Three-dimensional susceptibility-weighted imaging at 3 T using various image analysis methods in the estimation of grading intracranial gliomas

Object

Although three-dimensional (3D), high-spatial resolution susceptibility-weighted imaging (SWI) appears to be valuable in the evaluation of central nervous system gliomas, several evaluation methods are proposed in the literature. The purpose of this study was to evaluate the use of 3D SWI for grading intracranial gliomas with various analysis methods.

Materials and Methods

Twenty-three patients suspected of having gliomas participated in this study. SWI was performed in addition to conventional MR sequences. In 15 cases, post-gadolinium enhanced SWI was also obtained. Imaging evaluation criteria were conventional grade, hypointensity ratio in the tumor-dominant structure of hypointensity on SWI (hemorrhage or vascular structure) and presence of abnormal enhancement surrounding the tumor.

Results

Mean grading scores of conventional grade showed no statistically significant difference among WHO grades. Mean grading scores of hypointensity ratios in the tumor were higher for WHO Grades 3 and 4 than for lower grade tumors (P=.05, Mann–Whitney U test). Hemorrhagic foci were more frequently seen in the higher grade tumor. Post-contrast susceptibility-weighted images of five of 11 WHO Grade 3 and 4 cases showed bright enhancement surrounding the tumor, suggesting a breakdown of the blood–brain barrier.

Conclusions

SWI at 3 T may be a useful method to analyze the structural characteristics of gliomas and to evaluate pathology in vivo. Assessment of hypointensity ratios in the glioma was the most preferable method in grading glioma. However, more studies, specifically concerning a suitable method for image analysis, are needed to establish SWI at 3 T as a useful tool in clinical routine.     

Sensitive detection of hydroxymethylcytosine levels in normal and neoplastic cells and tissues

A new sensitive analytical method using capillary electrophoresis with laser induced fluorescence (CE‐LIF) was applied for the simultaneous detection of DNA methylation and hydroxymethylation levels in human cancers of different origin. DNA hydroxymethylation, measured as 5‐hydroxymethylcytosine (5hmC) levels, was decreased in gliomas with mutation in the isocitrate dehydrogenase 1 (IDH1) gene when compared to IDH1‐wildtype gliomas. Independent from IDH1 mutation, 5hmC levels were decreased in lung carcinomas when compared to normal lung tissue. Reduced DNA hydroxymethylation was also observed upon dedifferentiation in cultured murine embryonic fibroblasts. Our data show that reduced DNA hydroxymethylation is related to cellular dedifferentiation and can be detected in various types of cancers, independent from the IDH1 mutation status. Quantitative determination of altered 5hmC levels may therefore have potential as a biomarker linked to cellular differentiation and tumorigenesis.     

A new method for characterization of low grade gliomas using ultra low field magnetic resonance imaging

Low grade gliomas were studied with ultra low field magnetic resonance imaging (ULF MRI). The tumors exhibited high tissue contrast in both T₁ and T₂-weighted images as compared to normal brain tissue. Moreover they were sharply delineated towards the surrounding brain tissue. When compared with X-ray computed tomography the tumors were more readily detected and delineated by using ultra-low field magnetic imaging. A computerassisted classification procedure was used to define new regions of interest for relaxation time estimation. By using this procedure more accurate estimations of the T₁ and T₂ values were obtained.     

Biomimetic Nanocomposites Camouflaged with Hybrid Cell Membranes for Accurate Therapy of Early-Stage Glioma

Glioma features high fatality rate and short survival time of patients due to its fast growth speed and high invasiveness, hence timely treatment of early-stage glioma is extremely important. However, the blood brain barrier (BBB) severely prevents therapeutic agents from entering the brain; meanwhile, the non-targeted distribution of agents always causes side effects to vulnerable cerebral tissues. Therefore, delivery systems that possess both BBB penetrability and precise glioma targeting ability are keenly desired. We herein proposed a hybrid cell membrane (HM) camouflage strategy to construct therapeutic nanocomposites, in which HM consisting of brain metastatic breast cancer cell membrane and glioma cell membrane was prepared with a simple membrane fusion pathway. By coating HM onto drug-loaded nanoparticles, the as-obtained biomimetic therapeutic agent (termed HMGINPs) inherited satisfying BBB penetrability and homologous glioma targeting ability simultaneously from the two source cells. HMGINPs exhibited good biocompatibility and superior therapeutic efficacy towards early-stage glioma.     

