. Clin Neurophysiol 2003; 114:1210-6.
    55. Olazaran J, Alvarez-Linera J, de Santiago R, Escribano J, et al. Regional correlations between MR imaging perfusion and SPECT in Alzheimer's disease. Neurologia 2005;20:240-4.
    56. Sandson TA, O'Connor M, Sperling RA, Edelman RR, et al. Noninvasive perfusion MRI in Alzheimer's disease:a preliminary report. Neurology 1996;47:1339-42.
    57. Johnson NA, Jahng GH, Weiner MW, Miller BL, et al. Pattern of cerebral hypoperfusion in Alzheimer disease and mild cognitive impairment measured with arterial spin-labeling MR imaging:initial experience. Radiology 2005;234:851-9.
    58. Xu G, Antuono PG, Jones J, Xu Y, et al. Perfusion fMRI detects deficits in regional CBF during memory-encoding tasks in MCI subjects. Neurology 2007; 69:1650-6.
    59. Asllani I, Habeck C, Scarmeas N, Borogovac A, et al. Multivariate and univariate analysis of continuous arterial spin labeling perfusion MRI in Alzheimer's disease. JCereb Blood Flow Metab 2008;28:725-36.
    60. Alsop DC, Casement M, de Bazelaire C, Fong T, et al. Hippocampal hyperperfusion in Alzheimer's disease. Neuroimage 2008;42:1267-74.
    61. Yoshiura T, Hiwatashi A, Yamashita K, Ohyagi Y, et al. Simultaneous measurement of arterial transit time, arterial blood volume, and cerebral blood flow using arterial spin-labeling in patients with Alzheimer disease. AJNR Am J Neuroradiol 2009;30:1388-93.
    62. Schuff N, Matsumoto S, Kmiecik J, Studholme C, et al. Cerebral blood flow in ischemic vascular dementia and Alzheimer's disease, measured by arterial spin-labeling magnetic resonance imaging. Alzheimer's and Dementia 2009;5:454-62.
    63. Dai W, Lopez OL, Carmichael OT, Becker JT, et al. Mild cognitive impairment and Alzheimer disease:patterns of altered cerebral blood flow at MR imaging. Radiology 2009;250:856-66.
    64. Du AT, Jahng GH, Hayasaka S, Kramer JH, et al. Hypoperfusion in frontotemporal dementia and Alzheimer disease by arterial spin labeling MRI. Neurology 2006;67:1215-20.
    65. Yoshiura T, Hiwatashi A, Noguchi T, Yamashita K, et al. Arterial spin labelling at 3-T MR imaging for detection of individuals with Alzheimer's disease. Eur Radiol 2009; 19:2819-25.
    66. Fleisher AS, Podraza KM, Bangen KJ, Taylor C, et al. Cerebral perfusion and oxygenation differences in Alzheimer's disease risk. Neurobiol Aging 2009; 30:1737-48.
    67. Xu G, Rowley HA, Wu G, Alsop DC, et al. Reliability and precision of pseudo-continuous arterial spin labeling perfusion MRI on 3.0 T and comparison with (15)O-water PET in elderly subjects at risk for Alzheimer's disease. NMR Biomed 2010; 23:286-93.
    68. LaFrance ND, Parker JR, Smith MD, McGhan WF, et al. Dynamic susceptibility contrast MR imaging for the evaluation of probable Alzheimer disease:a cost-effectiveness analysis. Acad Radiol 1998;5 Suppl 1:S231-5.
    69. Krishnan S, Talley BD, Slavin MJ, Doraiswamy PM, et al. Current status of functional MR imaging, perfusion-weighted imaging, and diffusion-tensor imaging in Alzheimer's disease diagnosis and research. Neuroimaging Clin N Am 2005;15:853-68.
    70. Ishii K, Minoshima S. PET is better than perfusion SPECT for early diagnosis of Alzheimer's disease-for. Eur JNucl Med Mol Imaging 2005;32:1463-5.
