扩散张量及纤维束成像在正常人与脑梗死病人的临床应用研究
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摘要
第一部分正常成人脑扩散张量成像的可重复性研究
目的：
利用3.0T超高场磁共振扫描仪进行DTI技术在中枢神经系统的应用研究,通过测量不同部位灰白质的FA值及ADC值,探讨同一测量者内部、不同测量者间及不同时间点扫描所得DTI数据的一致性及可重复性。
材料与方法：
对8例正常成人行MR检查,男3例,女5例,年龄23～29岁,平均25.3岁。所有研究对象均无神经系统或影响神经系统的疾病。使用GE signa Excite3.0T超导型核磁共振扫描仪,8通道头部线圈。采用EPI序列,在25个方向上施加扩散敏感梯度,扩散加权系数(b值)为1000s/mm2。
8例受试者均行3次DTI扫描,前两次扫描为当天重复扫描两次,保证了定位线及受试者位置的一致性,一个月以后进行第三次扫描。在AW4.3工作站上,利用Functool软件获得部分各向异性(FA)图、表观扩散系数(ADC)图及方向编码彩色(DEC)图。分别于双侧半球的七个不同部位放置感兴趣区。为了比较测量者内部的差异,由同一名医生对8位受试者的第一次扫描数据不同部位的FA值及ADC值测量三次；为了比较测量者之间的差异,由三位有经验的放射科医师对8位受试者第一次扫描数据进行测量,在同一天进行；为了比较不同扫描时间点所得数据的变异程度,由同一位医师对8位受试者三次扫描所得数据进行测量,在同一天进行。采用信度分析比较测量者内部、不同测量者间及不同扫描间的可重复性及稳定性,并分别进行三次测量的组间比较(测量者内部、测量者间及扫描间)。
为了比较重建者内部锥体束DTT重建的可重复性,由同一名医生对8位受试者的第一次扫描数据进行三次DTT重建；为了比较重建者之间的差异,由三位有经验的放射科医师对8位受试者第一次扫描数据进行DTT重建,在同一天进行；为了比较不同扫描时间点所得数据DTT重建的稳定性,由同一位医师对8位受试者三次扫描所得数据进行DTT重建,在同一天进行。分别用目测法比较不同组三次重建所得锥体束形态学有无差异。
结果：
1、同一测量者对单次扫描所测得数据的稳定性
(1)同一测量者在双侧半球的七个不同部位三次测量所得的ADC值及FA值符合正态分布。同一测量者在相同部位三次测量所得ADC值、FA值差异均无统计学意义(P≥0.682)。
(2)不同部位3次测量的信度分析显示有较好的一致性。Alpha系数均大于0.947；ICC均大于0.939,显示同一测量者三次测量有较高的信度和可重复性。在不同部位三次测量所得ADC值及FA值的变异系数CV均小于1.8%,显示三次测量变异程度较小。
2、不同测量者对单次扫描所测得数据的稳定性
(1)三个不同测量者在七个不同部位测量所得的ADC值及FA值符合正态分布。3名测量者在相同部位测量ADC、FA值,差异均无统计学意义,最小P值为0.135(P>0.05)。
(2)不同部位3名测量者间所得数据的信度分析显示较好的一致性,Alpha系数在3名测量者间均大于0.823；ICC均大于0.833,显示不同测量者间有较高的信度和可重复性。在不同部位3名测量者所得ADC值及FA值的变异系数小于1.9%,显示三次测量数据变异程度较小。
3、不同时间点三次扫描所得数据的稳定性
(1)三个不同时间点扫描所得数据在七个不同部位测量所得的ADC值及FA值,除了半卵圆中心、内囊后肢、豆状核及丘脑四个位置的ADC值不满足正态分布以外,其他部位的ADC值及FA值均符合正态分布。比较3次扫描在相同部位的ADC、FA值,差异均无统计学意义,最小P值为0.392(P>0.05)。
(2)3次扫描所得数据具有较好的一致性,Alpha系数均大于0.801；ICC均大于0.796,除了尾状核头、豆状核及丘脑区Alpha系数、ICC小于0.9,其余部位ADC值及FA值组内相关系数均大于0.9,显示3次不同时间点扫描数据间有较高的信度和可重复性。在不同部位3次扫描所得ADC值及FA值得变异系数CV均小于1.8%,显示三次测量数据变异程度较小。
4、测量者内部、不同测量者间以及不同扫描间DTT重建所得锥体束均有较高一致性及可重复性。
结论：
1、3.0T磁共振DTI能够很好的在分子层面的基础上显示大脑灰白质的解剖结构,为精确定位及定量分析脑显微结构提供条件。
2、同一测量者内部、不同测量者间以及不同时间点采集所得不同解剖部位的数据间均有较高的稳定性和准确性,为DTI在神经系统疾病的诊断及监测治疗效果提供了理论依据。
3、DTT可以三维立体观察锥体束形态学特点,为锥体束相关性疾病的研究提供了一种较为直观的方法,该方法具有较高的可重复性。
第二部分正常成人锥体束年龄相关性变化的DTI研究
目的：
利用3.0T超高场磁共振扫描仪进行DTI研究,探讨正常成人锥体束的各向异性及扩散特征,描述其部分各向异性(FA)和表观扩散系数(ADC)及其与年龄之间的相关性变化。
材料与方法：
95例正常成人行MR检查,其中男47例,女48例,年龄20～79岁,平均44.9岁。所有研究对象均无神经系统或影响神经系统的疾病。将研究对象按年龄分为3组：20-39岁为青年组(50例)、40-59岁为中年组(25例)、60岁及以上为老年组(20例)。所有受试对象均行常规MR检查和DTI检查(同第一部分)。分别用Functool软件的自由笔在半卵圆中心、内囊后肢、大脑脚层面的彩色编码图上描出锥体束,测量其FA值及ADC值。描绘出不同脑组织结构的扩散及各向异性特征,并对其FA和ADC值进行两两比较；对每个部位的FA、ADC值均进行与年龄的相关性分析,并分别进行三个组的组间比较,P值<0.05认为差异-有统计学意义。
结果：
1、不同层面正常锥体束的各向异性及扩散特征
(1)左右半球双侧对称部位的FA、ADC值差异均无统计学意义(P>0.05)。男性与女性同一部位的FA、ADC值间差异无统计学意义(P>0.05)。
(2)不同层面锥体束之间的FA、ADC值差异有统计学意义。两两比较发现不同层面锥体束的FA值之间的差异均具有统计学意义(P<0.001)。不同层面锥体束ADC值间两两比较差异均具有统计学意义(P<0.001)。
(3)得出不同年龄组不同层面锥体束的FA、ADC值((?)±s)。
2、大脑不同层面锥体束FA、ADC值与年龄因素的相关性
(1)随着年龄的增加,半卵圆中心及内囊后肢的FA值与年龄呈负相关,相关性不是很强,大脑脚的FA值随年龄的增加有减低的趋势,但无统计学意义。
(2)半卵圆中心的ADC值与年龄呈正相关,相关性不是很强,内囊后肢的ADC值呈增加的趋势,大脑脚的ADC值呈减低趋势,但均无统计学意义。
3、各年龄组间不同层面锥体束FA、MD值的比较
(1)FA值的组间比较：半卵圆中心以及内囊后肢层面的FA值各年龄组间的差异具有统计学意义。
(2)ADC值的组间比较：半卵圆中心、内囊后肢及大脑脚层面锥体束ADC值在各组间差异均无统计学意义。
结论：
1、获得了3.0TMR检查条件下不同年龄组正常成人锥体束的FA、ADC参数的正常值,为临床研究锥体束相关疾病提供了参考信息。
2、正常成人锥体束的各向异性与年龄有相关性,并且存在一定的规律。随着年龄的增长,锥体束的不同层面的FA值会降低,ADC值会增高。
3、在不同年龄组间,大多数脑结构的FA、ADC值表现为老年组与青、中年组之间的差异,这说明在60岁以后正常老年人的大脑显微结构发生了显著变化,这种正常的老年性表现有助于与其他神经退行性疾病相鉴别。
第三部分脑梗死的DTI初步研究
目的：
利用3.0TMR进行脑梗死的DTI研究。利用DTT研究梗死灶与锥体束的关系,用FA、ADC及本征矢量定量评价受累锥体束的顺行性和逆行性变性,并研究康复治疗前后患侧及健侧锥体束显微结构的变化。
材料与方法：
对37例脑梗死患者进行DTI检查,其中男24例,女13例,年龄31～80岁,平均44.9岁。根据纤维束成像(DTT)梗死灶与锥体束的关系分为受压组和破坏组,受压组18例,破坏组19例。所有患者均在发病1周以内行常规MR检查及DTI检查,检查当天由神经内科医师进行神经功能评分,采用美国国立卫生研究院卒中量表(NIHSS).破坏组中11例病人发病3～6个月以后行第二次常规MRI及DTI检查。分别于患侧及健侧半球的半卵圆中心、内囊后肢、大脑脚放置感兴趣区。重建出患侧的锥体束,观察与梗死灶的关系及锥体束的完整性。比较患侧、健侧半球间同一解剖部位的FA、ADC及本征矢量值；对受压组及破坏组患侧、健侧的DTI参数及NIHSS评分进行比较；比较破坏组前后两次检查患侧、健侧的FA、ADC及本征矢量值。P值<0.05认为差异有统计学意义。
结果：
1、受压组、破坏组锥体束形态学观察及两组受累锥体束DTI参数的比较
(1)破坏组DTT显示患侧锥体束部分缺失,局部纤维束连续性中断。受压组DTT显示患侧锥体束与梗死灶相邻,锥体束形态保持完整。
(2)两组双侧锥体束的FA值差异具有统计学意义,ADC值在双侧大脑半球间差异无统计学意义；
(3)锥体束FA值在大脑脚层面两组患侧间差异具有统计学意义,受压组FA值要高于破坏组。锥体束ADC值在两组健侧半卵圆中心层面及患侧大脑脚层面差异具有统计学意义。破坏组及受压组NIHSS评分差异具有统计学意义。
2、锥体束破坏组治疗前后患侧及健侧锥体束动态变化
治疗前后两次DTI检查患侧半球间及健侧半球间FA值差异具有统计学意义,在患侧锥体束FA值呈现降低的趋势,健侧FA值呈增高的趋势；
结论：
1、扩散张量纤维束成像能够反映常规MRI所发现不了的锥体束变化,通过三维重建可以显示梗死灶对锥体束的影响,判断锥体束破坏或者受压,有利于预后判断。
2、DTI可以对受累锥体束做出定量评价,在脑梗死早期受压组锥体束FA值要高于破坏组锥体束,破坏组患侧锥体束FA值随着时间的推移有降低的趋势。可用FA值来定量评价锥体束受累程度。
3、健侧锥体束FA值随着时间的推移有升高趋势,有助于解释健侧半球在脑梗死患者患侧肢体康复中的作用,配合fMRI有助于揭示神经功能可塑性。
Part one:The repeatability study of normal adult brain with DTI
Objective:To evaluated intra-rater, inter-rater, and between-scan reproducibility, through measure the FA/ADC value of white matter fibers and gray matter nucleus with a clinical diffusion tensor imaging (DTI) protocol at 3.0T.
