摘要
[背景和目的]脑神经胶质瘤(简称脑胶质瘤)是最常见的颅内恶性肿瘤。近年来,随着影像学技术的进步,脑胶质瘤术前定位、定性诊断水平均已有长足进步,许多新的治疗方法在临床应用中也取得显著进展。但在总体上,脑胶质瘤治疗并未获得突破性进展,仍是临床公认的难题。基本的治疗手段是手术切除结合放疗和化疗。其中,外科手术质量是影响患者预后的决定性因素,肿瘤切除彻底与否与患者预后直接相关。在保留神经功能的同时,争取手术完全切除肿瘤是脑胶质瘤治疗的理想方法。脑胶质瘤能否完全切除,一方面取决于术中对肿瘤病灶的准确定位;另一方面取决于术中对肿瘤边界的精确判断和对残余肿瘤的准确识别。随着神经导航系统在神经外科临床应用,绝大多数脑胶质瘤的手术入路选择、术中定位和快速准确发现病灶的问题已获解决。由于脑胶质瘤浸润性生长的生物学特性,术中往往难以完全切除,术后肿瘤残余病例可高达70%左右。为了解决胶质瘤手术残余的问题,实现在保护神经功能前提下,最大限度切除肿瘤,延长患者生存期的目标,许多先进技术手段相继引入、应用于神经外科术中,如神经导航系统、术中影像手段(包括术中CT、术中MRI等)、术中荧光显微镜、术中流式细胞仪等。但受各种条件限制,上述方法尚不能在临床广泛使用。
相对其他术中影像技术手段,超声不仅具有经济、易行和可随时反复检查的特点,更突出优势在于它可以获得实时影像。术中超声实时肿瘤病灶定位及引导手术的价值已为神经外科临床认可。对超声判断肿瘤边界,识别残余肿瘤,控制肿瘤切除范围方面的应用价值尚有争论。其原因在于,目前所见相关研究中,评价超声诊断的对照标准各异,大多数采用术后早期CT或MRI检查,少数则采用病理组织学检查,且均通过病理学对照评价超声诊断残余肿瘤准确性及提高肿瘤切除率价值;所采用超声探查技术各异,尚未建立统一、规范的方法;超声判断肿瘤边界和残余肿瘤的标准各异,缺乏统一认识。
目前所见脑胶质瘤术中超声应用研究中,研究对象均是拟行肿瘤根治术患者,单纯考虑超声对提高肿瘤完全切除的作用与价值。而对在功能区胶质瘤常选择的肿瘤部分或次全切除术中,利用术中超声在指导切除更多肿瘤组织的同时,如何利用超声保护重要皮层结构、避免导致或进一步加重神经功能障碍尚无深入研究。
术中超声在高级别脑胶质瘤术中应用识别肿瘤边界和残余肿瘤,虽经技术学改进,结果仍不理想。势必需要根据肿瘤病理组织学改变的特点,如肿瘤血管生成等,寻找新的超声技术途径,如多普勒超声、声学造影、谐波超声等,提高术中超声对高级别胶质瘤边界和残余肿瘤的识别能力。
针对上述脑胶质瘤术中超声应用背景,本课题对下面几个目的进行探讨。
(1)、通过病理学对照,评价超声诊断残余肿瘤价值。改进脑胶质瘤术中超声操作技术和方法,改善超声影像质量,减少不明确征象干扰,提高术中超声判断和识别能力
(2)、在脑胶质瘤根治术中应用术中超声,辅助切除残余肿瘤,通过与病理学检查结果对比,评价术中超声对提高肿瘤完全切除率的辅助价值。
(3)、于功能区皮层下脑胶质瘤次全切除术中,在应用超声识别残余肿瘤、提高肿瘤切除率的同时,研究利用超声保护功能区皮层的方法和价值。
(4)、通过能量多普勒超声(power Doppler ultrasound,PDU)测量血管指数(vascularity index,Ⅵ),反映高级别脑胶质瘤和瘤周水肿组织血管生成水平,比较其间是否存在显著差异。通过与免疫组化检查对比,判断不同部位Ⅵ与免疫组化测定微血管密度(microvessel density,MVD)间相关性。明确在高级别脑胶质瘤术中,应用PDU测量血管生成水平的病理学基础,及其临床应用对提高超声识别高级别胶质瘤边界能力的可靠性。
第一部分脑胶质瘤术中超声诊断残余肿瘤价值病理学评价
[目的]建立规范的脑胶质瘤术中超声探查方法,改善超声影像质量,通过病理学对照,全面、准确评价术中超声诊断残余肿瘤价值。
[方法]选择37例拟行肿瘤根治术脑胶质瘤病例。男性21例,女性16例,年龄14岁～62岁,中位年龄40岁。术前MRI诊断肿瘤单发病灶36例,多发1例,共38个病灶。所有患者均在超声辅导下手术,超声检查使用专用高频术中探头,气体消毒,检查时直接使用,无需无菌塑料套。根据术前MRI检查,选择手术切口和手术入路,颅骨骨窗必要时略扩大,以保障超声探头可满意于脑表面操作。当神经外科医生判断肿瘤病灶已完全切除后,取出手术残腔内脑棉片、清除组织碎片及凝血块等,反复冲洗后注满生理盐水。采用环形双平面扫查法,分别于肿瘤切除残腔内及邻近脑表面扫查。残腔内部探查时,变换探头角度与方向,始终保持扫查面与残腔表面贴近且平行。残余肿瘤超声判断标准:残腔壁内或表面见实质性强回声光团,则为阳性;未见异常回声则为阴性。残腔表面薄层强回声环不作为阳性判断标准。完整记录超声检查过程。超声判定无残余肿瘤时,于残腔各侧壁及底部共5处表面取少许组织,并标记取材部位。超声作出肿瘤残留阳性诊断时,除上述5处外,另于超声判定肿瘤残留处取材。所有术中取材术后均行病理组织学检查。对比超声与病理组织学检查结果,评价超声判断胶质瘤残余肿瘤能力和价值。
