多发性硬化和视神经脊髓炎MR成像研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
背景
     原发性脱髓鞘病变主要包括多发性硬化(multiple sclerosis, MS)、视神经脊髓炎(neuromyelitis optica, NMO)和急性播散性脑脊髓炎(acute demyelinating encephalomyelitis,ADEM)等疾病。MS是常见的神经科疾病,在发达国家是造成中青年非外伤性致残的首要原因。我国属于MS的中发区。目前MS的病因和发病机制未明,其诊断标准也在不断修订。MRI是MS最重要、最敏感的影像检查工具,包括常规和功能MR成像,对该病的诊断、治疗后的随访以及诠释疾病的病理生理等特点具有不可替代的作用。
     NMO与MS的关系目前尚无定论。既往认为NMO属于选择性累及视神经和脊髓的单相性疾病。目前的证据显示,NMO也呈多相性,并亦可累及CNS其它结构,在临床、影像学和免疫病理等方面与MS有明显区别。
     目的
     分析重庆地区MS患者常规MRI和氢质子磁共振波谱(1H-MRS)成像代谢特点。探讨扩散加权成像(DWI)的定量指标表观扩散系数(ADC)值对MS各种病灶的评估价值。探讨NMO脑部MRI影像特点,对鉴别MS与NMO、建立NMO的诊断标准提供帮助。最后评估MS患者MRI影像特点与临床MS各种评分的相关性。
     方法
     1.以重庆医科大学附属第一医院和本市其他部分三甲医院神经内科就诊的门诊、住院和随访的MS和NMO患者作为研究对象。
     2. 180例MS患者均符合2005年修订的McDonald诊断标准,按照国际MS诊断小组制定的MRI扫描序列,所有患者作脑部、脊髓和视神经扫描。
     3.对部分依从关系较好的MS患者作1H-MRS扫描,采用多体素和单体素分析MS不同病灶、不同亚型之间的代谢差别。
     4.将60例临床确诊的RRMS型纳入研究对象,比较不同信号病灶ADC值是否有统计学差别。
     5.符合2006年Wingerchuck诊断标准的NMO患者纳入研究对象,按照标准的MS扫描方法,分析脑部MRI正常和异常影像特点。
     6.由一位神经科医师在不知道影像学结果的条件下对所有患者进行EDSS评分、MS生活质量54项评分(MSQOL-54)和简易智力状态检查量表(MMSE)评分,所有评分与MRI检查在同一天完成,分析常规和功能MR成像相关影像特点与临床各种评分的相关性。
     结果
     1.据病灶累及部位:单纯脑部受累最多共82例(45.56%),单纯脊髓受累53例(29.44%),脑和脊髓均受累45例(25%)。
     2.脊髓病灶中,下颈髓和上胸髓最易受累,≤3个椎体节段的病灶数占了74.49%,而>3椎体节段的病灶数占了25.52%。
     3. PD/T2WI和FLAIR像对幕下、侧脑室周围以及深部灰白质交界区病灶的检出率比较没有统计学差异(p>0.05),对皮质及皮质下病灶,FLAIR较T2WI病灶的检出率高,二者有统计学意义(p<0.05)。
     4. RRMS和进展型MS与对照组NAWM区NAA/Cr、Cho/NAA、Cho/Cr有明显统计学差异,P<0.01;强化病灶、非强化病灶与对照组的NAA/Cr、Lac+Lip/Cr有统计学差异,p<0.05;急性病灶Cho、Lac+Lip升高,NAA不同程度降低;扣带回与对照组NAA/Cr和Cho/Cr无统计学差异,p>0.05。
     5. ADC值结果:低信号与等信号病灶ADC值分别为(127.54±9.31)×10~(-5) mm~2/s和(95.71±6.25)×10~(-5) mm~2/s,二者统计学差异(P<0.05);融合与分散病灶ADC值分别为(141.35±6.51)×10~(-5) mm~2/s和(105.38±13.89)×10~(-5) mm~2/s,二者有统计学差异(P<0.01)。
     6. NMO脑部MRI结果:脑内有异常表现28/33例(84.8%),脑实质有明确病灶22例(66.7%),幕上近皮质、皮质下和深部脑白质区的点状非特异性病灶最多;幕下脑干是易受累的部位(14/33, 42.4%),特别是延髓(7/33, 21.2%)。
     7.单纯脊髓受累、单纯脑部受累和脑脊髓混合受累MS患者的EDSS评分有统计学差异(P<0.05),脊髓萎缩与EDSS评分之间无相关性(r=2.31,P=0.2516,但与病程呈明显相关,r=0.40, P=0.0267。NAA/Cr与EDSS评分呈负相关p<0.05;NAA/Cr、Ins/Cr与病程呈正相关,p<0.05。单纯脑受累的MSQOL-54评分与单纯脊髓受累、脑脊髓均受累患者的相应评分之间有统计学差异(P<0.01);扣带回NAA/Cr与认知功能(MMSE)评分之间有明显相关性,p<0.05。
     结论
     1.常规MRI扫描是诊断MS最敏感的影像技术,本研究支持MS是一个累及全脑的弥漫性病变,增加脊髓扫描有助于提高MS诊断的敏感性以及与其他疾病的鉴别诊断。
     2.采用PD/T2WI和FLAIR像,改善MRI对MS病灶检出的定量诊断能力,特别是FLAIR像对诊断皮质及皮质下病灶较好,PD/T2WI对后颅窝的显示较好。
     3.通过1H-MRS对MS不同亚型和各种病灶的波谱比较,阐述了MS不同亚型和病灶中神经元的轴索和髓鞘破坏、胶质增生以及炎性反应等病理生理异质性。
     4.通过各种病灶ADC值的定量分析对解释MS病灶的病理变化、监测其病程有一定的价值。
     5. NMO患者出现脑内非特异病灶很常见,有脑部病变不能排除NMO的诊断,本研究的结果有助于NMO诊断标准的修订。
     6.单纯脊髓受累、单纯脑部受累和脑脊髓混合受累MS患者的EDSS评分和认知功能均有统计学差别,单纯脑损害MS患者的MSQOL-54生活质量最好。不同的代谢率与EDSS评分、MSQOL-54评分以及病程之间的相关性不同。
Background
     The primary demyelinating diseases include multiple sclerosis (MS), neuromyelitis optica (NMO), acute demyelinating encephalomyelitis (ADEM) and so on. MS is one of the most important neurological diseases, which is the leader cause of non-trauma disability among youths in developed country. Now China is considered as a medium incident area. At present, the pathogenesis of MS is not clear and the diagnostic criteria for MS change constantly. Magnetic resonance imaging (MRI) is the most important and most sensitive imaging diagnostic tool. It is important value to diagnose, follow up after therapy and explain the patho-physiology for MS with the conventional and functional MRI, and is unable to be substituted.
     No final conclusion has yet been reached for NMO and MS, and no golden diagnostic criteria for NMO are found. NMO is an idiopathic inflammatory demyelinating disorder that was thought to preferentially affect the optic nerves and spinal cord but without brain MRI abnormalities. Lots of other evidences suggested that NMO differs MS from clinical presentations, experimentation findings, image features, immunopathologic characteristics and therapeutics. It is of great importance to display brain abnormalities of NMO and discriminate diagnosis for NMO and MS with MRI scans.
     Purposes
     This study was to identify image characteristics and metabolite changes in patients with MS in the district of Chongqing with the conventional MRI and 1H-proton MR spectroscopy (1H-MRS), to explore the values of diffusion-weighted imaging(DWI)and apparent diffusion coefficient (ADC) measurements in various pattern lesions of MS, to identify brain abnormalities in NMO by MRI, which are helpful to the revision of diagnostic criteria for NMO. At last this study was to evaluate the correlations between the various image features and clinical scores of MS patients.
