氢质子磁共振波谱在颅内常见肿瘤中的应用研究
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摘要
【目的】
1、探讨二维多体素氢质子磁共振波谱(2D-1~H MRS)在颅内常见肿瘤强化区的代谢物改变特点及其对颅内肿瘤的鉴别诊断价值;
2、探讨二维多体素氢质子磁共振波谱在颅内常见肿瘤近侧水肿区的代谢物改变特点及其对颅内肿瘤的鉴别诊断价值;
3、探讨二维多体素氢质子磁共振波谱在不同级别胶质瘤间的波谱代谢差异及其对胶质瘤术前分级的应用价值。
【材料与方法】
1、研究对象
对61例未接受过任何治疗的脑肿瘤患者行常规MRI平扫、增强扫描及2D-1~HMRS检查。除部分转移瘤经临床证实外,其余所有病例均经术后病理明确诊断,分为三组:胶质瘤组26例,其中又分为低级别(Ⅰ-Ⅱ级)胶质瘤14例,高级别(Ⅲ-Ⅳ级)胶质瘤12例,脑膜瘤组17例,转移瘤组18例。
2、MRI检查方法
采用GE signa exciteⅡ3.0T磁共振扫描设备。常规MRI平扫及增强扫描使用头部八通道线圈,由自旋回波(SE)序列和快速自旋回波(FSE)序列获得T1、T2加权像(T1WI、T2WI)以及增强后T1加权像,扫描参数如下:T1WI(TR/TE,/144ms,频率编码设定为16,频率编码方向A/P,体素厚度(voxel thickness)10mm,层间距20mm,NEX 1,FOV 18mm×18mm。于T1WI增强或T2WI平扫的纯轴位上进行波谱定位,波谱扫描野(VOI)大小根据病变情况而定,应包括肿瘤强化区域、水肿区域及部分远离病灶的正常脑组织区域,并尽量避免包括颅骨、头皮脂肪、含气窦腔等影响波谱成像质量的组织。定位完毕后先行预扫描,显示自动匀场达到半高线宽(FWHM)＜10,水抑制＞98%以上方开始正式进行波谱扫描,扫描时间大约5分钟。
3、图像后处理与数据测量
采用FuncTool后处理软件进行图像后处理。于“代谢-解剖叠加图(AI+MI)”上放置三个感兴趣区(ROI),分别位于肿瘤强化明显区域(ROI-1)、强化周边1-2cm、T2WI呈高信号的区域(ROI-2),以及远离病变的正常脑组织区域(ROI-3),感兴趣区大小根据病变情况由1-4个体素组成。在“代一解”图上观察各代谢物的浓度分布,在相应波谱图(SI)上观察各感兴趣区的波峰表现。同时,图形分析软件自动识别并计算各代谢物峰下面积代表其浓度,并自动计算各代谢物间的相对比值。记录各ROI的Cho/Cr、NAA/cr及Cho/NAA三个代谢物相对比值,及Lip峰或Lac峰在各组内分别出现的例数。
4、统计学处理
采用SPSS13.0统计软件进行统计学分析,分别计算三组肿瘤三个不同区域各代谢物比值的平均值,用均数±标准差((?)±SD)形式表示。(1)、比较三组肿瘤正常参照区之间各代谢物比值有无统计学差异;(2)、比较各组肿瘤强化区与正常参照区之间各代谢物比值有无统计学差异,并比较三组肿瘤强化区之间各代谢物比值有无统计学差异;(3)、比较各组肿瘤近侧水肿区与正常参照区之间各代谢物比值有无统计学差异,并比较三组肿瘤近侧水肿区之间各代谢物比值有无统计学差异;(4)、比较高、低级别胶质瘤之间在强化区及近侧水肿区的各代谢物比值分别有无统计学差异。三组肿瘤间的比较采用单因素方差分析,总体有显著差异的情况下,采用LSD两两比较。同组肿瘤两个区域间的比较采用配对t检验。高、低级胶质瘤之间的比较采用独立样本t检验。检验水准α值均取0.05。
【结果】
1、正常参照区波谱代谢有无统计学差异;(4)、比较高、低级别胶质瘤之间在强化区及近侧水肿区的各代谢物比值分别有无统计学差异。三组肿瘤间的比较采用单因素方差分析,总体有显著差异的情况下,采用LSD两两比较。同组肿瘤两个区域间的比较采用配对t检验。高、低级胶质瘤之间的比较采用独立样本t检验。检验水准α值均取0.05。
【结果】
1、正常参照区波谱代谢
波谱图显示三组肿瘤正常参照区的波谱表现相似,均表现为NAA峰最高,Cr峰与Cho峰不同程度较低。Cho/cr、NAA/Cr、Cho/NAA在三组间均无显著差异,各组正常区均未出现Lac峰及Lip峰;
2、强化区波谱代谢
波谱图显示各组肿瘤强化区均表现为Cho为明显增高的第一高峰,NNA峰及cr峰不同程度降低,其中脑膜瘤NAA降低更明显。相对比值的比较,各组肿瘤强化区Cho/cr、Cho/NAA均较正常参照区明显增高并有统计学差异,NAA/cr较正常参照区明显降低并有统计学差异。三组间比较,脑膜瘤组NAA/cr较胶质瘤及转移瘤组减低并有统计学差异p＜0.01,Cho/NAA较胶质瘤组及转移瘤组明显增高并有统计学差异p＜0.01,其余两两比较均无统计学差异。Lac峰在胶质瘤组出现6例,在脑膜瘤组出现3例,在转移瘤组出现4例;Lip峰在胶质瘤组出现4例,在转移瘤组出现8例,在脑膜瘤组未见出现。
3、近侧水肿区波谱代谢
波谱图显示胶质瘤近侧水肿区Cho峰仍有不同程度的增高,NAA及cr两峰相对较低,波谱表现与肿瘤强化区的各峰高低分布相似,而脑膜瘤与转移瘤在近侧水肿区多数表现为NAA峰较高,Cho峰与cr峰相对较低,波谱表现更接近于正常区波峰高低分布。相对比值的比较,胶质瘤组Cho/cr、Cho/NAA较脑膜瘤及转移瘤组明显增高并有统计学差异,NAA/cr较其余两组降低并有统计学意义;脑膜瘤、转移瘤组之间及其与正常参照区的各代谢物比值均无统计学差异。NAA及Cr峰有不同程度降低。相对比值的比较,高级别组Cho/cr较低级别组增高并有统计学差异,而NAA/Cr和Cho/NAA在两级别间均无统计学差异。
【结论】
1、2D-1~H MRS检查于一次扫描即可同时获取多个部位的波谱信号,在节省时间的前提下能更全面、细致地了解病变及其周围组织的生化代谢特点,有利于病变内部及其周围区域间的相互对比;同时2D-1~H MRS可以自由选择适当采样体素进行分析,避免了非研究组织的干扰,提高了研究的准确性;
2、不同肿瘤在其正常参照区的波谱均表现为较高的NAA峰,相对较低的Cho及cr峰,各代谢物比值在三组间均无显著差异,符合正常脑组织的波谱特征。进行波谱分析时可将病灶对侧区作为正常参照。
3、三组肿瘤强化区波谱较正常区均有显著差异,共同表现为Cho跃居第一高峰,NAA及cr不同程度下降,这是一般脑肿瘤性病变的共同波谱特点,有助于发现常规MRI上显示不明显的脑肿瘤。脑膜瘤NAA峰较其余两组降低更明显,脑膜瘤组NAA/Cr较其余两组显著减低,Cho/NAA较其余两组显著增高,差异基础可能在于脑膜瘤为脑外肿瘤,代表神经元的NAA较低或缺如。据强化区的波谱差异可将不典型脑膜瘤或其他脑外肿瘤与脑内肿瘤更好的进行鉴别。胶质瘤与转移瘤组间各代谢物比值均无显著差异,提示强化区波谱对于胶质瘤与转移瘤的鉴别较为困难。Lac峰在三组中均有出现,提示肿瘤组织相对缺血缺氧,但对于良恶性肿瘤的鉴别意义不大;Lip峰在胶质瘤及转移瘤组均有出现,而脑膜瘤组未见出现,可能对恶性肿瘤的诊断有一定价值,但对胶质瘤或转移瘤的鉴别意义不大;