Materials and Methods:8 normal adults (3 men,5 women; age range 23～29 years, mean age 25.3 years) were included in this study. All subjects have no neurological diseases or disorders affect the central nervous system. The examination all with GE Signa Excite 3.0T using 8 channels head coil. Use of EPI sequence with diffusion sensitive gradients in 25 directions, b value is equal to 1000 s/mm2.
8 cases of subjects were performed three times DTI scan, we performed the first and second times of scan at the same day, and repeated the sequence to ensure the positioning line and location of the subjects consistency, a month later undergone the third scanning. With the help of AW4.3 workstation, using Functool software to obtain fractional anisotropy (FA) maps, apparent diffusion coefficient (ADC) maps and color coded the direction (DEC) maps. Placed regions of interest in seven different parts of bilateral hemispheres, respectively, using the software at different levels of color-coded map to delineate pyramidal tract. In order to compare the differences within the surveyor, a doctor measured the FA and ADC values three times in different parts of brain on eight subjects for the first time scan. In order to compare the differences between raters, three experienced radiologists measured the FA and ADC values of different structures of the eight subjects for the data first time scan on the same day. In order to compare the degree of variation of the data obtained at different scanning time points, one rater measured the three times scanning data of the eight subjects in the same day. We used the reliability analysis to compare reproducible and stability intra-rater, inter-rater and between-scan, and compare between every two groups (intra-rater, inter-rater and between-scan). Meanwhile we make comparision of pyramidal tract through diffusion tensor tractography reconstruction.
Results: 1. The stability and precision of intra-rater on the data of single-scan
(1) The ADC and the FA values measured by one rater with normal distribution. The same rater three times measurement acquired the ADC /FA values were not statistically significant difference (P≥0.682).
(2) The reliability analysis showed a better consistency of three times measurements in different parts of brain. Alpha coefficients were greater than 0.947; intraclass correlation coefficients (ICC) were greater than 0.939, showed that intra-rater there have a higher reliability and repeatability. The coefficient of variation (CV) of ADC and FA values between three times measurements in different parts of brain were less than 1.8%, indicating that variation of the three times measurements to a lesser extent.
2. The stability and precision of inter-rater on the data of single-scan
(1) The ADC and FA values measured by three raters in line with the normal distribution. Comparison of the ADC and FA values of the three measurements by different raters at the same structures, have no statistically significant difference, and the minimum P value is 0.135 (P> 0.05).
(2) Reliability analysis showed three measurements in different parts of brain of inter-rater have good agreement, Alpha coefficient between the 3 measurements were greater than 0.823; ICC were greater than 0.833, showing the different measurements between those who have a higher reliability and repeatability. The variant of ADC and the FA values acquired in different parts of the brain by different raters showed is less than 1.9%.
3. The stability and precision of between-scan
(1) Apart from the ADC values of centrum semiovale, posterior limb of internal capsule, lentiform nucleus and thalamic does not meet the normal distribution, other parts of the ADC and the FA values are in line with the normal distribution. Compare the ADC, FA values of three scans, there have no statistically significant difference, the minimum P value is 0.392 (P> 0.05).
(2) The reliability analysis showed good agreement between 3 times scans, Alpha coefficients were greater than 0.801; intraclass correlation coefficients were greater than 0.796. In addition to the Alpha coefficient, ICC of the head of caudate nucleus, lenticular nucleus and thalamus is less than 0.9, the remaining structures of ADC and the FA values of intraclass correlation coefficients were larger than 0.9, showed a higher reliability and repeatability between the three times scan. In the three scans obtained in different parts, the coefficient of variation of ADC and FA values were less than 1.8%, indicating that variation of the three scans to a lesser extent.