     Methods
     1. The following-up outpatients and hospitalization of clinically diagnosed patients with MS and NMO were included at the First Affiliated Hospital of Chongqing Medical University and other hospitals in Chongqing.
     2. 180 Patients who fulfilled the MS diagnostic criteria of McDonald et al were selected to perform MRI scans of the brain, spinal cord and optic nerves. The brain and spinal cord images were analyzed.
     3. Some patients with MS who can endure a long time MRI scans were selected to perform 1H-MRS. The metabolite difference of various pattern lesions and subtypes of patients with MS were analyzed with multiple-voxel long and short echoes, single-voxel short echo magnetic resonance spectrum.
     4. 60 patients with clinically diagnosed remitting-relapsing MS (RRMS) were included and underwent conventional brain MRI and DWI scans, mean ADC values were measured for various lesions of MS. The statistical analyses were performed to determine the differences of mean ADC values among various lesions of MS.
     5. Patients who fulfilled the latest diagnostic criteria of NMO proposed by Wingerchuk et al were selected to perform standard MRI scans of the brain, spinal cord and optic nerves. The normal and abnormal brain images were analyzed.
     6. Expanded Disability Status Scale (EDSS), Multiple sclerosis quality of life-54 instrument (MSQOL-54) and Mini-Mental State Examination (MMSE) of all patients were scored within the same day of MRI scans by a professional neurologist. The correlations were analyzed between MRI findings and clinical various scores.
     Results
     1. The patients with simple brain lesions were involved in 82 cases (45.56%), for spinal cords , 53 case(s29.44%),for both brain and spinal cord, 45 cases(25%),based on the locations of lesion involvements.
     2. The lower cervical and upper thoracic spinal cords for patients with MS were easily involved; the length of cord lesions which were less than three vertebral segments was 74.49%, for more than three vertebral segments, 25.52%.
     3. The detection rates with PD/T2WI and FLAIR imagings were no statistical differences among infratentorium, surroundings of cerebral lateral ventricles and deep white matter(p>0.05).The statistical difference was found between the FLAIR and T2WI in cortical and subcortical lesions(p<0.05).
     4. The metabolite ratios of NAA/Cr,Cho/NAA and Cho/Cr in normal-appearing white matter (NAWM) are statistical differences among RRMS, progressive MS and the control group (P<0.01). The metabolite ratios of NAA/Cr and Lac+Lip/Cr are significant different between the enhanced lesions, non-enhanced lesions and the control group (p < 0.05) , The Cho and Lac + Lip peaks are revealed elevatation markedly in acute plagues and NAA peak is displayed decrease. However, the metabolite ratios of NAA/Cr and Cho/Cr are not statistical different between the cingulate gyrus and the control group (p>0.05).
     5. The ADC values of hypointense lesions were significantly higher than that of isointense lesions ( P < 0.001 ) , the ADC values were (127.54±9.31)×10~(-5) mm~2/sec and(95.71±6.25)×10~(-5) mm~2/sec respectively. The ADC values of confluent lesions had a substantially higher than that of discrete lesions(P<0.001), the ADC values were(141.35±6.51)×10~(-5) mm~2/sec and(105.38±13.89)×10~(-5) mm~2/sec respectively. No correlation was found between ADC values of lesions and EDSS scores(P>0.05).
     6. Brain abnormal findings of NMO were detected in 28 out of 33 patients (84.8%). 22 patients (66.7%) showed well-defined brain parenchymal lesions. In the supratentorial lesions,most were punctate or small round dots and nonspecific hyperintensities in juxtacortical,subcortical and deep white matter regions. In the infratentorium,brainstem was an easily involved region (14/33, 42.4%), especially in medulla (7/33, 21.2%).
     7. The EDSS scores were statistical difference among the patients with simple brain involvement, simple spinal cord involvement, both brain and spinal cord involvement(sP<0.05). The MSQOL-54 scores of MS with simple brain involvement were significantly higher than those of the two later subtype(sP<0.05). There was no correlation between the spinal cord atrophy and EDSS scores (r=2.31,P=0.2516), but rather than that of disease course (r=0.40, P=0.0267). There was negative correlation between the NAA/Cr ratio and EDSS scores, (p<0.05). A significant correlation was found between the NAA/Cr ratio of the cingulate gyrus and cognition function (p<0.05), but for that of EDSS scores, no correlation was found (p>0.05).
     Conclusions
     1. The conventional MRI is the most important tool for diagnosis of MS. It is helpful to renew the concept that only brain white matter was involved. In fact, the whole brain is diffusing involved in patients with MS. Spinal cord MRI scans can improve the sensitivity of the diagnosis and differential diagnosis of MS from other diseases.
     2. The PD, T2WI and FLAIR can improve the quantity diagnostic ability of the lesions for MS; especially the cortical and subcortical lesions are detected well by FLAIR images. The lesions of the posterior cranial fossa are displayed well by PD and T2WI.
     3. The pathophysiological heterogeneities including the axial damages, myelinolysis, gliosis and inflammatory reactions are explained well by the 1H-MR spectrum among the subtypes MS and various pattern lesions.
     4. DWI and quantitative ADC measurements are useful tools to explain the pathological changes in different lesions and monitor the disease duration of MS.
     5. Non-specific abnormalities in brain MRI are common in Chinese NMO patients, and the patients with brain lesions do not exclude the diagnosis of NMO. The observation of brain lesions is helpful to improve and revise diagnostic criteria of NMO.
     6. The scores of EDSS and cognition function in the subtypes (simple spinal cord involvement, simple brain involvement, both brain and spinal cord involvement) are all different. The MSQOL-54 is observed the best in simple brain involvement. The different correlations are found between the different metabolite ratios and EDSS scores, and disease courses and MSQOL-54 scores.
引文
[1] Traboulsee A, Zhao GJ, Li DK, et al. Neuroimaging in multiple sclerosis. Neurol Clin, 2005, 23:131-148.
    [2] 黄德晖,吴卫平,蒲传强,等.多发性硬化 226 例临床分析.中国神经免疫学和神经病学杂志,2003,10(3):152-155.
    [3] 许贤豪.多发性硬化研究进展.中华神经科杂志, 2004,37(1):3-6.
    [4] Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols.Ann Neurol 1983,13:227-31.
    [5] McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the international panel on the diagnosis ofmultiple sclerosis. Ann Neurol, 2001, 50:121-127.
    [6] Polman C, Reingold S, Edan G, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the 2001 McDonald criteria. Ann Neurol, 2005, 58:840-846.
    [7] Barkhof F, Filippi M, Miller DH, et al. Comparison of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis. Brain, 1997, 120 (11):2059-69.
    [8] Tintore M, Rovira A, Rio J, et al. New diagnostic criteria for multiple sclerosis: application in first demyelinating episode. Neurology, 2003, 60:27-30.
    [9] Rui-pena JL, Pinero P, Sellers G, et al. Magnetic Resonance spectroscopy of normal-appearing white matter in early relapsing-remitting multiple sclerosis: correlations between disability and spectroscopy. BMC Neurology, 2004, 10, 4-8.
    [10] Pirko I,Lucchinetti CF, Sriram S, et al. Gray matter involvement in multiple sclerosis Neurology, 2007, 68:634-642.
    [11] Inglese M, Ge Yl,Filippi M,et al. Indirect evidence for early widespread gray matter involvement in relapsing-remitting multiple sclerosis NeuroImage, 2004, 1825-1829.