4、近侧水肿区波谱于胶质瘤仍可见较高的Cho峰及不同程度降低的NAA、Cr峰,胶质瘤组近侧水肿区Cho/cr、Cho/NAA较其余两组显著增高,NAA/cr较其余两组显著降低;而脑膜瘤与转移瘤在近侧水肿区具有较高NAA峰,较低的Cho及cr峰,两组之间及其与正常参照区的各代谢物比值均无显著差异。胶质瘤近侧水肿区出现波谱异常的病理基础在于胶质瘤具有向周围浸润生长的特性。根据近侧水肿区的波谱改变可更好的帮助胶质瘤等浸润性肿瘤与非浸润性肿瘤进行鉴别;础可能在于脑膜瘤为脑外肿瘤,代表神经元的NAA较低或缺如。据强化区的波谱差异可将不典型脑膜瘤或其他脑外肿瘤与脑内肿瘤更好的进行鉴别。胶质瘤与转移瘤组间各代谢物比值均无显著差异,提示强化区波谱对于胶质瘤与转移瘤的鉴别较为困难。Lac峰在三组中均有出现,提示肿瘤组织相对缺血缺氧,但对于良恶性肿瘤的鉴别意义不大;Lip峰在胶质瘤及转移瘤组均有出现,而脑膜瘤组未见出现,可能对恶性肿瘤的诊断有一定价值,但对胶质瘤或转移瘤的鉴别意义不大;
4、近侧水肿区波谱于胶质瘤仍可见较高的Cho峰及不同程度降低的NAA、cr峰,胶质瘤组近侧水肿区Cho/Cr、Cho/NAA较其余两组显著增高,NAA/cr较其余两组显著降低;而脑膜瘤与转移瘤在近侧水肿区具有较高NAA峰,较低的Cho及Cr峰,两组之间及其与正常参照区的各代谢物比值均无显著差异。胶质瘤近侧水肿区出现波谱异常的病理基础在于胶质瘤具有向周围浸润生长的特性。根据近侧水肿区的波谱改变可更好的帮助胶质瘤等浸润性肿瘤与非浸润性肿瘤进行鉴别;
5、高级别胶质瘤强化区Cho峰较低级别胶质瘤升高更加明显,NAA较低级别胶质瘤降低更加明显。高级别组强化区Cho/cr、Cho/NAA较低级别组显著增高,NAA/cr较低级别组显著降低;高级别组近侧水肿区Cho/cr较低级别组显著增高。依据以上高、低级别胶质瘤的波谱代谢差异可帮助进行胶质瘤的术前分级。Lac及Lip峰在高级别组出现的例数均较低级别组为多,但由于出现例数较少,其对胶质瘤分级的意义还有待进一步大样本研究。
6、影响波谱成像及分析的因素较多,现阶段MRS分析的精确性尚不高,各组肿瘤波谱存在着一定的重叠。MRS作为一种新的影像技术,虽然能提供病变及其周围组织丰富的代谢、生化信息,但不能完全代替常规MRI,只能作为MRI检查的有力补充。
【Objective】
1.To investigate the metabolic changes of 2D- multi-voxel proton magnetic resonance spectroscopy(2D-multi-voxel ~1H MRS) in enhancement areas of different brain tumors and to evaluate its role in differential diagnosis of brain tumors.
2.To investigate the metabolic changes of 2D-multi-voxel ~1H MRS in edema areas of different brain tumors and to evaluate its role in differential diagnosis of brain tumors.
3.To investigate the metabolic changes of 2D-multi-voxel ~1HMRS between high -grade and low-grade gliomas and to evaluate its role in preoperative judegment the grade of gliomas.
【Methods】
1.Investigation objects
61 cases of brain tumor patients underwent MR imaging,contrast-enhanced MR imaging and 2D-~1HMR spectroscopy imaging.In addition to some of Intracranial metastases tumors confirmed by clinical,all the remaining cases were Confirmed by postoperative pathology.In 61 cases,26 cases was glioma,in which 14 cases was low-grade(Ⅰ-Ⅱ) glioma,12 cases was high-grade(Ⅲ-Ⅳ) gliomas,andl7 cases was meningiomas,18 cases was metastatic tumor.
2.MRI scanning methods
All scanning adopt GE signa exciteⅡ3.0T MRI scanning equipment. Conventional MRI scan used eight Channel coil Dedicated for head.getting T1WI, T2WI image by SE and FSE Sequence and getting Enhanced image in T1WI after Gd-DTPA injection,Scan Parameters:T1WI(TR/TE,600/16ms),T2WI(TR/TE, 5100/138ms),Thickness 5-8mm,Pitch 2mm,FOV 24×18mm,matrix 512×288. ~1HMRS scanning used eight Channel Coil Dedicated for head.Adopted 2-D multi-voxel(PROBE/SI) PRESS sequence,and set TR /TE:1000ms/144ms. Frequency Coding set of 16,Direction is A/P,voxel thickness lOmm,Pitch 20mm, NEX 1,FOV18×18m.Scan positioning some in Enhanced-T1WI image of complete Axial and another in T2WI image of complete Axial,The MRS scan VOI Should Including tumor areas,peri-tumor edema areas and a part of normal areas away from tumor areas,but should try to avoid skull,fat,liquid Organization and so on.The MRS scan started after FWHM＜lOppm,chress＞98%.