脑胶质瘤中脂肪酸酰胺水解酶的表达及意义

目的研究内源性大麻素代谢酶脂肪酸酰胺水解酶(FAAH)在脑胶质瘤组织中的表达情况及其与胶质瘤病理级别的关系,探讨其临床意义.方法选取首次手术切除并经病理检查证实的脑胶质瘤标本23例,其中WHOⅠ级1例,Ⅱ级7例,Ⅲ级5例,Ⅲ~Ⅳ级2例,Ⅳ级8例.另取8例因颅脑外伤行内减压术切除的正常脑组织作为对照.应用实时荧光定量PCR和高效液相色谱-质谱联用技术分别检测各组织标本中FAAH mRNA和FAAH活性的表达.结果 FAAH mRNA、FAAH活性在低级别(WHOⅠ~Ⅱ级)和高级别(WHOⅢ~Ⅳ级)脑胶质瘤组织中的表达水平较正常脑组织明显降低,差异有统计学意义(均P<0.01),且随着肿瘤病理级别的增高而降低,与肿瘤的病理分级呈负相关(均P<0.01).FAAH mRNA与FAAH活性的表达水平呈正相关(P<0.01).结论 FAAH可能参与了脑胶质瘤的发生、发展过程,检测FAAH的表达可评价脑胶质瘤的生物学行为,为脑胶质瘤的临床治疗和预后判断提供参考.     

3D sensitivity encoded ellipsoidal MR spectroscopic imaging of gliomas at 3T

Purpose

The goal of this study was to implement time efficient data acquisition and reconstruction methods for 3D magnetic resonance spectroscopic imaging (MRSI) of gliomas at a field strength of 3T using parallel imaging techniques.

Methods

The point spread functions, signal to noise ratio (SNR), spatial resolution, metabolite intensity distributions and Cho:NAA ratio of 3D ellipsoidal, 3D sensitivity encoding (SENSE) and 3D combined ellipsoidal and SENSE (e-SENSE) k-space sampling schemes were compared with conventional k-space data acquisition methods.

Results

The 3D SENSE and e-SENSE methods resulted in similar spectral patterns as the conventional MRSI methods. The Cho:NAA ratios were highly correlated (P<.05 for SENSE and P<.001 for e-SENSE) with the ellipsoidal method and all methods exhibited significantly different spectral patterns in tumor regions compared to normal appearing white matter. The geometry factors ranged between 1.2 and 1.3 for both the SENSE and e-SENSE spectra. When corrected for these factors and for differences in data acquisition times, the empirical SNRs were similar to values expected based upon theoretical grounds. The effective spatial resolution of the SENSE spectra was estimated to be same as the corresponding fully sampled k-space data, while the spectra acquired with ellipsoidal and e-SENSE k-space samplings were estimated to have a 2.36–2.47-fold loss in spatial resolution due to the differences in their point spread functions.

Conclusion

The 3D SENSE method retained the same spatial resolution as full k-space sampling but with a 4-fold reduction in scan time and an acquisition time of 9.28 min. The 3D e-SENSE method had a similar spatial resolution as the corresponding ellipsoidal sampling with a scan time of 4:36 min. Both parallel imaging methods provided clinically interpretable spectra with volumetric coverage and adequate SNR for evaluating Cho, Cr and NAA.     

