摘要
研究背景
脑胶质瘤是最常见的颅内原发性肿瘤,文献报道约占颅内肿瘤的35.26%～60.96%。脑胶质瘤呈侵袭性生长,综合治疗总体疗效不佳,尤其是高级别胶质瘤术后复发快、预后差,严重威胁人类健康,是神经外科治疗中最棘手的恶性肿瘤之一。
胶质瘤的治疗已达成共识:其治疗原则为在不加重损伤神经系统功能前提下,尽量广泛切除肿瘤,术后给予个体化放化疗综合治疗。手术全切除是胶质瘤治疗的首要环节;其次是既要全切或次全切肿瘤,又要考虑患者术后生存质量。然而胶质瘤由于其浸润性弥漫性生长而边界不清使得全切困难,所以精确定位肿瘤手术边界非常重要。限于目前还没有更好的手段判断瘤组织边界,所以在临床上还是以T1加权像增强作为一种较可靠的指标,来反应瘤组织边界,手术亦沿着病灶强化与水肿带间胶质增生界面进行。然而MRI上强化区并非肿瘤的真实边界,仅仅代表血脑屏障的破坏程度,胶质瘤瘤周水肿区仍有肿瘤细胞浸润。但脑肿瘤尤其是胶质瘤其浸润的邻近组织区域通常不强化,这无疑将低估病灶范围,而T2高信号区内至少有一部分是由肿瘤浸润所致,但受肿瘤周围组织水肿的影响,此法易于导致高估肿瘤范围。
常规CT、MRI检查只能对颅内肿瘤位置、大小及形态做出初步诊断,而临床常常希望得到更全面、准确的术前定性、肿瘤分级及肿瘤范围等方面的信息。活体质子磁共振波谱(proton magnetic resonance spectroscopy,~1HMRS)近年来已越来越广泛的应用于临床,它能够无创性检测肿瘤组织及正常脑组织代谢物的变化,通过各种代谢物及其比值来对脑肿瘤进行诊断及鉴别诊断、分析肿瘤的恶性度并进行分级、对肿瘤疗效进行评价、检测肿瘤的复发及判断肿瘤的预后等。MRS成像能从纤维或正常组织中区别出原发或肿瘤浸润病灶,可根据肿瘤区波谱与正常脑组织及水肿区波谱的不同进行量化分析。对于观察肿瘤的生物学特性,确定肿瘤性质和范围有着重要作用。
如何做到广泛切除胶质瘤同时尽量保护神经功能?氢质子磁共振波谱成像应用于胶质瘤边界确定的前景如何?利用MRS实现对胶质瘤鉴别诊断、定性分级的研究非常多,但国内外尚无文献系统报道利用磁共振波谱评估胶质瘤瘤周浸润进而指导手术和放疗的研究。本实验旨在采用二维多体素氢质子磁共振波谱扫描系列(2D-multi-voxel ~1HMRS),术前前瞻性分析胶质瘤患者常见波谱代谢物及其比值情况,结合术后标本Ki-67阳性肿瘤细胞在瘤周水肿带的分布,探讨磁共振波谱在胶质瘤瘤周浸润、肿瘤细胞增殖活性方面的应用。
研究目的
1.采用二维多体素氢质子磁共振波谱成像(2D-~1HMRS)技术,前瞻性研究幕上可疑胶质瘤瘤体强化区、瘤周近侧水肿带及对侧相应解剖部位常见波谱代谢物比值改变特点;
2.分析增殖细胞的核抗原ki-67在胶质瘤术后标本中瘤体及瘤周近侧水肿带的表达情况;
3.比较胶质瘤瘤体、瘤周近侧水肿带波谱各代谢物比值与ki-67表达的相关性,探讨磁共振波谱成像技术评估胶质瘤瘤周浸润及增殖活性等生物学行为的可能性。
材料与方法
1.研究对象
2007年1月-2008年4月,前瞻性顺序收集幕上半球可疑胶质瘤患者16例,其中男9例,女7例;年龄21～52岁,平均38.4岁。所有病例经术后病理证实,其中低级别胶质瘤(WHOⅠ—Ⅱ)6例,高级别胶质瘤(WHOⅢ一Ⅳ级,GBM如坏死囊变明显则予以剔除)10例。所有患者术前均无放化疗病史,既往无颅内炎症、外伤等相关病史。
2.MRI检查方法