3.Image postprocessing and survey data
On the" FuncTool' Workstations,All of cases setting three regions of interest (ROI),which are located respectively in enhanced tumor regions,edema regions near the enhanced areas for 1-2cm and normal regions away from tumor,in the "AI+MI" Images.Observed the changes of the metabolism in the corresponding spectrum images(SI),measured the relative ratio of Cho / Cr,NAA / C,Cho / NAA,and Recorded Lip and Lac whether appeare in Every cases.
4.Statistical analysis
SPSS 13.0 statistical package was used.The measurement data were represented as mean±standard.(1).comparing each relative ratio of metabolites of normal areas in the three tumor groups;(2).Comparing each relative ratio of metabolites between the enhanced areas and normal areas in each groups,and comparing each relative ratio of metabolites of enhanced areas in three tumor groups;(3).comparing each relative ratio of metabolites of edema regions in the three tumor groups;(4).Comparing each relative ratio of metabolites Respectively in enhanced region,edema regions between the high-grade gliomas and low-grade gliomas.one-way ANOVA was used in Comparison in different tumor groups,paired-samples T-test was used in Comparison between two regions in same tumor group,one sample T-test was used in Comparison between high-grade and low-grade gliomas.Testing standards "α" adopted 0.05.
【Results】
1.MRS appearance in normal areas
Spectrum image showed There were similar metabolites situation in normal regions among three groups,appearing highest NAA peak,lower Cr and Cho peak. Cho/Cr,NAA/C,Cho/NAA all showed no significance among three groups.No Lac or Lip peak appeared in normal areas.
2.MRS appearance in enhanced tumor areas
Spectrum image showed roughly similar metabolites situation in enhanced regions among three groups,appearing highest Cho peak,lower Cr and NAA peak Varying degrees,particular,Lower NAA appeared in meningiomas group. Comparison between enhanced and normal regions,showed higher Cho/Cr,Cho/ NAA and lower NAA/Cr in enhanced regions in each tumor groups,there was statistically significant difference between meningiomas and each of other tumor groups for NAA / Cr,Cho / NAA,appearing there were higher Cho / NAA and lower NAA/Cr in meningiomas group.There was no significant between glioma and metastatic tumor for all The relative ratio of Metabolites,There was no significant among Threee groups for Cho/Cr.Lac appeared in 3 cases of meningiomas,6 cases of gliomas and 4 cases of metastatic tumor,lip not appeared in no case of meningiomas group,4 cases of gliomas and 8 cases of metastatic tumor.
3.MRS appearance in edema areas
Spectrum image showed The metabolites situation in edema regions is different from glioma group to each of other groups,appearing higher Cho peak, lower NAA and Cr peak in glioma group,the similar metabolites situation between meningiomas and metastatic tumor groups,appearing higher NAA peak,lower Cho and Cr peak.on all metabolites ratio,there was statistically significant differences between glioma groups and each of other groups,appeared higher Cho / Cr and Cho / NAA,lower NAA/ Cr in glioma group.There was no significant between meningiomas and metastatic tumor groups for Cho / Cr,Cho / NAA and NAA/Cr.
4.different MRS appearance between high-grade and lowe-grade glioma
(1).different MRS appearance in enhanced regions
The Spectrum image showed in enhanced regions there were Increase Cho Peak both in high-grade and lowe-grade glioma groups,but higher in high-grade glioma groups than low-grade group,there were Reduced NAA Peak both in high-grade and lowe-grade glioma groups,but lower in high-grade glioma groups than low-grade group,Cr peak change little.There was significance in enhanced regions between high-grade glioma groups and low-grade group for Cho/Cr,Cho / NAA,NAA/Cr, showed higher Cho/Cr,Cho / NAA and lower NAA/Cr in high-grade glioma group. Lac appeared in 4 case of high-grade group,2 cases of lowe-grade group,Lip appeared in 3 cases of high-grade group,1 case of lowe-grade group.
(2).different MRS appearance in edema regions
The Spectrum image showed in edema regions there were higher Cho Peak and lower NAA peak both in high-grade and lowe-grade glioma groups.There was significance in edema regions between high-grade glioma groups and low-grade glioma group for Cho/Cr,showed higher Cho / Cr in high-grade group,but no significance for Cho / NAA,NAA/Cr between high-grade and lowe-grade group in edema regions.
【Conclusions】
1.2D-~1HMRS Technology can get Spectrum signals from different areas at one scanning,so that it not only get more comprehensive and Full information about the metabolism of tumor and The surrounding region tissues but also save time Greatly. At the same time,2D-~1HMRS Technology can select More appropriate and more exact voxel without inclusion of unwanted structures which may degrade the spectrum quality;
2.There were similar metabolites situation in normal regions among three groups, appearing highest NAA peak,lower Cr and Cho peak.no significance for all metabolites ratio among three groups,that is MRS appearance of normal brain.
3.Metabolites situation of enhanced areas were all different from normal areas in three groups,all appearing highest Cho peak,lower Cr and NAA peak Varying degrees,particular,Lower NAA appeared in meningiomas group,there was statistically significant difference between meningiomas and each of other tumor groups for NAA / Cr,Cho / NAA,appearing there were higher Cho / NAA and lower NAA / Cr in meningiomas group.The difference basis may lain in meningiomas does not contain neuron,so have lower or hiatus NAA peak therefore,based on all above MRS difference in enhanced areas,we can better distinguish meningiomas from other tumor.There was not significant for all the relative ratio of Metabolites between glioma and metastatic tumor in enhanced tumor areas,that is to say there was difficulty to differential diagnosis between glioma and metastatic tumor depend on MRS appearance in enhanced tumor areas.Lac is less significance to diagnosis from malignant tumor to benign tumor because Lac appeared in all tumor groups but appeared number was less in each groups.lip appeared in both gliomas and metastatic tumor groups,but no one in meningiomas groups,for this reason,it is possible for Lip can help diagnosis from malignant tumor to benign tumor better,but Lip is less significance to diagnosis between glioma and metastatic tumor.
4.Spectrum image showed that the metabolites situation in edema regions is different from glioma group to each of other groups,appearing higher Cho peak, lower NAA and Cr peak in glioma group,the similar metabolites situation between meningiomas and metastatic tumor groups,appearing higher NAA peak,lower Cho and Cr peak.There was statistically significant differences between glioma groups and each of other groups,appeared higher Cho / Cr and Cho / NAA,lower NAA/Cr in glioma group,The difference basis may lain in the characteristic of Infiltrate growth in glioma,based on different MRS appearance in edema regions,it is more easy to diagnosis glioma from other intracal tumor.
