中西医结合治疗脑肿瘤的临床研究进展

脑肿瘤（brain tumor）又称颅内肿瘤（intracranial tumors）,是恶性程度高、治疗难度大、预后差、严重危害人类健康的恶性肿瘤之一,虽然手术、化疗、放疗对颅内肿瘤治疗效果明显,但同时毒副作用大、预后差也是影响脑肿瘤患者恢复和继续治疗的重要因素。中医药联合手术、化疗、放疗治疗脑肿瘤较单纯手术、化疗、放疗治疗脑肿瘤有着毒副反应轻,治疗效果好的优点。全文就近年来中西医结合治疗脑肿瘤的临床研究进展作一综述。     

脑磁图、磁源成像和脑肿瘤

脑磁图作为一种无创性记录大脑生物磁场的新技术，能相对直接反映神经元的活动状态：并且可将采集到的脑磁信号分析结果重叠到MRI图像上，从而将生理功能和解剖结构融合在一起，这一技术又称为磁源成像（magnetic source imaging，MSI）。MSI不仅能够准确地提供癫痫灶及所需要功能区的定位信息，而且可使临床神经外科医生更好地了解肿瘤与癫痫灶、肿瘤与功能区的关系，以便在术前制定出合理有效的手术计划。本文对脑磁图、MSI及其在脑肿瘤方面的应用做一简单综述。     

脑部恶性肿瘤热消融治疗的现状研究

恶性脑肿瘤极具侵袭性，尽管随着医学的发展，恶性脑肿瘤已经有了很多种标准治疗方法，如手术、放疗和化疗等，但患者的平均生存时间仍然很短。热消融作为一种新兴的脑肿瘤治疗方式，目前已经在动物实验和人类的临床治疗中证明其有效性和优越性。随着影像学发展，融合成像导航的热消融治疗作为更前沿的脑肿瘤的新兴治疗手段，因其术前肿瘤定位、术中融合成像引导消融位置较深或不宜手术切除的脑肿瘤及消融引发积极免疫等优势，在恶性脑肿瘤治疗领域中得到广泛研究。在本综述中，我们主要总结几种主要的恶性脑肿瘤热消融方法的发展及现状。     

胶质瘤手术及辅助技术的进展

胶质瘤的治疗是高度个体化的治疗。过去的20年里有许多手术及辅助技术被广泛应用于胶质瘤的手术中,使得胶质瘤外科手术这一领域取得了迅速的发展。通过应用显微神经外科技术和影像技术如PET、fMRI、术中MRI、脑磁图、DTI以及手术的辅助技术如神经导航、荧光显像技术、唤醒麻醉及术中超声等的应用,神经外科医生能在术前精准勾画出肿瘤的解剖和病理结构,也能在术中精确定位功能区,达到最大程度地切除肿瘤,同时使神经功能损伤等并发症降到最低。如今神经外科医生更加注重病人的术后功能状态。     

影像导航脑肿瘤切除术的Me ta分析

目的：通过 Meta分析评估不同影像导航脑肿瘤切除术和传统手术对比治疗的效果。方法：计算机检索 PubMed、CBM、Cochrane library、Web of Science 数据库至2014年11月15日,以获得有关不同影像导航脑肿瘤切除术的随机对照研究。采用 RevMan 5．3软件分析数据,计算比值比（OR）及95％的可信区间,检验异质性并寻找其来源,应用漏斗图评估发表偏倚。结果：总共纳入10篇随机对照研究（RCT）,共计669例病人,其中影像导航手术者329例,传统手术者340例。Meta分析结果显示：与传统手术相比,影像导航切除脑肿瘤的全切率较高,术后功能障碍发生率减低,差异具有统计学意义（P＜0．05）。在全切率方面,不同影像导航之间无统计学差异（P＞0．05）。但在降低术后功能障碍方面,术中磁共振优于超声,超声优于弥散张量成像（DTI）（P＝0．02）。结论：影像导航脑肿瘤切除术相比传统手术可以提高肿瘤全切率,最大程度保护功能区,降低术后并发症发生率,从而提高患者生活质量。     

科研与临床并重——纪念斯隆-凯特琳癌症中心脑肿瘤中心简介

纪念斯隆-凯特琳癌症中心始建于1884年,是世界上历史最悠久、规模最大的私立癌症中心。2007年,为了加强临床与基础研究的合作,纪念斯隆-凯特琳癌症中心成立了脑肿瘤中心。神经外科、神经肿瘤科、放疗科、影像科医生与基础研究学者密切合作,旨在为脑肿瘤患者提供高质量的多学科综合治疗,同时探索治疗治疗脑肿瘤的新方法。本文将对纪念斯隆-凯特琳癌症中心脑肿瘤中心进行简要介绍。     

中枢神经系统肿瘤的放射治疗(综述)

