【作者】 施莺燕；

【导师】 耿道颖； 刘含秋； 何慧瑾； 汤伟军； 帕米尔；

【作者基本信息】 复旦大学 ， 影像医学与核医学， 2007， 博士

【摘要】 磁共振T2弛豫时间测量在癫痫中的应用研究第一部分正常人脑组织的T2弛豫时间测量及其随年龄变化规律目的：确定正常人脑组织各个部位的T2弛豫时间值及其正常值参考范围，同时也分析半球间、性别间是否存在差异，以及年龄对T2弛豫时间值影响。材料和方法：无神经系统或影响神经系统疾病的正常志愿者38名。年龄：9-59岁，平均31.19±15.4岁。并根据年龄分为2组，未成年组≤17岁和成年人组≥18岁。所有志愿者常规颅脑MRI检查无阳性征象，行T2弛豫时间扫描。T2弛豫时间扫描数据传入Functool工作站的T2弛豫时间测量软件计算获得的每个体素的T2弛豫时间值，所得的T2 map图重叠在质子加权图像进行融合以便与对感兴趣区进行正确定位，然后测量双侧大脑的杏仁核，海马头部、尾状核、豆状核、丘脑、颞叶白质、枕叶白质、额叶白质、顶叶白质的T2弛豫时间并行统计分析。结果：各部位脑组织T2弛豫时间值，杏仁核：108.32±8.68ms，海马头114.99±9.16ms，尾状核头98.98±5.67ms，壳核86.00±7.95ms，丘脑86.34±5.47ms，，颞叶白质92.28±5.95ms，枕叶白质102.95±5.75ms；额叶白质96.49±5.62ms；顶叶白质107.28±6.01ms。各个不同部位间T2弛豫时间值差别存在统计学差别(P＜0.05)，而除壳核和丘脑外其余各部位灰质的T2弛豫时间高于白质结构。多个部位的脑组织T2弛豫时间值与年龄负相关，其中杏仁核r=-0.387，海马r=-0.348，尾状核r=-0.526，壳核r=-0.764，(P＜0.05)。在未成年人组和成年人组之间T2弛豫时间(ms)比较：杏仁核113.41±10.75：105.78±6.13；海马119.85±9.47：112.56±8.05；尾状核103.02±6.12：96.97±4.22．；壳核93.59±5.91：82.21±5.85；丘脑89.18±5.72：84.91±4.79，颞叶白质94.62±5.63：89.11±1.68；枕叶白质102.53±4.68：103.15±6.25；额叶白质96.88±6.11：96.29±5.41；顶叶白质106.87±6.01：107.48±0.05。这一差别在壳核中最为明显。结论：脑内各个部位的T2弛豫时间无半球间差异，但有性别差异存在。各个部位的T2弛豫时间值存在差异，随着年龄的增长大部分的脑组织T2弛豫时间值呈下降趋势尤以壳核最明显。第二部分MRI阴性的癫痫T2弛豫时间测量及其与临床相关性分析目的：研究常规磁共振阴性的隐源性癫痫患者是否存在T2弛豫时间的改变，确定癫痫患者各部位T2驰豫时间值与临床发作类型、癫痫发病年龄、发作频率、癫痫病持续时间、末次发作与检查时时间间隔是否存在关系。材料和方法：本研究对象包括54例MRI阴性的癫痫患者和20例健康志愿者。病例组54例癫痫患者的诊断标准：根据国际抗癫痫联盟(ILAE)推荐的根据临床的脑电图特点进行分类诊断，所有患者行常规磁共振扫描和海马磁共振扫描以排除目测可见的疾病。对照组20名年龄性别与病例组相匹配的健康志愿者，行T2弛豫时间扫描和后处理，测量双侧大脑的杏仁核，海马头部、尾状核、豆状核、丘脑、颞叶白质、枕叶白质、额叶白质、顶叶白质的T2弛豫时间值。并根据ILAE推荐的根据临床和脑电图的国际分类(1989)将患者的临床发作类型分成4组：第1组为单纯部分性发作，第2组为复杂部分性发作和部分性继发全面发作者；第3组失神发作；第4组为强直—阵挛性发作。按发作频率分成4级：1级，每天一次以上；2级，每周一次以上，少于每天一次；3级，每月一次以上，少于每周一次；4级，每年数次以上，少于每月一次。分析癫痫临床发作类型、发作频率与脑内各部位T2驰豫时间的关系。结果：癫痫组杏仁核的T2弛豫时间高于正常人组(115.92±9.15：110.36±5.4，P=0.001)。单纯部分性发作组在尾状核、壳核、颞叶、丘脑、枕叶T2驰豫时间值均高于失神发作组，p值分别为：尾状核0.006，壳核0.042，颞叶0.020，丘脑0.026，枕叶0.044；海马、尾状核、壳核、丘脑、颞叶、T2驰豫时间低于强直—阵挛性发作组(p值分别为0.005，0.001，0.003，0.009)。复杂部分性发作和部分性继发全面发作组的杏仁核、海马，尾状核，丘脑、颞叶、顶叶T2弛豫时间延长较失神发作组更明显(p值分别为0.007，0.021，0.010，0.000，0.006，与强直—阵挛性发作组比，杏仁核、海马、尾状核、颞叶(p值分别为0.001，0.002，0.013，0.001)均高于强直—阵挛性发作组。全身性发作的两组之间未见有统计学意义的差异。不同的发作频率组间颞叶第二组、第三组和第四组的差别存在统计学差异(p值分别为0.046，0.017)；枕叶第一组和第三组的差别存在统计学差异(p=0.044)；顶叶第三组和第四组的差别存在统计学差异(p=0.047)。在排除检查时年龄对T2驰豫时间的影响后发现除枕叶和顶叶白质外，癫痫发病年龄与脑内各部位的T2驰豫时间的相关性如下：杏仁核r=-0.419，p=0.000；海马r=-0.320，p=0.001；尾状核r=-0.362，p=0.000；壳核r=-0.586，p=0.000；丘脑r=-0.481，p=0.000；颞叶白质r=-0.265，p=0.006；额叶白质r=-0.212，p=0.028。末次发作时间与检查时间的间隔和各部位T2弛豫时间之间可见曲线呈轻度下降趋势，但未见显著性差异。结论：常规磁共振阴性的癫痫患者杏仁核的T2弛豫时间延长。磁共振阴性的癫痫患者T2弛豫时间改变和癫痫的发作频率和时间有关；不同的临床发作类型间T2弛豫时间值存在一定的差别。第三部分继发性癫痫患者的磁共振T2弛豫时间测量目的：比较有无诱因的常规MRI阴性癫痫患者的T2弛豫时间改变的特点。材料和方法：本组研究对象包括原发性癫痫患者54例，继发性癫痫患者9例和20例健康志愿者。病例组无诱因的隐源性癫痫患者54名，9名继发性癫痫，继发原因：第一组，脑外伤史1例，第二组：新生儿缺血缺氧脑病史1例，第三组：病毒性脑炎史5例，第四组：可疑海马硬化1例。由癫痫专科医生根据国际抗癫痫联盟(ILAE)的诊断标准进行。