    71. Pupi A, Nobili FM. PET is better than perfusion SPECT for early diagnosis of Alzheimer's disease-against. Eur J Nucl Med Mol Imaging 2005;32:1466-72.
    72. McKhann G, Drachman D, Folstein M, Katzman R, et al. Clinical diagnosis of Alzheimer's disease:report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984;34:939-44.
    73. Hamalainen A, Pihlajamaki M, Tanila H, Hanninen T, et al. Increased fMRI responses during encoding in mild cognitive impairment. Neurobiol Aging 2007;28:1889-903.
    74. Kircher TT, Weis S, Freymann K, Erb M, et al. Hippocampal activation in patients with mild cognitive impairment is necessary for successful memory encoding. J Neurol Neurosurg Psychiatry 2007;78:812-18.
    75. Sperling R. Functional MRI studies of associative encoding in normal aging, mild cognitive impairment, and Alzheimer's disease. Ann N YAcad Sci 2007; 1097:146-55.
    76. Grady CL, McIntosh AR, Beig S, Keightley ML, et al. Evidence from functional neuroimaging of a compensatory prefrontal network in Alzheimer's disease. J Neurosci 2003;23:986-93.
    77. Gould RL, Arroyo B, Brown RG, Owen AM, et al. Brain mechanisms of successful compensation during learning in Alzheimer disease. Neurology 2006;67:1011-7.
    78. Han D, Bangen KJ, Bondi MW. Functional magnetic resonance imaging of compensatory neural recruitment in aging and risk for Alzheimer's disease: Review and recommendation. Dementia and Geriatric Cognitive Disorders 2009;27:1-10.
    79. Kessler RM. Imaging methods for evaluating brain function in man. Neurobiol Aging2003;24 Suppl 1:S21-35; discussion S37-9.
    80. Wang J, Alsop DC, Li L, Listerud J, et al. Comparison of quantitative perfusion imaging using arterial spin labeling at 1.5 and 4.0 tesla. Magn Reson Med 2002;48:242-54.
    81. Golay X, Petersen ET. Arterial spin labeling:benefits and pitfalls of high magnetic field. Neuroimaging Clin NAm 2006; 16:259-68.
    82. Yongbi MN, Fera F, Yang Y, Frank JA, et al. Pulsed arterial spin labeling: comparison of multisection baseline and functional MR imaging perfusion signal at 1.5 and 3.0T:initial results in six subjects. Radiology 2002;222:569-75.
    83. Talagala SL, Ye FQ, Ledden PJ, Chesnick S. Whole-brain 3D perfusion MRI at 3.0 T using CASL with a separate labeling coil. Magn Reson Med 2004;52:131-40.
    84. Wang J, Zhang Y, Wolf RL, Roc AC, et al. Amplitude-modulated continuous arterial spin-labeling 3.0-T perfusion MR imaging with a single coil:feasibility study. Radiology 2005;235:218-28.
    85. Jahng GH, Weiner MW, Schuff N. Improved arterial spin labeling method: applications for measurements of cerebral blood flow in human brain at high magnetic field MRI. Med Phys 2007;34:4519-25.
    86. Mitnitski A, Rockwood K. Transitions in cognitive test scores over 5 and 10 years in elderly people:evidence for a model of age-related deficit accumulation. BMC Geriatr 2008;8:3.
    87. Wu WC, Wong EC:Feasibility of velocity selective arterial spin labeling in functional MRI. JCereb Blood Flow Metab 2007;27:831-8.
    88. Wong EC, Cronin M, Wu WC, Inglis B, et al:Velocity-Selective Arterial Spin Labeling. Magn Reson Med 2006;55:1334-41.
    1. Alzheimer's Association.2009 Alzheimer's disease facts and figures. Alzheimers Dement.2009;5:234-270.
    2. Mattsson N, Blennow K, Zetterberg H. CSF biomarkers:pinpointing Alzheimer pathogenesis. Ann NY Acad Sci.2009;1180:28-35.
    3. Viswanathan A, Rocca WA, Tzourio C. Vascular risk factors and dementia:how to move forward? Neurology.2009;72:368-374.