[结果]本组脑胶质瘤术中,超声诊断残余肿瘤敏感性、特异性及准确性分别为65.71%、98.34%和95.25%。假阴性诊断中的91.67%发生于高级别胶质瘤。
[结论]通过改进超声检查技术,采取环形双平面探查法获得高质量术中实时影像,降低了病理基础不确定的超声征象的出现率。病理学对照研究证实,超声可以作为脑胶质瘤切除术中实时判断残余肿瘤安全可靠的影像手段。
第二部分超声对提高脑胶质瘤完全切除率辅助价值评价
[目的]探讨在脑胶质瘤根治术中应用超声检查对减少残余肿瘤、提高肿瘤完全切除率的辅助价值。
[方法]脑胶质瘤根治术患者64例,选择高频专用术中探头,在常规显微手术结束时采用环形双平面扫查法行超声检查,判断有无残余肿瘤。并于超声判断残余肿瘤处及5处超声阴性部位取材。在超声辅助下,神经外科医生进一步切除所见肿瘤,术毕于切除处再次取材。所有取材术后送病理学检查。对比超声诊断与病理学结果,评价超声判断胶质瘤残余肿瘤能力和提高肿瘤完全切除率的辅助价值。采用SPSS13.0统计软件,应用x~2检验比较超声应用前后肿瘤完全切除率有无显著改变,取α=0.05水平。
[结果]常规手术结束时,肿瘤彻底切除13例(20.31%),低级别胶质瘤(世界卫生组织(WHO,World health organization)分级Ⅰ级、Ⅱ级)12例、高级别(Ⅲ级、Ⅳ级)1例;术中超声检查并进一步切除后,26例(40.63%,低级别胶质瘤24例、高级别2例)病理学证实肿瘤完全切除。低级别胶质瘤完全切除率显著提高(x~2=7.273,P=0.007),高级别胶质瘤完全切除率无明显改变(x~2=0.356,P=0.551)。
[结论]在低级别胶质瘤根治术中,超声可准确判断残余肿瘤,对提高肿瘤完全切除率有显著辅助价值,在高级别胶质瘤根治术中,对提高肿瘤完全切除率无明显作用,有待新技术、新方法的研究与应用。
第三部分脑功能区皮层下脑胶质瘤次全切除术中超声应用
[目的]研究功能区皮层下脑胶质瘤次全切除术中,利用超声保护功能区皮层,避免重要功能结构破坏导致神经功能障碍。
[方法]在术中超声辅助下,对功能区皮层下胶质瘤实施肿瘤切除共15例。肿瘤部位:近中央功能区10例,近枕叶视觉中枢3例,近外侧裂2例。所有患者术前均行MRI检查,明确病灶与功能区皮层关系,计算肿瘤病灶容积。根据术前MRI、CT影像检查资料,选择手术切口。颅骨骨窗范围以确保超声能直接于功能区皮层表面检查为度。在骨窗开放后,于硬膜外行超声检查,确定功能区皮层和肿瘤病灶具体位置及相互关系。选择功能区皮层范围外,距离肿瘤最近,且无较大血管走行的脑沟作为手术入路。于皮层下潜行,逐步接近肿瘤病灶。切除过程中,根据需要,可随时重复超声检查,了解切除范围。在切除与功能区皮层紧密相邻肿瘤部分时,可采取实时超声监视,于脑表面进行超声动态观察,判断切除腔壁与功能区皮层间的距离与关系,指导手术切除过程。在避免损伤功能区皮层的前提下,尽可能完全切除该处肿瘤组织。当术中超声显示切除范围到达肿瘤与功能区皮层交界处时,无论术中超声是否观察到残余肿瘤,均提示手术者不再于该部位进一步手术。记录残余肿瘤位置与残留病灶大小。对于远离皮层的其他部位肿瘤组织,则在超声指导下,作完全切除。术后病理诊断低级别胶质瘤8例,高级别7例。所有患者均于术后早期(7d内)行MRI检查,判断有无残余肿瘤并计算残余肿瘤容积。超声与MRI计算残余肿瘤容积方法采用以下公式:V=π×L×D~2/6(V:容积;L:长度;D:厚度)。比较术中超声与术后MRI对邻近功能区皮层的残余肿瘤容积测量结果,二者对应关系以好、一般、差表示,判定标准分别是超声与MRI计算结果间差别＜20%,20～30%和＞30%。采用SPSS13.0统计软件,应用两独立样本间t检验比较术中超声与术后MRI测量结果间差异,以两独立样本间秩和检验判断肿瘤容积和病理分级对超声判断准确性的影响。
[结果]手术结束时,超声于13例皮层下可见残余肿瘤,残余肿瘤容积0.62～17.78ml,平均5.49±5.69ml,2例超声未见残余肿瘤。所有病灶其他部位超声均未见残余肿瘤。术后早期MRI检查结果:与术前相比,全部15例功能区皮层结构均无影像学上进一步破坏表现。2例邻近皮层处未见肿瘤残留,与超声一致。另外13例可见皮层下残余肿瘤。MRI计算容积0.37～24.56ml,平均7.15±8.43ml。术后MRI与术中超声测量结果间无统计学差异(t=0.616,P=0.543)。3例手术切除腔其他部位可见残余肿瘤。术中超声与术后MRI测量皮层下残余肿瘤容积对应关系好9例(60.00%)、一般2例(13.33%)、差4例(26.67%)。统计学处理结果:超声与MRI间符合程度与胶质瘤病理分级无显著关系(Z=0.198,P=0.843);当肿瘤容积大于30ml时,二者间符合程度显著下降(Z=2.239,P=0.025)。全组无手术死亡,未发生与术中超声相关手术并发症。
[结论]在脑功能区脑胶质瘤切除术中,应用超声可帮助外科医生选择安全的手术入路。在超声监测下,可实时观察、判断肿瘤手术切除面与功能区皮层相互关系,在避免皮层损伤同时尽量切除肿瘤。肿瘤容积增大可导致术中超声判断准确性下降。