    [12] Filippi M, Valsasina P, Rocca MA. Magnetic Resonance Imaging of grey matter damage in people with MS. The international MS Journal, 2007, 14:12-21.
    [13] Tiberio M,Chard D T,Altmann D R,et al. Metabolite changes in early relapsing-remitting multiple sclerosis :A two year follow-up study. J Neurol, 2006, 253: 224-23.
    [14] Pike GB, Stefano ND, Narayanan S, et al. Multiple sclerosis: magnetization transfer MR imaging of white before lesions appearance on T2-weighted images.Radiology, 2002, 20(3):483-491
    [15] Rovaris M, Gass A, Bammer R, et al. Diffusion MRI in multiple sclerosis. Neurology, 2005, 65:1526-1532.
    [16] Law M, Saindane AM, Yulin G, et al. Microvascular Abnormality in Relapsing-Remitting Multiple Sclerosis: Perfusion MR Imaging Findings in Normal-appearing white Matter. Neuroradiology, 2004, 231:645-652.
    [17] Cheng Q,Miao L,Zhang J,et al. A population-based survey of multiple sclerosis in Shanghai. China Neurology, 2007,68:1495-1500.
    [18] Chang K-H,Lyu R-K,Chen C-M,et al. Clinical characteristics of multiplesclerosis in Taiwan: a cross-sectional study. Multiple Sclerosis, 2006, 12: 501-506.
    [19] Houzen H, Niino M, Kikuchi S, et al. The prevalence and clinical characteristics of MS in northern Japan. J Neurol Sci, 2003, 211:49-53.
    [20] Alshubaili AF, Alramzy K, Ayyad YM, et al. Epidemiology of multiple sclerosis in Kuwait: new trends in incidence and prevalence. Eur Neurol, 2005, 53:125-131.
    [21] Grytten N, Glad SB, Aarseth JH, et al. A 50-year follow-up of the incidence of multiple sclerosis in Hordaland County, Norway. Neurology, 2006, 66:182-186.
    [22] Ranzato F, Perini P, Tzintzeva E, et al. Increasing frequency of multiple sclerosis in Padova, Italy: a 30 year epidemiological survey. Mult Scler, 2003, 9:387-392.
    [23] Kantarci O, Wingerchuk D. Epidemiology and natural history of multiple sclerosis: new insights. Curr Opin Neurol, 2006, 19: 248-254.
    [1] Traboulsee A, Zhao GJ, Li DK, et al. Neuroimaging in multiple sclerosis. Neurol Clin, 2005, 23:131-148.
    [2] Paty DW, Oger JJ, Kastrukoff LF, et al. MRI in the diagnosis of MS: a prospective study with comparison of clinical evaluation, evoked potentials, oligoclonal banding and CT. Neurology, 1988,38:180-185.
    [3] McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the international panel on the diagnosis of multiple sclerosis. Ann Neurol, 2001, 50:121-127.
    [4] Polman C, Reingold S, Edan G, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the 2001 McDonald criteria.Ann Neurol,2005,58:840-846.
    [5] John F. Kurtzke Rating Neurologic impairment in Multiple Sclerosis an Expanded Disability Status Scale (EDSS).Neurology, 1983, 33:1444 -453.
    [6] Paul G, Jill S, Deborah M, et al. Multiple Sclerosis Quality of Life Inventory: A User's Manual. New York, the Consortium of Multiple Sclerosis Centers Health Services Research Subcommittee, 1997, 1574-1601.
    [7] 张明国主编,精神科评定量表手册, 长沙:湖南科学技术出版社,1993,162-165.
    [8] Filippi M, Falini A, Atnold DL, et al. Magnetic Resonance Techniques for the in vivo assessment of multiple sclerosis pathology: consensus report of the white matter study group.Journal of magnetic resonance imaging, 2005,21: 669-675
    [9] 于春水,李坤成 ,段云云,等. 182 例多发性硬化临床与 MR1 分析. 中国医学影像技术,2005,21(5):684-688.
    [10] Barkhof F, Filippi M, Miller DH, et al. Comparison of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis. Brain, 1997,120 (11):2059-69.
    [11] 初曙光, 沈天真,陈星荣。多发性硬化患者的脑部磁共振成像表现. 中华神经科杂志,2005,38(3):167-170.
    [12] Palmer S,Bradley W,Chen DY,et al. Subcallosal Striations: Early finding of multiple sclerosis on sagittal, thin –section, fast Flair MR imaging. Radiology, 1999 ,210:149-153.
    [13] Gean-Marton A, Vezina LG, Marton K, et al. Abnormal corpus callosum: A sensitive and specific indicator of multiple sclerosis. Radiology, 1991 ,180:215-221.
    [14] Ruiz-pena JL, Pinero P, Sellers G, et al. Magnetic Resonance Spectroscopy of normal-appearing white matter in early relapsing-remitting multiple sclerosis: correlations between disability and Spectroscopy. Biomedical central neurology, 2004, 4(8):2377-2383.
    [15] Geurts JJG,Bo L,Pouwels PJW,et al. Cortical Lesions in Multiple Sclerosis: Combined Postmortem MR Imaging and Histopathology. AJNR , 2005 ,26:572-577.
    [16] WooL JH,Henry P,Krejza J, et al. Detection of Simulated Multiple Sclerosis Lesions on T2-weighted and FLAIR Images of the Brain: Observer Performance. Radiology, 2006,241(1):206-210.
    [17] Bakshi R, Ariyaratana S, Benedict RH, et al. Fluid-attenuated inversion recovery magnetic resonance imaging detects cortical and juxtacortical multiple sclerosis lesions. Arch Neurol, 2001, 58(5):742-8.
    [18] Geurts JJG, Pouwels WPJ, Uitdeha BMJ,et al. Intracortical Lesions in Multiple Sclerosis: Improved Detection with 3D Double Inversion-Recovery MR Imaging. Radiology, 2005,236:254-260.
    [19] Nelson F,Poonawalla AH, Hou P,et al. Improved Identification of Intracortical Lesions in Multiple Sclerosis with Phase-Sensitive Inversion Recovery in Combination with Fast Double Inversion Recovery MR Imaging. Am J Neuroradiol,2007,28:1645-1649.
    [20] Wattjes MP,Lutterbey GG,Gieseke J, et al. Double Inversion Recovery Brain Imaging at 3T: Diagnostic Value in the Detection of Multiple Sclerosis Lesions. Am. J. Neuroradiol,2007,28:54-59.
    [21] Kangarlu A,Bourekas EC ,Ray-Chaudhury A et al. Cerebral Cortical Lesions in Multiple Sclerosis Detected by MR Imaging at 8 Tesla. Am. J. Neuroradiol,2007,28:262-266.
    [22] Duan Y,Hildenbrand PG, Sampat MP et al. Segmentation of Subtraction Images for the Measurement of Lesion Change in Multiple Sclerosis.AJNR Am. J. Neuroradiol,2008, 29(2): 340-346.
    [23] Lycklama G, Thompson A, Filippi M, et al. Spinal-cord MRI in multiple sclerosis. Lancet Neurol,2003,2:555-562.
    [24] Tench CR, Morgan PS, Constantinescu CS. Measurement of cervical spinal cord cross-sectional area by MRI using edge detection and partial volume correlation. J Magn Reson Imaging, 2005,21:197-203.
    [25] Rocca M.A, Hickman SJ, Mrcp LB et al. Imaging spinal cord damage in multiple sclerosis. J Neuroimaging, 2005,15:297-304.
    [26] Cooke FJ, Blamire AM, Manners DN, et al. Quantitative proton magnetic resonance spectroscopy of the cervical spinal cord. Magn Reson Med, 2004,51:1122-1128.