    4. de la Torre JC. Cerebrovascular and cardiovascular pathology in Alzheimer's disease. Int Rev Neurobiol.2009;84:35-48.
    5. Scheltens P. Imaging in Alzheimer's disease. Dialogues Clin Neurosci. 2009;11:191-199.
    6. Festa EK, Insler RZ, Salmon DP, Paxton J, Hamilton JM, Heindel WC. Neocortical disconnectivity disrupts sensory integration in Alzheimer's disease. Neuropsychology.2005;19(6):728-738.
    7. Sperling RA, Bates JF, Chua EF, Cocchiarella AJ, Rentz DM, Rosen BR, Schacter DL, Albert MS. fMRI studies of associative encoding in young and elderly controls and mild Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2003;74(1):44-50.
    8. Sperling R. Functional MRI studies of associative encoding in normal aging, mild cognitive impairment, and Alzheimer's disease. Ann N Y Acad Sci. 2007;1097:146-155.
    9. Grossman M, Koenig P, Glosser G, DeVita C, Moore P, Rhee J, Detre J, Alsop D, Gee J; fMRI study. Functional magnetic resonance imaging. Neural basis for semantic memory difficulty in Alzheimer's disease:an fMRI study. Brain. 2003;126(Pt2):292-311.
    10. Schwindt GC, Black SE. Functional imaging studies of episodic memory in Alzheimer's disease:a quantitative meta-analysis. Neuroimage.2009;45(1):181-190.
    11. Grady CL, McIntosh AR, Beig S, Keightley ML, Burian H, Black SE. Evidence from functional neuroimaging of a compensatory prefrontal network in Alzheimer's disease. J Neurosci.2003;23(3):986-993.
    12. Pariente J, Cole S, Henson R, Clare L, Kennedy A, Rossor M, Cipoloti L, Puel M, Demonet JF, Chollet F, Frackowiak RS. Alzheimer's patients engage an alternative network during a memory task. Ann Neurol.2005;58(6):870-879.
    13. Rombouts SA, Barkhof F, Goekoop R, Stam CJ, Scheltens P. Altered resting state networks in mild cognitive impairment and mild Alzheimer's disease:an fMRI study. Hum Brain Mapp.2005;26(4):231-239.
    14. Fleisher AS, Sherzai A, Taylor C, Langbaum JB, Chen K, Buxton RB. Resting-state BOLD networks versus task-associated functional MRI for distinguishing Alzheimer's disease risk groups. Neuroimage.2009;47(4):1678-1690.
    15. Zhang HY, Wang SJ, Liu B, Ma ZL, Yang M, Zhang ZJ, Teng GJ. Resting brain connectivity:changes during the progress of Alzheimer disease. Radiology. 2010;256(2):598-606.
    16. Wintermark M, Sesay M, Barbier E, Borbely K, et al. Comparative overview of brain perfusion imaging techniques. J Neuroradiol.2005;32(5):294-314.
    17. Harris GJ, Lewis RF, Satlin A, English CD, Scott TM, Yurgelun-Todd DA, Renshaw PF. Dynamic susceptibility contrast MRI of regional cerebral blood volume in Alzheimer's disease. Am J Psychiatry.1996;153:721-724.
    18. Bozzao A, Floris R, Baviera ME, Apruzzese A, Simonetti G. Diffusion and perfusionMRimaging in cases of Alzheimer's disease:correlations with cortical atrophy and lesion load. AJNR Am J Neuroradiol.2001;22:1030-1036.
    19. Luckhaus C, Flu"b MO, Wittsack HJ, Grass-Kapanke B, Ja'nner M, Khalili-Amiri R, et al. Detection of changed regional cerebral blood flow in mild cognitive impairment and early Alzheimer's dementia by perfusion-weighted magnetic resonance imaging. Neuroimage.2008; 40:495-503.
    20. Johnson NA, Jahng GH, Weiner MW, Miller BL, Chui HC, Jagust W.T, et al. Pattern of cerebral hypoperfusion in Alzheimer disease and mild cognitive impairment measured with arterial spin-labeling MR imaging:initial experience. Radiology.2005;234:851-859.