所有检查经患者家属知情同意,于术前72h以内检查并采集数据。采用GEsigna 3.0T超导磁共振扫描设备。自旋回波(SE)序列和快速自旋回波(FSE)序列获得常规MRI平扫T1、T2加权像(T1WI、T2WI)。扫描参数如下:T1WI(TR/TE,600/16ms),T2WI(TR/TE,5100/138ms),层厚5—8mm,层间距1.5mm。磁共振波谱扫描采用二维多体素(2D—multi—voxel)点分辨波谱(pointed—resolvedspectroscopy sequence,PRESS)成像序列,TR/TE:1000ms/144ms,体素厚度(voxel thickness)10mm,层间距2mm,NEX 1。于T2WI平扫病变最大直径轴位层面作为定位层面。波谱扫描野(field of view,FOV)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。相位矩阵160×160,感兴趣区(region of interest,ROI)大小1cm×1cm×1cm～1.5cm×1.5cm×1cm。体素定位尽量避免含骨、血管、脑脊液、脑皮层,囊变坏死、钙化或瘤卒中区域。自动预扫描完成匀场及水抑制。以T1WI增强区域定义为瘤体,瘤周水肿带定义为T2WI高信号且无增强区域,分别于瘤体内、瘤周水肿带2厘米范围内及对侧相应解剖部位采集数据。为避免顺磁性对比剂对检查结果的影响,波谱数据采集尽量在增强扫描前完成。
3.图像后处理与数据测量
采用Sun sparc ADW4.0图像处理工作站,仪器自带FuncTool软件包进行图像后处理。同时获得波谱图(spectrum)、代谢与解剖图的叠加图(简称“代解图”)。感兴趣区(ROI)分别位于肿瘤强化明显区域(ROI—1)、瘤周近侧水肿带2cm范围内(ROI-2)以及远离病变的正常脑组织区域(ROI-3)。以水为参考物,其化学位移为4.7ppm×10—6,NAA位于2.02ppm,Cr位于3.02ppm,Cho位于3.22ppm。在“代-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。以曲线下面积的积分代表峰值,记录各ROI的Cho/Cr、NAA/Cr及Cho/NAA三个代谢物相对比值,结果以均数±标准差(x±s)表示。
4.组织学检查
以脑沟(额上沟及颞上、下沟)、侧裂或皮层血管定位方向,术中瘤体及瘤周水肿带完整连续切除以获得波谱ROI区与病理标本的一致性。所获手术标本即刻甲醛固定,石蜡包埋切片(4μm层厚),常规HE染色并Ki-67标记。染色结果经神经病理医师单盲检查,细胞核异形性明显并染色阳性者视为具有增殖活性的肿瘤细胞。200倍镜下随机选取大小为33μm×33μm的6个视野,于瘤细胞密度最高区域计数活性肿瘤细胞。引用Stadlbauer的方法,具增殖活性的肿瘤细胞百分数为肿瘤细胞计数与总细胞数比值,结果TI以(?)±s(%)表示。
5.统计学分析
分别计算肿瘤三个不同区域波谱各代谢物比值的平均值,计量资料结果以(?)±s表示,SPSS13.0统计软件分析资料。采用单因素重复测量方差分析,两两比较采用LSD法;瘤体强化区与水肿带样本均数间两两比较采用配对t检验。波谱代谢物比值与增殖细胞核抗原ki-67表达采用一元直线相关分析,结果以Pearson系数表示,相关程度描述引自ZOU等对相关系数定义。P＜0.05认为有统计学差异。
结果
1.胶质瘤不同区域波谱代谢物浓度特点
与正常脑组织波谱代谢峰值图一致,胶质瘤肿瘤对侧相应白质内波谱代谢物均表现为NAA峰最高,Cr峰与Cho峰不同水平较低;肿瘤组织与瘤周近侧水肿带Cho明显上升成最高峰,NAA与Cr出现不同程度的下降,其中以NAA更为显著。上述变化以瘤体尤其明显,但从瘤体、瘤周近侧水肿带至病灶对侧相应白质,上述变化并不总是具有“渐变”性。
2.胶质瘤不同区域波谱代谢物比值变化
胶质瘤肿瘤对侧白质内波谱代谢物浓度比值NAA/Cr最高为1.559±0.200,Cho/Cr次之为0.878±0.138,Cho/NAA最小为0.605±0.123;肿瘤强化区Cho/Cr、Cho/NAA比值上升,分别为2.212±0.566,2.880±0.677;NAA/Cr比值下降为0.762±0.177;瘤周近侧水肿带波谱代谢物比值变化趋势同瘤体强化区,Cho/Cr、Cho/NAA比值分别为1.488±0.156、1.490±0.355,NAA/Cr比值为1.152±0.139。从瘤体、瘤周近侧水肿带至对侧白质,上述比值变化亦并非总具有“渐变”性。瘤体中心强化区域,瘤周近侧水肿带及对侧脑白质相应区域上述代谢物比值差异性两两比较,具有统计学意义。