对照组20名年龄、性别与病灶组相匹配的正常人，所有受试者行常规MRI、海马MRI(病例组)和T2弛豫时间测量。结果：脑内各部位的T2驰豫时间值为继发性癫痫组＞原发性癫痫组＞正常人组。癫痫组杏仁核、海马头T2驰豫时间值均高于正常人组(杏仁核116.02±8.16：110.36±5.4ms和海马头120.30±10.48：116.42±8.13ms，P值分别为0.000，0.025)；继发性癫痫组高于正常人组的部位包括杏仁核(119.07±8.14：110.36±5.4；，P值分别为0.001)、海马(125.88±8.80：116.42±8.13，P=0.001)，尾状核、壳核。原发性癫痫组高于正常人组的部位只有杏仁核具有统计学差异，115.92±9.15：110.36±5.4ms，P=0.000。继发性癫痫组间两两比较发现，脑外伤：枕叶的T2驰豫时间与其他各组之间的差异具有统计学意义，P值分别为0.001，0.015；0.005、0.002、0.001。HIE：杏仁核、壳核的T2驰豫时间值高于正常人；壳核高于原发性癫痫组及正常人组。脑炎组：于正常人组相比，杏仁核、尾状核的T2驰豫时间值高于正常人。与原发性癫痫组相比，尾状核、额叶、顶叶的T2驰豫时间值脑炎组高于原发性癫痫组。可疑海马硬化患者杏仁核和壳核的T2驰豫时间值与原发性癫痫组及正常人组差别具有统计学意义。结论：、磁共振阴性的继发性癫痫患者杏仁核和海马头的T2驰豫时间值较正常人延长；原发性癫痫组杏仁核T2驰豫时间值延长。继发性癫痫T2驰豫时间值高于原发性癫痫高于正常人；不同继发性癫痫患者的不同部位的T2驰豫时间延长。第四部分磁共振弥散张量成像、T2弛豫时间测量在癫痫中的联合应用目的：探索癫痫患者脑组织的弥散特性，探讨T2弛豫时间值和弥散特性的改变是否相关。材料和方法：研究对象包括21例癫痫患者(平均年龄12.81±6岁)，其中常规结构影像无异常改变的19例患者中，根据患者的脑电图特点分成颞叶癫痫组共15例，额叶癫痫2例，顶叶癫痫2例。另外有2例常规影像学提示灰质异位、脑外伤各一例。所有患者行常规头颅磁共振、DTI和T2弛豫时间扫描。健康对照组性别、年龄相匹配的正常人共10例(14.5±4.54岁)，分别测量双侧颞叶、枕叶白质、额叶白质、顶叶白质、内囊和胼胝体膝部平均弥散系数、各向异性分数和T2弛豫时间值，比较各组间有无差异。结果：本组中颞叶癫痫组中病灶侧颞叶内侧的平均弥散系增高(P=0.039)。癫痫组病灶侧多个部位的各向异性分数(FA值)降低，其中颞叶白质FA值降低具有统计学意义(P=0.038)。颞叶癫痫患者中，癫痫组病灶侧杏仁核的的T2弛豫时间值高于正常人组(P=0.037)，对侧杏仁核与正常对照组之间未见显著性差异。其余各部位未见显著性组间差异。相关性分析示：颞叶白质的各向异性分数与杏仁核的T2弛豫时间呈负相关(r=0.286，P=0.044)。杏仁核和海马及颞叶白质的T2弛豫时间值显著性相关(r=0.399，P=0.004；r=0.487，P=0.000)，余未见显著相关性。另外在两例继发性癫痫中DTI可更加清晰地显示局部白质结构的改变。结论：常规磁共振阴性的颞叶癫痫患者中，癫痫发放侧的部分脑组织弥散系数增高，各向系数下降；与T2弛豫时间延长的部位有一定的相关性，说明在“隐源性”癫痫存在一定的病理改变，需要结合多种检查手段才能发现。在常规磁共振显示病灶的癫痫患者中，弥散张量成像较之于常规磁共振提供了更多关于白质结构的信息。结合多种技术，可从不同的角度揭示癫痫患者脑区的各种改变，揭示癫痫的发病机制和癫痫网络。更多还原

【Abstract】 Part I T2 Relaxation Time of Normal Human Brainand it’s Change with AgingPurpose: To determine whether the average T2 relaxation time values of brain differ with age, sex and hemisphere, and the effect of aging on T2 relaxation time values, also to establish reference values of the absolute T2 relaxation time for further pathological studies. Material and Methods: Subjects （18 men and 20 women） were chosen from a healthy population; Two age groups were defined as adolescent group（age≤17 years old） and adult group（over 17 years old）. All subjects were examined, including routine cranial MRI scan and T2 relaxometry sequence in oblique axial plane which is parallel to the long axis of hippocampus at 3.0 T MR. The data were transferred to the workstation ,analyzed by research T2 mapping software on Functool. Bilateral T2 relaxation time values were determined in 9 regions of interest encompassing the entire brain, including: the amygdala, the hippocampus , the caudate nucleus; the putamen, the thalamus ,frontal, parietal, occipital, temporal white matter. Results: The T2 relaxation time values in different brain regions were as follows: the amygdala 108.32±8.68ms, the hippocampus 114.99±9.16ms, caudate