    21. Dai W, Lopez OL, Carmichael OT, Becker JT, Kuller LH, Gach HM. Mild cognitive impairment and Alzheimer disease:patterns of altered cerebral blood flow at MR imaging. Radiology.2009;250:856-866.
    22. Yoshiura T, Hiwatashi A, Yamashita K, Ohyagi Y, Monji A, Takayama Y, et al. Simultaneous measurement of arterial transit time, arterial blood volume, and cerebral blood flow using arterial spin-labeling in patients with Alzheimer disease. AJNR Am J Neuroradiol.2009;30:1388-1393.
    23. Alsop DC, Detre JA, Grossman M. Assessment of cerebral blood flow in Alzheimer's disease by spin-labeled magnetic resonance imaging. Ann Neurol. 2000;47:93-100.
    24. Du AT, Jahng GH, Hayasaka S, Kramer JH, Rosen HJ, Gorno-Tempini ML, et al. Hypoperfusion in frontotemporal dementia and Alzheimer disease by arterial spin labeling MRI. Neurology.2006;67:1215-1220.
    25. Alsop DC, Casement M, de Bazelaire C, Fong T, Press DZ. Hippocampal hyperperfusion in Alzheimer's disease. Neuroimage.2008; 42:1267-1274.
    26. Fleisher AS, Podraza KM, Bangen KJ, Taylor C, Sherzai A, Sidhar K, et al. Cerebral perfusion and oxygenation differences in Alzheimer's disease risk. Neurobiol Aging.2009;30:1737-1748.
    27. Xu G, Antuono PG, Jones J, Xu Y, Wu G, Ward D, et al. Perfusion fMRI detects deficits in regional CBF during memory-encoding tasks in MCI subjects. Neurology.2007;69:1650-1656.
    28. Garcia Santos JM, Gavrila D, Antunez C, Tormo MJ, et al. Magnetic resonance spectroscopy performance for detection of dementia, Alzheimer's disease and mild cognitive impairment in a community-based survey. Dement Geriatr Cogn Disord.2008,26(1):15-25.
    29. Waldman AD, Rai GS. The relationship between cognitive impairment and in vivo metabolite ratios in patients with clinical Alzheimer's disease and vascular dementia:a proton magnetic resonance spectroscopy study. Neuroradiology. 2003,45(8):507-512.
    30. Kantarci K, Jack CR Jr, Xu YC, Campeau NG, O'Brien PC, Smith GE, Ivnik RJ, Boeve BF, Kokmen E, Tangalos EG, Petersen RC. Mild cognitive impairment and Alzheimer disease:regional diffusivity of water. Radiology.2001;219(1):101-107.
    31. Kantarci K, Petersen RC, Boeve BF, Knopman DS, Weigand SD, O'Brien PC, Shiung MM, Smith GE, Ivnik RJ, Tangalos EG, Jack CR Jr. DWI predicts future progression to Alzheimer disease in amnestic mild cognitive impairment. Neurology.2005;64(5):902-904.
    32. Bozzali M, Falini A, Franceschi M, Cercignani M, Zuffi M, Scotti G, Comi G, Filippi M. White matter damage in Alzheimer's disease assessed in vivo using diffusion tensor magnetic resonance imaging.J Neurol Neurosurg Psychiatry. 2002;72(6):742-746.
    33. Fellgiebel A, Wille P, Miiller MJ, Winterer G, Scheurich A, Vucurevic G, Schmidt LG, Stoeter P. Ultrastructural hippocampal and white matter alterations in mild cognitive impairment:a diffusion tensor imaging study. Dement Geriatr Cogn Disord.2004;18(1):101-108.
    34. Naggara O, Oppenheim C, Rieu D, Raoux N, Rodrigo S, Dalla Barba G, Meder JF. Diffusion tensor imaging in early Alzheimer's disease. Psychiatry Res. 2006;146(3):243-249.

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