3.胶质瘤瘤体及瘤周近侧水肿带病理形态学观察
光镜下见瘤体强化区与瘤周水肿带常规病理明显不一。瘤周水肿带细胞稀疏背景透亮,肿瘤细胞密度明显降低、瘤细胞核异型性及核分裂相程度等形态学大体观察较瘤体区明显减轻,未见明显的肿瘤坏死区域,但瘤周水肿带内同样可见不同程度的血管内皮细胞增生。此外,瘤体强化区与瘤周水肿带似乎可见一组织学界限明显的移行带。
4.增殖细胞的核抗原Ki-67在胶质瘤瘤体及瘤周近侧水肿带的表达
术后病理ki-67染色结果,瘤体强化区具增殖活性的肿瘤细胞密度为7.87%±2.02%,瘤周近侧水肿带1.58%±0.44%;重症脑外伤手术切除的内减压脑水肿组织ki-67染色结果阴性。瘤体强化区与瘤周近侧水肿带组织两者ki-67染色结果比较差异性具有统计学意义。
5.波谱代谢物比值与增殖细胞的核抗原ki-67表达相关性
瘤体Cho/Cr比值与ki-67表达正相关(r=0.603,P=0.000),瘤周近侧水肿带Cho/Cr比值与ki-67表达不相关(P=0.075);瘤体及瘤周NAA/Cr比值与ki-67表达均不相关(P=0.632、0.835);瘤体及瘤周近侧水肿带Cho/NAA比值与ki-67表达水平均显著正相关,相关系数r分别为0.842、0.514(P=0.000)。
结论
1胶质瘤瘤周近侧水肿带存在病理性波谱,提示胶质瘤水肿带内浸润生长特性,现有强化边界不能准确反应病灶范围。2D-1H MRS能进一步发现常规MRI上未能显示的肿瘤区域,从而具有确定胶质瘤瘤周肿瘤浸润范围的潜能。
2自瘤体强化区、瘤周水肿带至对侧相应部位,胶质瘤波谱代谢物浓度及比值并非总是阶梯式“渐变”;强化区亦并非总是波谱浓度及比值最高点,部分患者瘤周近侧水肿带代谢更为活跃。既反应胶质瘤不均匀生长,又可为临床靶向活检明确病理级别提供可靠依据。
3瘤周近侧水肿带显微镜下见瘤细胞密度,核大小、异型性、核分裂相等核形态学与瘤体强化区不一致,瘤周近侧水肿带与瘤体强化区似有一组织学移形带。而Ki-67蛋白在两个区域染色同样存在差异,提示不同的细胞增殖活性。
4瘤体强化区Cho/Cr比值与Ki-67蛋白染色强度正相关,而Cho/NAA比值在瘤体强化区及瘤周近侧水肿带均与Ki-67蛋白染色强度正相关,说明Cho/NAA比值更能准确评价胶质瘤的浸润和增殖生物学特性。
5现有波谱代谢物比值界定的只是瘤周浸润的大致范围,本组资料尚不能得出波谱代谢物比值的精确临界值来区分肿瘤浸润组织与正常脑组织,上述问题的解决有待进一步研究。
Background
Glioma is the most common primary intracranial tumor,it account for about 35.26%~ 60.96%of intracranial primary tumor.Because of its invasively growth,the outcome were poor even after all kinds of treatment for glioma patients,especially for high grade gliomas such as multiform gliolbastoma,rhey recurrent quickly with very poor prognosis.Nowadays glioma is a serious threat to human health and one of the most difficult malignant tumors for the neurosurgeon.