第四部分能量多普勒评价高级别脑胶质瘤血管生成病理学对照研究
[目的]通过与病理学、免疫组化检查对比,判断PDU检测VI与MVD水平相关性,明确PDU在高级别脑胶质瘤术中应用提高超声识别肿瘤边界能力的病理学基础及其应用的可靠性。
[方法]我院神经外科脑胶质瘤根治术中完成PDU检查,且术后病理检查证实高级别胶质瘤(WHOⅢ级、Ⅳ级)25例为本组研究对象。其中男性16例,女性9例,年龄26～54岁。21例为首次手术,4例为胶质瘤复发再次手术。PDU检查选用Philips HD11型超声诊断仪,配有PDU血流成像软件。采用C3—12型宽频探头。将探头直接放置于肿瘤表面或邻近肿瘤脑组织表面,常规二维超声探查后,于肿瘤边缘处行PDU检查。PDU检查取样容积包括部分瘤灶及瘤周组织。所有PDU检查均在相同检查条件下完成。选择PDU显示血流信号最丰富处图像存档分析。于此图像取样容积内,明确为肿瘤病灶和瘤周组织范围内,分别选取目标区域。术后采用Photoshop7.0定量分析各目标区域内彩色像素值、像素值及二者间比值。以VI值(VI=目标区彩色像素值/目标区像素值×100%)作为PDU定量血管指数(VI)。肿瘤切除过程中,在术中超声引导下,分别于PDU检查所选择的目标区域取材。术后采用CD34鼠抗人单克隆抗体SP法行免疫组织化学染色测定MVD,于低倍镜(40×)选择“热点”区域,然后于高倍镜(200×)下选取3个热点,计数染色呈阳性的血管数目,取3次平均数为MVD值。统计学处理:不同组之间VI及MVD比较采用组间t检验;组内VI与MVD进行双变量相关分析,以直线相关计算相关系数。
[结果]胶质瘤内部VI测定结果为13.52±3.57,明显高于瘤周组织(VI=7.69±2.46,t=6.73,P＜0.01)。免疫组化染色测定胶质瘤病灶中MVD为38.48±8.47个/HP,瘤周组织MVD为14.60±3.49个/HP,二者间差异显著(t=13.04,P＜0.01)。在肿瘤病灶内及瘤周组织,VI与MVD测值均有良好相关性(瘤灶内r=0.7471,P=0.0000;瘤周组织r=0.6718,P=0.0002)。
[结论]术中实时PDU对高级别脑胶质瘤瘤灶及瘤周水肿组织VI测值存在显著差异,且均与免疫组化MVD测值具有良好相关性,PDU可作为脑胶质瘤术中实时、无创的血管生成水平检测手段。证实了术中PDU准确地区分高级别脑胶质瘤瘤灶与瘤周水肿组织的病理学基础及其临床应用的可靠性,具体应用技术方法尚待进一步完善。
[Background and Objection]:Glial neoplasms are the most common malignant brain tumor.The reported incidence of primary glioma is 16.7 per 100,000 persons.In our country,gliomas constituted about 35.26%-60.96%(average 44.69%) of intracranial tumors.In the past decades,advances in neuroimaging techniques,as in computed tomography(CT),magnetic resonance imaging(MRI),functional MRI (fMRI),magnetic resonance angiography(MRA),position emission tomography (PET),magnetic resonance spectroscopy(MRS) and magnetoencephalography(MEG) etc,provided the means of high resolution imaging of the head and its contents. Preoperative accurate localization and differential diagnosis of brain glioma are not puzzlement for neurosurgeons.By the main time,accompaniment of those new concept and technique of therapy,there have been considerable progresses in the treatment of gliomas.But the prognoses of this malignant tumor are still unacceptable. The mean survival times for glioma are no more than several years,for glioblastomas