    [27] 于春水,林富春,李坤成,等.脊髓型多发性硬化脑灰质弥散张量成像研究.中国医学影像技术,2005,21(9):1364-1368.
    [28] 胡学强,麦卫华,王敦敬.多发性硬化 413 例患者的 l 临床表现特点.中华神经科学杂志,2004,37(1):7-10.
    [29] 黄德晖,吴卫平,蒲传强,等.多发性硬化 226 例临床分析.中国神经免疫学和神经病学杂志,2003,10(3):152-155.
    [30] 包颜明,田伟,毛青等.脊髓型多发性硬化的 MRI 诊断。中国医学影像技术,2005;21(5):693-695.
    [31] Tintore M, Rovira A, Rio J, et al. New diagnostic criteria for multiple sclerosis: application in first demyelinating episode. Neurology, 2003; 60:27–30.
    [32] Bozzali M, Cercignani M, Sormani MP, et al. Quantification of brain gray matter damage in different MS phenotypes by use of diffusion tensor MR imaging. AJNR,2002, 23(6):985-8.
    [33] Nocentini U, Pasqualetti P,Bonavita S,et al. Cognitive dysfunction in patients with relapsing-remitting multiple sclerosis. Multiple Sclerosis, 2006, 12: 77-87.
    [34] Brass SD,Benedict RHB,Weinstock-Guttman B,et al. Cognitive impairment is associated with subcortical magnetic resonance imaging grey matter T2 hypointensity in multiple sclerosis. Multiple Sclerosis, 2006, 12: 437-444.
    [35] 陈丽萍,吴卫平,毛燕玲.多发性硬化患者的认知功能障碍及其与头颅 MRI病灶的相关性.临床神经病学杂志,2004,17(5):327-330.
    [36] Sastre-Garriga J, Ingle GT, Chard DT, et al. Grey and white matter atrophy in early clinical stages of primary progressive multiple sclerosis. NeuroImage, 2004, 22:353-359.
    [37] Bagnato F,Butman JA,Gupta S,et al. In Vivo Detection of Cortical Plaques by MR Imaging in Patients with Multiple Sclerosis. AJNR 2006,27:161-167.
    [1] Filippi M, Rocca MA. Magnetic resonance imaging techniques to define and monitor tissue damage and repair in multiple sclerosis. 2007, 254 Suppl 1:I55-I62.
    [2] De Stefano N, Bartolozzi ML, Guidi L, et al. Magnetic resonance spectroscopy as a measureof brain damage in multiple sclerosis. J Neurol Sci, 2005, 233:203-208.
    [3] Mader I, Seeger U, Weissert R, et al. Proton MR spectroscopy with metabolite-nulling reveals elevated macromolecules in acute multiple sclerosis. Brain, 2001, 124:953-961.
    [4] Lin A, Ross BD, Harris K, Wong W. Efficacy of proton magnetic resonance spectroscopy in neurological diagnosis and neurotherapeutic decision making. Neuro Rx, 2005, 2:197-214.
    [5] Ponnada A. Narayana, Magnetic Resonance Spectroscopy in the Monitoring of Multiple Sclerosis. J Neuroimaging, 2005, 15(4 Suppl): 46S-57S
    [6] Paul G, Jill S, Deborah M, et al. Multiple Sclerosis Quality of Life Inventory: A User's Manual. New York, The Consortium of Multiple Sclerosis Centers HealthServices Research Subcommittee, 1997, 1574-1601.
    [7] 张明国主编,精神科评定量表手册, 长沙:湖南科学技术出版社,1993,162-165.
    [8] Ferguson B, Matyszak MK, et al. Axonal damage in acute multiple sclerosis lesions. Brain, 1997, 120:393–399.
    [9] Trapp BD, Peterson J, Ransohoff RM,et al. Axonal transection in the lesions of multiple sclerosis. N Engl J Med, 1998; 338:278-285.
    [10] De Stefano N, Matthews PM, Fu L, et al. Axonal damage correlates with disability in patients with relapsing-remitting multiple sclerosis: results of a longitudinal magnetic resonance spectroscopystudy. Brain, 1998, 121:1469-1477.
    [11] Ruiz-Pena JL, Pinero P, Sellers G, et al. Magnetic resonance spectroscopy of normal-appearing whitematter in early relapsing-remitting multiple sclerosis: correlations between disability and spectroscopy, BMC Neurol, 2004, 4:8.
    [12] De Stefano N, Narayanan S, Francis GS, et al. Evidence of axonal damage in the early stages of multiple sclerosis and its relevance to disability. Arch Neurol, 2001, 58 :65-70.
    [13] 段云云,李坤成,于春水,秦 文.多发性硬化的磁共振波谱研究. 中国医学影像技术, 2006,22(1):67-69.
    [14] Vrenken H, Barkhol F,Uitdehaag BMJ,et al. MR spectroscopic evidence for glial increase but not for neuro-axonal damage in MS normal-appearing white matter. Magnetic Resonance in Medicine, 2005, 53:256-266.
    [15] Kapeller P, Ropele S, Enzinger C et al. Discrimination of white matter lesions and multiple sclerosiplaques by short echo quantitative 1H-magnetic resonance spectroscopy.Journalof Neurol, 2005,252:1229-1234.
    [16] Wattjes MP, Harzheim M, Lutterbey GG, et al.High field MR imaging and (1)H-MR spectroscopy in clinically isolated syndromes suggestive of multiple sclerosis: Correlation between metabolic alterations and diagnostic MR imaging criteria. J Neurol, 2008, 255(1):56-63.
    [17] Narayana PA, Wolinsky JS, Rao SB, He R, Mehta M. Multicentre proton magnetic resonance spectroscopy imaging of primary progressive multiple sclerosis. Mult Scler, 2004, 10(suppl 1):S73-S78.
    [18] Mader I, Seeger U, Weissert R, et al. Proton MR spectroscopy with metabolite-nulling reveals elevated macromolecules in acute multiple sclerosis.Brain, 2001, 124: 953-961.
    [19] He J, Inglese M,Li Y, et al, Relapsing-Remitting Multiple Sclerosis: Metabolic Abnormality in Nonenhancing Lesions and Normal-appearing White Matter at MR Imaging: Initial Experience Radiology, 2005, 234:211-217.
    [20] Inglese M, Li BS, Rusinek H, et al. Diffusely elevated cerebral choline and creatine in relapsing-remitting multiple sclerosis. Magn Reson Med, 2003, 50:190-195.
    [21] Siger-Zajdel M , Selmaj K. Proton magnetic resonance spectroscopy of normal appearing white matterin asymptomatic relatives of multiple sclerosis patients. European Journal of Neurology, 2006, 13: 296-298.
    [22] Tiberio M,Chard D T,Altmann D R,et al. Metabolite changes in early relapsing-remitting multiple sclerosis :A two year follow-up study. J Neurol, 2006, 253: 224-23.
    [23] Gadea M, Martinez-Bisbal MC, Marti-Bonmati L, et al. Spectroscopic axonal damage of the right locus coeruleus relates to selective attention impairment in early stage relapsing-remitting multiple sclerosis. Brain, 2004, 127:89-98.
    [24] Christodoulou C, Krupp LB, Liang Z, et al. Cognitive performance and MR markers of cerebral injury in cognitively impaired MS patients. Neurology, 2003,60:1793-1798.
    [25] S?rensen PS, J?nsson A, Mathiesen HK, Blinkenberg M, Andresen J, Hanson LG, Ravnborg M.The relationship between MRI and PET changes and cognitive disturbances in MS. J Neurol Sci, 2006, 245(1-2):99-102.
