The role of 2-hydroxyglutarate (2HG) in the methylation process of O6-methylguanine-DNA methyltransferase (MGMT) promoter remains unclear. This study aimed to investigate the predictive efficacy and role of 2HG in MGMT promoter methylation. Patients who met the inclusion criteria were retrospectively included and divided into MGMT promoter methylation group (M) and MGMT promoter unmethylation group (UM). 2HG, Glutamate (Glu), N-acetylaspartate (NAA), Choline (Cho), 2HG/Creatine (Cr), 2HG/Glu and Cho/NAA were calculated. Intergroup differences were estimated using Mann-Whitney U test and Chi-square test. Subsequently, the receiver operating characteristic (ROC) curves were plotted for evaluating diagnostic efficacy of metabolic indices with statistical differences. Then, the causal steps approach was performed for discussing the mediation effect of 2HG. 75 patients (male: 52, female: 23, age: 46.81 ± 1.52 years) were included (48 in M, 27 in UM). Compared with UM, M exhibited higher 2HG, 2HG/Cr, 2HG/Glu, Cho/NAA and lower Glu, the differences were statistically significant (P < 0.05). 2HG/Glu exhibited the best diagnostic efficacy (area under curve: 0.788, [95

Purpose Currently, there remains a scarcity of established preoperative tests to accurately predict the isocitrate dehydrogenase (IDH) mutation status in clinical scenarios, with limited research has explored the potential synergistic diagnostic performance among metabolite, perfusion, and diffusion parameters. To address this issue, we aimed to develop an imaging protocol that integrated 2-hydroxyglutarate (2HG) magnetic resonance spectroscopy (MRS) and intravoxel incoherent motion (IVIM) by comprehensively assessing metabolic, cellular, and angiogenic changes caused by IDH mutations, and explored the diagnostic efficiency of this imaging protocol for predicting IDH mutation status in clinical scenarios. Methods Patients who met the inclusion criteria were categorized into two groups: IDH-wild type (IDH-WT) group and IDH-mutant (IDH-MT) group. Subsequently, we quantified the 2HG concentration, the relative apparent diffusion coefficient (rADC), the relative true diffusion coefficient value (rD), the relative pseudo-diffusion coefficient (rD*) and the relative perfusion fraction value (rf). Intergroup differences were estimated using t-test and Mann–Whitney U test. Finally, we performed receiver operating characteristic (ROC) curve and DeLong’s test to evaluate and compare the diagnostic performance of individual parameters and their combinations. Results 64 patients (female, 21; male, 43; age, 47.0 ± 13.7 years) were enrolled. Compared with IDH-WT gliomas, IDH-MT gliomas had higher 2HG concentration, rADC and rD ( P < 0.001), and lower rD* ( P = 0.013). The ROC curve demonstrated that 2HG + rD + rD* exhibited the highest areas under curve (AUC) value (0.967, 95%CI 0.889–0.996) for discriminating IDH mutation status. Compared with each individual parameter, the predictive efficiency of 2HG + rADC + rD* and 2HG + rD + rD* shows a statistically significant enhancement (DeLong’s test: P < 0.05). Conclusions The integration of 2HG MRS and IVIM significantly improves the diagnostic efficiency for predicting IDH mutation status in clinical scenarios.

异柠檬酸脱氢酶(IDH)是WHO中枢神经系统肿瘤分类中最重要的分子表型参数之一.作为IDH突变型胶质瘤的特征性代谢产物,2-羟基戊二酸(2-HG)可从多方面影响肿瘤发生、发展及侵袭过程.磁共振波谱(MRS)为无创性检测2-HG的影像学手段,通过改进技术及优化判读指标,可改善MRS对2-HG谱峰的显示能力并拓展其临床应用范围.本文对2-HG在IDH突变型胶质瘤发生、发展中的作用及其MRS检测方法进展进行综述.