are about 8 months.It is a great challenge for neurosurgeon to improve the therapy outcome that to prolong the free survival time.The concept has been confirmed by some uncontrolled and retrospective studies of surgical series and accepted by majority of the neurosurgeons that the most effective management course of gliomas, whether low-or high-grade,is maximum surgical resection followed by adjuvant irradiation and chemotherapy.Among these processes,the most dominating one is the surgical resection.Appropriate neurosurgical dissection often offers the patients with gliomas an improved quality of life,a prolonged survival,and an improved control of neurological defects.In order to obtain the best possible outcome for the patients,a real gross total glioma resection is desirable.An ideal surgical resection of glioma acquires accurate localization and precise delineation of the margin.With preoperative identify of the morphological features of gliomas by CT and MRI, especially guided by neuro-navigation system,it is a facility task for neurosurgeons to find a safe and quick route reaching the lesions.
It had been verified that a neurosurgeon's view of residual glioma alone could be incorrect.In about 70%of the high-grade gliomas,residual tumor could be demonstrated by early postoperative MRI.Therefore,many different intraoperative techniques are chosen to optimize the surgical result.It is well known that intraoperative MRI is the most reliable and valuable intraoperative imaging to evaluate the extent of resection,identify the residual glioma and improve the operative outcome,but it is too expensive for most clinics around the world.The intraoperative MRI technologies demand special equipment and solutions in the operating room.It cannot be adopted as routine application except few neurosurgical centers.One of the disadvantages of the navigation system is the inability to provide real time information during the operation if the neurosurgeons want;the other is brain shift caused by removal of tumor tissue and the lose of CFS,which will make navigation based on preoperative images inaccurate.
