【作者】 张伟；

【导师】 李传福；

【作者基本信息】 山东大学 ， 影像医学与核医学， 2009， 博士

【摘要】 目的:将磁敏感加权成像（susceptibility-weighted imaging,SWI）、弥散加权成像（diffusion-weighted imaging,DWI）、弥散张量成像（diffusion tensor imaging,DTI）、磁共振灌注成像（perfusion weighted magnetic resonance imaging,PWI）、二维（two-dimension,2D）氢质子MR波谱（proton MR spectroscopy,¹H-MRS）序列应用于转移瘤及瘤周区域,对其诊断特征进行研究。在组织学上,转移瘤和高级别胶质瘤（Ⅲ级、Ⅳ级）的内部结构、弥散、代谢产物等都存在差异,本研究通过MRI不同功能序列对肿瘤瘤体和瘤周区域的研究,探讨其在二者鉴别诊断中的应用价值。方法:采用GE Signa EXCITEⅡ3.0T MR机扫描。除常规MRI平扫外,95例转移瘤患者同时接受T2^*WI和SWI检查、MRI强化;55例转移瘤（肿瘤数目不多于3个,其中20例为单发）和33例高级别胶质瘤同时接受了DWI和DTI、PWI和MRI强化、二维¹H-MRS检查。1.常规MRI检查常规MRI扫描序列包括横轴位、冠状位T₂WI（TR/TE=4500/102 ms,层厚6.0mm,间隔1.0 mm,矩阵320×224,视野（field of view,FOV）24 cm×24 cm,采集时间1分53秒）、横轴位T₁WI（TR/TE=500/8 ms,层厚6.0 mm,间隔1.0 mm,矩阵320×224,FOV24 cm×24 cm,采集时间2分11秒）、横轴位T₂液体衰减恢复（fluid-attenuated inversion-recovery,FLAIR）（TR/TE=9000/120 ms,层厚6.0mm,间隔1.0 mm,矩阵320×224,FOV24 cm×24 cm,采集时间3.0分）。2.T2^*WI检查和SWI检查T2^*WI检查采用GRE序列,TR/TE=520/20 ms,反转角度20°,层厚6.0 mm,间隔1.0 mm,矩阵256×224,FOV24 cm×24 cm,采集时间2分58秒。SWI检查采用3D SPGR序列,TR/TE=23/13 ms,反转角度20°,扫描块的厚度56 mm,矩阵512×448,FOV 24 cm×24 cm,采集时间6分28秒。原始数据采用Functool 3.1 software;Sun,GE Healthcare进行重建得到校正的相位图和磁矩图,再对得到的磁矩图进行重建得到最小密度投影（minimum intensity projection,Min IP）图像。3.DWI检查和DTI检查DWI检查采用SE/EPI技术,3个垂直平面的弥散梯度,b值为0和1000s/mm²,TR/TE=5000/65 ms,层厚6.0 mm,间隔1.0 mm,矩阵256×192,FOV 24cm×24 cm,采集时间1分钟。首先经后处理产生表观弥散系数（apparent diffusion coefficient,ADC）图;然后,在ADC图上手工绘制感兴趣区（regions of interest,ROI）,分别选择在肿瘤的实质区、坏死区、瘤周带及对侧大脑半球正常白质区,瘤周带定义为强化的肿瘤实质周围2cm区域,在大多数病例表现为T1WI低信号、T2WI高信号、增强无强化,少数病例则T1WI、T2WI、增强扫描均与正常脑组织信号相近。ROI的ADC值直接测量得出,随后进行标准化处理,计算ADC比值（relativeADC,rADC）,即病变区域的ADC值与对侧大脑半球正常白质区相同大小ROI的ADC值之比。DTI检查采用单次激励平面回波（Echo planner imaging,EPI）自旋（Spin echo,SE）序列。扫描参数为:层厚5.0mm,层间距0,层数26层,每层采集25个非共线的梯度方向的数据,b值为0和1000s/mm²,TR/TE=6000ms/minimum,FOV24cm×24 cm,矩阵128×128,NEX=2,采集时间为2分48秒。后处理时,首先用correction程序对图像进行校正,以减少运动伪影和图像变形;然后进行域值设定,要求既能使图像背景噪声尽可能减少,又要包含所有脑组织;得到分数各向异性（fractional anisotropy,FA）图、ADC图。选择与DWI一致的ROI,分别记录ADC值、ADC比值（r ADC）、FA值及FA比值（relative FA,r FA）,以进行定量分析。4.灌注成像和增强检查灌注成像用EPI SE序列:单次激发,TR/TE=1900/80ms,激励1次,FOV24cm×24 cm,层厚6mm,间隔1mm,矩阵128×128,单次扫描时间为4s（覆盖11层）,间隔时间500ms,共扫描24次,总计扫描时间为1分36秒。在肘静脉内置入20号针头,与高压注射器相接。在第1个扫描时相末以5ml/s的流率注射0.2mmol/kg体重钆-二乙烯五胺乙酸（Gadolinium diethylene- triamine pentaceticacid,Gd-DTPA）,随后以相同流率注射生理盐水20ml。数据处理包括:（1）获取ROI时间-信号强度曲线;（2）测量ROI的脑血容积（cerebral blood volume,CBV）和平均通过时间（mean transi-time,MTT）,计算相对CBV（relaive CBV,r CBV）和相对MTT（relative MTT,r MTT）（与对侧正常脑白质比较）。在以轴位CBV伪彩图中目测肿瘤实质的最高灌注处（对应常规MRI中无明显囊变、坏死或出血区）、瘤周带的最高灌注处及对侧正常脑白质内分别放置ROI,平均测量3～5次,取最大值。每个ROI大小为20～30mm²,在选择ROI时注意避开粗大血管。然后行横轴位、冠状位和矢状位增强扫描,扫描参数同平扫T₁WI。5.二维¹H-MRS检查在增强MRI扫描后行2D ¹H-MRS检查,此时可以准确分辨强化的肿瘤实质、无强化的坏死囊变区以及水肿区,分析时¹H-MRS的感兴趣体（volume of interest,VOI）可准确放置于ROI域。2D ¹H-MRS的扫描参数为:采用点分辨波谱（point resolved surface coilspectroscopy,PRESS）序列,水抑制,TR/TE=1500/144 ms;FOV 16 cm;矩阵16×16;层厚10 mm;采集次数为1;采集时间为4分20秒。VOI放置于横轴位上,且与增强横轴位T₁WI上的强化区域相对应。放置VOI时应避开头皮脂肪组织和颅脑骨质。在VOI周围使用高度选择性的饱和（very selective saturation,VSS）脉冲。