磁共振灌注加权成像与弥散加权成像在脑胶质瘤分级诊断中的应用

目的:探讨磁共振灌注加权成像(perfusion weighted imaging,PWI)与弥散加权成像(diffusion weighted imaging,DWI)在脑胶质瘤分级诊断中的应用价值。方法:选取2012年1月-2017年6月在我院就诊并经病理证实为脑胶质瘤患者100例,其中高、低级别胶质瘤患者各44、56例。对所有患者行PWI、DWI检查,比较肿瘤不同区域表观扩散系数(apparent diffusion coefficient,ADC)、局部脑血流量(regional cerebral blood flow,rCBF),不同级别肿瘤实质区、瘤周水肿区rADC、rrCBF,根据ROC曲线分析rADC、rrCBF对不同级别胶质瘤的诊断阈值、敏感性、特异性。结果:与对侧相应正常脑实质比较,瘤周水肿区及肿瘤实质区ADC、rCBF均显著升高(P0.05);与瘤周水肿区比较,肿瘤实质区ADC、rCBF均显著升高(P0.05)。高级别肿瘤实质区rADC显著低于低级别肿瘤实质区(P0.05),rrCBF显著高于肿瘤实质区(P0.05)。高级别瘤周水肿区与低级别瘤周水肿区rADC间无显著差异(P0.05),高级别瘤周水肿区rrCBF显著高于低级别瘤周水肿区(P0.05)。在对高、低级别脑胶质瘤的分级中,rADC、rrCBF的曲线下面积(under the receiver operating characteristic curve,AUC)分别为0.957、0.978,均0.9。rADC诊断不同分级胶质瘤的敏感度是90.12%,特异度是95.26%,诊断阈值是13.12;rrCBF诊断不同分级胶质瘤的敏感度是92.31%,特异度是98.57%,诊断阈值是2.62。rADC与rrCBF诊断不同分级胶质瘤敏感度、特异度间无显著差异(P0.05)。结论:PWI、DWI能够为脑胶质瘤的分级诊断提供参考依据。     

Quantitative Evaluation of Diffusion and Dynamic Contrast-Enhanced MR in Tumor Parenchyma and Peritumoral Area for Distinction of Brain Tumors

Purpose

To quantitatively evaluate the diagnostic efficiency of parameters from diffusion and dynamic contrast-enhanced MR which based on tumor parenchyma (TP) and peritumoral (PT) area in classification of brain tumors.

Methods

45 patients (male: 23, female: 22; mean age: 46 y) were prospectively recruited and they underwent conventional, DCE-MR and DWI examination. With each tumor, 10–15 regions of interest (ROIs) were manually placed on TP and PT area. ADC and permeability parameters (K^trans, Ve, Kep and iAUC) were calculated and their diagnostic efficiency was assessed.

Results

In TP, all permeability parameters and ADC value could significantly discriminate Low- from High grade gliomas (HGG) (p<0.001); among theses parameters, Ve demonstrated the highest diagnostic power (iAUC: 0.79, cut-off point: 0.15); the most sensitive and specific index for gliomas grading were K^trans (84%) and Kep (89%). While, in PT area, only K^trans could help in gliomas grading (P = 0.009, cut-off point: 0.03 min^-1). Moreover, in TP, mean Ve and iAUC of primary central nervous system lymphoma (PCNSL) and metastases were significantly higher than that in HGG (p<0.003). Further, in PT area, mean K^trans (p≤0.004) could discriminate PCNSL from HGG and ADC (p≤0.003) could differentiate metastases with HGG.

Conclusions

Quantitative ADC and permeability parameters from Diffusion and DCE-MR in TP and PT area, especially DCE-MR, can aid in gliomas grading and brain tumors discrimination. Their combined application is strongly recommended in the differential diagnosis of these tumor entities.     