nucleus 98.98±5.67ms, putamen 86.00±7.95ms, the thalamus 86.34±5.47ms, temporal white matter 92.28±5.95ms,occipital white matter 102.95±5.75ms, frontal white matter 96.49±5.62ms; parietal white matter 107.28±6.01ms （P<0.05） . The T2 relaxation time values in gray matter except the putamen and thalamus is higher than that in white matter. No difference was observed between hemispheres, difference between different genders is found. The T2 relaxation time values significantly differ in different age groups in caudate nucleus; the putamen; the thalamus; the amygdala and the hippocampus. The T2 relaxation time values significantly decreased with advancing age in amygdala（r=-0.387, P<0.05）, the hippocampus （r=-0.348, P<0.05）, caudate nucleus （r=-0.526 P<0.05）and putamen（r=-0.764, P<0.05）. Conclusion: Gray matter has a highter T2 relaxation time values than the white matter, the T2 relaxation time values of adult human brain show difference between genders in different regions, but no difference is found between the hemispheres. The T2 relaxation time values significantly decreased with advancing age in the amygdala, the hippocampus, caudate nucleus and putamen ; this change is most obviously in the putamen.Part II T2 Relaxometry in the MRI-negative Epilepsy and its Correlation with Clinical CharacteristicsPurpose: To determine whether the T2 relaxation time values in brain correlate with the clinical characteristic, the onset age and the frequency of seizure. Material and Methods: Subjects including 54 MRI-negative patients; 20 controls from healthy population. Bilateral T2 relaxation time values were determined in 9 regions of interest encompassing the entire brain, including: the amygdala and the hippocampus, the caudate nucleus; the putamen; the thalamus; frontal, parietal, occipital, temporal, white matter;.The clinical characteristics is divided into four groups:the 1^st group,simple partial seizure, the 2^nd group ,complex partial seizure, the 3^rd group ,absence seizures ,the 4^th group generalised tonic-clonic seizure. The patient group is divided into four frequency levels: the 1^st level with frequency more than once a day ;the 2nd level with frequency more than once a week, less than once a day; the 3rd level with frequency more than once a month, less than once a week; the 4^th level with frequency more than once a year, less than once a month. Results: The T2 relaxation time values in amygdala in epilepsy group is higher than the controls （115.92±9.15:110.36±5.4, P=0.001）. The T2 relaxation time values in caudate nucleus, the putamen, thalamus ,temporal and occipital white matter in the first epilepsy group were higher than the 3^rd group, with p values as 