然后执行预扫描,自动匀场结果:如果最大半宽（full-width half-maximum,FWHM）≤15Hz,水抑制为95%～99%,则开始扫描,否则再次进行自动匀场,如果仍不能到达要求,则重新设定VOI。后处理时,首先产生代谢—解剖图,移动体素选择ROI,并在波谱图上观察代谢物的变化情况,每个体素大小为1 cm×1 cm×1 cm,评价代谢物的波谱为:N-乙酰天冬氨酸（N-acetylaspartate,NAA）、胆碱（choline,Cho）、肌酸（creatine,Cr）、脂质（lipid,Lip）、乳酸（lactate,Lac）。各种代谢物的数值（即波峰下的面积）可自动得出,然后手工计算代谢物的比值（NAA/Cr、Cho/Cr、Lip/Cr、Lac/Cr和Cho/NAA）。5.统计学分析统计学分析使用SPSS 13.0软件（SPSS Inc,Chicago,IL,USA）,采用t检验比较:（1）T2^*WI与SWI序列检测瘤内出血敏感性;（2）转移瘤组与胶质瘤组之间ADC参数（ADC值和ADC比值）、FA参数（FA值和FA比值）、灌注参数、MRS各代谢参数的差异。所有数值结果以均数±标准差表示。p＜0.05为差异有统计学意义。结果:1.T2^*WI、SWI检查结果1.1以MRI增强扫描图像为参照,SWI可检出79.2%的脑内转移瘤,对于合并水肿和/或出血的瘤灶显示率达100%。1.2 SWI序列对转移瘤瘤内出血的检出能力显著高于T2^*WI序列。2.DWI和DTI检查结果2.1高级别胶质瘤组瘤周带ADC值较转移瘤有明显增高;而两组间在肿瘤实质、囊变坏死组织的ADC值测量方面差异无统计学意义。2.2高级别胶质瘤组肿瘤实质实质FA值显著高于转移瘤组。2.3转移瘤主要对周围脑白质束产生压迫作用,三维神经纤维束成像以变形、移位为主;高级别胶质瘤对周围脑白质有浸润和破坏,三维神经纤维束成像显示明显地中断、残缺。3.PWI检查结果高级别胶质瘤组肿瘤实质、瘤周带的最大rCBV均高于脑转移瘤,差异有统计学意义;二者rMTT差异无统计学意义。4.2D ¹H-MRS检查结果4.1转移瘤组和高级别胶质瘤组肿瘤实质各主要代谢物比值差异无统计学意义。4.2转移瘤组与胶质瘤组瘤周带波谱比较,胶质瘤组Cho/Cr、Cho/NAA明显升高。两组肿瘤之间的NAA/Cr、Lac/Cr无统计学差异。结论:1.SWI可检出绝大部分转移瘤,对合并瘤内出血和瘤周水肿的瘤灶更为敏感。可应用于有原发肿瘤史患者的临床随访。2.瘤周带的各项功能MRI参数转移瘤组和高级别胶质瘤组之间均存在显著性差异。瘤周带ADC值、rCBV值和Cho峰的升高以及纤维束连接性中断、局限性消失可作为高级别胶质瘤的特征性表现。3.联合应用MRI功能序列鉴别转移瘤和胶质瘤时,应重点观察瘤周带的MRI特征。更多还原

【Abstract】 Objective:To investigate the characterization of brain metastases in different MRI sequences including susceptibility-weighted imaging(SWI),difffusion-weighted imaging(DWI), perfusion weighted imaging(PWI) and two-dimension proton MR spectroscopy(2D ~1H-MRS).To distinguish between brain metastases and high-grade gliomas(gradeⅢand gradeⅣ) on the basis of differences in vascularity,water self-diffusion, microarchitecture and metabolite levels in the tumor and peritumoral regions.Methods:MRI examinations were performed using a 3.0T MR scanner(Signa EXCITEⅡ; GE Medical Systems).In 95 cases with brain metastases,T2~*WI,SWI and contrast-enhanced(CE) T1WI were performed.In 55 cases with brain metastases and 33 cases with high-grade gliomas,DWI,DTI,PWI,CE T1WI and 2D ~1H-MRS were performed.1.The conventional MRI examinationThe protocol consisted of axial T1-weighted(TR/TE=500/8 ms) spin-echo(SE), T2-weighted(4500/102 ms) fast SE,and fluid-attenuated inversion-recovery(FLAIR) (TR/TE=9000/120 ms) with 6 mm slice thickness,240 mm field of view(FOV) and 320×224 matrix.2.T2~*WI and SWI2.1 T2~*WI was obtained using the following parameters:TR/TE=520/20ms;flip angle,20 degrees;matrix,512×512;FOV,256×256 mm;20 slices;slice thickness/gap,6 mm/1mm.Acquisition time was 2 minutes and 14 seconds.2.2 SWI was obtained as a fully velocity-compensated three-dimensional gradient echo sequence using the following parameters:TR/TE=23/13ms;flip angle,20 degrees;matrix,512×448;field of view(FOV),240×240 mm.Acquisition time was 6 minutes and 28 seconds.3.DWI and DTI3.1 DWI was obtained using an axial echo-planar SE sequence:TR/TE= 5000/65 ms;one average;6 mm slice thickness;diffusion