大多数神经胶质瘤呈浸润性生长,无法用手术根治,有些肿瘤因位置险恶或因位重要功能区而不能手术。而放射治疗相对来说适应症较宽且危险性较小,治疗得宜,后遗症也极少。一般说来,不论中枢神经系统肿瘤的恶性度如何,凡行术后放疗者的生存期皆长于单纯手术者。在放疗期间或放疗结束后均有不同程度的自觉或他觉症状改善。长期生存者有很好或较好的生存质量(恢复正常的生理或精神功能、或部分功能障碍改善持续3～6个月以上)。脑肿瘤的治疗选择 (一)单纯手术:恶性度低的星形细胞瘤(Ⅰ级)及少枝胶质细胞瘤、良性肿瘤如垂体腺     

脑胶质瘤新型治疗方案研究进展

脑胶质瘤是最常见的原发性恶性脑肿瘤,具有较高的复发率和死亡率,单纯依赖手术切除难以根治,必须采用综合治疗方法。随着分子和免疫学研究的发展,以脑肿瘤电场治疗、靶向治疗和免疫治疗为代表的新型治疗方法逐渐增多,并且取得了一些新的进展,本综述旨在介绍近年来脑胶质瘤治疗领域的重要成果及对未来发展方向的展望。     

麻萨诸塞州总医院脑肿瘤中心简介

麻萨诸塞州总医院是哈佛大学医学院的附属教学医院，是全美历史最悠久的医院之一。其下属的脑肿瘤中心核心团队由神经肿瘤科、神经科、神经外科及放射肿瘤科医生构成，并与神经病理科及神经影像科密切合作。脑肿瘤中心旨在通过多学科协作为脑肿瘤患者提供高质量的医疗服务。同时，通过基础及临床科学研究探索脑肿瘤发生及进展的机制，开发新型治疗手段，改善脑肿瘤患者预后。本文将对麻萨诸塞州总医院脑肿瘤中心进行简要介绍。     

家族性脑肿瘤多学科诊疗进展

中枢神经系统肿瘤指起源于中枢神经系统内的组织或结构的一组良恶性疾病。常见的中枢神经系统肿瘤为散发性的，但也有少数出现家族性发病。相比散发性脑肿瘤，家族性脑肿瘤的临床症状、诊断思路和随诊复查计划更复杂。多学科诊疗（MDT）模式，通常指针对某种涉及多器官、多系统的病例进行讨论，在综合各学科意见的基础上为患者制定出最佳的治疗方案的治疗模式。由于家族性脑肿瘤常涉及多器官、多学科、多系统，并且发病率较低，神经外科医生对其临床经验较少，所以MDT模式更有利于高效率诊治、管理家族性脑肿瘤。本文将详细阐述以神经外科医生为主导的MDT模式，以常见的家族性脑肿瘤为引导，针对关于家族性脑肿瘤的流行病学、遗传特点、临床表现、诊断思路和多学科管理办法方面进行综述并对最新研究加以介绍。     

磁共振功能成像在脑肿瘤诊断中的应用

目前,MRI因软组织分辨率高、无辐射及多平面成像等优势已成为脑肿瘤疾病的一种常规检查手段。近年来,随着磁共振技术的发展及磁场强度的增加,一些新的MR功能成像技术已开始越来越多的应用于临床,如磁共振波谱、脑功能成像、灌注成像、磁敏感加权成像、弥散张量成像等,主要用于脑肿瘤之间及脑肿瘤与非肿瘤性疾病的鉴别、肿瘤的分级、指导外科术式的选择、放疗方案的制订等。     

磁共振弥散加权成像诊断及鉴别脑脓肿与脑肿瘤坏死

目的:探讨磁共振弥散加权成像诊断及鉴别脑脓肿与脑肿瘤坏死。方法:回顾性分析2010年1月-2013年4月脑脓肿与脑肿瘤坏死患者,对在磁共振常规图像上表现液化的颅脑病变45例患者测量液化区域弥散系数值,观察影像学变化。结果:在磁共振弥散加权成像中,脑脓肿表现为明显的异常高信号影,脑肿瘤坏死则表现为明显低信号影,其中7例信号稍低。脑脓肿在脓肿或囊变坏死、对侧脑实质、脑脊液、脓液的液化区域弥散系数值分别为（0.32±0.12）、（1.11±0.23）、（0.43±0.12）、（0.42±0.12）,脑肿瘤坏死则分别为（2.43±0.89）、（1.32±0.54）、（0.67±0.15）、0,两者之间比较差异有统计学意义（P＜0.05）。结论:脑脓肿与脑肿瘤坏死在常规磁共振上鉴别困难,磁共振弥散加权成像则能明显鉴别。     