Conclusions:1.3.0T magnetic resonance DTI technology can be a very good method to display the anatomy of the brain gray and white matter on molecular level, which can precise location for the study and quantitative analysis of micro-structural changes in the brain.
2. Intra-rater, inter-rater and between-scan have a higher stability and accuracy, provides a theoretical basis for the diagnosis and treatment monitoring in the nervous system.
3. With the help of diffusion tensor tractography we can observe the pyramidal tract hree dimensional, provide a visualized method for the study of disease correlated with pyramidal.
Part two:DTI study of age-related changes of pyramidal tract of normal adult
Objectives:To investigate the anisotropy and diffusion characteristics of pyramidal tract of normal adult, describe the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) and its relationship with age.
Materials and Methods:95 cases of normal adult undergone MR examination, 47 cases were male and 48 cases female, aged from 20 to 79 years with an average 44.9 years. All subjects have no neurological diseases or disorders affect the central nervous system. The studies were divided into three groups according to age:20-39 years old for the young group (50 cases),40-59 years old middle-aged group (25 cases),60 years and over for the older group (20 cases). All Subjects underwent routine MR examination and DTI inspection (same with part one). With the help of Functool software, we delineate pyramidal tract on three planes (centrum semiovale, posterior limb of internal capsule and pedunculus cerebri). Then we measured the FA and ADC values. Depicts the diffusion and anisotropy characteristics of different brain structures, then the FA/ADC value of different brain structures of normal adults were compared multiply. They also were correlated with the age respectively and compared among three groups. P value less than 0.05 was considered as statistical significance..
Results:1.The diffusion and anisotropic characteristics of normal pyramidal tract
(1) The FA, ADC values of bilateral hemispheric symmetrical parts were not statistically significant difference (P> 0.05). The FA/ADC value was no significant difference between Men and women (P> 0.05).
(2) The FA/ADC values of the difference planes were statistically significant.
(3) To arrive at the FA/ADC value (x±s) of normal pyramidal tract on different levels.
2. The correlation of FA/ADC of pyramidal tract in different structures with age
(1) The FA value of centrum semiovale and posterior limb of internal capsule were negatively correlated with age, the FA values in pedunculus cerebri have a downward trend with age increase and have no statistical significance.
(2)The ADC value of centrum semiovale were positively correlated with age, the ADC values in posterior limb of internal capsule have a incremental trend and have a downward trend in pedunculus cerebri with age increase.
3. The comparison of FA and ADC of pyramidal tract in different levels among age groups
(1) FA values between the groups:the FA value in centrum semiovale and posterior limb of internal capsule in all age groups was statistically significant difference.
(2) ADC values between the groups:The ADC value of pyramidal tract in all levels has no statistically significant difference.
Conclusions:1.The pyramidal tract has different anisotropic characteristics at different levels; there have higher level in posterior limb of internal capsule. With 3.0T MR scanner obtained the normal parameters of normal FA, ADC value in normal adults of different age groups. Provide important reference information for clinical studies about pyramidal tract-related diseases.
2. Anisotropy of pyramidal tract in normal adult is related with age, and there is a certain patterns, with age increase, there will be a lower FA values and an increased ADC values.
3. In different age groups, the FA, ADC value in most of the brain structure is expressed as the difference between elderly groups with middle-aged group and younger age group. This shows that after the age of 60 normal elderly brain micro-structures have a significant change, this normal age-related neurodegenerative can make for differentiation diagnosis with other similar nervous degenerative disease.
Part three:Preliminary DTI study of cerebral infarction DTI
Objective: Study of cerebral infarction with 3.0TMR for the use of DTI technology. Study the relationship between pyramidal tract with infarction lesions use DTT. Use FA, ADC, and eigenvector of involvement pyramidal tract to quantitative evaluation of anterograde and retrograde degeneration. Studies microscopic level changes of ipsilateral and contralateral pyramidal tract before and after rehabilitation.
Materials and Methods:37 infraction patients (24 men,13 women; age range 31～80 years, mean age 44.9) were included in this study. According to fiber tractography (DTT) and based on the relationship between pyramidal tract with infarction, Divided into two groups (compression group and the destruction groups), pressure group have 18 patients, destruction group 19 cases. All patients were undergone conventional MR examination and DTI examination within 1 week the onset of illness. Using the U.S. National Institutes of Health Stroke Scale (NIHSS) standard acquire the score of every patient by a doctor of neurology the same day of examination. In destruction group there have 11 cases of patients undergone second times regular MRI and DTI examination after 3 to 6 months of onset. Place ROIs on centrum semiovale, posterior limb of internal capsule and cerebral peduncle in ipsilateral and contralateral hemispheres, respectively. Reconstruct the pyramidal tract of the affected side; observe the relationship between infarction and the pyramidal tract and the integrity of pyramidal tract. Compare the FA, ADC and eigenvector value of the same anatomical structures of affected side with uninjured side. Compared DTI parameters and NIHSS score of two groups. Compare the FA, ADC and eigenvector of ipsilateral, contralateral of two groups. P values are less than 0.05 was considered statistically significant difference.
Conclusion:1. Morphological characteristics of involved pyramidal tract in two groups and the comparison of DTI parameters between two groups
(1) Destruction groups DTT shows that the destruction of affected pyramidal tract partial deletion, partial interruption of the continuity of fiber bundles. In pressure group DTT showed infarction close to pyramidal tract and the pyramidal shape keep intact.
(2) There has a statistically significant difference in FA values of bilateral pyramidal tract in two groups, ADC values in the bilateral cerebral hemispheres was no significant difference.
(3) There has statistically significant difference between the two groups about the FA values of pyramidal tract in the ipsilateral cerebral peduncle level; compression group is higher than destruction group. There have statically significant difference between two groups at centrum semiovale level (uninjured side) and cerebral peduncle level (affected side). There has statically significant difference between two groups in NIHSS score.
2. The DTI study of pyramidal tract of affected side and contralateral before and after treatment
DTI examination shows that the FA values have statistically significant difference before and after treatment between ipsilateral- ipsilateral and contralateral-contralateral hemispheres. The FA value in affected side shows a falling trend and in uninjured side shows a rising trend.
Conclusion:1. Diffusion tensor fiber tractography can found the changes of pyramidal tract which conventional MRI can not be found; through three-dimensional reconstruction can show the relationship of infarction lesions between with the pyramidal tract. Determine pyramidal tract damage or compression is conducive to prognosis judgments.
2. DTI can make a quantitative evaluation of involvement pyramidal tract; in early stage of infraction the FA value in compression is higher than damage groups. The FA value of affected pyramidal tract in damage groups has a falling trend, and we can use FA to quantitative evaluate the degree of pyramidal tract being involved.
3. The FA value of pyramidal tract in uninjured side has a rising trend, can help explain the role of uninjured hemisphere in patients with cerebral infarction in the course of rehabilitation. With the help of fMRI can reveal the plasticity of neural function.