Objective:To investigate the functional imaging parameters that effectively distinguish isocitrate dehydrogenase (IDH) gene mutation status in clinical practice with long echo time (TE) point-resolved spectroscopy (PRESS) MRS.Methods:Totally 25 patients with suspected diagnosis of low grade gliomas(LGGs; Grade II) were recruited prospectively and divided into IDH mutation group and IDH wild group according to pathological results in the study. All patients were scanned with long TE PRESS MRS. In addition, IDH mutational status was determined by post-operation Sanger sequencing. The t test or Mann-Whitney U test was used to analyze the differences of 2-hydroxyglutarate (2HG), Glutamate (Glu), Glutamine (Gln) and 2HG/Glu+Gln between the IDH mutation group and the IDH wild group, then ROC curve was plotted with statistically significant indexes to obtain the efficacy of predicting IDH mutation status. Results:Of the 25 patients, 19 had IDH mutant gliomas and 6 had IDH wild-type gliomas. 2HG, Glu, Gln and 2HG/Glu+Gln in IDH mutated group were 1.42 (1.09, 1.93)mmol/L, (1.74±1.31)mmol/L, (1.68±0.66)mmol/L, 0.55 (0.28, 0.77), respectively; while the corresponding values were 0.00 (0.00, 1.30)mmol/L, (3.28±1.02)mmol/L, (2.55±1.47)mmol/L, 0.00 (0.00, 0.26) in IDH gene wild type group, respectively. The differences of 2HG, Glu, and 2HG/Glu+Gln between the two groups were statistically significant ( P values were 0.030, 0.016, 0.004, respectively). The area under the ROC curve of 2HG/Glu+Gln was the largest (0.877), and the sensitivity was the highest (84.2%). Conclusion:The integration of 2HG with Glu and Gln can effectively realize the noninvasive assessment of IDH mutation status.

目的 探讨体素内不相干运动模型(intravoxel incoherent motion,IVIM)参数在预测胶质瘤术前分级中的价值,及其与Ki-67标记指数表达的相关性.材料与方法 回顾性分析63例经组织病理学证实为胶质瘤患者,男43例,女20例,年龄16～74(47±13)岁,分为低级别组(WHOⅡ级30例)和高级别(WHOⅢ级、Ⅳ级33例),经免疫组化获得胶质瘤的Ki-67标记指数.患者术前均行颅脑MRI常规扫描、IVIM-DWI检查,分别测量肿瘤最大层面实性区域和对侧正常白质区域的IVIM参数,获得ADC、假扩散系数(pseudo-diffusion coefficient,D*)、纯水扩散系数(pure water diffusion coefficient,D)、灌注分数(perfusion fraction,f)值,将肿瘤实质区测量值除以对侧正常脑实质测量数值,获得校正后参数,包括相对表观扩散系数(relative ADC,rADC)、相对假扩散系数(relative D*,rD*)、相对纯水扩散系数(relative D,rD)以及相对灌注分数(relative f,rf).利用秩和检验(Mann-Whitney U检验)比较高、低级别组间4个定量参数、Ki-67标记指数的差异.利用Spearman法分析4组定量参数与Ki-67标记指数之间的相关性.应用ROC曲线评估4组定量参数在脑胶质瘤分级中的诊断效能.结果 低级别胶质瘤组rADC值、rD值及rf值均高于高级别胶质瘤组(P值均<0.05),两组间rD*值无统计学差异(P=0.139),高级别胶质瘤组平均Ki-67标记指数明显高于低级别胶质瘤组,两组间差异有统计学意义(P<0.01).rADC、rD、rf值的ROC曲线下面积分别为0.912、0.911、0.714;阈值分别为1.280、1.295、1.171;敏感度分别为93.3％、90.0％、86.7％;特异度分别为75.8％、78.8％、48.5％.rADC、rD与Ki-67标记指数存在较强的负相关性,rD*与Ki-67标记指数存在低度相关性,rf与Ki-67标记指数不具有明显相关性.结论 IVIM可以无创地评估胶质瘤级别,其中rADC的诊断效能最高.Ki-67标记指数在高、低级别胶质瘤间存在显著差异,且与rADC、rD存在较强负相关,可以为临床诊断、治疗及预后判断提供帮助.