胶质瘤恶性程度分级的功能性磁共振成像研究进展

胶质细胞瘤是最常见的颅内恶性肿瘤,其生长特点为浸润性生长,与正常脑组织无明显界限,偏良性者生长缓慢,病程较长,恶性者瘤体生长快,病程短。因此,对于临床治疗而言,胶质瘤的准确分级是非常必要的。目前,随着影像学技术的快速发展,功能磁共振成像不仅可为临床提供精细解剖信息,还可以提供肿瘤功能及代谢等方面的信息。因此,该文综述了扩散加权成像（DWI）、磁共振波谱成像（MRS）、扩散张量成像（DTI）、灌注加权成像（PWI）、磁敏感加权成像（SWI）等功能MRI技术在胶质瘤恶性程度分级诊断中的应用,从而更准确地指导临床个体化治疗。     

功能磁共振成像在胶质瘤精确诊断中的研究

目的 应用多种功能磁共振成像对胶质瘤进行评估,术前对脑胶质瘤进行较精准的诊断。方法 收集35例经病理诊断证实的胶质瘤患者,均行常规磁共振成像(Magnetic resonance imaging,MRI)及功能MRI检查,对体素内不相干运动扩散加权成像(Intravoxel incoherent motion diffusion weighted imaging,IVIM-DWI)中快速扩散系数(D*)、慢扩散系数(D)、灌注分数(f)和分布扩散系数(DDC)的值进行统计学分析。结果 高级别胶质瘤患者病灶侧IVIM的D、D*、DDC值较对侧正常脑白质增高(D:0.71±0.05×10^-3mm²/s vs.0.14±0.03×10^-3mm²/s;D*:0.06±0.04mm²/s vs.0.03±0.02mm²/s;DDC:1.29±0.33×10^-3mm²/s vs.0.43±0.14×10^-3mm²/s)、f值较对侧正常脑白质降低(f:0.41±0.11 vs.0.51±0.05),差异均具有统计学意义(P＜0.05)。结论 多种磁共振功能成像序列协同分析胶质瘤,可以避免肿瘤的异质性,显著提高了磁共振检查对高级别脑胶质瘤实性部分的识别能力及精确性。     

磁共振弥散加权成像在胶质瘤分级中的价值

目的 探讨磁共振弥散加权成像(DWI)及表观弥散系数(ADC)在鉴别胶质瘤瘤体区、瘤周区和正常组织中的应用及鉴别胶质瘤良、恶性的价值.方法 采用Philips 1.5T Achieva超导型磁共振成像仪,对46例胶质瘤患者行常规MRI及DWI,弥散系数b值分别取0和1 000 s/mm2,测量瘤体区、瘤周区及对侧正常组...     

Canine spontaneous glioma: A translational model system for convection-enhanced delivery

Canine spontaneous intracranial tumors bear striking similarities to their human tumor counterparts and have the potential to provide a large animal model system for more realistic validation of novel therapies typically developed in small rodent models. We used spontaneously occurring canine gliomas to investigate the use of convection-enhanced delivery (CED) of liposomal nanoparticles, containing topoisomerase inhibitor CPT-11. To facilitate visualization of intratumoral infusions by real-time magnetic resonance imaging (MRI), we included identically formulated liposomes loaded with Gadoteridol. Real-time MRI defined distribution of infusate within both tumor and normal brain tissues. The most important limiting factor for volume of distribution within tumor tissue was the leakage of infusate into ventricular or subarachnoid spaces. Decreased tumor volume, tumor necrosis, and modulation of tumor phenotype correlated with volume of distribution of infusate (Vd), infusion location, and leakage as determined by real-time MRI and histopathology. This study demonstrates the potential for canine spontaneous gliomas as a model system for the validation and development of novel therapeutic strategies for human brain tumors. Data obtained from infusions monitored in real time in a large, spontaneous tumor may provide information, allowing more accurate prediction and optimization of infusion parameters. Variability in Vd between tumors strongly suggests that real-time imaging should be an essential component of CED therapeutic trials to allow minimization of inappropriate infusions and accurate assessment of clinical outcomes.     

A feline model for experimental studies of peritumor brain edema

Summary An in vivo model for correlative imaging studies of intracerebral glial tumors and peritumor brain edema has been developed. Adult male and female cats implanted with 1 × 10⁶ or 5 × 10⁵ 9L glioma cells had parietal tumors of 4 mm or greater in diameter and showed signs of increased intracranial pressure 13.7±1.9 days or 19.2±1.3 days after implantation. No immunosuppression was required and the success rate for tumor growth after implantation was 88%. Histologically, the tumor resembles a malignant astrocytoma.The tumor contained the highest water content (85.94%); peritumor white matter was more edematous (73.01%) than white matter in the contralateral hemisphere (69.04%), sham-operated (69.41%) and control brain (68.76%). There was no correlation between the size of the tumor and water content in tumor or white matter. Increased tissue albumin in peritumor white matter indicated blood-brain barrier dysfunction within the tumor and confirmed the vasogenic origin of the edema.Proton magnetic resonance imaging provided good spatial and contrast resolution with increased signal intensity in edematous white matter, decreasing with distance from the tumor. The large brain of this animal model allows the use of serial imaging and regional correlative biochemical measurements in a single animal. Other advantages of this model are its predictability and the short time required to produce tumors with marked peritumor edema.     