    [26] Ruiz-pena JL, Pinero P, Sellers G, et al. Magnetic Resonance Spectroscopy of normal-appearing white matter in early relapsing-remitting multiple scerosis: correlations between disability and Spectroscopy. Biomedical central neurology, 2004, 4(8):2377-2385.
    [27] Pelletier D, Nelson SJ, Oh J, et al. MRI lesion volume heterogeneity in primary progressive MS in relation with axonal damage and brain atrophy. J Neurol Neurosurg Psychiatry, 2003, 74:950-952.
    [28] Sijens PE, Irwan R, Potze J H. Analysis of the human brain in primary progressive multiple sclerosis with mapping of the spatial distributions using 1H MR spectroscopy and diffusion tensor imaging. Eur Radiol, 2005, 15: 1686-1693.
    [29] Strasser-Fuchs S, Enzinger C, Ropele S, et al.Clinically benign multiple sclerosis despite large T2 lesion load: Can we explain this paradox? J Neuroimaging, 2007, 17 Suppl 1:31S-35S.
    [30] Tartaglia MC, Arnold DL.The role of MRS and fMRI in multiple sclerosis. Adv Neurol, 2006, 98:185-202.
    [31] Caramanos Z, Narayanan S, Arnold DL. 1H-MRS quantification of tNA and tCr in patients with multiple sclerosis: a meta-analytic review. Brain, 2005, 128(Pt 11):2483-506.
    [32] Cader S, Johansen-Berg H, Wylezinska M, et al. Discordant white matter N-acetylasparate and diffusion MRI measures suggest that chronic metabolic dysfunction contributes to axonal pathology in multiple sclerosis. Neuroimage, 2007, 36(1):19-27.
    [33] Arnold DL. Changes observed in multiple sclerosis using magnetic resonance imaging reflect a focal pathology distributed along axonal pathways. J Neurol, 2005,252 Suppl 5: 25-9.
    [34] Siger-Zajdel M, Filippi M, Selmaj K. MTR discloses subtle changes in the normal-appearing tissue from relativesof patients with MS. Neurology, 2002, 58: 317-320.
    [35] De Stefano N, Filippi M.MR spectroscopy in multiple sclerosis. Neuroimage, 2007, 15, 36(1):19-27.
    [36] Staffen W, Zauner H, Mair A, et al. Magnetic resonance spectroscopy of memory and frontal brain region in early multiple sclerosis. J Neuropsychiatry Clin Neurosci, 2005, 17(3):357-63
    [37] Narayanan S, Francis SJ, Sled JG, et al. Axonal injury in the cerebral normal-appearing white matter of patients with multiple sclerosis is related to concurrent demyelination in lesions but not to concurrent demyelination in normal-appearing white matter. Neuroimage, 2006, 15, 29(2):637-42.
    [38] Sijens PE, Irwan R, Potze JH, et al. Analysis of the human brain in primary progressive multiple sclerosis with mapping of the spatial distributions using 1H MR spectroscopy and diffusion tensor imaging. Eur Radiol, 2005, 15(8):1686-93.
    [39] Mathiesen HK, Tscherning T, Sorensen PS, et al. Multi-slice echo-planar spectroscopic MR imaging provides both global and local metabolite measures in multiple sclerosis. Magn Reson Med, 2005, 53(4):750-9.
    [1] McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the international panel on the diagnosis of multiple sclerosis. Ann Neurol, 2001; 50:121-127.
    [2] Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol, 1983, 13:227-31.
    [3] Yurtsever I, Hakyemez B, Taskapilioglu O , et al. The contribution of diffusion-weighted MR imaging in multiple sclerosis during acute attack. European Journal of Radiology, 2008 (65):421-426.
    [4] Castillo M, Mukherji SK. Diffusion-weighted imaging in the evaluation of intracranial lesions. Semin Ultrasound CT MRI,2000,21:405-15.
    [5] Castriota SA, Tomaiuolo F, Sabatini U, et al. Demyelinating plaques in relapsing-remitting and secondary-progressive multiple sclerosis: assessment withdiffusion MR imaging. AJNR Am J Neuroradiol,2000,21: 862-8.
    [6] Rovaris M, Gass A, Bammer R, et al. Diffusion MRI in multiple sclerosis. Neurology,2005,65:1526-32.
    [7] Caramia F,Pantano P,Di Legge S,et al. A longitudinal study of MR diffusion changes in normal appearing white matter of patients with early multiple sclerosis. Magnetic Resonance Imaging, 2002, 20:383-388.
    [8] Kuker W, Ruff J, Gaertner S, et al. Modern MRI tools for the characterization of acute demyelinating lesions: value of chemical shift and diffusion-weighted imaging. Neuroradiology,2004,46: 421-6.
    [9] Nusbaum AO, Tang CY, Wei TC, et al. Whole-brain diffusion MR histograms differ between MS subtypes. Neurology,2000,54: 1421-7.
    [10] Filippi M, Iannucci G, Cercignani M, et al. quantitative study of water diffusion in multiple sclerosis lesions and normal-appearing white matter using echo-planar imaging. Arch Neurol, 2000, 57: 1017- 21.
    [11] 韩鸿宾,谢敬霞,刘溢, 等. 多发性硬化的 MR 扩散加权成像研究. 中华放射学杂志,2002,36:334-338.
    [12] Zivadinov R, Tavazzi E, Weinstock-Guttman B, et al. Diffusion weighted entropy in patients with multiple sclerosis. Mult Scler, 2005, 11: S146-47.
    [13] Phuttharak W, Galassi W, Laopaiboon V,et al. ADC Measurements in Various Patterns of Multiple Sclerosis Lesions. J Med Assoc Thai, 2006, 89 (2): 196-204.
    [14] Tavazzi E, Dwyer M G, Weinstock-Guttman B,et al. Quantitative diffusion weighted imaging measures in patients with multiple sclerosis. NeuroImage,2007, 36:746-754.
    [15] Barnett MH, Prineas JW. Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion. Ann Neurol, 2004, 55: 458-68.
    [16] Pagani E, Bammer R, Horsfield MA, et al. Diffusion MR Imaging in Multiple Sclerosis: Technical Aspects and Challenges. AJNR, 2007, 28:411-20.
    [17] Cassol E, Ranjeva JP, Ibarrola D, et al. Diffusion tensor imaging in multiple sclerosis: a tool for monitoring changes in normal-appearing white matter. Mult Scler, 2004, 10:188-96.
    [18] Filippi M, Inglese M. Overview of diffuse-weighted magnetic resonance studies in multiple sclerosis. J Neurol Sci,2001,186:S37-43.
    [19] Garaci FG,Colangelo V,Ludovici A, et al. A Diffusion Longitudinal MR Imaging Study in Normal-Appearing White Matter in Untreated Relapsing-Remitting Multiple Sclerosis. AJNR,2007, 28:475-78.
    [20] Rosso C, Remy p, Creange A , et al. Diffusion-Weighted MR Imaging Characteristics of an acute stroke like form of multiple sclerosis. AJNR, 2006, 27:1006-1008.
    [21] 段云云, 李坤成,于春水,等.多发性硬化患者的磁化传递及弥散张量成像特点.中华神经科杂志, 2006, 39(12):799-802.
    [22] Chen JT, Kuhlmann T, Jansen GH, et al. Voxel-based analysis of the evolution of magnetization transfer ratio to quantify remyelination and demyelination with histopathological validation in a multiple sclerosis lesion. Neuroimaging, 2007,36(4):1152-8.
    [23] Gallo A, Rovaris M, Riva R, et al. Diffusion-tensor magnetic resonance imaging detects normal-appearing white matter damage unrelated to short-term disease activity in patients at the earliest clinical stage of multiple sclerosis. Arch Neurol, 2005, 62:803-08.