Diffusion Tensor Imaging in Patients with Glioblastoma Multiforme Using the Supertoroidal Model

Purpose

Diffusion Tensor Imaging (DTI) is a powerful imaging technique that has led to improvements in the diagnosis and prognosis of cerebral lesions and neurosurgical guidance for tumor resection. Traditional tensor modeling, however, has difficulties in differentiating tumor-infiltrated regions and peritumoral edema. Here, we describe the supertoroidal model, which incorporates an increase in surface genus and a continuum of toroidal shapes to improve upon the characterization of Glioblastoma multiforme (GBM).

Materials and Methods

DTI brain datasets of 18 individuals with GBM and 18 normal subjects were acquired using a 3T scanner. A supertoroidal model of the diffusion tensor and two new diffusion tensor invariants, one to evaluate diffusivity, the toroidal volume (TV), and one to evaluate anisotropy, the toroidal curvature (TC), were applied and evaluated in the characterization of GBM brain tumors. TV and TC were compared with the mean diffusivity (MD) and fractional anisotropy (FA) indices inside the tumor, surrounding edema, as well as contralateral to the lesions, in the white matter (WM) and gray matter (GM).

Results

The supertoroidal model enhanced the borders between tumors and surrounding structures, refined the boundaries between WM and GM, and revealed the heterogeneity inherent to tumor-infiltrated tissue. Both MD and TV demonstrated high intensities in the tumor, with lower values in the surrounding edema, which in turn were higher than those of unaffected brain parenchyma. Both TC and FA were effective in revealing the structural degradation of WM tracts.

Conclusions

Our findings indicate that the supertoroidal model enables effective tensor visualization as well as quantitative scalar maps that improve the understanding of the underlying tissue structure properties. Hence, this approach has the potential to enhance diagnosis, preoperative planning, and intraoperative image guidance during surgical management of brain lesions.     

Optic Radiation Fiber Tractography in Glioma Patients Based on High Angular Resolution Diffusion Imaging with Compressed Sensing Compared with Diffusion Tensor Imaging - Initial Experience

Objective

Up to now, fiber tractography in the clinical routine is mostly based on diffusion tensor imaging (DTI). However, there are known drawbacks in the resolution of crossing or kissing fibers and in the vicinity of a tumor or edema. These restrictions can be overcome by tractography based on High Angular Resolution Diffusion Imaging (HARDI) which in turn requires larger numbers of gradients resulting in longer acquisition times. Using compressed sensing (CS) techniques, HARDI signals can be obtained by using less non-collinear diffusion gradients, thus enabling the use of HARDI-based fiber tractography in the clinical routine.

Methods

Eight patients with gliomas in the temporal lobe, in proximity to the optic radiation (OR), underwent 3T MRI including a diffusion-weighted dataset with 30 gradient directions. Fiber tractography of the OR using a deterministic streamline algorithm based on DTI was compared to tractography based on reconstructed diffusion signals using HARDI+CS.

Results

HARDI+CS based tractography displayed the OR more conclusively compared to the DTI-based results in all eight cases. In particular, the potential of HARDI+CS-based tractography was observed for cases of high grade gliomas with significant peritumoral edema, larger tumor size or closer proximity of tumor and reconstructed fiber tract.

Conclusions

Overcoming the problem of long acquisition times, HARDI+CS seems to be a promising basis for fiber tractography of the OR in regions of disturbed diffusion, areas of high interest in glioma surgery.     

Glioma models.

Gliomas are primary central nervous system tumors that arise from astrocytes, oligodendrocytes or their precursors. Gliomas can be classified into several groups according to their histologic characteristics, the most malignant of the gliomas is glioblastoma multiforme. In contrast to the long-standing and well-defined histopathology, the underlying molecular and genetic bases for gliomas are only just emerging. Many genetic alterations have been identified in human gliomas, however, establishing unequivocal correlation between these genetic alterations and gliomagenesis requires accurate animal models for this disease. Here we are reviewing the existing animal models for gliomas with different strategies and our current knowledge on the important issues about this disease, such as activation of signal transduction pathways, disruption of cell cycle arrest pathways, cell-of-origin of gliomas, and therapeutic strategies.     