Because of its simple,quick and cheap handling,intraoperative ultrasound (IOUS) has been performed as an alterative real time imaging modality.Ultrasound has been shown to be especially efficacious for several functions,namely localizing, defining borders of lesions and differentiating the tumor from cyst or necrosis.A series reported results showed IOUS to be 100%effective in localizing almost all types of brain tumor.But the value of ultrasound for resection control was still controversial.The possible sources of this argument include:no unified technological manual for performing ultrasound exam during the operation;multiplicity of ultrasonic imaging standard for residual tissue and tumor borders;comparison of ultrasonic image with difference references;no study assessed the value of IOUS pathologically,for detecting residual glioma and improving removal rate.
An unobvious blind-spot in the reported papers about neurosurgical IOUS can be sough that almost all of the studies were focused on the patients intended total resection,but the value of it for protecting anatomy structure and neurological function in the patients with gliomas in eloquent areas who intended subtotal resection was ignored.Another notable weakness of routine IOUS for resection control is unascertainable in delineating the margin between the high-grade glioma and the peritumoral edema tissue.Some new ultrasonic concepts,namely Doppler ultrasound,harmonic imaging,contrasted-ultrasound,etc,were suggested useful to improve value of resection control on the basement of malignant pathology of glioma, especially the significant difference between the levels of angiogenesis within the tumor and outsides edema tissue.Reflecting these specifics,these studies included following objectives.
1.To evaluate the value of IOUS for detecting residual glioma by comparing with pathology.To retrofit the previously reported intraoperative artifices with new measures to overcome the uncertain variances among ultrasonographic images for the residual tumor caused by a diversity of the intraoperative ultrasonographic technique.
2.To evaluate the benefit of IOUS with technological improvements for detecting residual glioma and improving completely removal rate.
3.To evaluate the reliability and contribution of IOUS,in patients with gliomas in functional important regions and intended subtotal resections,for archiving the purpose to obtain maximum surgical dissection of glioma without violating the cortex of eloquent area.
4.To confirm the pathological mechanism of the PDU in improving the preciseness of routine ultrasound in delineating the gliomal margin.The capability and reliability of intraoperative PDU for distinguish glioma from edema tissue.The angiogenesis of high-grade gliomas and peritumoral edema are investigated by intraoperative PDU during the predictive gross total resection.Whether there is a significant difference between the levels of macroscopic angiogenesis within gliomas and surrounding edemas,measured by PDU shown asⅥ,is determined.The correlation between theⅥmeasured by PDU and microscopic angiogenesis (microvessel density) will be assessed by immunohistochemical examination.
Part One The value of intraoperative high-resolution ultrasound for detecting residual glioma:a histopathologial study
[Objective]:Some technological improvements were adapted:to elevate the imaging quality of intraoperative high-resolution ultrasound;to establish the intraoperative performing manual of ultrasound;increase the reliability and security of ultrasound in the resection of brain gliomas.The value of the retrofitted ultrasound for detecting residual glioma was assessed by comparing with histopathology.
[Methods]:Thirty-seven gliomas,gross total resection was intended in all cases, were examined by technologically improved high-resolution ultrasound at the end of conventional microneurosurgery.There were 21 men and 16 women,who ranged in age from 14 to 62 years(median 40 years).There were 38 brain lesions shown on preoperative MRI images.Single lesion was revealed in 36 cases and double in the other one.All of the operations were navigated by ultrasonography.Instrument used for IOUS scan was a GE-LOGIQ Book XP scanner.A special intraoperative high-frequency probe with small-footprint design,sterilized by epoxyethane,was used.The functional area of the transducer was moved on the surface of brain or inner wall of dissection cavity directly.The sterile plastic sheath that used in previous reported study was then unnecessary,There was no separate layer between the probe and the aim region except saline coupling the two superficies.Operative route was designed according to the preoperative MRI.Sometime,a slightly widen cranial hole was unavoidable for unrestricted local and perform of the probe.The ultrasound scanning was performed at the time that there was no residual tumor detected by neurosurgeon under the microscopy.Before ultrasound exam,the operation cavity was filled with saline,after the spatula and cottonoids in the operation cavity were removed completely to ensure good image quality.The scanning surface of the transducer was kept on a parallel with the target surface during the whole process. The positive ultrasonic diagnosis of residual tumor was made by revealed hyperechoic mass adhered to or under the cavity wall.The thin hyperechoic rim on the surface was considered no predictive value.The biopsy specimens were matched with every positive sonographic site as well as with every negative resection cavity in five sites.The ultrasonic diagnoses were compared to histopathology.