gradient encoding in 3 orthogonal directions;b=0,1000 s/mm~2;240 mm FOV;160×192 matrix.Acquisition time was 1 minute.Postprocessing of apparent diffusion coefficient(ADC) maps was performed using standard software on a workstation(Functool 3.1 software;GE Healthcare).In brief,regions of interest(ROIs) were drawn manually in the enhancing tumor, necrosis,peritumoral region and edema outside of peritumoral regionin CE T1WI based ADC images.The ADC value was calculated automatically by the Functool 3.1 software.For normalizing ADC levels,an ADC ratio was calculated as the quotient of the ADC values of the enhancing region and those of an ROI of the same size in the contralateral normal white matter.3.2 DTI was obtained using an axial echo-planar(EPI) spin echo(SE) sequence: TR/TE=6000/minimum ms;5 mm slice thickness;no gap;diffusion gradient encoding in 3 orthogonal directions;b=0,1000 s/mm~2;240 mm FOV;128×128 matrix;NEX=2.Acquisition time was 2 minutes and 48 seconds.Postprocessing was perforned using standard DTI software on a workstation (Functool 3.1 software;GE Healthcare).ROIs were carried over the DWI postprocessing.The ADC/ FA values were calculated automatically.ADC values, relative ADC(rADC),fractional anisotropy(FA) value and relative FA(rFA) were calculated and recorded.4.PWI and CE T1WIFollowing institutional protocol,SE-EPI PWI(TR/TE=1900/ 80ms;slice thickness 6mm;matrix 128×128) was performed using a 5ml/s bolus injection of gadopentetate dimeglumine(Magnevist;Bayer HealthCare Pharmaceuticals) (0.2mmol/kg) and was coregistered with delayed postgadolinium T1-weighted imaging.Postprocessing was perforned using a perfusion processing software package, which generates color cerebral blood volume(CBV) and mean transit-time(MTT) maps.ROIs were selected within the region of maximal CBV for three times and recorded the average CBV,relative CBV(rCBV),MTT and relative MTT(rMTT) values.CE T1WI was then performed in axial,coronal and sagital planes.5.2D ~1H-MRS2D ~1H-MRS was always performed based on CE T1WI to insure accurate voxel placement since the enhanced umor,low intensity necrosis and edema can be distinguished easily.The following parameters were used:a point-resolved spectroscopy sequence (PRESS);TR/TE=1500/144 ms;16 cm FOV;160×160 matrix;10-mm slice thickness;acquisition,1 average;scanning time,4 minutes and 20 seconds.A volume of interest(VOI) was placed on axial T1-weighted images corresponding to the contrast-enhancing area.Automatic prescanning was performed before the spectroscopic scan to ensure adequate water suppression.The full-width half-maximum was kept under 15 Hz and water saturation between 95%and 99%.The details of the postprocessing used for MR spectroscopy was as follows.Within the obtained VOI,separate 1cm×1cm×1cm voxels were individually placed in the enhancing tumor and peritumoral region.The following metabolite