Background Intracranial solitary fibrous tumor(SFT)/hemangiopericytoma (HPC) is an aggressive malignant tumor originating from the intracranial vasculature. Angiomatous meningioma (AM) is a benign tumor with a good prognosis. The imaging manifestations of the two are very similar. Thus, novel noninvasive diagnostic method is urgently needed in clinical practice. Texture analysis and model building through machine learning may have good prospects. Aim To evaluate whether a 3D-MRI texture feature model could be used to differentiate malignant intracranial SFT/HPC from AM. Method A total of 97 patients with SFT/HPC and 95 with AM were included in this study. Patients from each group were randomly divided into the train (70%) and test (30%) sets. ROIs were drawn along the edge of the tumor on each section of T1WI, T2WI, and contrasted T1WI using ITK-SNAP software. The segmented image was imported into the AK software for texture feature extraction, and the 3D ROI signal intensity histograms of T1WI, T2WI, and contrasted T1WI were automatically obtained along with all the parameters. Modeling was performed using the language R. Confusion matrix was used to analyze the accuracy of the model. ROC curve was constructed to assess the grading ability of the logistic regression model. Results After Lasso dimension reduction, 5, 9, and 7 texture features were extracted from T1WI, T2WI, and contrasted T1WI, respectively; additional 8 texture features were extracted from the combined sequence for modeling. The ROC analyses on four models resulted in an area under the curve (AUC) of 0.885 (sensitivity 76.1%, specificity 87.9%) for T1WI model, 0.918 (73.1%, 95.5%) for T2WI model, 0.815 (55.2%, 93.9%) for contrasted T1WI model, and 0.959 (92.5%, 84.8%) for the combined sequence model and were enough to correctly distinguish the two groups in 71.2%, 81.4%, 69.5%, and 83.1% of cases in test set, respectively. Conclusions The radiological model based on texture features could be used to differentiate SFT/HPC from AM.

目的 通过氢质子磁共振波谱技术(proton magnetic resonance spectroscopy, 1H-MRS)离体及在体检测异柠檬酸脱氢酶(isocitrate dehydrogenase,IDH)突变后产生的代谢物2-羟基戊二酸(2-hydroxyglutarate,2HG),探索临床3.0 T核磁共振机应用长回波时间(echo time,TE)单体素不对称自旋回波点解析波谱(point-resolved spectroscopy, PRESS)序列检测2HG的效能.材料与方法 配制包含不同代谢物的两组体外水模,于T2WI 液体衰减反转恢复序列(fluid attenuated inversion recovery,FLAIR)像上对各水模中心位置进行MRS感兴趣定位,采用长TE PRESS序列进行MRS成像.使用相同扫描参数,结合患者T1WI、T1WI增强图像,对拟诊为低级别胶质瘤的4例患者进行脑MRS成像,以术后基因检测获得的IDH基因突变状态作为金标准.水模及在体波谱中代谢物的绝对浓度值均通过LC model软件拟合后获得.结果 体外水模扫描结果显示,当2HG配制浓度在2～16 mmol/L时,均能有效检测出2HG,相比2HG配制的真实浓度值,通过LC model计算得到的2HG绝对浓度值降低,而水模中2HG/谷氨酸(glutamate,Glu)的浓度比值与实际比值接近.在体扫描结果显示,在符合入组标准的3例患者中,2例IDH突变型胶质瘤患者均有效检测出2HG蓄积,1例IDH野生型胶质瘤未检测出2HG蓄积.结论 水模扫描结果表明,临床环境中通过长TE PRESS序列检测2HG浓度水平时,低浓度2HG会被掩盖,从而增加假阴性的结果.而2HG/Glu的比值与实际比值较为接近,提示用比值替代绝对浓度可能更具准确性.结合在体扫描结果表明,临床环境中,在常规胶质瘤影像序列中加入长TE PRESS序列检测2HG蓄积水平,从而间接预测IDH基因突变状态具有较好的可行性,这对于胶质瘤分子分型的术前无创诊断、指导治疗策略及预后评估具有重要意义.

In order to study the sistution that Saccharomyces cerevisiae uptake the external sources of chloroplast,through PEG-induced cell protoplasts of Saccharomyces cerevisiae cells in vitro uptake of spinach chloroplasts,and then use optical microscopy and fluorescence microscopy to observe the fusion of chloroplast and yeast,there may be some cells fusioning.At the same time the shape of certain fusion cells may change.By extracting the cells in spinach chloroplasts,induced protoplast Saccharomyces cerevisiae cells on the uptaked chloroplast.In the fluorescence microscope observation,since the chloroplast in the Blu-ray excitation can spontaneous emits red fluorescence,while yeast cells in Centre acridine orange staining conditions and in the Blu-ray emit significant green color,from which can we judge whether the cells have fusioned.