Identifying the Association of Contrast Enhancement with Vascular Endothelia Growth Factor Expression in Anaplastic Gliomas: A Volumetric Magnetic Resonance Imaging Analysis

Contrast enhancement is a crucial radiologic feature of malignant brain tumors, which are associated with genetic changes of the tumor. The purpose of the current study was to investigate the potential relationship among tumor contrast enhancement with MR imaging, vascular endothelial growth factor (VEGF) expression, and survival outcome in anaplastic gliomas. MR images from 240 patients with histologically confirmed anaplastic gliomas were retrospectively analyzed. The volumes of T2 hyperintense, contrast enhanced regions and necrotic regions on postcontrast T1-weighted images were measured. The ratio of the enhanced volume to necrotic volume was compared between patients with high versus low levels of VEGF expression and was further used in the survival analysis. The volumetric ratio of enhancement to necrosis was significantly higher in patients with low VEGF expression than in those with high VEGF expression (Mann-Whitney, p = 0.009). In addition, the enhancement/necrosis ratio was identified as a significant predictor of progression-free survival (Cox regression model, p = 0.004) and overall survival (Cox regression model, p = 0.006) in the multivariate analysis. These results suggest that the volumetric ratio of enhancement to necrosis could serve as a noninvasive radiographic marker associated with VEGF expression and that this ratio is an independent predictor for progression-free survival and overall survival in patients with anaplastic gliomas.     

Glioma models

Gliomas are primary central nervous system tumors that arise from astrocytes, oligodendrocytes or their precursors. Gliomas can be classified into several groups according to their histologic characteristics, the most malignant of the gliomas is glioblastoma multiforme. In contrast to the long-standing and well-defined histopathology, the underlying molecular and genetic bases for gliomas are only just emerging. Many genetic alterations have been identified in human gliomas, however, establishing unequivocal correlation between these genetic alterations and gliomagenesis requires accurate animal models for this disease. Here we are reviewing the existing animal models for gliomas with different strategies and our current knowledge on the important issues about this disease, such as activation of signal transduction pathways, disruption of cell cycle arrest pathways, cell-of-origin of gliomas, and therapeutic strategies.     

Co-deletion of chromosome 1p/19q and IDH1/2 mutation in glioma subsets of brain tumors in Chinese patients

Objective

To characterize co-deletion of chromosome 1p/19q and IDH1/2 mutation in Chinese brain tumor patients and to assess their associations with clinical features.

Methods

In a series of 528 patients with gliomas, pathological and radiological materials were reviewed. Pathological constituents of tumor subsets, incidences of 1p/19q co-deletion and IDH1/2 mutation in gliomas by regions and sides in the brain were analyzed.

Results

Overall, 1p and 19q was detected in 339 patients by FISH method while the sequence of IDH1/2 was determined in 280 patients. Gliomas of frontal, temporal and insular origin had significantly different pathological constituents of tumor subsets (P<0.001). Gliomas of frontal origin had significantly higher incidence of 1p/19q co-deletion (50.4%) and IDH1/2 mutation (73.5%) than those of non-frontal origin (27.0% and 48.5%, respectively) (P<0.001), while gliomas of temporal origin had significantly lower incidence of 1p/19q co-deletion (23.9%) and IDH1/2 mutation (41.7%) than those of non-temporal origin (39.9% and 63.2%, respectively) (P = 0.013 and P = 0.003, respectively). Subgroup analysis confirmed these findings in oligoastrocytic and oligodendroglial tumors, respectively. Although the difference of 1p/19q co-deletion was not statistically significant in temporal oligodendroglial tumors, the trend was marginally significant (P = 0.082). However, gliomas from different sides of the brain did not show significant different pathological constituents, incidences of 1p/19q co-deletion or IDH1/2 mutation.

Conclusion

Preferential distribution of pathological subsets, 1p/19q co-deletion and IDH1/2 mutation were confirmed in some brain regions in Chinese glioma patients, implying their distinctive tumor genesis and predictive value for prognosis.     