目的：
利用3.0T超高场磁共振扫描仪进行DTI技术在中枢神经系统的应用研究,通过测量不同部位灰白质的FA值及ADC值,探讨同一测量者内部、不同测量者间及不同时间点扫描所得DTI数据的一致性及可重复性。
材料与方法：
对8例正常成人行MR检查,男3例,女5例,年龄23～29岁,平均25.3岁。所有研究对象均无神经系统或影响神经系统的疾病。使用GE signa Excite3.0T超导型核磁共振扫描仪,8通道头部线圈。采用EPI序列,在25个方向上施加扩散敏感梯度,扩散加权系数(b值)为1000s/mm2。
8例受试者均行3次DTI扫描,前两次扫描为当天重复扫描两次,保证了定位线及受试者位置的一致性,一个月以后进行第三次扫描。在AW4.3工作站上,利用Functool软件获得部分各向异性(FA)图、表观扩散系数(ADC)图及方向编码彩色(DEC)图。分别于双侧半球的七个不同部位放置感兴趣区。为了比较测量者内部的差异,由同一名医生对8位受试者的第一次扫描数据不同部位的FA值及ADC值测量三次；为了比较测量者之间的差异,由三位有经验的放射科医师对8位受试者第一次扫描数据进行测量,在同一天进行；为了比较不同扫描时间点所得数据的变异程度,由同一位医师对8位受试者三次扫描所得数据进行测量,在同一天进行。采用信度分析比较测量者内部、不同测量者间及不同扫描间的可重复性及稳定性,并分别进行三次测量的组间比较(测量者内部、测量者间及扫描间)。
为了比较重建者内部锥体束DTT重建的可重复性,由同一名医生对8位受试者的第一次扫描数据进行三次DTT重建；为了比较重建者之间的差异,由三位有经验的放射科医师对8位受试者第一次扫描数据进行DTT重建,在同一天进行；为了比较不同扫描时间点所得数据DTT重建的稳定性,由同一位医师对8位受试者三次扫描所得数据进行DTT重建,在同一天进行。分别用目测法比较不同组三次重建所得锥体束形态学有无差异。
结果：
1、同一测量者对单次扫描所测得数据的稳定性
(1)同一测量者在双侧半球的七个不同部位三次测量所得的ADC值及FA值符合正态分布。同一测量者在相同部位三次测量所得ADC值、FA值差异均无统计学意义(P≥0.682)。
(2)不同部位3次测量的信度分析显示有较好的一致性。Alpha系数均大于0.947；ICC均大于0.939,显示同一测量者三次测量有较高的信度和可重复性。在不同部位三次测量所得ADC值及FA值的变异系数CV均小于1.8%,显示三次测量变异程度较小。
2、不同测量者对单次扫描所测得数据的稳定性
(1)三个不同测量者在七个不同部位测量所得的ADC值及FA值符合正态分布。3名测量者在相同部位测量ADC、FA值,差异均无统计学意义,最小P值为0.135(P>0.05)。
(2)不同部位3名测量者间所得数据的信度分析显示较好的一致性,Alpha系数在3名测量者间均大于0.823；ICC均大于0.833,显示不同测量者间有较高的信度和可重复性。在不同部位3名测量者所得ADC值及FA值的变异系数小于1.9%,显示三次测量数据变异程度较小。
3、不同时间点三次扫描所得数据的稳定性
(1)三个不同时间点扫描所得数据在七个不同部位测量所得的ADC值及FA值,除了半卵圆中心、内囊后肢、豆状核及丘脑四个位置的ADC值不满足正态分布以外,其他部位的ADC值及FA值均符合正态分布。比较3次扫描在相同部位的ADC、FA值,差异均无统计学意义,最小P值为0.392(P>0.05)。
(2)3次扫描所得数据具有较好的一致性,Alpha系数均大于0.801；ICC均大于0.796,除了尾状核头、豆状核及丘脑区Alpha系数、ICC小于0.9,其余部位ADC值及FA值组内相关系数均大于0.9,显示3次不同时间点扫描数据间有较高的信度和可重复性。在不同部位3次扫描所得ADC值及FA值得变异系数CV均小于1.8%,显示三次测量数据变异程度较小。
4、测量者内部、不同测量者间以及不同扫描间DTT重建所得锥体束均有较高一致性及可重复性。
结论：
1、3.0T磁共振DTI能够很好的在分子层面的基础上显示大脑灰白质的解剖结构,为精确定位及定量分析脑显微结构提供条件。
2、同一测量者内部、不同测量者间以及不同时间点采集所得不同解剖部位的数据间均有较高的稳定性和准确性,为DTI在神经系统疾病的诊断及监测治疗效果提供了理论依据。
3、DTT可以三维立体观察锥体束形态学特点,为锥体束相关性疾病的研究提供了一种较为直观的方法,该方法具有较高的可重复性。
第二部分正常成人锥体束年龄相关性变化的DTI研究
目的：
利用3.0T超高场磁共振扫描仪进行DTI研究,探讨正常成人锥体束的各向异性及扩散特征,描述其部分各向异性(FA)和表观扩散系数(ADC)及其与年龄之间的相关性变化。
材料与方法：
95例正常成人行MR检查,其中男47例,女48例,年龄20～79岁,平均44.9岁。所有研究对象均无神经系统或影响神经系统的疾病。将研究对象按年龄分为3组：20-39岁为青年组(50例)、40-59岁为中年组(25例)、60岁及以上为老年组(20例)。所有受试对象均行常规MR检查和DTI检查(同第一部分)。分别用Functool软件的自由笔在半卵圆中心、内囊后肢、大脑脚层面的彩色编码图上描出锥体束,测量其FA值及ADC值。描绘出不同脑组织结构的扩散及各向异性特征,并对其FA和ADC值进行两两比较；对每个部位的FA、ADC值均进行与年龄的相关性分析,并分别进行三个组的组间比较,P值<0.05认为差异-有统计学意义。
结果：
1、不同层面正常锥体束的各向异性及扩散特征
(1)左右半球双侧对称部位的FA、ADC值差异均无统计学意义(P>0.05)。男性与女性同一部位的FA、ADC值间差异无统计学意义(P>0.05)。
(2)不同层面锥体束之间的FA、ADC值差异有统计学意义。两两比较发现不同层面锥体束的FA值之间的差异均具有统计学意义(P<0.001)。不同层面锥体束ADC值间两两比较差异均具有统计学意义(P<0.001)。
(3)得出不同年龄组不同层面锥体束的FA、ADC值((?)±s)。
2、大脑不同层面锥体束FA、ADC值与年龄因素的相关性
(1)随着年龄的增加,半卵圆中心及内囊后肢的FA值与年龄呈负相关,相关性不是很强,大脑脚的FA值随年龄的增加有减低的趋势,但无统计学意义。
(2)半卵圆中心的ADC值与年龄呈正相关,相关性不是很强,内囊后肢的ADC值呈增加的趋势,大脑脚的ADC值呈减低趋势,但均无统计学意义。
3、各年龄组间不同层面锥体束FA、MD值的比较
(1)FA值的组间比较：半卵圆中心以及内囊后肢层面的FA值各年龄组间的差异具有统计学意义。
(2)ADC值的组间比较：半卵圆中心、内囊后肢及大脑脚层面锥体束ADC值在各组间差异均无统计学意义。
结论：
1、获得了3.0TMR检查条件下不同年龄组正常成人锥体束的FA、ADC参数的正常值,为临床研究锥体束相关疾病提供了参考信息。
2、正常成人锥体束的各向异性与年龄有相关性,并且存在一定的规律。随着年龄的增长,锥体束的不同层面的FA值会降低,ADC值会增高。
3、在不同年龄组间,大多数脑结构的FA、ADC值表现为老年组与青、中年组之间的差异,这说明在60岁以后正常老年人的大脑显微结构发生了显著变化,这种正常的老年性表现有助于与其他神经退行性疾病相鉴别。
第三部分脑梗死的DTI初步研究
目的：
利用3.0TMR进行脑梗死的DTI研究。利用DTT研究梗死灶与锥体束的关系,用FA、ADC及本征矢量定量评价受累锥体束的顺行性和逆行性变性,并研究康复治疗前后患侧及健侧锥体束显微结构的变化。
材料与方法：
对37例脑梗死患者进行DTI检查,其中男24例,女13例,年龄31～80岁,平均44.9岁。根据纤维束成像(DTT)梗死灶与锥体束的关系分为受压组和破坏组,受压组18例,破坏组19例。所有患者均在发病1周以内行常规MR检查及DTI检查,检查当天由神经内科医师进行神经功能评分,采用美国国立卫生研究院卒中量表(NIHSS).破坏组中11例病人发病3～6个月以后行第二次常规MRI及DTI检查。分别于患侧及健侧半球的半卵圆中心、内囊后肢、大脑脚放置感兴趣区。重建出患侧的锥体束,观察与梗死灶的关系及锥体束的完整性。比较患侧、健侧半球间同一解剖部位的FA、ADC及本征矢量值；对受压组及破坏组患侧、健侧的DTI参数及NIHSS评分进行比较；比较破坏组前后两次检查患侧、健侧的FA、ADC及本征矢量值。P值<0.05认为差异有统计学意义。
结果：
1、受压组、破坏组锥体束形态学观察及两组受累锥体束DTI参数的比较
(1)破坏组DTT显示患侧锥体束部分缺失,局部纤维束连续性中断。受压组DTT显示患侧锥体束与梗死灶相邻,锥体束形态保持完整。
(2)两组双侧锥体束的FA值差异具有统计学意义,ADC值在双侧大脑半球间差异无统计学意义；
(3)锥体束FA值在大脑脚层面两组患侧间差异具有统计学意义,受压组FA值要高于破坏组。锥体束ADC值在两组健侧半卵圆中心层面及患侧大脑脚层面差异具有统计学意义。破坏组及受压组NIHSS评分差异具有统计学意义。
2、锥体束破坏组治疗前后患侧及健侧锥体束动态变化
治疗前后两次DTI检查患侧半球间及健侧半球间FA值差异具有统计学意义,在患侧锥体束FA值呈现降低的趋势,健侧FA值呈增高的趋势；
结论：
1、扩散张量纤维束成像能够反映常规MRI所发现不了的锥体束变化,通过三维重建可以显示梗死灶对锥体束的影响,判断锥体束破坏或者受压,有利于预后判断。
2、DTI可以对受累锥体束做出定量评价,在脑梗死早期受压组锥体束FA值要高于破坏组锥体束,破坏组患侧锥体束FA值随着时间的推移有降低的趋势。可用FA值来定量评价锥体束受累程度。
3、健侧锥体束FA值随着时间的推移有升高趋势,有助于解释健侧半球在脑梗死患者患侧肢体康复中的作用,配合fMRI有助于揭示神经功能可塑性。
Part one:The repeatability study of normal adult brain with DTI
Objective:To evaluated intra-rater, inter-rater, and between-scan reproducibility, through measure the FA/ADC value of white matter fibers and gray matter nucleus with a clinical diffusion tensor imaging (DTI) protocol at 3.0T.
Materials and Methods:8 normal adults (3 men,5 women; age range 23～29 years, mean age 25.3 years) were included in this study. All subjects have no neurological diseases or disorders affect the central nervous system. The examination all with GE Signa Excite 3.0T using 8 channels head coil. Use of EPI sequence with diffusion sensitive gradients in 25 directions, b value is equal to 1000 s/mm2.