People have reached a consensus on the treatment for gliomas:the principle of treatment for gliomas are resecting the tumor as much as possible and mostly protecting the nervous system function,then giving comprehensive treatment such as radiotherapy and chemotherapy individually after the operation.Surgical resection is always the primary treatment for gliomas;Meanwhile,it is necessary to consider the patients'quality of life while resecting the whole or sub-total of tumor.However,because of its infiltrative growth and unclear border, it is difficult to make total resction for gliomas.So get the precise border is very important for the glioma operation.Since there is no better means to determine the tumor boundaries,neurosurgeons still consider the enhanced tumor region on T1-weithted images as a reliable indicator for the border.The resection is also operated along the gliosis band between the enhanced tumor centre and the edeme tissue.However, the enhanced tumor border on MRI is not the real boundary of gliomas, it is only the representative of damage to the blood-brain barrier, There is still tumor cells infiltration in the peritumoral edeme zone.But the infiltrated neighboring region of brain tumor do not usually enhance on routine MRI,this will undoubtedly underestimate the extend of lesions.The high signal area on T2-weighted imaging are caused by the tumor cell infiltration
Partly,this method is easy to overestimate the tumor extent by the impact of the surrounding edema tissue.
Conventional CT、MRI examination can only provide preliminary information for diagnosis about tumor location、size and shape.Doctors usually want to obtain much more comprehensive and accurate preoperative information about tumor grading,the extend of tumor infiltrating and so on.The in vivo magnetic resonance spectroscopy has been used more and more widely by clinical research in recent years,It can detect the metabolic changes of both tumor area and normal brain tissue non-invasively.It can make diagnosis and differential diagnosis for varying brain tumor by the metabolic concentration and ratios changes, analyse the malignance and grading for the tumor,evaluate the treatment outcome,detecte the recurrences and evaluate the prognosis for varying tumors.MRS imaging can find the difference between the normal tissue and primary or infiltrating tumor region in the fiber,analyse the changes in the tumor centre,the normal brain tissue and the edema zone.It plays an important role in observing the biological characteristics and determining the extent and nature of tumors.
How to reach extensive resection and greatest protection of nerve function for glioma patients? How about the prospect of hydrogen proton magnetic resonance spectroscopy imaging in determining the border of glioma?There are to much research on differential diagnosis、malignance grading for glioma by using of magnetic resonance spectroscopy,but systemic research about using magnetic resonance spectroscopy to assess glioma infiltration and then to guide surgery and radiotherapy is rare both at home and abroad.The purpose of our experiment is prospectively analyzing the common spectroscopic metabolic ratios of glioma patients by using two-dimensional multi-voxel proton magnetic resonance spectroscopy scan sequence(2D-multi-voxel 1H-MRS),detecting the express of Ki-67 antigen in the different area of the post-operative pathological sample,and then investigating the application of magnetic resonance spectroscopy in evaluating glioma tumor cell invasion,tumor proliferation activity.
Purposes of the research
A prospective study was performed on 16 cases of consecutive patients with suspected supratentorial hemispheric gliomas.All the patients underwent routine MR and MRS examination using uniform procedures,and then surgical resection within 72 hours of the MR examination.The common spectroscopy metabolic ratios were obtained from the enhanced tumor center、the peritumoral edema zone and the contralateral corresponding area by two-dimensional multi-voxel proton magnetic resonance spectroscopy imaging(2D-1HMRS) technology. Proliferative activity of the tumors in both the tumor center and the peritumoral edema zone were assessed by Ki-6? immunochemistry(Mb-1) on paraffin embedded tumor sections.Spectroscopic data was compared with Ki-67 labeling index,we also observe the histologic changes such as histological subtype,cellular atypia,cellular density in the different regions.By studing the correlation between spectroscopy metabolic ratios and the expression of ki-67 antigen in both the enhanced tumor center and peritumoral edema zone,we seek to explore the possibility of magnetic resonance spectroscopy in evaluating the biological behavior of invasion and proliferative activity in glioma patients.
Materials and Methods
1.objects of research
Between January 2007 and April 2008,a prospective study was performed on 16 cases of consecutive patients with suspected supratentorial hemispheric gliomas.There were nine male and seven female patients, aging from 21 to 52 years old,the average age was 38.4 years old.All of the cases were confirmed by postoperative pathology.There were six low-grade(WHO gradeⅠ-Ⅱ) and ten high-grade tumors(WHO gradeⅢ-Ⅳ, multiform glioblastomas showed cystic or obvious necrosis were removed). All of the patients had no preoperative history of radiotherapy and chemotherapy,no previous intracranial inflammation or infection,no brain trauma and other related medical administration history.
