Simultaneous multi‐slice spin‐ and gradient‐echo dynamic susceptibility‐contrast perfusion‐weighted MRI of gliomas

Although combined spin‐ and gradient‐echo (SAGE) dynamic susceptibility‐contrast (DSC) MRI can provide perfusion quantification that is sensitive to both macrovessels and microvessels while correcting for T₁‐shortening effects, spatial coverage is often limited in order to maintain a high temporal resolution for DSC quantification. In this work, we combined a SAGE echo‐planar imaging (EPI) sequence with simultaneous multi‐slice (SMS) excitation and blipped controlled aliasing in parallel imaging (blipped CAIPI) at 3 T to achieve both high temporal resolution and whole brain coverage. Two protocols using this sequence with multi‐band (MB) acceleration factors of 2 and 3 were evaluated in 20 patients with treated gliomas to determine the optimal scan parameters for clinical use. ΔR₂*(t) and ΔR₂(t) curves were derived to calculate dynamic signal‐to‐noise ratio (dSNR), ΔR₂*‐ and ΔR₂‐based relative cerebral blood volume (rCBV), and mean vessel diameter (mVD) for each voxel. The resulting SAGE DSC images acquired using MB acceleration of 3 versus 2 appeared visually similar in terms of image distortion and contrast. The difference in the mean dSNR from normal‐appearing white matter (NAWM) and that in the mean dSNR between NAWM and normal‐appearing gray matter were not statistically significant between the two protocols. ΔR₂*‐ and ΔR₂‐rCBV maps and mVD maps provided unique contrast and spatial heterogeneity within tumors.     

63例高级别胶质瘤中IDH1和TERT突变状态的预后价值

目的:探讨异柠檬酸脱氢酶-1（IDH1）和端粒酶逆转录酶（TERT）启动子突变对高级别胶质瘤患者的预后价值。方法:选取2014年9月至2017年6月于我院行手术切除且术后病理提示为高级别胶质瘤的患者63例（WHO Ⅲ级27例，Ⅳ级36例），完善临床资料、随访资料、分子检测结果。应用Sanger测序法检测样本中IDH1和TERT启动子突变情况，根据结果将患者分为不同亚组，通过比较其生存期的差异，分析基因突变与患者预后的关系。结果:63例高级别胶质瘤中，IDH1突变型和野生型患者的中位生存期分别为24和10个月，差异有统计学意义（P＜0.01）；TERT突变型和野生型的中位生存期无明显差异（P＞0.05）。IDH1突变为高级别胶质瘤患者预后良好的因素，TERT突变不能单独提示预后，二者联合分析提示:IDH1突变／TERT突变组预后最好，IDH1野生／TERT突变组预后最差，IDH1突变／TERT野生组预后稍好于IDH1野生／TERT野生组，四组间预后有明显差异。结论:IDH1突变的高级别胶质瘤患者有较好的临床预后，在此基础上，TERT启动子突变检测有助于进一步划分其预后分层。     

Editor's choice: New concepts in the management of diffuse low-grade glioma: Proposal of a multistage and individualized therapeutic approach

Diffuse low-grade glioma grows, migrates along white matter tracts, and progresses to high-grade glioma. Rather than a “wait and see” policy, an aggressive attitude is now recommended, with early surgery as the first therapy. Intraoperative mapping, with maximal resection according to functional boundaries, is associated with a longer overall survival (OS) while minimizing morbidity. However, most studies have investigated the role of only one specific treatment (surgery, radiotherapy, chemotherapy) without taking a global view of managing the cumulative time while preserving quality of life (QoL) versus time to anaplastic transformation. Our aim is to switch towards a more holistic concept based upon the anticipation of a personalized and long-term multistage therapeutic approach, with online adaptation of the strategy over the years using feedback from clinical, radiological, and histomolecular monitoring. This dynamic strategy challenges the traditional approach by proposing earlier therapy, by repeating treatments, and by reversing the classical order of therapies (eg, neoadjuvant chemotherapy when maximal resection is impossible, no early radiotherapy) to improve OS and QoL. New individualized management strategies should deal with the interactions between the course of this chronic disease, reaction brain remapping, and oncofunctional modulation elicited by serial treatments. This philosophy supports a personalized, functional, and preventive neuro-oncology.     

基于不同扩散模型的扩散加权成像在脑胶质瘤分级和预测IDH-1突变的对比分析

对比分析基于不同扩散模型的扩散加权成像（扩散张量成像：DTI,扩散峰度成像：DKI,和神经突起方向离散度与密度成像：NODDI）在脑胶质瘤术前预测脑胶质瘤级别和异柠檬酸脱氢酶-1（IDH-1）突变的诊断效能。     

基于MRI增强T1WI影像组学预测模型鉴别高级别胶质瘤IDH 1突变型与野生型的价值

目的：探讨基于术前增强T1WI构建的影像组学模型预测高级别胶质瘤患者异柠檬酸脱氢酶-1（IDH 1）突变型与野生型的价值。方法：回顾性分析2012 年6 月至2020 年12 月在温州医科大学附属第五医院行颅脑增强T1WI图像的高级别胶质瘤患者89 例,IDH 1突变型32 例（WHO III级15 例,WHO IV级17例）,IDH 1野生型57例（WHO III级12例,WHO IV级45例）,按7:3随机分为训练组和验证组。使用A.K软件对原始增强T1WI图像进行影像特征提取,Kruskal-Wallis非参数检验、Spearman相关性分析、LASSO回归及10 倍交叉验证进行特征降维,筛选出最具特征的参数。采用受试者操作特征（ROC）曲线评价模型对高级别胶质瘤IDH 1突变型和IDH 1野生型识别的预测效能。决策曲线分析（DCA）评价模型的获益情况。结果：每位患者增强T1WI图像共提取396个不同的纹理参数,通过LASSO降维及10倍交叉验证筛选,最终得到5个最具特征性纹理参数,并计算得到相应放射值,构建训练组和验证组的预测模型,训练组模型的ROC曲线下面积为0.902（95%CI：0.826～0.978）,灵敏度和特异度分别为84.6%和81.8%,验证组模型的ROC曲线下面积为0.844（95%CI：0.676～1.000）,敏感度为77.8%,特异度为80.1%。DCA显示影像组学模型在风险阈值0.1～1.0间较大范围内的净收益优于不作处理模型和全部处理模型。结论：基于MRI增强T1WI构建的影像组学模型可有效识别高级别胶质瘤的IDH 1突变型和野生型。     