0.006,0.042,0.020, 0.026,0.044; The T2 relaxation time values in the hippocampus, the caudate nucleus, the putamen, thalamus,temporal white matter were lower than the 4^th group （p value as follows 0.005,0.001,0.003,0.009）. The T2 relaxation time values in amygdala, hippocampus, caudate nucleus, thalamus, temporal and occipital white matter in the 2^nd epilepsy group were higher than the 3^rd group（p value as follows 0.007, 0.021, 0.010, 0.000, 0.006）. The T2 relaxation time values in amygdala, hippocampus, caudate nucleus, thalamus ,temporal white matter in the 2^nd epilepsy group were higher than the 4^th group（p value as follows 0.001, 0.002, 0.013, 0.001）. Difference was found in the different frequency levels, the temporal, occipital, parietal white matter. After excluding the age factors, the onset age in various regions was correlate with the T2 relaxation time, except occipital and parietal regions (amygdala r=-0.419,p=0.000; hippocampus r=-0.320,p=0.001; caudate nucleus r=-0.362 , p=0.000; putamen r=-0.586, p=0.000;r=-0.481, p=0.000; the temporal white matter r=-0.265, p=0.006; the frontal white matter r=-0.212, p=0.028.No statistical significance was found in the correlation of the T2 relaxation time and the interval between the last onset and the examination day. Conclusion: T2 relaxation time in multiple regions in the epilepsy group is higher than the normal control, T2 relaxation time change in amygdala is of statistical significance. T2 relaxation time in the epilepsy group is correlated with the frequency and the duration,and difference is also found in different clinical group.Part III Application of T2 Relaxometry in Secondary Epilepsy withNegative MRIPurpose: To determine compare the T2 relaxation time values in MRI-negative epilepsy patients with induce factor and those without induce factor. Material and Methods: Subjects including: 9 epilepsy patients with induce factor and 54 without any induce factor. The induce factor including injury, HIE, virus encephalitis, and suspected hippocampal sclerosis. The twenty controls came from healthy population. Results: The T2 relaxation time values in various regions in the epilepsy with induce factor were higher than those without induce factor, and controls. The T2 relaxation time values in amygdala and hippocampus in the epilepsy were higher than the controls （amygdala 116.02±8.16 :110.36±5.4ms, and hippocampus 120.30±10.48 :116.42±8.13ms, P value as 0.000, 0.025）. The T2 relaxation time values in amygdale（119.07±8.14:110.36±5.4, P=0.001）, hippocampus （125.88±8.80:1 16.42±8.13, P=0.001）, caudate nucleus, putamen in the epilepsy with induce factor were higher than the normal controls. The amygdala relaxation time in the