A multimodal nanoparticle for preoperative magnetic resonance imaging and intraoperative optical brain tumor delineation

The determination of brain tumor margins both during the presurgical planning phase and during surgical resection has long been a challenging task in the therapy of brain tumor patients. Using a model of gliosarcoma with stably green fluorescence protein-expressing 9L glioma cells, we explored a multimodal (near-infrared fluorescent and magnetic) nanoparticle as a preoperative magnetic resonance imaging contrast agent and intraoperative optical probe. Key features of nanoparticle metabolism, namely intracellular sequestration by microglia and the combined optical and magnetic properties of the probe, allowed delineation of brain tumors both by preoperative magnetic resonance imaging and by intraoperative optical imaging. This prototypical multimodal nanoparticle has unique properties that may allow radiologists and neurosurgeons to see the same probe in the same cells and may offer a new approach for obtaining tumor margins.     

Characterization of brain tumors by MRS,DWI and Ki-67 labeling index

Summary With the advent of fast imaging hardware and specialized software, additional non-invasive magnetic resonance characterization of tumors has become available through proton magnetic resonance spectroscopy (MRS), hemodynamic imaging and diffusion-weighted imaging (DWI). Thus, patterns could be discerned to discriminate different types of tumors and even to infer their possible evolution in time. The purpose of this study was to investigate the correlation between MRS, DWI, histopathology and Ki-67 labeling index in a large number of brain tumors. Localized proton spectra were obtained in 47 patients with brain tumors who subsequently underwent surgery (biopsy or tumor removal). We performed MRS with short echo-time (30ms) and metabolic values in spectra were measured using an external software with 25 peaks. In all patients who had DWI, we measured apparent diffusion coefficients (ADC) in the same region of interest (ROI) where the voxel in MRS was located. In most tumors the histological diagnosis and Ki-67 labeling index had been determined on our original surgical specimen. Cho/Cr, (Lip+Mm)/Cr, NAA/(Cho+Cr) and Glx/Cr indexes in MRS allowed discriminating between low- and high-grade gliomas and metastases (MTs). Likewise, absolute ADC values differentiated low- from high-grade gliomas expressed by Ki-67 labeling index. A novel finding was that high Glx/Cr in vivo MRS index (similar to other known indexes) was a good predictor of tumor grading.     

Noninvasive detection of temozolomide in brain tumor xenografts by magnetic resonance spectroscopy

Poor drug delivery to brain tumors caused by aberrant tumor vasculature and a partly intact blood-brain barrier (BBB) and blood-brain tumor barrier (BTB) can significantly impair the efficacy of chemotherapy. Determining drug delivery to brain tumors is a challenging problem, and the noninvasive detection of drug directly in the tumor can be critically important for accessing, predicting, and eventually improving effectiveness of therapy. In this study, in vivo magnetic resonance spectroscopy (MRS) was used to detect an anticancer agent, temozolomide (TMZ), in vivo in murine xenotransplants of U87MG human brain cancer. Dynamic magnetic resonance imaging (MRI) with the low-molecular-weight contrast agent, gadolinium diethylenetriaminepentaacetic acid (GdDTPA), was used to evaluate tumor vascular parameters. Carbon-13-labeled TMZ ([¹³C]TMZ, 99%) was intraperitoneally administered at a dose of ∼140 mg/kg (450 mg/m², well within the maximal clinical dose of 1000 mg/m² used in humans) during the course of in vivo MRS experiments. Heteronuclear multiple-quantum coherence (HMQC) MRS of brain tumors was performed before and after i.p. administration of [¹³C]TMZ. Dynamic MRI experiments demonstrated slower recovery of MRI signal following an intravenous bolus injection of GdDTPA, higher vascular flow and volume obtained by T*₂-weighted MRI, as well as enhanced uptake of the contrast agent in the brain tumor compared with normal brain detected by T₁-weighted MRI. These data demonstrate partial breakdown of the BBB/BTB and good vascularization in U87MG xenografts. A [¹³C]TMZ peak was detected at 3.9 ppm by HMQC from a selected volume of about 0.15 cm³ within the brain tumor with HMQC pulse sequences. This study clearly demonstrates the noninvasive detection of [¹³C]TMZ in xenografted U87MG brain tumors with MRS. Noninvasive tracking of antineoplastic agents using MRS can have a significant impact on brain tumor chemotherapy.