5.Cho Peak is higher in high-grade glioma groups than low-grade group in enhanced regions,NAA Peak lower in high-grade glioma groups than low-grade group in enhanced regions,there was significance in enhanced regions between high-grade glioma groups and low-grade group for Cho/Cr,Cho / NAA,NAA/Cr, showed higher Cho/Cr,Cho / NAA and lower NAA/Cr in high-grade glioma group. There was significance in edema regions between high-grade glioma groups and low-grade glioma group for Cho/Cr,showed higher Cho / Cr in high-grade group. based on different MRS appearance between high -grade and low-grade gliomas,it is better to help Preoperative pathological grade of gliomas.Though,"Lac","Lip" all appeared more in high -grade gliomas than in low-grade gliomas,the value of helping Preoperative pathological grade of gliomas is pend for studying further.
6.Here are a lot of Influencing factor for MRS Imaging and analysis,and there existence overlaps in Various tumor spectrum each other.the accuracy of MRS also is not high.Therefore,MRS as a new method can provide us More Metabolism information about tumor and the vicinity organizes,but only as the powerful replenish for MRI,not substitution.
1、探讨二维多体素氢质子磁共振波谱(2D-1~H MRS)在颅内常见肿瘤强化区的代谢物改变特点及其对颅内肿瘤的鉴别诊断价值;
2、探讨二维多体素氢质子磁共振波谱在颅内常见肿瘤近侧水肿区的代谢物改变特点及其对颅内肿瘤的鉴别诊断价值;
3、探讨二维多体素氢质子磁共振波谱在不同级别胶质瘤间的波谱代谢差异及其对胶质瘤术前分级的应用价值。
【材料与方法】
1、研究对象
对61例未接受过任何治疗的脑肿瘤患者行常规MRI平扫、增强扫描及2D-1~HMRS检查。除部分转移瘤经临床证实外,其余所有病例均经术后病理明确诊断,分为三组:胶质瘤组26例,其中又分为低级别(Ⅰ-Ⅱ级)胶质瘤14例,高级别(Ⅲ-Ⅳ级)胶质瘤12例,脑膜瘤组17例,转移瘤组18例。
2、MRI检查方法
采用GE signa exciteⅡ3.0T磁共振扫描设备。常规MRI平扫及增强扫描使用头部八通道线圈,由自旋回波(SE)序列和快速自旋回波(FSE)序列获得T1、T2加权像(T1WI、T2WI)以及增强后T1加权像,扫描参数如下:T1WI(TR/TE,/144ms,频率编码设定为16,频率编码方向A/P,体素厚度(voxel thickness)10mm,层间距20mm,NEX 1,FOV 18mm×18mm。于T1WI增强或T2WI平扫的纯轴位上进行波谱定位,波谱扫描野(VOI)大小根据病变情况而定,应包括肿瘤强化区域、水肿区域及部分远离病灶的正常脑组织区域,并尽量避免包括颅骨、头皮脂肪、含气窦腔等影响波谱成像质量的组织。定位完毕后先行预扫描,显示自动匀场达到半高线宽(FWHM)＜10,水抑制＞98%以上方开始正式进行波谱扫描,扫描时间大约5分钟。
3、图像后处理与数据测量
采用FuncTool后处理软件进行图像后处理。于“代谢-解剖叠加图(AI+MI)”上放置三个感兴趣区(ROI),分别位于肿瘤强化明显区域(ROI-1)、强化周边1-2cm、T2WI呈高信号的区域(ROI-2),以及远离病变的正常脑组织区域(ROI-3),感兴趣区大小根据病变情况由1-4个体素组成。在“代一解”图上观察各代谢物的浓度分布,在相应波谱图(SI)上观察各感兴趣区的波峰表现。同时,图形分析软件自动识别并计算各代谢物峰下面积代表其浓度,并自动计算各代谢物间的相对比值。记录各ROI的Cho/Cr、NAA/cr及Cho/NAA三个代谢物相对比值,及Lip峰或Lac峰在各组内分别出现的例数。
4、统计学处理
采用SPSS13.0统计软件进行统计学分析,分别计算三组肿瘤三个不同区域各代谢物比值的平均值,用均数±标准差((?)±SD)形式表示。(1)、比较三组肿瘤正常参照区之间各代谢物比值有无统计学差异;(2)、比较各组肿瘤强化区与正常参照区之间各代谢物比值有无统计学差异,并比较三组肿瘤强化区之间各代谢物比值有无统计学差异;(3)、比较各组肿瘤近侧水肿区与正常参照区之间各代谢物比值有无统计学差异,并比较三组肿瘤近侧水肿区之间各代谢物比值有无统计学差异;(4)、比较高、低级别胶质瘤之间在强化区及近侧水肿区的各代谢物比值分别有无统计学差异。三组肿瘤间的比较采用单因素方差分析,总体有显著差异的情况下,采用LSD两两比较。同组肿瘤两个区域间的比较采用配对t检验。高、低级胶质瘤之间的比较采用独立样本t检验。检验水准α值均取0.05。
【结果】
1、正常参照区波谱代谢有无统计学差异;(4)、比较高、低级别胶质瘤之间在强化区及近侧水肿区的各代谢物比值分别有无统计学差异。三组肿瘤间的比较采用单因素方差分析,总体有显著差异的情况下,采用LSD两两比较。同组肿瘤两个区域间的比较采用配对t检验。高、低级胶质瘤之间的比较采用独立样本t检验。检验水准α值均取0.05。
【结果】
1、正常参照区波谱代谢
波谱图显示三组肿瘤正常参照区的波谱表现相似,均表现为NAA峰最高,Cr峰与Cho峰不同程度较低。Cho/cr、NAA/Cr、Cho/NAA在三组间均无显著差异,各组正常区均未出现Lac峰及Lip峰;
2、强化区波谱代谢
波谱图显示各组肿瘤强化区均表现为Cho为明显增高的第一高峰,NNA峰及cr峰不同程度降低,其中脑膜瘤NAA降低更明显。相对比值的比较,各组肿瘤强化区Cho/cr、Cho/NAA均较正常参照区明显增高并有统计学差异,NAA/cr较正常参照区明显降低并有统计学差异。三组间比较,脑膜瘤组NAA/cr较胶质瘤及转移瘤组减低并有统计学差异p＜0.01,Cho/NAA较胶质瘤组及转移瘤组明显增高并有统计学差异p＜0.01,其余两两比较均无统计学差异。Lac峰在胶质瘤组出现6例,在脑膜瘤组出现3例,在转移瘤组出现4例;Lip峰在胶质瘤组出现4例,在转移瘤组出现8例,在脑膜瘤组未见出现。