epilepsy without induce factor was higher than the normal controls （115.92±9.15:110.36±5.4ms, P=0.000）. In the injury group the T2 relaxation time in the occipital white matter was higher than others（P value as 0.001, 0.015; 0.005、0.002、0.001）, the amygdala and putamen T2 relaxation time in HIE was higher than the controls, the amygdala and caudate nucleus T2 relaxation time in the encephalitis groups were higher than the normal control, T2 relaxation time in caudate nucleus, frontal and parietal white matter were higher than the epilepsy without inducement, the amygdala and putamen T2 relaxation time in suspected hippocamal sclerosis were higher than the epilepsy without induce factor and normal controls. Conclusions: In the epilepsy patients with induce factors the amygdala and hippocampus T2 relaxation higher than epilepsy patients without induce factor and normal controls. T2 relaxation time in different regions is changed with different induce factor. T2 relaxation can show the abnormality which routine image is normal so that we can probe into the epilepsy network in the point of relaxation time.Part IV Application of Diffusion Tensor ImagingCombined with T2 Relaxometry in the EpilepsyPurpose: To explore the diffusion characteristic in the epilepsy, compare whether the diffusion characteristic correlates with T2 relaxation time values in MRI-negative epilepsy. Material and Methods: Twenty-one epilepsy patients including 19 MRI-negtive epilepsy patients, with 15 temporal ,2 frontal epilepsy and another 2 parietal epilepsy; another two epilepsy patients with positive routine MRI,which hints the diagnosis of ectopic gray matter were included. Ten controls came from healthy population. The MD, FA values and T2 relaxation time values in various regions in the epilepsy were evaluated. Results: The T2 relaxation time values in amygdala in the epilepsy were higher than the controls. Increased MD and decreased FA were found in the temporal lobe. There was statistically significant correlation between the amygdale T2 relaxtion time and the FA value in the temporal white matter. Further more, in the MRI positive cases the DTI demostrated the change of related white matter. Conclusions: In the MRI negative epilepsy patients, the increased MD with decreased ADC in the ipislatral temporal regions, there is correlation between the diffusion change and the T2 relaxation time, which demonstrate there maybe occult pathological change in the idiopathic epilepsy.As for the MRI positive epilepsy, DTI gives more information about white matter. Multimodality MRI is helpful in the exploration of the complicated change in the epilepsy brain, and the onset mechanism and network of epilepsy.更多还原