2.Magnetic resonance imaging examination
All the patients had informed consent with the families,the spectroscopy data collection were carried out within 72h before the surgical resection.Here we use the signa 3.0T superconducting magnetic resonance scanning equipment by GE company.The routine MR T1 and T2-weighted image were completed
by Spin-echo(SE) and fast spin-echo(FSE) sequences.The scanning parameters were as follows:T1WI(TR/TE,600/16ms)、T2WI(TR/TE, 5100/138ms)、thickness 5-8mm、Pitch 1.5mm.The point resolved spectroscopy(pointed-resolved spectroscopy sequence,PRESS) sequence was used for the multi-voxel two-dimensional magnetic resonance spectroscopy scanning.TR/TE:1000ms/144ms,voxel thickness 10mm, Pitch 2mm,NEX 1.The maximum lesion diameter on the T2WI axial imaging was selected as the reference.The field of spectral scanning(field of view,FOV) vary depending on the volume of the lesions,it should include the enhanced tumor center,the peritumoral edema zone and the contralateral corresponding normal brain tissue far away from the lesion itself.Phase matrix 160×160,the ROI(region of interest)were 1cm×1cm×1cm～1.5cm×1.5cm×1cm.The voxel positioning should avoid including the bone、blood vessels、cerebrospinal fluid、cerebral cortex、cystic necrosis、calcification and hematoma by tumor themselves.The shimming and water suppression were fulfilled automatically by pre-scanning.The enhanced regions on T1WI were defined as the tumor center,the peritumoral edema zone were defined as high signal on T2WI without enhancement.The spectroscopy data were acquired from the tumor center、the peritumoral edema zone about two centimeters away from the tumor center and the contralateral corresponding white matter respectively.In order to avoid the impact of paramagnetic contrast agent on the spectral data results,the spectroscopy acquisition were achieved before the enhancing scan as much as possible.
3.Image post-processing and spectroscopy data acquisition
The Sun sparc ADW4.0 image processing workstation and its own FuncTool image post-processing software were used to analyze the data.It can automatically obtain spectral peak map and metabolic-anatomic imaging at the same time.Regions of interest(ROI) were located in significantly enhanced tumor region(ROI-1),peritumoral edema zone 2cm away(ROI-2) and the normal brain tissue(ROI-3).The water signal was the internal reference,its chemical shift is 4.7ppm,NAA is located at 2.02ppm,Cr 3.02ppm and Cho 3.22ppm.Observe the metabolite concentrations distribution on the metabolic-anatomic map and the peak value on the spectroscopy map.The area under the curve representative the peak concentrations.Record the Cho/Cr、NAA/Cr and Cho/NAA ratios of the three ROI,the result were expressed in way of mean±standard deviation(x±s).
4.Histology examination
During the surgical resection,we orient the direction by distinguishing the brain sulcus that can be seen clearly such as the superior frontal sulcus、the superior and inferior temporal sulcus、the sylvian fissure and so on.In order to ensure the spectral ROI and the pathological specimens were point-to-point consistent,we consecutively and completely resect the tumor and the peritumoral edema zone tissue.The surgical specimens obtained were immediately fixed with formalin,the thickness of paraffin-embedded sections were 4μm, conventional HE staining and Ki-67 antigen staining were finished.The results were judged single-blindly by skilled neurological pathologists.The cell with significantly nuclear atypia and Ki-67 staining positive were regarded as proliferative activity tumor cell.Six field by size of 33μm×33μm were randomly selected under the 200 times microscope,we count the highest density for tumor cells activity.Quote Stadlbauer'method,The ratio of positive tumor cells /total cells as a percentage was defined as the proliferative activity tumor cell density.
5.Statistical analysis
Calculate separately the average value of metabolic ratios in the three different regions,the results measured were expressed as(?)±s.SPSS13.0 statistical analysis software was used.Using repeated measure ANOVA,the means were further compared by LSD method;The differences between the tumor center and the edema zone were compared by paired-samples T test.The linear correlation were used to analyze the relationship between the spectroscopy metabolite ratio and the Ki-67 protein expression,we describe the correlation by using Pearson coefficients,the results were explained from ZOU.P＜0.05 was considered there were significant differences.
Results
1.The spectroscopy concentrations of different tumor regions.