[Result]:With the benefits of special-design intrao-perative probe and new technique,the appearance of the ambiguous sonographic signs,matched with inhomogeneous histopathologic results,had been reduced.Sensitivity,specificity and accuracy of improved ultrasound in detecting residual tumor were 65.71%,98.34% and 95.25%,respectively.91.67%(11/12) of the ultrasonic pseudo-negative cases occurred in high-grade glioma.
[Conclusion]:With proper technological adjustments and then high image quality, IOUS could be used as a reliable real-time imaging measure with great security for detecting residual glioma.
Part Two The value of intraoperative ultrasound for improving the completely removal rate of brain gliomas
[Objective]:To evaluate the benefit of IOUS in detecting residual glioma and improving the completely removal rate.
[Methods]:Between Jun 2005 and Dec 2007,totally 64 gliomas intended gross total resection preoperatively were included in our study.IOUS was performed at the end of conventional micro-neurosurgery to detect residual tumor.Biopsy specimen was taken in each sonographic positive site and the other five negative sites scattered in the wall of resection cavity.Pathologic diagnosis of the biopsy specimens was matched with every positive sonographic site as well as with every negative site.If a sonographic positive diagnosis was upheld by neurosurgeon,with the navigation of ultrasound,an additional dissection for residual tumor was undertaken.A x~2 test was used to analyses whether there was a significant difference of the rate of radical resection caused by IOUS.
[Results]:Confirmed by postoperative histopathology,8 cases,32 cases,15 cases and 9 cases were sorted into WHO gradeⅠ-gradeⅣ,respectively.Among the 53 positive sites marked by ultrasound,48 true and 5 false positive diagnoses were revealed by histopathology.In the 320 sonographic negative sites,diagnoses of 284 sites were true and of other sites were false.Sensitivity,specificity and accuracy of ultrasound in detecting residual tumor were 57.14%,98.27%and 89.01%, respectively.Pathologic total glioma resection was recorded in 13 cases(20.31%,4 gradeⅠ,8 gradeⅡ,1 gradeⅢ) at the end of conventional micro-neurosurgery.After additional resections navigated by ultrasound,total resection was obtained in 26 cases(40.63%,7 gradeⅠ,17 gradeⅡ,2 gradeⅢ).The results show the rate of total resection in low-grade glioma group was increased significantly(P＜0.05) and almost no change of the rate could be recorded in high-grade group.
[Conclusion]:IOUS was a reliable real-time imaging technique with great security for detecting residual glioma.With the aid of IOUS,neurosurgical surgeons could gain a significantly improved rate of radical resection in low-grade gliomas.
Part Three Subtotal resection of subcortical gliomas in eloquent areas controlled by intraoperative ultrasound
[Objective]:To evaluate reliability and contribution of IOUS for avoiding damages of anatomic structures and neurological injuries as well as increasing resection rate by the mean time,in the subtotal resection of gliomas located in functionally important regions.