3、近侧水肿区波谱代谢
波谱图显示胶质瘤近侧水肿区Cho峰仍有不同程度的增高,NAA及cr两峰相对较低,波谱表现与肿瘤强化区的各峰高低分布相似,而脑膜瘤与转移瘤在近侧水肿区多数表现为NAA峰较高,Cho峰与cr峰相对较低,波谱表现更接近于正常区波峰高低分布。相对比值的比较,胶质瘤组Cho/cr、Cho/NAA较脑膜瘤及转移瘤组明显增高并有统计学差异,NAA/cr较其余两组降低并有统计学意义;脑膜瘤、转移瘤组之间及其与正常参照区的各代谢物比值均无统计学差异。NAA及Cr峰有不同程度降低。相对比值的比较,高级别组Cho/cr较低级别组增高并有统计学差异,而NAA/Cr和Cho/NAA在两级别间均无统计学差异。
【结论】
1、2D-1~H MRS检查于一次扫描即可同时获取多个部位的波谱信号,在节省时间的前提下能更全面、细致地了解病变及其周围组织的生化代谢特点,有利于病变内部及其周围区域间的相互对比;同时2D-1~H MRS可以自由选择适当采样体素进行分析,避免了非研究组织的干扰,提高了研究的准确性;
2、不同肿瘤在其正常参照区的波谱均表现为较高的NAA峰,相对较低的Cho及cr峰,各代谢物比值在三组间均无显著差异,符合正常脑组织的波谱特征。进行波谱分析时可将病灶对侧区作为正常参照。
3、三组肿瘤强化区波谱较正常区均有显著差异,共同表现为Cho跃居第一高峰,NAA及cr不同程度下降,这是一般脑肿瘤性病变的共同波谱特点,有助于发现常规MRI上显示不明显的脑肿瘤。脑膜瘤NAA峰较其余两组降低更明显,脑膜瘤组NAA/Cr较其余两组显著减低,Cho/NAA较其余两组显著增高,差异基础可能在于脑膜瘤为脑外肿瘤,代表神经元的NAA较低或缺如。据强化区的波谱差异可将不典型脑膜瘤或其他脑外肿瘤与脑内肿瘤更好的进行鉴别。胶质瘤与转移瘤组间各代谢物比值均无显著差异,提示强化区波谱对于胶质瘤与转移瘤的鉴别较为困难。Lac峰在三组中均有出现,提示肿瘤组织相对缺血缺氧,但对于良恶性肿瘤的鉴别意义不大;Lip峰在胶质瘤及转移瘤组均有出现,而脑膜瘤组未见出现,可能对恶性肿瘤的诊断有一定价值,但对胶质瘤或转移瘤的鉴别意义不大;
4、近侧水肿区波谱于胶质瘤仍可见较高的Cho峰及不同程度降低的NAA、Cr峰,胶质瘤组近侧水肿区Cho/cr、Cho/NAA较其余两组显著增高,NAA/cr较其余两组显著降低;而脑膜瘤与转移瘤在近侧水肿区具有较高NAA峰,较低的Cho及cr峰,两组之间及其与正常参照区的各代谢物比值均无显著差异。胶质瘤近侧水肿区出现波谱异常的病理基础在于胶质瘤具有向周围浸润生长的特性。根据近侧水肿区的波谱改变可更好的帮助胶质瘤等浸润性肿瘤与非浸润性肿瘤进行鉴别;础可能在于脑膜瘤为脑外肿瘤,代表神经元的NAA较低或缺如。据强化区的波谱差异可将不典型脑膜瘤或其他脑外肿瘤与脑内肿瘤更好的进行鉴别。胶质瘤与转移瘤组间各代谢物比值均无显著差异,提示强化区波谱对于胶质瘤与转移瘤的鉴别较为困难。Lac峰在三组中均有出现,提示肿瘤组织相对缺血缺氧,但对于良恶性肿瘤的鉴别意义不大;Lip峰在胶质瘤及转移瘤组均有出现,而脑膜瘤组未见出现,可能对恶性肿瘤的诊断有一定价值,但对胶质瘤或转移瘤的鉴别意义不大;
4、近侧水肿区波谱于胶质瘤仍可见较高的Cho峰及不同程度降低的NAA、cr峰,胶质瘤组近侧水肿区Cho/Cr、Cho/NAA较其余两组显著增高,NAA/cr较其余两组显著降低;而脑膜瘤与转移瘤在近侧水肿区具有较高NAA峰,较低的Cho及Cr峰,两组之间及其与正常参照区的各代谢物比值均无显著差异。胶质瘤近侧水肿区出现波谱异常的病理基础在于胶质瘤具有向周围浸润生长的特性。根据近侧水肿区的波谱改变可更好的帮助胶质瘤等浸润性肿瘤与非浸润性肿瘤进行鉴别;
5、高级别胶质瘤强化区Cho峰较低级别胶质瘤升高更加明显,NAA较低级别胶质瘤降低更加明显。高级别组强化区Cho/cr、Cho/NAA较低级别组显著增高,NAA/cr较低级别组显著降低;高级别组近侧水肿区Cho/cr较低级别组显著增高。依据以上高、低级别胶质瘤的波谱代谢差异可帮助进行胶质瘤的术前分级。Lac及Lip峰在高级别组出现的例数均较低级别组为多,但由于出现例数较少,其对胶质瘤分级的意义还有待进一步大样本研究。
6、影响波谱成像及分析的因素较多,现阶段MRS分析的精确性尚不高,各组肿瘤波谱存在着一定的重叠。MRS作为一种新的影像技术,虽然能提供病变及其周围组织丰富的代谢、生化信息,但不能完全代替常规MRI,只能作为MRI检查的有力补充。
【Objective】
1.To investigate the metabolic changes of 2D- multi-voxel proton magnetic resonance spectroscopy(2D-multi-voxel ~1H MRS) in enhancement areas of different brain tumors and to evaluate its role in differential diagnosis of brain tumors.
2.To investigate the metabolic changes of 2D-multi-voxel ~1H MRS in edema areas of different brain tumors and to evaluate its role in differential diagnosis of brain tumors.
3.To investigate the metabolic changes of 2D-multi-voxel ~1HMRS between high -grade and low-grade gliomas and to evaluate its role in preoperative judegment the grade of gliomas.
【Methods】
1.Investigation objects
61 cases of brain tumor patients underwent MR imaging,contrast-enhanced MR imaging and 2D-~1HMR spectroscopy imaging.In addition to some of Intracranial metastases tumors confirmed by clinical,all the remaining cases were Confirmed by postoperative pathology.In 61 cases,26 cases was glioma,in which 14 cases was low-grade(Ⅰ-Ⅱ) glioma,12 cases was high-grade(Ⅲ-Ⅳ) gliomas,andl7 cases was meningiomas,18 cases was metastatic tumor.