The spectroscopy peak map of the contralateral corresponding white matter were the same as normal brain tissue:NAA was the highest,Cr and Cho peaks were lower in different levels.The Cho concentration were increased significantly in both tumor center and the peritumoral edema zone,Cr and NAA were decreased,especially remarkable for the concentration of NAA.But from the tumor center、the peritumoral edema zone to the contralateral corresponding white matter,these changes do not always have a“gradual”nature.
2.The spectroscopy metabolite ratios in different tumor regions.
The spectroscopy metabolite ratios of NAA/Cr、Cho/Cr and Cho/NAA in the contralateral white matter region were 1.559±0.200、0.878±0.138、0.605±0.123 respectively;In the enhanced tumor center,the Cho/Cr and Cho/NAA ratios were increased to 2.212±0.566,2.880±0.677, the NAA/Cr ratios were decreased to 0.762±0.177;In the peritumoral edema zone,the ratios of Cho/Cr、Cho/NAA and NAA/Cr were 1.488±0.156、1.490±0.355 and 1.152±0.139 respectively.All of the metabolic ratios changed in the same trend as the tumor center. But from the enhanced tumor center、the peritumoral edema zone to the contralateral corresponding white matter regions,the ratios were not always changed step by step in the same way as the metabolic concentration.There were significant statistical differences among these metabolite ratios when compared with each other.
3.Pathomorphological observation of tumor center and the peritumoral edema zone tissue.
The conventional pathology were significant different between the tumor center and the peritumoral edema zone tissue under light microscope.The background of edema tissue weresparse with significantly reduced tumor cells density.The nuclear morphology such as atypia and mitosis in the edema zone were not so significant as the tumor center.There was no obvious necrosis in this region,we could also see different degrees of vascular endothelial cell proliferation.In addition,there seemed to be an obvious transition band between the enhanced tumor center and the peritumoral edema zone.
4.The expression of Ki-67 protein.
The ki-67 staining results in the postoperative pathologic Samples were shown as follows:the proliferative activity tumor cells density of the tumor center were7.87%±2.02%,while the peritumoral edema zone were 1.58%±0.44%;we could not see positive staining in the surgical resected edema tissue from traumatic brain injury patients.The difference Of ki-67 staining results betweent the enhanced tumor area and peritumoral edema zone were statistically significant.
5.The correlation between the spectroscopy metabolite ratios and the expression of ki-67 protein.
There was a positive correlation between the Cho/Cr ratios and the expression of ki-67 protein in the tumor center,the value of correlation coefficient was 0.603,but in the peritumoral edema zone this correlation did not exist,We could not see any relevance between the NAA/Cr ratios and the ki-67 protein expression both in the tumor center or in the peritumoral edema zone.The Cho/NAA ratios and the ki-67 protein levels were positive correlated in both the tumor center and the adjacent edema tissue.The Correlation coefficient were 0.842 and 0.514 respectively.
Conclusions
1.The pathological spectrum existed in the peritumoral edema zone suggested that there were infiltrating tumor cells in this area and the routine MRI can not define the accurate boundary of gliomas.The 2D-1HMRS can find new lesions that were not showed on routine MRI and have the potential of determining the accurate tumor cells infiltrating boundary.
2.From the enhanced tumor center、the peritumoral edema zone to the contralateral corresponding white matter,the spectroscopic metabolic concentration and ratios do not always change step by step.The highest spectral concentration and ratios were not always positioned in the tumor center.
The metabolism were more active in the edema zone in some patients.It suggest that glioma growth inhomogeneous,the MRS could provide a reliable targeted biopsy point for the pathological diagnosis.
3.The tumor cells density,nuclear morphology index such as the nuclear size、atypia and mitosis in the peritumoral edema zone under the microscope were obviously different with the Enhanced tumor center.There seemed to be a transitional tissue band between these two regions.The difference of the Ki-67 protein staining between these two region were signicant,suggesting the different tumor cells proliferative activity.
4.The Cho/Cr ratios and Ki-67 protein staining intensity were positive correlated in the enhanced tumor center,there were also positive correlation between the Cho/NAA ratio and Ki-67 protein staining both in the tumor center and the peritumoral edema zone,suggesting that the Cho/NAA ratios were more accurate for evaluating the biological properties of invasion and proliferation in gliomas.
5.The infiltrating tumor boundary defined by spectroscopy metabolite ratios were not accurate,our research can not obtain the precise cut-off value to distinguish the tumor-infiltrating tissue from the normal brain tissue.These questions mentioned above still need further study.
引文
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