8 cases of subjects were performed three times DTI scan, we performed the first and second times of scan at the same day, and repeated the sequence to ensure the positioning line and location of the subjects consistency, a month later undergone the third scanning. With the help of AW4.3 workstation, using Functool software to obtain fractional anisotropy (FA) maps, apparent diffusion coefficient (ADC) maps and color coded the direction (DEC) maps. Placed regions of interest in seven different parts of bilateral hemispheres, respectively, using the software at different levels of color-coded map to delineate pyramidal tract. In order to compare the differences within the surveyor, a doctor measured the FA and ADC values three times in different parts of brain on eight subjects for the first time scan. In order to compare the differences between raters, three experienced radiologists measured the FA and ADC values of different structures of the eight subjects for the data first time scan on the same day. In order to compare the degree of variation of the data obtained at different scanning time points, one rater measured the three times scanning data of the eight subjects in the same day. We used the reliability analysis to compare reproducible and stability intra-rater, inter-rater and between-scan, and compare between every two groups (intra-rater, inter-rater and between-scan). Meanwhile we make comparision of pyramidal tract through diffusion tensor tractography reconstruction.
Results: 1. The stability and precision of intra-rater on the data of single-scan
(1) The ADC and the FA values measured by one rater with normal distribution. The same rater three times measurement acquired the ADC /FA values were not statistically significant difference (P≥0.682).
(2) The reliability analysis showed a better consistency of three times measurements in different parts of brain. Alpha coefficients were greater than 0.947; intraclass correlation coefficients (ICC) were greater than 0.939, showed that intra-rater there have a higher reliability and repeatability. The coefficient of variation (CV) of ADC and FA values between three times measurements in different parts of brain were less than 1.8%, indicating that variation of the three times measurements to a lesser extent.
2. The stability and precision of inter-rater on the data of single-scan
(1) The ADC and FA values measured by three raters in line with the normal distribution. Comparison of the ADC and FA values of the three measurements by different raters at the same structures, have no statistically significant difference, and the minimum P value is 0.135 (P> 0.05).
(2) Reliability analysis showed three measurements in different parts of brain of inter-rater have good agreement, Alpha coefficient between the 3 measurements were greater than 0.823; ICC were greater than 0.833, showing the different measurements between those who have a higher reliability and repeatability. The variant of ADC and the FA values acquired in different parts of the brain by different raters showed is less than 1.9%.
3. The stability and precision of between-scan
(1) Apart from the ADC values of centrum semiovale, posterior limb of internal capsule, lentiform nucleus and thalamic does not meet the normal distribution, other parts of the ADC and the FA values are in line with the normal distribution. Compare the ADC, FA values of three scans, there have no statistically significant difference, the minimum P value is 0.392 (P> 0.05).
(2) The reliability analysis showed good agreement between 3 times scans, Alpha coefficients were greater than 0.801; intraclass correlation coefficients were greater than 0.796. In addition to the Alpha coefficient, ICC of the head of caudate nucleus, lenticular nucleus and thalamus is less than 0.9, the remaining structures of ADC and the FA values of intraclass correlation coefficients were larger than 0.9, showed a higher reliability and repeatability between the three times scan. In the three scans obtained in different parts, the coefficient of variation of ADC and FA values were less than 1.8%, indicating that variation of the three scans to a lesser extent.
Conclusions:1.3.0T magnetic resonance DTI technology can be a very good method to display the anatomy of the brain gray and white matter on molecular level, which can precise location for the study and quantitative analysis of micro-structural changes in the brain.