    [24] Agosta F, Benedetti B, Rocca MA, et al. Quantification of cervical cord pathology in primary progressive MS using diffusion tensor MRI. Neurology, 2005, 64:631-35.
    [25] 于春水,李坤成,林富春,等. 复发缓解型多发性硬化患者脑灰质弥散张量成像研究.中华神经科杂志,2006,39 (4):229-333.
    [26] Filippi M, Tortorella C, Rovaris M, et al. Changes in the normal appearing brain tissue and cognitive impairment in multiple sclerosis. J Neurol Neurosurg Psychiatry, 2000, 68: 157-61.
    [27] Benedict RHB, Bruce J, Dwyer MG,et al. Diffusion-weighted imaging predicts cognitive impairment in multiple sclerosis. Multiple Sclerosis, 2007, 13: 722-730.
    [1] Wingerchuk DM, Pittock SJ, Lennon VA et al. Neuromyelitis optica diagnostic criteria revisited: validation and incorporation of the NMO-IgG serum autoantibody. Neurology, 2006, 66:1485-1489.
    [2] Cabre P, Heinzlef O, Merle H et al. Multiple sclerosis and neuromyelitis optica in Martinique. Neurology, 2001, 56: 507-514.
    [3] Ghezzi A, Bergamaschi R, Martinelli V et al. Italian Devic’s Study Group (IDESG). Clinical characteristics, course and prognosis of relapsing Devic’s neuromyelitis optica. J Neurol, 2004, 25: 47- 52.
    [4] De Seze J, Stojkovic T, Ferriby D et al. Devic’s neuromyelitis optica: clinical, laboratory, MRI and outcome profile. J Neurol Sci, 2002, 197: 57-61.
    [5] Cabrera-Go′mez JA, Quevedo-Sotolongo L, Gonza′lez-Quevedo A et al. Brain magnetic resonance imaging findings in relapsing neuromyelitis optica. Multiple Sclerosis, 2007, 13: 186-192.
    [6] Pittock SJ , Lennon VA,Wingerchuk DM et al. Brain Abnormalities in Neuromyelitis Optica. Arch Neurol, 2006, 63:390-396.
    [7] Weinshenker BG .Neuromyelitis optica is distinct from Multiple Sclerosis. Arch Neurol, 2007, 64(6): 899 - 901.
    [8] Chon HT, Li PC, Ong B et al. Severe spinal cord involvement is a universal feature of Asians with multiple sclerosis: a joint Asian study. Neurol J South East Asia, 2002, 7: 35-40.
    [9] Misu T, Fujihara K, Nakashima I et al. Pure optic-spinal form of multiple sclerosis in Japan. Brain 2002, 125: 2460-2468.
    [10] Modi G, Mochan A, Modi M, Saffer D. Demyelinating disorder of the central nervous system occurring in black South Africans. J Neurol Neurosurg Psychiatry, 2001, 70:500-505
    [11] Simon JH, Li D, Traboulsee A, et al. Standardized MR imaging protocol for multiple sclerosis: consortium of MS centers consensus guidelines. Am J Neuroradiol, 2006, 27: 455-461.
    [12] Barkhof F, Filippi M, Miller DH et al. Comparison of MR imaging criteria at first presentation to predict conversion to clinically definite multiple sclerosis. Brain, 1997, 120:2059-2069.
    [13] Tintore′ M, Rovira A, Mart?′nez MJ et al. Isolated demyelinating syndromes: comparison of different MR imaging criteria to predict conversion to clinically definite multiple sclerosis. Am J Neuroradiol, 2000, 21:702-706.
    [14] 吕传真.中国多发性硬化及相关中枢神经系统脱髓鞘疾病的诊断和治疗专家共识( 草案). 中华神经科杂志, 2006, 39(12):862-867.
    [15] O’Riordan JI, Gallagher HL, Thompson AJ et al. Clinical, CSF, and MRI findings in Devic’s neuromyelitis optica. J Neurol Neurosurg Psychiatry, 1996, 60:382-387.
    [16] Bergamaschi R, Ghezzi A. Devic’s neuromyelitis optica: clinical features and prognostic factors. Neurol Sci, 2004, 25:S364-S367.
    [17] Lennon VA, Wingerchuk DM, Kryzer TJ et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet, 2004, 364: 2106-2112.
    [18] Lennon VA, Kryzer TJ, Pittock SJ, et al. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med, 2005, 202:473-477.
    [19] Baudoin D, Gambarelli D, Gayraud D et al. Devic’s neuromyelitis optica: a clinicopathological review of the litterature in connection with a case of showing fatal dysautonomia. Clin Neuropathol, 1998, 17:175-183.
    [20] Sinclair C, Kirk J, Herron B, Fitzgerald U, McQuaid S. Absence of aquaporin-4 expression in lesions of neuromyelitis optica but increased expression in multiple sclerosis lesions and normal-appearing white matter. Acta Neuropathol, 2007, 113:187-194.
    [21] Yu CS, Lin FC, Li KC et al. Diffusion tensor imaging in the assessment of normal-appearing brain tissue damage in relapsing neuromyelitis optica. AJNR, 2006, 27:1009-1015.
    [22] Rocca MA, Agosta F, Mezzapesa DM et al. Magnetization transfer and diffusion tensor MRI show gray matter damage in neuromyelitis optica. Neurology, 2004, 62:476-478.
    [23] Yu CS, Zhu CZ, Li KC et al. Relapsing neuromyelitis optica and relapsing-remitting multiple sclerosis: differentiation at diffusion-tensor MR imaging of corpus callosum. Radiology, 2007, 244(1): 249 - 256.
    [24] 褚晓凡,付学军,王德文等.视神经脊髓炎 7 例临床和病理特点.中华神经科杂志,2004,37,(3):282-283.
    [25] Vernant JC, Cabre P, Smadja D, et al. Recurrent optic neuromyelitis with endocrinopathies: a new syndrome. Neurology, 1997, 48:58–64.
    [26] Wingerchuk DM, Weinshenker BG. Neuromyelitis optica: clinical predictors of a relapsing course and survival. Neurology, 2003, 60: 848-853.
    [27] Fardet L, Genereau T, Mikaeloff Y et al. Devic’s neuromyelitis optica: study of nine cases. Acta Neurol Scand, 2003, 108:193-200.
    [28] Poppe AY, Lapierre Y, Melancon D et al. Neuromyelitis optica with hypothalamic involvement. Mult Scler, 2005, 11:617-621.
    [29] Wingerchuk D M. Diagnosis and treatment of neuromyelitis optica. The Neurologist, 2007, 13 (1):2-7.
    [1] Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis :guidelines for research protocols[R].Ann Neurol 1983;13:227-31。
    [2] Traboulsee A, Zhao GJ, Li DK, et al. Neuroimaging in multiple sclerosis Neurol Clin, 2005,23:131-148.
    [3] Consortium of Multiple Sclerosis Centers. Available at :http://www.mscare.org/.Accessed November,2004.
    [4] Li DK, Paty DW. Magnetic resonance imaging results of the PRISMS trial:a randomized, double-blind, placebo-contronlled study of interferon-beta la in relapsing-remitting multiple sclerosis.:prevention of Ralapses and Disability by Interferon-beta la Subcutaneously in Multiple Sclerosis[J].Ann Neurol 1999;46:197-206.
    [5] Filippi M, Yousry T, Campi A, et al. Comparison of trial dose versus standard dose gadolinium-DTPA for detection of MRI enhancing lesions in patients with MS[J].Neurology,1996;46:379-84.