Histogram Analysis Parameters Apparent Diffusion Coefficient for Distinguishing High and Low-Grade Meningiomas: A Multicenter Study

Low grade meningiomas have better prognosis than high grade meningiomas. The aim of this study was to measure apparent diffusion coefficient (ADC) histogram analysis parameters in different meningiomas in a large multicenter sample and to analyze the possibility of several parameters for predicting tumor grade and proliferation potential. Overall, 148 meningiomas from 7 institutions were evaluated in this retrospective study. Grade 1 lesions were diagnosed in 101 (68.2%) cases, grade 2 in 41 (27.7%) patients, and grade 3 in 6 (4.1%) patients. All tumors were investigated by MRI (1.5 T scanner) by using diffusion weighted imaging (b values of 0 and 1000 s/mm²). For every lesion, the following parameters were calculated: mean ADC, maximum ADC, minimum ADC, median ADC, mode ADC, ADC percentiles P10, P25, P75, P90, kurtosis, skewness, and entropy. The comparison of ADC values was performed by Mann–Whitney-U test. Correlation between different ADC parameters and KI 67 was calculated by Spearman's rank correlation coefficient. Grade 2/3 meningiomas showed statistically significant lower ADC histogram analysis parameters in comparison to grade 1 tumors, especially ADC median. A threshold value of 0.82 for ADC median to predict tumor grade was estimated (sensitivity?=?82.2%, specificity?=?63.8%, accuracy?=?76.4%, positive and negative predictive values were 83% and 62.5%, respectively).All ADC parameters except maximum ADC showed weak significant correlations with KI 67, especially ADC P25 (P?=??.340, P?=?.0001).     

Apparent diffusion coefficient measurements on a novel diffusion weighted MRI phantom utilizing EPI and HASTE sequences

PurposeThe aim of this study is to introduce a novel DWI-MRI phantom and to compare Apparent Diffusion Coefficient (ADC) measurements, utilizing EPI-DWI and HASTE-DWI sequences and two different fitting algorithms.Materials and Methods23 test tubes with different sucrose concentrations and polyacrylamide gels were used as a phantom for ADC measurements. The phantom was scanned on a clinical MRI system (1.5 T) over a two-month period utilizing an EPI-DWI and a HASTE-DWI sequence. ADC maps were calculated using a Weighted Linear (WL) and a Non Linear (NL) fitting algorithm. Measurements were performed with two sequences and two fitting algorithms. Geometric Distortions (GD), Ghosting Ratios (GR) and Signal to Structured Noise Ratios (SSNRs) were estimated using both sequences from the resultant ADC parametric maps.ResultsPolyacrylamide gels reveal lower coefficient of variation (CV%) as compared to sucrose solutions. ADC measurements performed with WL and NL algorithms reveal identical results with both sequences. WL and NL algorithms require approx. 3 s and 7 min respectively, for a single slice. EPI-DWI reveals a mean percent ADC value difference of (+4.5%) as compared to HASTE-DWI, regardless the type of fitting algorithm.ConclusionPolyacrylamide gels can serve as a better means for simulating ADC values, compared with sucrose solutions used in this study. WL can be proposed as the method for ADC measurements in daily clinical practice. WL is significantly faster than NL fitting method and equally precise. SSNR measured directly on ADC maps is an excellent means for testing the precision of ADC measurements.     