2. Intra-rater, inter-rater and between-scan have a higher stability and accuracy, provides a theoretical basis for the diagnosis and treatment monitoring in the nervous system.
3. With the help of diffusion tensor tractography we can observe the pyramidal tract hree dimensional, provide a visualized method for the study of disease correlated with pyramidal.
Part two:DTI study of age-related changes of pyramidal tract of normal adult
Objectives:To investigate the anisotropy and diffusion characteristics of pyramidal tract of normal adult, describe the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) and its relationship with age.
Materials and Methods:95 cases of normal adult undergone MR examination, 47 cases were male and 48 cases female, aged from 20 to 79 years with an average 44.9 years. All subjects have no neurological diseases or disorders affect the central nervous system. The studies were divided into three groups according to age:20-39 years old for the young group (50 cases),40-59 years old middle-aged group (25 cases),60 years and over for the older group (20 cases). All Subjects underwent routine MR examination and DTI inspection (same with part one). With the help of Functool software, we delineate pyramidal tract on three planes (centrum semiovale, posterior limb of internal capsule and pedunculus cerebri). Then we measured the FA and ADC values. Depicts the diffusion and anisotropy characteristics of different brain structures, then the FA/ADC value of different brain structures of normal adults were compared multiply. They also were correlated with the age respectively and compared among three groups. P value less than 0.05 was considered as statistical significance..
Results:1.The diffusion and anisotropic characteristics of normal pyramidal tract
(1) The FA, ADC values of bilateral hemispheric symmetrical parts were not statistically significant difference (P> 0.05). The FA/ADC value was no significant difference between Men and women (P> 0.05).
(2) The FA/ADC values of the difference planes were statistically significant.
(3) To arrive at the FA/ADC value (x±s) of normal pyramidal tract on different levels.
2. The correlation of FA/ADC of pyramidal tract in different structures with age
(1) The FA value of centrum semiovale and posterior limb of internal capsule were negatively correlated with age, the FA values in pedunculus cerebri have a downward trend with age increase and have no statistical significance.
(2)The ADC value of centrum semiovale were positively correlated with age, the ADC values in posterior limb of internal capsule have a incremental trend and have a downward trend in pedunculus cerebri with age increase.
3. The comparison of FA and ADC of pyramidal tract in different levels among age groups
(1) FA values between the groups:the FA value in centrum semiovale and posterior limb of internal capsule in all age groups was statistically significant difference.
(2) ADC values between the groups:The ADC value of pyramidal tract in all levels has no statistically significant difference.
Conclusions:1.The pyramidal tract has different anisotropic characteristics at different levels; there have higher level in posterior limb of internal capsule. With 3.0T MR scanner obtained the normal parameters of normal FA, ADC value in normal adults of different age groups. Provide important reference information for clinical studies about pyramidal tract-related diseases.
2. Anisotropy of pyramidal tract in normal adult is related with age, and there is a certain patterns, with age increase, there will be a lower FA values and an increased ADC values.
3. In different age groups, the FA, ADC value in most of the brain structure is expressed as the difference between elderly groups with middle-aged group and younger age group. This shows that after the age of 60 normal elderly brain micro-structures have a significant change, this normal age-related neurodegenerative can make for differentiation diagnosis with other similar nervous degenerative disease.
Part three:Preliminary DTI study of cerebral infarction DTI
Objective: Study of cerebral infarction with 3.0TMR for the use of DTI technology. Study the relationship between pyramidal tract with infarction lesions use DTT. Use FA, ADC, and eigenvector of involvement pyramidal tract to quantitative evaluation of anterograde and retrograde degeneration. Studies microscopic level changes of ipsilateral and contralateral pyramidal tract before and after rehabilitation.
Materials and Methods:37 infraction patients (24 men,13 women; age range 31～80 years, mean age 44.9) were included in this study. According to fiber tractography (DTT) and based on the relationship between pyramidal tract with infarction, Divided into two groups (compression group and the destruction groups), pressure group have 18 patients, destruction group 19 cases. All patients were undergone conventional MR examination and DTI examination within 1 week the onset of illness. Using the U.S. National Institutes of Health Stroke Scale (NIHSS) standard acquire the score of every patient by a doctor of neurology the same day of examination. In destruction group there have 11 cases of patients undergone second times regular MRI and DTI examination after 3 to 6 months of onset. Place ROIs on centrum semiovale, posterior limb of internal capsule and cerebral peduncle in ipsilateral and contralateral hemispheres, respectively. Reconstruct the pyramidal tract of the affected side; observe the relationship between infarction and the pyramidal tract and the integrity of pyramidal tract. Compare the FA, ADC and eigenvector value of the same anatomical structures of affected side with uninjured side. Compared DTI parameters and NIHSS score of two groups. Compare the FA, ADC and eigenvector of ipsilateral, contralateral of two groups. P values are less than 0.05 was considered statistically significant difference.
Conclusion:1. Morphological characteristics of involved pyramidal tract in two groups and the comparison of DTI parameters between two groups
(1) Destruction groups DTT shows that the destruction of affected pyramidal tract partial deletion, partial interruption of the continuity of fiber bundles. In pressure group DTT showed infarction close to pyramidal tract and the pyramidal shape keep intact.
(2) There has a statistically significant difference in FA values of bilateral pyramidal tract in two groups, ADC values in the bilateral cerebral hemispheres was no significant difference.
(3) There has statistically significant difference between the two groups about the FA values of pyramidal tract in the ipsilateral cerebral peduncle level; compression group is higher than destruction group. There have statically significant difference between two groups at centrum semiovale level (uninjured side) and cerebral peduncle level (affected side). There has statically significant difference between two groups in NIHSS score.
2. The DTI study of pyramidal tract of affected side and contralateral before and after treatment
DTI examination shows that the FA values have statistically significant difference before and after treatment between ipsilateral- ipsilateral and contralateral-contralateral hemispheres. The FA value in affected side shows a falling trend and in uninjured side shows a rising trend.
Conclusion:1. Diffusion tensor fiber tractography can found the changes of pyramidal tract which conventional MRI can not be found; through three-dimensional reconstruction can show the relationship of infarction lesions between with the pyramidal tract. Determine pyramidal tract damage or compression is conducive to prognosis judgments.
2. DTI can make a quantitative evaluation of involvement pyramidal tract; in early stage of infraction the FA value in compression is higher than damage groups. The FA value of affected pyramidal tract in damage groups has a falling trend, and we can use FA to quantitative evaluate the degree of pyramidal tract being involved.
3. The FA value of pyramidal tract in uninjured side has a rising trend, can help explain the role of uninjured hemisphere in patients with cerebral infarction in the course of rehabilitation. With the help of fMRI can reveal the plasticity of neural function.
引文
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[6]肖江喜,郭雪梅,王霄英,等.头部扩散张量磁共振成像扫描方案的优选.中国医学影像技术,2003,19：1433-1435.
[7]Yoshiura T, WU O, Zaheer A, et al. Highly diffusion-sensitized MRI of brain: dissociation of gray and white matter. Magn Reson Med,2001,45(5):734-740.
[8]Zhou XJ. Diffusion tensor MRI and functional connectivity.第十一届中华医学会放射学分会全国学术会议论文汇编,2003,32-33.
[9]Neil JJ, Siran SI, Mckinstry RC, et al. Normal brain in human newborns: apparent diffusion coefficient and diffusion anisotropy measured by using diffusion tensor MR imaging. Radiology,1998,209:57-66.