    [6] Tjoa CW, Benedict RHB, Guttman BW, et al. MRI T2 hypointensity of the dentate nucleus is related to ambulatory impairment in multiple sclerosis [J]. Journal of the Neurological Sciences, 2005, 234:17-24.
    [7] Miwa H, kajimoto Y, Nakanishi I, et al. T2-low signal intensity in the cortex in multiple system atrophy. Journal of the Neurological Sciences, 2003, 211:85-88
    [8] .Lycklama, Nijeholt, G.J. Reduction of brain volume in MS.MRI and pathology findings. Journal of the Neurological Sciences, 2005, 233: 199-202.
    [9] Bakshi R, Ariyaratana S, Benedict RH, et al. Fluid-attenuated inversion recovery magnetic resonance imaging detects cortical and juxtacortical multiple sclerosis lesions. Arch Neurol, 2001,58(5):742-8.
    [10] Pike GB, Stefano ND, Narayanan S,et al. Multiple sclerosis: magnetization transfer MR imaging of white before lesions appearance on T2-weighted images.Radiology, 2002(3):483-491.
    [11] Santos AC, Narayanan S, De S, et al. Magnetization transfer can predict clinicalevaluation in patients with multiple sclerosis.J Neurol, 2002, 249:662-668.
    [12] Yulin G, Grossman RI, Udupa JK, et al. In multiple sclerosis demyelinating plaques, white matter ischemic lesions and edema.AJNR,1996,17(6):1051-1055.
    [13] Chen JT, Collins DL, Freedman MS, et al. Local magnetization transfer ratio signal inhomogeneity is related to subsequent change in MTR in lesion and normal-appearing white-matter of multiple sclerosis patients. NeuroImage, 2005, 25:1272-1278.
    [14] Atalay KS, Diren HB, Gelmez S, et al. The effectiveness of magnetization transfer technique in the evaluation of acute plaques in the central nervous system of multiple sclerosis patients and its correlation with the findings. Diagnostic and Interventional Radiology, 2005,11(3):147-141.
    [15] Rui-pena JL, Pinero P, Sellers G, et al. Magnetic Resonance spectroscopy of normal appearing white matter in early relapsing-remitting multiple sclerosis: correlations between disability and spectroscopy.BMC Neurology ,2004,June 10,4-8
    [16] Fernando KT, Mclean MA, Chard DT, et al. Elevated white matter myo-inositol in clinincally isolated syndromes suggestive of multiple sclerosis .Brain,2004,127(Pt16):1361-1369.
    [17] Hu JH, Xu YB, Jiang Q, et al. Spectral pattern of total creatine and trimethyl ammonium in multiple sclerosis. Magnetic Resonance Imaging, 2004, 22:427-429.
    [18] Filipp M, Bozzali M, Comi G, et al. Magnetization transfer and diffusion tensor MR imaging of basal ganglia from patients with multiple sclerosis. Journal of the Neurological Sciences, 2001, 183:69-72.
    [19] Rovaris M, Gallo A, Valsaina P, et al. Short-term accrual of gray matter pathology in patients with progressive multiple sclerosis: an in vivo study using diffusion tensor MRI. NeuroImaging, 2005,24:1139-1146.
    [20] Valsasina P, Rocca MA, Agosta F, et al. Mean diffusivity and fractional anisotropy histogram analysis of the cervical cord in MS patients.NeuroImaging, 2005 26:822-828.
    [21] Filippi M, Rocca MA, Comi, et al. the use of quantitative magnetic resonance-based techniques to monitor the evolution of multiple sclerosis. Lancet Neurol , 2: 337-346.
    [22] Rovaris M, Gass A, Bammer R, et al. Diffusion MRI in multiple sclerosis.Neurology, 2005,65:1526-1532.
    [23] Law M, Saindane AM, Yulin G, et al. Microvascular Abnormality in Relapsing-Remitting Multiple Sclerosis: Perfusion MR Imaging Findings in Normal-appearing white Matter. Neuroradiology, 2004, 231:645-652.
    [24] Hakyemez B, Erdogan C, Yildiz, H, et al. Tumefactive demyelinating lesion: perfusion-weighted imaging findings. European Jourmal of Radiology Extra 2005, 53: 95-98.
    [25] Cha S, Knopp EA, Johnson G, et al. Intracrannial mass lesions: dynamic contrast-enhanced susceptibility-weighted echo-planar perfusion MR imaging.Radiology, 2002;223:11-29.
    [26] Filippi M, Rocca MA, Falini A, et al. Correlations between structural CNS damage and functional MRI changes in primary progressive MS.NeuroImage,2002,58(8):1147-1153
    [27] Rocca MA, Colombo B, Falinia A, et al. Cortical adaptation in patient with MS: a cross-sectional functional MRI study of disease phenotype.Lancet Neurol, 2005,4:618-26.
    [28] Scott H, Feroze B. Quantitative functional MR imaging of the visual cortex at 1.5T as a function of luminance contrast in healthy volunteers and patients with multiple sclerosis.AJNR, 2002,23(1):59-65.
    [29] Filippi M, Falini A, Atnold DL, et al. Magnetic Resonance Techniques for the in vivo assessment of multiple sclerosis pathology: consensus report of the white matter study group[R].Journal of magnetic resonance imaging. 2005,21: 669-675
    [30] Ding ZH, Preiningerova J, Cannistraci CJ, et al. Quantification of multiple sclerosis lesion load and brain tissue volumetry using multiparameter MRI methodology and reproducibility. Magnetic Resonance Imaging, 2005, 23:445-452.
    [1] Filippi M, Rocca MA. Magnetic resonance imaging techniques to define and monitor tissue damage and repair in multiple sclerosis. 2007, 254 Suppl 1:I55-I62.
    [2] De Stefano N, Bartolozzi ML, Guidi L, et al. Magnetic resonance spectroscopy as a measureof brain damage in multiple sclerosis. J Neurol Sci, 2005, 233:203–208.
    [3] Mader I, Seeger U, Weissert R, et al. Proton MR spectroscopy with metabolite-nulling reveals elevated macromolecules in acute multiple sclerosis. Brain, 2001, 124:953–961.
    [4] Lin A, Ross BD, Harris K, Wong W. Efficacy of proton magnetic resonance spectroscopy in neurological diagnosis and neurotherapeutic decision making. Neuro Rx, 2005, 2:197–214.
    [5] Srinivasan R, Sailasuta N, Hurd R, et al. Evidence of elevated glutamate in multiple sclerosis using magnetic resonance spectroscopy at 3 T. Brain , 2005, 128:1016–1025.
    [6] He J, Inglese M, Li BS, et al. Relapsing-remitting multiple sclerosis: metabolic abnormality in nonenhancing lesions and normal-appearing white matter at MR imaging—initial experience. Radiology, 2005, 234:211–217.
    [7] Vrenken H, Barkhof F, Uitdehaag BMJ, et al. spectroscopic evidence for glial increase but not for neuro-axonal damage in MS normal-appearing white matter. Magn Reson Med, 2005, 53:256–266.
    [8] Inglese M, Li BS, Rusinek H, et al. Diffusely elevated cerebral choline and creatine in relapsing-remitting multiple sclerosis. Magn Reson Med, 2003,50:190–195.
    [9] Siger-Zajdel M , Selmaj K. Proton magnetic resonance spectroscopy of normal appearing white matterin asymptomatic relatives of multiple sclerosis patients. European Journal of Neurology, 2006, 13: 296–298.
    [10] Tiberio M,Chard D T,Altmann D R,et al. Metabolite changes in early relapsing-remitting multiple sclerosis :A two year follow-up study. J Neurol, 2006,253 : 224–23.