类风湿性关节炎活动性病变MRI征象及其与FIB、FDP、D-D的相关性研究

摘要 目的：探讨类风湿性关节炎（RA）活动性病变磁共振成像（MRI）征象及其与纤维蛋白原（FIB）、纤维蛋白(原)降解产物（FDP）、D-二聚体（D-D）的相关性研究。方法：选取2020年1月-2021年2月期间我院诊治的61例RA患者,根据28个关节疾病活动指数（DAS28）评分将其分为活动组（35例）和稳定组（26例）。对比两组MRI征象,血清FIB、FDP、D-D水平。采用Spearman相关性分析RA活动期患者MRI各征象间的相关性及MRI各征象与血清FIB、FDP、D-D水平间的相关性。结果：活动组滑膜增厚或滑膜炎、骨髓水肿、软骨及骨侵蚀、腱鞘炎或周围软组织受累、关节腔积液征象人数占比均高于稳定组（P＜0.05）。活动组患者血清FIB、FDP、D-D水平均高于稳定组（P＜0.05）。Spearman相关性分析结果显示,RA活动期患者滑膜增厚或滑膜炎征象与骨髓水肿、软骨及骨侵蚀、关节腔积液征象均呈正相关（P＜0.05）,骨髓水肿征象与软骨及骨侵蚀征象呈正相关（P＜0.05）;RA活动期患者滑膜增厚或滑膜炎、骨髓水肿、关节腔积液征象与血清FIB、FDP、D-D水平均呈正相关（P＜0.05）,软骨及骨侵蚀征象与FIB呈正相关（P＜0.05）。结论：MRI征象可清晰显示RA患者的滑膜、骨质、关节腔及周围肌腱、软组织等异常改变,且MRI征象之间具有相关性,可在一定程度上反映RA的病理改变;血清FIB、FDP、D-D的检测有助于反映RA活动情况;MRI征象与血清FIB、FDP、D-D水平间具有相关性,二者联合应用有助于进一步评估RA活动情况。     

脑胶质瘤组织CMTM1、ME2表达与临床病理特征和复发的关系研究

摘要 目的：探讨脑胶质瘤组织含CKLF样MARVEL跨膜结构域的蛋白1（CMTM1）、苹果酸酶2（ME2）表达与临床病理特征和复发的关系。方法：选取2018年1月～2021年1月徐州医科大学附属医院接受切除手术的92例脑胶质瘤患者，根据术后是否复发分为复发组和未复发组。采用免疫组化法检测脑胶质瘤组织和瘤旁组织CMTM1、ME2表达，分析二者与临床病理特征的关系，采用多因素Logistic回归分析脑胶质瘤患者术后复发的影响因素。结果：与瘤旁组织比较，脑胶质瘤组织中CMTM1、ME2阳性表达率升高（P＜0.05）。不同分化程度、世界卫生组织（WHO）中枢神经系统肿瘤分类脑胶质瘤组织中CMTM1、ME2阳性表达率比较，差异有统计学意义（P＜0.05）。随访2年，92例脑胶质瘤患者术后复发率为47.83%（44/92）。多因素Logistic回归分析显示，低分化、WHO中枢神经系统肿瘤分类Ⅲ～Ⅳ级、部分切除和CMTM1、ME2阳性表达为脑胶质瘤患者术后复发的独立危险因素（P＜0.05）。结论：脑胶质瘤组织中CMTM1、ME2阳性表达率升高，与分化程度、WHO中枢神经系统肿瘤分类等级和术后复发有关，可能成为脑胶质瘤患者术后复发的辅助评估指标。     

Molecular biology of glioma tumorigenesis

Gliomas are the most common intracranial malignant tumors in humans, and high-grade gliomas in particular pose a unique challenge due to their propensity for proliferation and tissue invasion. Our understanding of glioma oncogenesis, proliferation, and invasion has been greatly advanced in the past 10 years as researchers have gained a better understanding of the molecular biology of these tumors. This article highlights glioma histopathology, as well as cytogenetic and molecular alterations associated with the pathogenesis of human gliomas. It is hoped that better understanding of the molecular pathogenesis of gliomas will improve tumor classification as well as lead to novel targets for therapy and prognostic markers.     

ASPM-associated stem cell proliferation is involved in malignant progression of gliomas and constitutes an attractive therapeutic target

Background

ASPM (Abnormal Spindle-like Microcephaly associated) over-expression was recently implicated in the development of malignant gliomas.

Results

To better characterize the involvement of ASPM in gliomas, we investigated the mRNA expression in 175 samples, including 8 WHO Grade II, 75 WHO Grade III and 92 WHO Grade IV tumors. Aspm expression was strongly correlated with tumor grade and increased at recurrence when compared to the initial lesion, whatever the initial grade of the primary tumor. ASPM expression also increased over serial passages in gliomaspheres in vitro and in mouse xenografts in vivo. Lentivirus-mediated shRNA silencing of ASPM resulted in dramatic proliferation arrest and cell death in two different gliomasphere models.