[Methods]:Fifteen patients with gliomas located subcortically in the eloquent areas were operated on using IOUS.There were 9 men and 6 women in gender,ranged in age from 16 to 53 years(median 37 years).There were ten lesions in central eloquent regions,three near the optic center and two near the lateral fissure.Post-operative pathological confirmed that there were eight low-grade gliomas and the others were high-grade gliomas.The localization of the focus and the correlation of them with the cortex were ascertained by preoperative MRI,as well as the preoperative volume of each lesion.Operations were navigated by ultrasonography.Instrument used for IOUS scan was a GE LOGIQ BookXP scanner.A special intraoperative probe with small-footprint design,sterilized by epoxyethane,was adopted.The initial ultrasound exam was performed through the unopened dura.The real time images both of lesion and eloquent cortex were recorded to design the operation route.In vicinity of the cortex,the nearest sulcus without any large vessels was chosen as the pathway to reach the aim.From the outsides to the inner lesion,an underlying way of the cortex to the aim was guided by ultrasound.When the resection cavity enlarged and the wall extended proximity to the upper cortex,a real time monitor of the residual tumor in this region was shown by ultrasound.The resection withdrew until extent marched the boundary zone between glioma and the cortex,whether there were residual tumors revealed or not.The volume and localization of the residual gliomas were measured and recorded.The other part of glioma,which was beyond the superficial cortex,was intended total resection.All patients underwent an early postoperative MRI.The efficacy of ultrasound for resection control was determined by comparing the volumes measured by IOUS with that measured by postoperative MRI.The variance of the volumes measured by both modalities was no more than 20 percent, 20～30 percent,or＞30 percent,a good,a moderate or a poor define level of the ultrasound was determined,respectively.An independent-samples T test was used to evaluate the difference between the IOUS and MRI volumes.The influence of WHO grades and volume of tumors on the correlation between the IOUS and MRI was analysis by an independent-samples rank sum test.
[Results]:At the end of the operations,residual gliomas under the cortex were shown by ultrasound in 13 cases,with volume range 0.62ml～17.78ml(5.49±5.69ml).The volumes of these residual gliomas measured postoperative MRI were 0.37～24.56ml(7.14±8.43ml).There was no significant difference between these two groups(t=0.616,P=0.543).Compared with preoperative MRI,no more anatomic damages of functional areas could be revealed.A good correlation in comparing IOUS-and MRI-tumor volumetric result of subtotal resection was recorded in 9 cases (60.00%).Two(13.33%) and four(26.67%) cases showed a moderate and poor correlation respectively.The deviation between the different imaging grew obviously with tumor volume much than 30ml(Z=-2.239,P=0.025).WHO grade of gliomas shown no significant influence on the variances(Z=-0.198,P=0.843).
[Conclusion]:IOUS was not only helpful in determining the secure route to reaching the subcortical lesions in eloquent areas,but also useful in reaching the target that dissected tumor volume as much as possible without detriment of normal cortex.The reliability of IOUS relate with tumor size in an inverse feedback.
Part Four Intraoperative evaluation of angiogenesis within high-grade gliomas and peritumoral edema by power Doppler ultrasound
[Objective]:The angiogenesis in high-grade gliomas and peritumoral edema were investigated by intraoperative PDU during the predictive gross total resection.The correlation between angiogenesis level measured by PDU and pathological level was assessed by immunohistochemical examination.
[Methods]:In twenty-five high-grade gliomas predicted gross total tumor resections, PDU was performed in every case,and the imaging was recorded on cine clips. Regions of interest within tumor and peritumor edema zone were analyzed off-line by Photoshop soft.Tumoral and peritumoral blood flow were quantified by intraoperative PDU shown as power Doppler vascularity index(Ⅵ).Tumoral and peritumoral MVD were evaluated at immunohistochemical staining of CD34.The Student t-test was used to evaluate potential difference in both of ultrasonic and immunohistochemical parameters between the tumor mass and the surrounding edema tissue zone.The correlation between the ultrasonic measure of vascularity(Ⅵ) in gliomas and edema with the MVD in corresponding areas respectively were investigated by Spearman correlation test.
[Results]:Both of ultrasonic measurement(Ⅵ) and immunohistochemical analysis (MVD) revealed significant difference in vascularity levels of gliomas and edema (both t=0.000,P＜0.01).For the entire cohort,theⅥcorrelated with the MVD(within tumor,r=0.747;in peritumoral edema zone,r=0.672,respectively).
[Conclusions]:Between the vascularity in tumor and peritumor edema tissue,eitherⅥmeasured by PDU or MVD assessed by immunohistochemical staining,significant differences was revealed.A significant correlation,in glioma or edema,was shown between PDU measurement of glioma vascularity and the MVD assessed by immunohistochemical analysis.PDU was accurate and reliable in measuring different vascularity in glioma and edema tissue.Because it is rapid and non-invasive, intraoperative ultrasonic quantification is beneficial in real time distinguishing glioma from surrounding edema zone.Further improvement in intraoperative PDU techniques to recognize tumor or edema should be establishment of the practical manual for real time handling
引文
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