peaks were indentified:N-acetylaspartate(NAA) at 2.02-ppm,choline-containing compounds (Cho) at 3.22-ppm,(phospho-) creatine(Cr) at 3.01-ppm,lipid-containing compounds (Lip) in the range of 0.9-1.3 ppm,and lactate(Lac) at 1.35-ppm(an invertedβ-methyl doublet).Metabolite values were calculated automatically from the area under each metabolite peak by the Functool 3.1 software.Metabolite ratios(NAA/Cr,Cho/Cr, Lip/Cr,Lac/Cr,and Cho/NAA) were calculated manually.6.Statistical analysisStatistical analysis was performed using SPSS for Windows release 13.0(SPSS Inc, Chicago,IL,USA).The number of hemorrhage BMs and the grading score between SWI and T2~*WI and different parameters between the brain metastases group and high-grade gliomas group were compared using an unpaired two-tailed Student t test. The level of significance was set at p＜0.05.Results:1.Results from T2~*WI and SWI1.1 SWI could detect 79.2%of all brain metastases,and 100%of brain metastases with intratumoral hemorrhage and/or peritumoral edema.1.2 To detect intratumoral hemorrhage the sensitivity of SWI was significantly higher than T2~*WI,which just detected 69.6%of hemorrhage detected on SWI.2.Results from DWI and DTI2.1 The ADC value of the peritumoral region of high-grade gliomas was significantly higher than that of brain metastases;while the ADC values of enhanced tumor,necrosis and edema outside of the peritumoral region were not significantly different between brain metastases and high-grade gliomas.2.2 The FA value of the enhancing high-grade gliomas was significantly higher than that of brain metastases.3.Results from PWIThe maximal rCBV of enhancing tumors and the peritumoral region of high-grade gliomas were significantly higher than that of brain metastases;while the rMTT was not statistically different between brain metastases and high-grade gliomas.4.Results from 2D ~1H-MRS4.1 The intratumoral Cho/Cr,Cho/NAA,NAA/Cr ratios in brain metastases did not differ statistically from that of high-grade gliomas.4.2 The peritumoral Cho/Cr and Cho/NAA ratios in brain metastases were statistically different from that of high-grade gliomas.The ratios for the high-grade gliomas were significantly higher.The NAA/Cr and Lac/Cr ratios between brain metastases and high-grade gliomas were not statistically different.Conclusion:1.SWI can detect most brain metastases without injection of contrast,and it is even more sensitive in dectecting metastases with intratumoral hemorrhage and peritumoral edema.2.The parameters of DWI,DTI,PWI and 2D ~1H-MRS of the peritumoral region are significantly different between brain metastases and high-grade gliomas,and can be used to demonstrate differences in solitary metastases and high-grade gliomas.3.We strongly suggest the use of a combination of the investigated diagnostic procedures for the peritumoral region to distinguish brain metastases and high-grade gliomas.更多还原