Conclusion

These data suggest that ASPM is involved in the malignant progression of gliomas, possibly through expansion of a cancer stem cell compartment, and is an attractive therapeutic target in glioblastoma multiforme.     

胶质瘤中CT联合MR动态扫描的诊断价值及其表观弥散系数的定量研究

摘要 目的：探讨胶质瘤中电子计算机断层扫描（CT）联合核磁共振（MR）动态扫描的诊断价值及其表观弥散系数（ADC）定量价值,以促进胶质瘤的有效早期诊断。方法：2017年4月到2021年3月选择在本院进行诊治的颅内肿瘤患者68例作为研究对象,所有患者均给予CT联合MR动态扫描,记录ADC值并判断诊断价值。结果：在68例患者中,病理诊断为胶质瘤38例（胶质瘤组）,非胶质瘤30例（非胶质瘤组）。胶质瘤组的CT出血、水肿、跨中线、界限不清等特征与非胶质瘤组对比差异有统计学意义（P<0.05）。胶质瘤组多表现为T1WI低信号、T2WI高信号,非胶质瘤组多表现为T1WI等信号或低信号、T2WI高信号,对比差异有统计学意义（P<0.05）。胶质瘤组的MR ADCmax、ADCmedian、ADCmin都低于非胶质瘤组（P<0.05）。胶质瘤中CT联合MR动态扫描诊断为胶质瘤37例,非胶质瘤31例,CT联合MR动态扫描诊断胶质瘤的敏感性与特异性为97.4 %（37/38）和100.0 %（30/30）。结论：CT联合MR动态扫描诊断胶质瘤具有很好的敏感性与特异性,ADC值能有效反映病灶组织的病理特征,为临床上提供了一种较为安全、有效的胶质瘤影像检查方法。     

Spatial characteristics of newly diagnosed grade 3 glioma assessed by magnetic resonance metabolic and diffusion tensor imaging

The spatial heterogeneity in magnetic resonance (MR) metabolic and diffusion parameters and their relationship were studied for patients with treatment-naive grade 3 gliomas. MR data were evaluated from 51 patients with newly diagnosed grade 3 gliomas. Anatomic, diffusion, and metabolic imaging data were considered. Variations in metabolite levels, apparent diffusion coefficient (ADC), and fractional anisotropy (FA) were evaluated in regions of gadolinium enhancement and T2 hyperintensity as well as regions with abnormal metabolic signatures. Contrast enhancement was present in only 21 of the 51 patients. When present, the enhancing component of the lesion had higher choline-to-N-acetylaspartate index (CNI), higher choline, lower N-acetylaspartate, similar creatine, similar ADC and FA, and higher lactate/lipid than the nonenhancing lesion. Regions with CNI ≥ 4 had higher choline, lower N-acetylaspartate, higher lactate/lipid, higher ADC, and lower FA than normal-appearing white matter and regions with intermediate CNI values. For lesions that exhibited gadolinium enhancement, the metabolite levels and diffusion parameters in the region of enhancement were consistent with it corresponding to the most abnormal portion of the tumor. For nonenhancing lesions, areas with CNI ≥ 4 were the most abnormal in metabolic and diffusion parameters. This suggests that the region with the highest CNI might provide a good target for biopsies for nonenhancing lesions to obtain a representative histologic diagnosis of its degree of malignancy. Metabolic and diffusion parameter levels may be of interest not only for directing tissue sampling but also for defining the targets for focal therapy and assessing response to therapy.     

Assessment of Optic Nerve Impairment in Patients with Neuromyelitis Optica by MR Diffusion Tensor Imaging

BackgroundDiffusion tensor imaging (DTI) has been used for the evaluation of the white matter integrity. In this study, we evaluated optic nerve impairment in patients with neuromyelitis optica (NMO) using DTI.Conclusions/SignificanceDecreased FA value in the intraorbital optic nerve, especially in the posterior part of the nerve, was demonstrated as a characteristic MR feature for NMO-related optic nerve impairment.