2.MRI scanning methods
All scanning adopt GE signa exciteⅡ3.0T MRI scanning equipment. Conventional MRI scan used eight Channel coil Dedicated for head.getting T1WI, T2WI image by SE and FSE Sequence and getting Enhanced image in T1WI after Gd-DTPA injection,Scan Parameters:T1WI(TR/TE,600/16ms),T2WI(TR/TE, 5100/138ms),Thickness 5-8mm,Pitch 2mm,FOV 24×18mm,matrix 512×288. ~1HMRS scanning used eight Channel Coil Dedicated for head.Adopted 2-D multi-voxel(PROBE/SI) PRESS sequence,and set TR /TE:1000ms/144ms. Frequency Coding set of 16,Direction is A/P,voxel thickness lOmm,Pitch 20mm, NEX 1,FOV18×18m.Scan positioning some in Enhanced-T1WI image of complete Axial and another in T2WI image of complete Axial,The MRS scan VOI Should Including tumor areas,peri-tumor edema areas and a part of normal areas away from tumor areas,but should try to avoid skull,fat,liquid Organization and so on.The MRS scan started after FWHM＜lOppm,chress＞98%.
3.Image postprocessing and survey data
On the" FuncTool' Workstations,All of cases setting three regions of interest (ROI),which are located respectively in enhanced tumor regions,edema regions near the enhanced areas for 1-2cm and normal regions away from tumor,in the "AI+MI" Images.Observed the changes of the metabolism in the corresponding spectrum images(SI),measured the relative ratio of Cho / Cr,NAA / C,Cho / NAA,and Recorded Lip and Lac whether appeare in Every cases.
4.Statistical analysis
SPSS 13.0 statistical package was used.The measurement data were represented as mean±standard.(1).comparing each relative ratio of metabolites of normal areas in the three tumor groups;(2).Comparing each relative ratio of metabolites between the enhanced areas and normal areas in each groups,and comparing each relative ratio of metabolites of enhanced areas in three tumor groups;(3).comparing each relative ratio of metabolites of edema regions in the three tumor groups;(4).Comparing each relative ratio of metabolites Respectively in enhanced region,edema regions between the high-grade gliomas and low-grade gliomas.one-way ANOVA was used in Comparison in different tumor groups,paired-samples T-test was used in Comparison between two regions in same tumor group,one sample T-test was used in Comparison between high-grade and low-grade gliomas.Testing standards "α" adopted 0.05.
【Results】
1.MRS appearance in normal areas
Spectrum image showed There were similar metabolites situation in normal regions among three groups,appearing highest NAA peak,lower Cr and Cho peak. Cho/Cr,NAA/C,Cho/NAA all showed no significance among three groups.No Lac or Lip peak appeared in normal areas.
2.MRS appearance in enhanced tumor areas
Spectrum image showed roughly similar metabolites situation in enhanced regions among three groups,appearing highest Cho peak,lower Cr and NAA peak Varying degrees,particular,Lower NAA appeared in meningiomas group. Comparison between enhanced and normal regions,showed higher Cho/Cr,Cho/ NAA and lower NAA/Cr in enhanced regions in each tumor groups,there was statistically significant difference between meningiomas and each of other tumor groups for NAA / Cr,Cho / NAA,appearing there were higher Cho / NAA and lower NAA/Cr in meningiomas group.There was no significant between glioma and metastatic tumor for all The relative ratio of Metabolites,There was no significant among Threee groups for Cho/Cr.Lac appeared in 3 cases of meningiomas,6 cases of gliomas and 4 cases of metastatic tumor,lip not appeared in no case of meningiomas group,4 cases of gliomas and 8 cases of metastatic tumor.
3.MRS appearance in edema areas
Spectrum image showed The metabolites situation in edema regions is different from glioma group to each of other groups,appearing higher Cho peak, lower NAA and Cr peak in glioma group,the similar metabolites situation between meningiomas and metastatic tumor groups,appearing higher NAA peak,lower Cho and Cr peak.on all metabolites ratio,there was statistically significant differences between glioma groups and each of other groups,appeared higher Cho / Cr and Cho / NAA,lower NAA/ Cr in glioma group.There was no significant between meningiomas and metastatic tumor groups for Cho / Cr,Cho / NAA and NAA/Cr.
4.different MRS appearance between high-grade and lowe-grade glioma
(1).different MRS appearance in enhanced regions
The Spectrum image showed in enhanced regions there were Increase Cho Peak both in high-grade and lowe-grade glioma groups,but higher in high-grade glioma groups than low-grade group,there were Reduced NAA Peak both in high-grade and lowe-grade glioma groups,but lower in high-grade glioma groups than low-grade group,Cr peak change little.There was significance in enhanced regions between high-grade glioma groups and low-grade group for Cho/Cr,Cho / NAA,NAA/Cr, showed higher Cho/Cr,Cho / NAA and lower NAA/Cr in high-grade glioma group. Lac appeared in 4 case of high-grade group,2 cases of lowe-grade group,Lip appeared in 3 cases of high-grade group,1 case of lowe-grade group.
(2).different MRS appearance in edema regions
The Spectrum image showed in edema regions there were higher Cho Peak and lower NAA peak both in high-grade and lowe-grade glioma groups.There was significance in edema regions between high-grade glioma groups and low-grade glioma group for Cho/Cr,showed higher Cho / Cr in high-grade group,but no significance for Cho / NAA,NAA/Cr between high-grade and lowe-grade group in edema regions.
【Conclusions】
1.2D-~1HMRS Technology can get Spectrum signals from different areas at one scanning,so that it not only get more comprehensive and Full information about the metabolism of tumor and The surrounding region tissues but also save time Greatly. At the same time,2D-~1HMRS Technology can select More appropriate and more exact voxel without inclusion of unwanted structures which may degrade the spectrum quality;
2.There were similar metabolites situation in normal regions among three groups, appearing highest NAA peak,lower Cr and Cho peak.no significance for all metabolites ratio among three groups,that is MRS appearance of normal brain.
3.Metabolites situation of enhanced areas were all different from normal areas in three groups,all appearing highest Cho peak,lower Cr and NAA peak Varying degrees,particular,Lower NAA appeared in meningiomas group,there was statistically significant difference between meningiomas and each of other tumor groups for NAA / Cr,Cho / NAA,appearing there were higher Cho / NAA and lower NAA / Cr in meningiomas group.The difference basis may lain in meningiomas does not contain neuron,so have lower or hiatus NAA peak therefore,based on all above MRS difference in enhanced areas,we can better distinguish meningiomas from other tumor.There was not significant for all the relative ratio of Metabolites between glioma and metastatic tumor in enhanced tumor areas,that is to say there was difficulty to differential diagnosis between glioma and metastatic tumor depend on MRS appearance in enhanced tumor areas.Lac is less significance to diagnosis from malignant tumor to benign tumor because Lac appeared in all tumor groups but appeared number was less in each groups.lip appeared in both gliomas and metastatic tumor groups,but no one in meningiomas groups,for this reason,it is possible for Lip can help diagnosis from malignant tumor to benign tumor better,but Lip is less significance to diagnosis between glioma and metastatic tumor.