Impact of drug size on brain tumor and brain parenchyma delivery after a blood–brain barrier disruption

Drug delivery to the brain is influenced by the blood–brain barrier (BBB) and blood–tumor barrier (BTB) to an extent that is still debated in neuro-oncology. In this paper, we studied the delivery across the BTB and the BBB of compounds with different molecular sizes in normal and glioma-bearing rats. Studies were performed at baseline as well as after an osmotic BBB disruption (BBBD) using dynamic contrast-enhanced magnetic resonance imaging and two T₁ contrast agents (CAs), Magnevist (743 Da) and Gadomer (17,000 Da). More specifically, we determined the time window for the BBB permeability, the distribution and we calculated the brain exposure to the CAs. A different pattern of accumulation and distribution at baseline as well as after a BBBD procedure was observed for both agents, which is consistent with their different molecular size and weight. Baseline tumor exposure was threefold higher for Magnevist compared with Gadomer, whereas postBBBD tumor exposure was twofold higher for Magnevist. Our study clearly showed that the time window and the extent of delivery across the intact, as well as permeabilized BTB and BBB are influenced by drug size.     

A new der(1;7)(q10;p10) leading to a singular 1p loss in a case of glioblastoma with oligodendroglioma component

The combined 1p‐/19q‐ deletions in oligodendrogliomas originate from translocation between both chromosomes. In the few cases of oligoastrocytomas and glioblastomas with an oligodendroglioma component (GBMO) where only 1p deletion was described, the origin remains unknown. We report the first case of GBMO, in which a single 1p deletion was detected and was linked to a translocation between chromosomes 1 and 7. Fresh surgical specimens were collected during surgery and the samples were used for cell culture, touch preparation smear slides (TP slides) and DNA extraction. Peripheral venous blood was also collected from the patient. G‐banding using Trypsin and stained with Giemsa (GTG) banding and karyotyping were performed and 1p‐/19q‐, TP53, PTEN and c‐MYC were analyzed by fluorescent in situ hybridization (FISH). Multicolor FISH (mFISH) and microsatellites analyses were also performed to complete the investigation. Three‐dimensional quantitative FISH (3D‐QFISH) of telomeres was performed on nuclei from TP slides and analyzed using TeloView^TM to determine whether the 3D telomere profile as an assessment of telomere dysfunction and a characterization of genomic instability could predict the disease aggressiveness. An unbalanced chromosomal translocation was found in all metaphases and confirmed by mFISH. The karyotype of the case is: 50～99,XXX, +der(1;7)(q10;p10),inc[47] The derivative chromosome was found in all 47 analyzed cells, but the number of derivatives varied from one to four. There was neither imbalance in copy number for genes TP53 and PTEN, nor amplification of c‐MYC gene. We did not find loss of heterozygosity with analysis of microsatellite markers for chromosomes 1p and 19q in tumor cells. The 3D‐telomere profile predicted a very poor prognostic and short‐term survival of the patient and highlights the potential clinical power of telomere signatures as a solid biomarker of GBMO. Furthermore, this translocation between chromosomes 1 and 7 led to a singular 1p deletion in this GBMO and may generate the 1p and 7q deletions.     

脑胶质瘤端粒酶活性表达的研究

目的：探讨端粒酶在脑胶质瘤发生、发展中的作用，并研究端粒酶活性是否与其恶性程度相关。方法：应用端粒重复序列扩增技术(TRAP)对48例胶质瘤标本和8例正常脑组织的端粒酶活性进行检测。结果：8例正常脑组织端粒酶活性均为阴性表达，48例胶质瘤标本中23例为表达阳性(47．92％)，低度恶性组与高度恶性组胶质瘤之间端粒酶活性阳性率有明显差异(P=0．001)。结论：端粒酶活性与胶质瘤恶性程度明显相关，端粒酶在胶质瘤发生发展过程中可能具有重要作用。     

P21WAF1/CIP1、P16蛋白表达与人脑神经胶质瘤的相关分析

背景与目的：探讨P21^WAF1/CIP1、P16、两种抑癌基因与人脑神经胶质瘤恶性程度的关系。材料与方法：采用SABC免疫组织化学方法对98例人脑胶质瘤组织及12例止常脑组织标本中P21^WAF1/CIP1和P16的表达进行检测,并进行相关分析。结果：P21^WAF1/CIP1和P16阳性表达率在人脑胶质瘤中分别为58．16％和42．86％,与正常脑组织中的表达情况差异有统计学意义;P21^WAF1/CIP1、蛋白和P16蛋白阳性表达率均随着胶质瘤的恶性程度的增高而降低;P21^WAF1/CIP1蛋白和P16蛋白可协同表达。结论：P21^WAF1/CIP1与P16蛋白的阳性表达率及协同表达率可在一定程度上反映胶质瘤细胞的恶性生物学行为,可以作为一项判断其恶性程度的有效指标。