[10]Sehaefer PW, Grant PE, Gonzalez RG Diffusion weighted MR imaging of the brain. Radiology,2000,217:331-345.
[11]Le Bihan D, Turner R, Pekar J, et al. Diffusion and perfusion imaging by gradient sensitization: design, strategy and significance. J Magn Reson Imaging,1991; 1; 7-8.
[12]Cercignani M, Iannucci G, Rocca MA, et al. Pathologic damage in MS assessed by diffusion-weighted and magnetization transfer MRI. Neurology, 2000; 54:1139-1144.
[13]Nusbaum AO, Tang CY, Wei TC, et al. Whole-brain diffusion MR histogram differ between MS subtypes. Neurology,2000; 54:1421-1427.
[14]Cercignani M, Inglese M, Pagani E, et al. Mean diffusivity and fractional anisotropy histograms of patients with multiple sclerosis. Am J Neuroradiol, 2001; 22:952-958.
[15]Filippi M, Cercignani M, Inglese M, Horsfield MA, Comi G. Diffusion tensor magnetic resonance imaging in multiple sclerosis. Neurology,2001;56:304-311.
[16]Bammer R, Augustin M, Strasser-Fuchs S, et al. Magnetic resonance diffusion tensor imaging for characterizing diffuse and focal white matter abnormalities in multiple sclerosis. Magn Reson Med,2000;44:583-591
[17]Warach S, Dashe JF, Edelman RR. Clinical outcome in ischemic lesion predicted by early diffusion-weighted and perfusion magnetic resonance imaging:a preliminary analysis. J Cereb Blood Flow Metab,1996; 16:53-59.
[18]Liang ZJ, Zeng JS, Liu SR, et al. A prospective study of secondary degeneration following subcortical infarction using diffusion tensor imaging. J Neurol Neurosurg Psychiatry,2007,78:581-586.
[19]Bozzali M, Franceschi M, Falini A, et al. Quantification of tissue damage in AD using diffusion tensor and magnetization transfer MRI. Neurology,2001; 157:1135-1137.
[20]Filippi M, van Waesberghe JH, Horsfield MA, et al. Interscanner variation in brain MRI lesion load measurements in MS:implications for clinical trials. Neurology,1997; 49:371-377.
[21]Sormani MP, Iannucci G, Rocca MA, et al. Reproducibility of magnetization transfer ratio histogram-derived measures of the brain in healthy volunteers. AJNR Am J Neuroradiol,2000;21:133-136.
[22]Heim, S, Hahn, K, Samann, PG, et al. Assessing DTI data quality using bootstrap analysis. Magn. Reson. Med.2004,52,582-589.
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[29]Chenevert TL, Brunberg JA, Pipe JG. Ansiotropic diffusion within human white matter:demonstration with NMR techniques in vivo. Radiology,1990; 177:401-405.
[30]Hajnal JV, Doran M, Hall AS. MR imaging of anisotropically restricted diffusion of water in the nervous system:technical, anatomic, and pathologic considerations. J Comput Assisted Tomogr,1991; 15:1-18.
[31]Bammer R, Acar B, Moseley ME. In vivo MR tractography using difusion imaging. Eur J Radiol,2003,45(3):223-234.
[32]Mori S, van Zijl PCM. Fiber tracking:principles and strategiesa technical review. NMR Biomed.2002.15(7-8):468-480.
[33]MellMn ER, Mori s'Mukundan G'et al. Diffusion tensor MR imaging of the brain and white matter tractography.AJR.2002,178(1):3-16
[1]芮德源,陈立杰主编临床神经解剖学,人民卫生出版社,2007,9
[2]朱长庚主编神经解剖学,人民卫生出版社,2002,3
[3]Kim DS, KimM, Ronen I, et al. In vivo mapping of functional domains and axonal connectivity in cat visual cortex using magnetic resonance imaging [J]. Magn Reson Imaging,2003,21:1131-1140.
[4]Pierpaoli C, Jezzard P, Basser PJ, et al. Diffusion tensor MR imaging of the human brain [J]. Radiology,1996,201:637-648.
[5]王海燕,赵斌.颅脑磁共振张量成像应用进展[J].医学影像学杂志,2005,15：908-911.
[6]卢洁,李坤成.正常成人脑组织弥散的定量研究[J].中国医学影像技术,2003,19：975-977.
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[10]钟维佳,赵建农,谢微波,等.磁共振扩散张量成像对正常人脑结构的显示及各向异性研究.临床放射学杂志,2006,25(9)：807-10.
[11]Svennerholm L, Bostrom K, Jungbjer B. Changes in weight and compositions of major membrane components of human life of Swedes. Acta Neuropathol, 1997,94:345-352.
[12]Tang Y, Whitman GT, Lopez I, et al. Brain volume changes on longitudinal magnetic resonance imaging in normal older people. J Neuroimaging,2001;11: 393-400.
[13]Marner L, Nyengaard JR, Tang Y, et al. Marked loss of myelinated nerve fibres in the human brain with age. J Comp Neurol,2003; 462:144-152.
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[17]Nusbaum AO, Tang CY, Buchsbaum MS, et al. Regional and global changes in cerebral diffusion with normal aging. Am J Neuroradiol,2001,22(1):136-42.
[18]Aboitiz F, Rodriguez E, Olivares R, et al. Age-related changes in fiber composition of the human corpus callosum: sex differences. NeyrorePort,1996, 7:1761-4.
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[2]Chenevert TL, Brunberg JA, Pipe JG Anisotropic diffusion in human white matter:demonstration with MR techniques in vivo. Radiology,1990, 177:401-405.
[3]Pierpaoli C, Jezzard P, Basser PJ, et al. Diffusion tensor MR imaging of the human brain. Radiology,1996,201:637-648.
[4]Basser PJ, Mattiello J, Le Bihan D.MR diffusion tensor spectroscopy and imaging. BioPhys J,1994,66:259-67.
[5]Clark CA, Hedehus Moseley M. In vivo mapping of the fast and slow diffusion tensor s in human brain.. Magn Reson Med,2002,47:623-628.
[6]肖江喜,郭雪梅,王霄英,等.头部扩散张量磁共振成像扫描方案的优选.中国医学影像技术,2003,19：1433-1435.
[7]Yoshiura T, WU O, Zaheer A, et al. Highly diffusion-sensitized MRI of brain: dissociation of gray and white matter. Magn Reson Med,2001,45(5):734-740.
[8]Zhou XJ. Diffusion tensor MRI and functional connectivity.第十一届中华医学会放射学分会全国学术会议论文汇编,2003,32-33.
[9]Neil JJ, Siran SI, Mckinstry RC, et al. Normal brain in human newborns: apparent diffusion coefficient and diffusion anisotropy measured by using diffusion tensor MR imaging. Radiology,1998,209:57-66.
[10]Sehaefer PW, Grant PE, Gonzalez RG Diffusion weighted MR imaging of the brain. Radiology,2000,217:331-345.
[11]Le Bihan D, Turner R, Pekar J, et al. Diffusion and perfusion imaging by gradient sensitization: design, strategy and significance. J Magn Reson Imaging,1991; 1; 7-8.
[12]Cercignani M, Iannucci G, Rocca MA, et al. Pathologic damage in MS assessed by diffusion-weighted and magnetization transfer MRI. Neurology, 2000; 54:1139-1144.