白山毛桃根抗脑胶质瘤活性成分及其纳米胶束的制备

采用溶剂提取和萃取方法得到白山毛桃根乙酸乙酯、 正丁醇和水层萃取物. 通过噻唑蓝(MTT)比色法考察了各萃取物对脑胶质瘤细胞U87MG活性的抑制作用. 采用高效液相色谱(HPLC)指纹图谱法比对确认活性部位的主要化学成分为2α,3α,24-三羟基-12-烯-28-乌苏酸. 采用溶剂挥发法制备了2α,3α,24-三羟基-12-烯-28-乌苏酸纳米胶束, 对其包封率、 粒径及ζ电位等进行了表征, 并考察了其抗肿瘤活性. 体外细胞实验结果表明, 白山毛桃根乙酸乙酯萃取物对脑胶质瘤细胞U87MG具有抑制作用, 通过与标准品比对确认2α,3α,24-三羟基-12-烯-28-乌苏酸为乙酸乙酯部位的主要成分, 且该成分对脑胶质瘤细胞活性具有较强抑制作用. 通过溶剂挥发法制备的2α,3α,4-三羟基-12-烯-28-乌苏酸纳米胶束包封率为64.7%, 粒径为20 nm, 粒径分布宽度(PDI)为0.246, ζ电位为-5.7 mV. 细胞实验结果进一步证明, 与单体化合物相比, 2α,3α,24-三羟基-12-烯-28-乌苏酸纳米胶束对脑胶质瘤细胞活性具有更强的抑制作用, 为白山毛桃根在脑胶质瘤治疗中的应用提供了实验依据.     

Evaluation of a potential epigenetic biomarker by quantitative methyl-single nucleotide polymorphism analysis

Tumorigenesis is characterized by alterations of methylation profiles including loss and gain of 5-methylcytosine. Recently, we identified a single CpG, which seemed to be consistently hypomethylated in pilocytic astrocytomas but not in other gliomas. To evaluate its applicability as a biomarker, we examined its methylation status in a large panel of gliomas (n = 97). Methylation-dependent DNA sequence variation may be considered a kind of single nucleotide polymorphism (methylSNP). MethylSNPs can be easily converted into common SNPs of the C/T type by sodium bisulfite treatment of the DNA and afterwards subjected to conventional SNP typing. We adapted SnaPshot trade mark and Pyrosequencing trade mark to determine the methylation of our test CpG in a quantitative manner. The adapted methods, called SNaPmeth and PyroMeth, respectively, gave nearly identical results, however data obtained with PyroMeth showed less scattering. Furthermore, the integrated software for allele frequency determination from Pyrosequencing could be used directly for data analysis while SnaPmeth data had to be exported and processed manually. Although data did not confirm our previous result of a preferential hypomethylation of the tested CpG in pilocytic astrocytomas, we consider quantitative methylSNP analysis by SNaPmeth or PyroMeth a favorable alternative to existing high-throughput methylation assays. It combines single CpG analysis with accurate quantitation and is amenable to high throughput.     

A biocompatible electrochemical sensor based on PtNi alloy nanoparticles-coupled N-GQDs for in situ monitoring of dopamine in glioma cells

We report the design and construction of enzyme-free sensor using platinum–nickel (PtNi) bimetallic alloy nanoparticle-conjugated nitrogen-doped graphene quantum dots (N-GQDs) for the highly specific in situ monitoring of dopamine (DA) secreted by glioma cells (C6). PtNi@N-GQDs nanocomposites were synthesized using a simple ultrasonication method. The resulting hybrid material was an excellent electrocatalyst for the redox activity of DA owing to the combined properties of PtNi alloys and highly conductive N-GQDs. The PtNi@N-GQDs-based sensing platform demonstrated substantial sensing ability with a detection range of 0.0125–952 μM, a sensitivity of 0.279 μA/μM/cm², and a limit of detection of 0.005 μM (S/N = 3). The sensing performance of PtNi@N-GQDs was highly stable, selective, and reproducible. We successfully showed the practical application of the PtNi@N-GQDs sensor by quantifying DA in the blood serum and human urine samples. Finally, we used the PtNi@N-GQDs biocompatible platform to quantify DA released from C6 cells.