4.Spectrum image showed that the metabolites situation in edema regions is different from glioma group to each of other groups,appearing higher Cho peak, lower NAA and Cr peak in glioma group,the similar metabolites situation between meningiomas and metastatic tumor groups,appearing higher NAA peak,lower Cho and Cr peak.There was statistically significant differences between glioma groups and each of other groups,appeared higher Cho / Cr and Cho / NAA,lower NAA/Cr in glioma group,The difference basis may lain in the characteristic of Infiltrate growth in glioma,based on different MRS appearance in edema regions,it is more easy to diagnosis glioma from other intracal tumor.
5.Cho Peak is higher in high-grade glioma groups than low-grade group in enhanced regions,NAA Peak lower in high-grade glioma groups than low-grade group in enhanced regions,there was significance in enhanced regions between high-grade glioma groups and low-grade group for Cho/Cr,Cho / NAA,NAA/Cr, showed higher Cho/Cr,Cho / NAA and lower NAA/Cr in high-grade glioma group. There was significance in edema regions between high-grade glioma groups and low-grade glioma group for Cho/Cr,showed higher Cho / Cr in high-grade group. based on different MRS appearance between high -grade and low-grade gliomas,it is better to help Preoperative pathological grade of gliomas.Though,"Lac","Lip" all appeared more in high -grade gliomas than in low-grade gliomas,the value of helping Preoperative pathological grade of gliomas is pend for studying further.
6.Here are a lot of Influencing factor for MRS Imaging and analysis,and there existence overlaps in Various tumor spectrum each other.the accuracy of MRS also is not high.Therefore,MRS as a new method can provide us More Metabolism information about tumor and the vicinity organizes,but only as the powerful replenish for MRI,not substitution.
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[20]. Shimizu H,Kumabe T,Shirane R,et al.Correlation between Choline level measured by Proton MR spectroscopy and Ki-67 labeling index Gliomas[J].American Journal of Neuroradiology,2000,21:659-665.
[21]. Go KG, Kamman R, Mooyaart El, et al. Localised proton spectroscopy and spectroscopy imaging in cerebral gliomas with comparison to positron emission tomography[J]. Neuroradiology,1995,37(3): 198.
[22]. Martin RC,Sawrie S, Hugg J,et al. Cognitive correlates of 1HMRS-detectedhippocampal abnormalities in temporal lobe epilepsy[J]. Neurology,1999,53(11):2052-2058.
[23]. Nelson E, Graves E, Pizkall A, et al. In vivo molecular imaging for planning radiation therapy of gliomas: an application of 1H MRS[J]. Magn Reson Imaging, 2002,16:464-762.
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[25].Hakumaki JM,Kauppinen RA.1H-NMR visible lipids in the life and death ofcells[J].Trends Biochem Sci,2000,25(8):357-362.
[26].Burger p.Apuzzo ML,ed.Classification,grading and patterns of Spread of malignant gliomas.American Assosiation of Neurological surgeons,1990:3-17
[27].Burger C,Vogel FS,Green SB,et al.Glioblastoma multiforme and anaplastic astrocytoma:pathologic criteria、and prognostic implications.Cancer,2000,56:1106-1111
[28].Burtscher IM,Skagerberg G,Geijer B,et al.Proton MR spectroscopy and preoperative diagnostic accuracy:an evaluation of intracranial mass lesions characterized by stereotactic biopsy findings.AJNR,2000,21:84-93.
[29].Croteau D,Scarpace L,Hearshen D,et al.Correlation between magnetic resonance spectroscopy imaging and image - guided biop- sies:semiquantitative and qualitative histopathological analyses of patientswith untreatedglioma[J].Neurosurgery,2001,49(4):823-829.
[30].Uematsu H,Maeda M,Itoh H.Peritumoral brain edema in intracranial meningiomas evaluated by dynamic perfusion weighted MR imaging:a preliminary study[J].Eur Radiol,2003,13(4):758-762.
[31].Law M.spectroscopy of brain tumors.Top Magn Reson Imaging,2004;15(5):291-313.
[32].许茂盛,潘智勇,曹志坚等.颅脑肿瘤强化周围区域的多体素氢质子波谱研究.中华放射学杂志,2003,37(12):1105-1110
[33].Fountas KN,Kapsalaki EZ,Gotsis SD,et al.In vivo proton magnetic resonance spectroscopy of brain tumors.Stereotact Funct Neurosurg,2000,74:83-94.
[34].HoweV FA,Barton SJ,Cudlip SA,et al.Metabolic profiles of human brain tumors using quantitative in vivo 1H magnetic resonance spectroscopy [J].Magn Reson Med.2003,49(2):223-232.
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[36].Tamiya T,Kinoshi to K,Ono Y,et al.Proton magnetic resonance spectroscopy reflects cellular proliFerative activity in astrocytomas.Neuroradiology,2000,42(5):333-338
[37].Kieffer SA,Chang JK.ed.Intracranial neoplasms in CT and MR imaging of the whole body.2003.124-206.
[38].Kim DG,Choe WJ,Chang KH,et al.In vivo proton magnetic resonance spectroscopy of central neurocytomas[J].Neurosurgery,2006,52(2):329-333.
[39].Weybright P,Maly P,Gomez-Hassan,et al.MR spectroscopy in the evaluation of recurrent contrast-enhancing lesions in the posterior fossa after tumort reatment[J].Neuroradiology,2005,47(7):541-549.
[40].Shimizu H,Kumabe T,Shirane R,et al.Correlation between Choline level measured by Proton MR spectroscopy and Ki-67 labeling index Gliomas.American Journal of Neuroradiology,2000;21:659-665
[41].Bendszus M,Warmuth-Metz M,Klein R,et aI.MR spectroscopy in glioma tosis cerebri[J].AJNR,2000,21(2):375-380.
[42].颅脑影像新技术诊断图谱.崔世民等.第一版,北京:人民卫生出版.2006.109
[43].Kimura T,Sako K,Gotoh T,et al.In vivo single-voxel proton MR spectroscopy in brain lesions with ring-like enhancement.NMR Biomed,2001,14:339
[44].Falini A,Calabrese G,Origgi D,et al.Proton magnetic resonance spectroscopy and intracranial tumours:clinical perspectives.J Neurol,1996,243:706
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[6].Ricci PE,Pitt A,Paul J.et al.Effect of voxel position on single-voxel MRspectroscopy findings[J].AJNR 2000,21:367-374.
[7].Robart D,Tien PH,Lai JS,et al.Single-voxel proton brain spectroscopy exam (PROBE/SV) in patiet with primary brain tumors[J].AJR,1996,167:201-209.
[8].(巴西)Brandao L.omingues R.C著:刘绮主译,脑磁共振波谱成像,天津:天津科技翻译出版公司,2005,119-156.
[9].雷霆.脑肿瘤学.第一版.北京:中国医药科技出版社.2004,3-5.
[10].Gonen o,Gruber S,Li SY.Multivoxel 3D proton spectroscopy in the brainat 1.5Versus 3.0 T:signal-to-noise ratio and resolution comparison[J].AJNR 2001,22:1727-1731.