    [11] Fernando KT, Mclean MA, Chard DT, et al. Elevated white matter myo-inositol in clinincally isolated syndromes suggestive of multiple sclerosis. Brain, 2004, 127(16):1361-1369.
    [12] Geurts JJ, Pouwels PJ, Uitdehaag BM, et al. Intracortical lesions in multiple sclerosis: improved detection with 3D double inversion-recovery MR imaging. Radiology, 2005, 236:254–260.
    [13] Inglese M, Liu S, Babb JS, et al. Three-dimensional proton spectroscopy of deep gray matter nuclei in relapsing-remitting MS. Neurology, 2004, 63:170–172.
    [14] Rui-pena JL, Pinero P, Sellers G, et al. Magnetic Resonance spectroscopy of normal-appearing white matter in early relapsing-remitting multiple sclerosis: correlations between disability and spectroscopy. BMC Neurology, 2004, 10: 4-8.
    [15] Pelletier D, Nelson SJ, Oh J, et al. MRI lesion volume heterogeneity in primary progressive MS in relation with axonal damage and brain atrophy. J Neurol Neurosurg Psychiatry, 2003, 74:950–952.
    [16] Tartaglia MC, Narayanan S, Francis SJ, et al. The relationship between diffuse axonal damage and fatigue in multiple sclerosis. Arch Neurol , 2004 , 61:201–207.
    [17] Hu JH, Xu YB, Jiang Q, et al. Spectral pattern of total creatine and trimethyl ammonium in multiple sclerosis. Magnetic Resonance Imaging, 2004, 22:427-429.
    [18] Gadea M, Martinez-Bisbal MC, Marti-Bonmati L, et al. Spectroscopic axonal damage of the right locus coeruleus relates to selective attention impairment in early stage relapsing-remitting multiple sclerosis. Brain, 2004;127:89–98.
    [19] Christodoulou C, Krupp LB, Liang Z, et al. Cognitive performance and MR markers of cerebral injury in cognitively impaired MS patients. Neurology, 2003,60:1793–1798.
    [20] Gonen O, Catalaa I, Babb JS, et al. Total brain N-acetylaspartate: a new measure of disease load in MS. Neurology, 2000, 54:15–19.
    [21] Sarchielli P, Presciutti O, Tarducci R, et al. 1H-MRS in patients with multiple sclerosis undergoing treatment with interferon β-1a: results of a preliminary study. J Neurol Neurosurg Psychiatry, 1998; 64:204–212.
    [22] Narayanan S, De Stefano N, Francis GS, et al. Axonal metabolic recovery in multiple sclerosis patients treated with interferon beta-1b. J Neurol,2001, 248:979–986.
    [23] Schubert F, Seifert F, Elster C, et al. Serial 1H-MRS in relapsing-remitting multiple sclerosis: effects of interferon-beta therapy on absolute metabolite concentrations. MAGMA,2002,14:213–222.
    [24] Liu L, Meier D, Polgar-Turcsanyi M, et al. Multiple sclerosis medical image analysis and information management. J Neuroimaging, 2005, 15(suppl 1):103S–117S.
    [25] Cader S, Johansen-Berg H, Wylezinska M, et al. Discordant white matter N-acetylasparate and diffusion MRI measures suggest that chronic metabolic dysfunction contributes to axonal pathology in multiple sclerosis. Neuroimage, 2007, 15; 36(1):19-27.
    [26] De SN, Folippi M. MR spectroscopy in multiple sclerosis. Neuroimaging, 2007, 17 suppl ,1:31s-35s
    [1] Wilkins MR, Sanchez JC, Gooley AA et al. Progress with proteome projects: why all proteins express with proteome projects: why all proteins expressed by a genome should be identified and how to do it. Biotechology, 1995, 13(1):19-50.
    [2] Jungblut PR, Zimny-Arndt U, Zeindl-Eberhart et al. Proteimics in human disease: cancer, heartand infectiousdiseases. Electrophoresis, 1999, 20(10):2100-2110.
    [3] Blackstock WP, Weir MP. Proteomics: quantitative and physical mapping of cellular proteins. Trends Biotechnol, 1999, 17(3):121-127.
    [4] .Langen H, Berndt P, Roder D, Fountoulakis M, et al. Two-dimensional map of human brain proteins.Electrophoresis,1999,20(4-5):907-916.
    [5] Tsugita A, Kawakami T, Uchida T, et al. Proteome analysis of mouse brain: two-dimensional electrophoresis profile of tissue proteins during the course of aging. Electrophoresis, 2002, 21(9):1853-1871.
    [6] Gauss C,Kalkum M,Lewe M,et al.Analysis of the mouse proteme(I).Brain protein:Seperation by two-dimcetional gel electrophoresis and identification by mass spectrometry and genetic variation.Electrophores is,1999, 20:575-600.
    [7] Fountoulakis M, Schuller E, Hardmeier R, et al. Rat brain proteins: two-dimensional protein database and variationa in the expression level. Electrophoresis, 1999, 20(18):3572-3579.
    [8] Grant SG, Blackstock WP. Proteomics in neuroscience: from protein to network.Neurosci, 2001, 21:8315-8318.
    [9] Zhang Jing,Goodlent DR, Peskind ER, et al. Quantitive proteomic analysis of age-related changes in human cerebrospinal fluid. Neurobilogy of Aging 2005 (26):207-227.
    [10] Yuan Xianglin, Desiderio DM. proteomic analysis of human cerebrospinal fluid.Journal of Chromatography B, 2005 (815):179-189.
    [11] Robinson WH, Utz pj, Steinman L. Genomic and of multiple sclerosis opinion. Current Opinion in Immunology, 2003, 15:660-667.
    [12] Kira J. Molecular immunogenetic approach to the pathogenesis of multiple sclerosis. Rinsho Shinkeigaku, 2002, 42(11):1198-200.
    [13] Rohlef C. Proteomics in molecular medicince: applications in central nervous systems disorders. Electrophoresis, 2002, 21:1227-1234.
    [14] Hammack BN, Owens GP, Burgoon MP, Gilden DH,et al. Improved resolution of human cerebrospinal fluid proteins on two-dimensional gels. Mult Scler. 2003, 9(5):472-5.
    [15] Hammack BN, Fung KY, Hunsucker SW, et al. Proteomic analysis of multiple sclerosis cerebrospinal fluids. Mult Scler, 2004, 10(3):245-60.
    [16] Dumont D, Noben JP,Raus J, et al .Proteomic analysis of cerebrospinal fluid from multiple sclerosis patients.Proteomics, 2004(4) :21
    [17] Almeras L, Lefras D, Drobecq H, et al. New antigenic candidates in multiple sclerosis: identification by serological proteome analysis. Proteomics, 2004, 4(7):2184-94.
    [18] Petricoin EF, Ardekani AM, Hitt BA, et al. Use of proteomic patterns in serum toidentify ovarian cancer. Lancet, 2002, 359:572-577.
    [19] Cho WC, Yip TTC,Yip C, et al.Identification of serum amyloid a protein as potentially useful biomarker to monitor relapse of nasopharyngeal cancer by serum proteomic profiling.Clin Cancer Res,2004,10(1):43-52.
    [20] Duzhak T, Emerson MR, Chakrabarty A, et al. Analysis of protein induction in the CNS of SJL mice with experimental allergic encephalomyelitis by proteomic screening and immunohistochemistry. Cell Mol Biol, 2003 (49): 723-732.
    [21] Newcombe J, Eriksson B, Ottervald J, et al. Extraction and proteomic analysis of proteins from normal and multiple sclerosis postmortem brain, Journal of Chromatography , 2005,(815):191-202.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700