[13]Nusbaum AO, Tang CY, Wei TC, et al. Whole-brain diffusion MR histogram differ between MS subtypes. Neurology,2000; 54:1421-1427.
[14]Cercignani M, Inglese M, Pagani E, et al. Mean diffusivity and fractional anisotropy histograms of patients with multiple sclerosis. Am J Neuroradiol, 2001; 22:952-958.
[15]Filippi M, Cercignani M, Inglese M, Horsfield MA, Comi G. Diffusion tensor magnetic resonance imaging in multiple sclerosis. Neurology,2001;56:304-311.
[16]Bammer R, Augustin M, Strasser-Fuchs S, et al. Magnetic resonance diffusion tensor imaging for characterizing diffuse and focal white matter abnormalities in multiple sclerosis. Magn Reson Med,2000;44:583-591
[17]Warach S, Dashe JF, Edelman RR. Clinical outcome in ischemic lesion predicted by early diffusion-weighted and perfusion magnetic resonance imaging:a preliminary analysis. J Cereb Blood Flow Metab,1996; 16:53-59.
[18]Liang ZJ, Zeng JS, Liu SR, et al. A prospective study of secondary degeneration following subcortical infarction using diffusion tensor imaging. J Neurol Neurosurg Psychiatry,2007,78:581-586.
[19]Bozzali M, Franceschi M, Falini A, et al. Quantification of tissue damage in AD using diffusion tensor and magnetization transfer MRI. Neurology,2001; 157:1135-1137.
[20]Filippi M, van Waesberghe JH, Horsfield MA, et al. Interscanner variation in brain MRI lesion load measurements in MS:implications for clinical trials. Neurology,1997; 49:371-377.
[21]Sormani MP, Iannucci G, Rocca MA, et al. Reproducibility of magnetization transfer ratio histogram-derived measures of the brain in healthy volunteers. AJNR Am J Neuroradiol,2000;21:133-136.
[22]Heim, S, Hahn, K, Samann, PG, et al. Assessing DTI data quality using bootstrap analysis. Magn. Reson. Med.2004,52,582-589.
[23]Pfefferbaum, A, Adalsteinsson, E, Sullivan, EV. Replicability of diffusion tensor imaging measurements of fractional anisotropy and trace in brain. J. Magn. Reson. Imaging.2003,18,427-433.
[24]Ciccarelli,O, Parker, GJ, Toosy, AT, et al. From diffusion tractography to quantitative white matter tract measures:a reproducibility study. Neurolmage. 2003,18:348-359.
[25]Bonekamp D, Nagae LM, Degaonkar M, et al. Diffusion tensor imaging in children and adolescents: Reproducibility, hemispheric, and age-related differences.NeuroImage,2007,24:733-742.
[26]Fukatsu H.3T MR for clinical use:update. Magn Reson Med Sci,2003, 2:37-45.
[27]Bastin ME, Armitage PA, Marshall I. A theoretical study of the effect of experimental noise on the measurement of anisotropy in diffusion imaging. Magn Reson Imaging,1998; 16:773-785.
[28]Basser PJ Pajevic S. Statistical artifacts in diffusion tensor MRI (DT-MRI) caused by background noise. Magn Reson Med,2000; 44:41-50.
[29]Chenevert TL, Brunberg JA, Pipe JG. Ansiotropic diffusion within human white matter:demonstration with NMR techniques in vivo. Radiology,1990; 177:401-405.
[30]Hajnal JV, Doran M, Hall AS. MR imaging of anisotropically restricted diffusion of water in the nervous system:technical, anatomic, and pathologic considerations. J Comput Assisted Tomogr,1991; 15:1-18.
[31]Bammer R, Acar B, Moseley ME. In vivo MR tractography using difusion imaging. Eur J Radiol,2003,45(3):223-234.
[32]Mori S, van Zijl PCM. Fiber tracking:principles and strategiesa technical review. NMR Biomed.2002.15(7-8):468-480.
[33]MellMn ER, Mori s'Mukundan G'et al. Diffusion tensor MR imaging of the brain and white matter tractography.AJR.2002,178(1):3-16
[1]芮德源,陈立杰主编临床神经解剖学,人民卫生出版社,2007,9
[2]朱长庚主编神经解剖学,人民卫生出版社,2002,3
[3]Kim DS, KimM, Ronen I, et al. In vivo mapping of functional domains and axonal connectivity in cat visual cortex using magnetic resonance imaging [J]. Magn Reson Imaging,2003,21:1131-1140.
[4]Pierpaoli C, Jezzard P, Basser PJ, et al. Diffusion tensor MR imaging of the human brain [J]. Radiology,1996,201:637-648.
[5]王海燕,赵斌.颅脑磁共振张量成像应用进展[J].医学影像学杂志,2005,15：908-911.
[6]卢洁,李坤成.正常成人脑组织弥散的定量研究[J].中国医学影像技术,2003,19：975-977.
[7]Chpuri NB, Yen YF, Burdette JH, et al. Diffusion anisotropy in the corpus callosum. AJNR Am J Neuroradiol,2002,23(5):803-8.
[8]Pierpaoli C, Jezzard P, Basser PJ, et al. Diffusion tensor MR imaging of the human brain. Radiology,1996,201(3):637-48.
[9]何光武,沈天真,陈星荣.正常成人大脑白质纤维各向异性特征的弥散张量磁共振成像研究.中国医学计算机成像杂志,2003,6：383.
[10]钟维佳,赵建农,谢微波,等.磁共振扩散张量成像对正常人脑结构的显示及各向异性研究.临床放射学杂志,2006,25(9)：807-10.
[11]Svennerholm L, Bostrom K, Jungbjer B. Changes in weight and compositions of major membrane components of human life of Swedes. Acta Neuropathol, 1997,94:345-352.
[12]Tang Y, Whitman GT, Lopez I, et al. Brain volume changes on longitudinal magnetic resonance imaging in normal older people. J Neuroimaging,2001;11: 393-400.
[13]Marner L, Nyengaard JR, Tang Y, et al. Marked loss of myelinated nerve fibres in the human brain with age. J Comp Neurol,2003; 462:144-152.
[14]Pfefferbaum A, Sullivan EV, Hedehus M, et al. Age-related decline in brain white matter anisotropy measured with spatially corrected echo-Planar diffusion tensor imaging. Magn Reson Med,2000,44(2):259-68.
[15]Sehmithorst VJ, Wilke M, Dardzinski BJ, et al. Correlatio of white matter diffusivity and anisotropy with age during childhood and adolescence: across-Sectional diffusion-tensor MR imaging study. Radiology,2002,222(1): 12-8.
[16]Rovaris M, Iannucci G, Cercignani M, et al. Aged-related changes in conventional, magnetization transfer and diffusion tensor MR imaging findings: study with whole brain tissue histogram analysis. Radiology,2003, 227(3):731-8.
[17]Nusbaum AO, Tang CY, Buchsbaum MS, et al. Regional and global changes in cerebral diffusion with normal aging. Am J Neuroradiol,2001,22(1):136-42.
[18]Aboitiz F, Rodriguez E, Olivares R, et al. Age-related changes in fiber composition of the human corpus callosum: sex differences. NeyrorePort,1996, 7:1761-4.
[19]Rakie P, Yakovlew Pl. DeveloPment of the corpus callousm and cavum septi in man. J Comp Neurol,1968,132(1):45-72.
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