[11].Sijens PE,van den Bent MJ,Nowak PJ,et al.chemical shift imaging reveals loss of brain tumor Choline signal after administration of Gd-contrast.Magn-Reson-Med,1997,37(2):222-225
[12].Tailor JS,Reddick WE,Kingsley PB,et al.Proton MRS after gadolinium contrast agent[R].Third Scientific Meeting and Exhibition of the Society of Magnetic Resonance.In:Proceeding of the Society of Magnetic Resonance. Nice, France, 1995,19-25.
[13]. Kendi T,Arikan OK, Koc C. MR spectroscopy in a cervical Abscess[J].Neuroradiology,2003;45:631-3.
[14]. Ott D,Hennig J,Emst T.Human brain tumors : Assessment with in vivo proton MR spectroscopy[J]. Radiology ,1993 ,186 :745-752.
[15]. von Kienlin M, Ziegler A, Fur YL, et al. 2D-spatial/ 2D-spectral spectroscopic imaging of intracerebral gliomas in rat brain. Mag Res Med ,2000,43:211-219.
[16]. Dowling C, Bollen AW, Noworolski SM,et, al. Preoperative proton MR spectroscopic imaging of brain tumors: correlation with histopathologic analysis of resection specimens[J]. AJNR 2001, 22: 604—612
[17]. Kugel H, Heindel W, Ernestus RI, et al. Human brain tumors, spectral patterns detected with localized 1HMR spectroscopy[J].Radiology, 1992, 183:701—709
[18]. Castillo M,Kwock L, Mukherji Sk.Clinical applications of proton MR spectroscopy[J]. AJNR, 1996,17.1-15.
[19]. Law M, Cha S,Knopp EA,et al.High-grade gliomas and solitary metastases:differentiation by using perfiision and proton spectroscopic MR imaging[J] .Radiology ,2002,222:715-721.
[20]. Shimizu H,Kumabe T,Shirane R,et al.Correlation between Choline level measured by Proton MR spectroscopy and Ki-67 labeling index Gliomas[J].American Journal of Neuroradiology,2000,21:659-665.
[21]. Go KG, Kamman R, Mooyaart El, et al. Localised proton spectroscopy and spectroscopy imaging in cerebral gliomas with comparison to positron emission tomography[J]. Neuroradiology,1995,37(3): 198.
[22]. Martin RC,Sawrie S, Hugg J,et al. Cognitive correlates of 1HMRS-detectedhippocampal abnormalities in temporal lobe epilepsy[J]. Neurology,1999,53(11):2052-2058.
[23]. Nelson E, Graves E, Pizkall A, et al. In vivo molecular imaging for planning radiation therapy of gliomas: an application of 1H MRS[J]. Magn Reson Imaging, 2002,16:464-762.
[24]. Angelie E, Bon martin A, Boudraa A, et al. Regional differences and metabolic changes in normal aging of the human brain:proton MR spectroscopicimaging study[J].AJNR,2001,22:119-27.
[25].Hakumaki JM,Kauppinen RA.1H-NMR visible lipids in the life and death ofcells[J].Trends Biochem Sci,2000,25(8):357-362.
[26].Burger p.Apuzzo ML,ed.Classification,grading and patterns of Spread of malignant gliomas.American Assosiation of Neurological surgeons,1990:3-17
[27].Burger C,Vogel FS,Green SB,et al.Glioblastoma multiforme and anaplastic astrocytoma:pathologic criteria、and prognostic implications.Cancer,2000,56:1106-1111
[28].Burtscher IM,Skagerberg G,Geijer B,et al.Proton MR spectroscopy and preoperative diagnostic accuracy:an evaluation of intracranial mass lesions characterized by stereotactic biopsy findings.AJNR,2000,21:84-93.
[29].Croteau D,Scarpace L,Hearshen D,et al.Correlation between magnetic resonance spectroscopy imaging and image - guided biop- sies:semiquantitative and qualitative histopathological analyses of patientswith untreatedglioma[J].Neurosurgery,2001,49(4):823-829.
[30].Uematsu H,Maeda M,Itoh H.Peritumoral brain edema in intracranial meningiomas evaluated by dynamic perfusion weighted MR imaging:a preliminary study[J].Eur Radiol,2003,13(4):758-762.
[31].Law M.spectroscopy of brain tumors.Top Magn Reson Imaging,2004;15(5):291-313.
[32].许茂盛,潘智勇,曹志坚等.颅脑肿瘤强化周围区域的多体素氢质子波谱研究.中华放射学杂志,2003,37(12):1105-1110
[33].Fountas KN,Kapsalaki EZ,Gotsis SD,et al.In vivo proton magnetic resonance spectroscopy of brain tumors.Stereotact Funct Neurosurg,2000,74:83-94.
[34].HoweV FA,Barton SJ,Cudlip SA,et al.Metabolic profiles of human brain tumors using quantitative in vivo 1H magnetic resonance spectroscopy [J].Magn Reson Med.2003,49(2):223-232.
[35].Meyerand ME,Pipas JM,Mamourian A,et al.Classification of biopsy confirmed brain tumors using single voxel MR spectroscopy[J].AJNR,1999,20(1):117-123.
[36].Tamiya T,Kinoshi to K,Ono Y,et al.Proton magnetic resonance spectroscopy reflects cellular proliFerative activity in astrocytomas.Neuroradiology,2000,42(5):333-338
[37].Kieffer SA,Chang JK.ed.Intracranial neoplasms in CT and MR imaging of the whole body.2003.124-206.
[38].Kim DG,Choe WJ,Chang KH,et al.In vivo proton magnetic resonance spectroscopy of central neurocytomas[J].Neurosurgery,2006,52(2):329-333.
[39].Weybright P,Maly P,Gomez-Hassan,et al.MR spectroscopy in the evaluation of recurrent contrast-enhancing lesions in the posterior fossa after tumort reatment[J].Neuroradiology,2005,47(7):541-549.
[40].Shimizu H,Kumabe T,Shirane R,et al.Correlation between Choline level measured by Proton MR spectroscopy and Ki-67 labeling index Gliomas.American Journal of Neuroradiology,2000;21:659-665
[41].Bendszus M,Warmuth-Metz M,Klein R,et aI.MR spectroscopy in glioma tosis cerebri[J].AJNR,2000,21(2):375-380.
[42].颅脑影像新技术诊断图谱.崔世民等.第一版,北京:人民卫生出版.2006.109
[43].Kimura T,Sako K,Gotoh T,et al.In vivo single-voxel proton MR spectroscopy in brain lesions with ring-like enhancement.NMR Biomed,2001,14:339
[44].Falini A,Calabrese G,Origgi D,et al.Proton magnetic resonance spectroscopy and intracranial tumours:clinical perspectives.J Neurol,1996,243:706