磁共振波谱分析在颅脑胶质瘤分级中的应用研究

目的 分析脑胶质瘤的氢质子磁共振波谱（proton magnetic resonance spectroscopy,1H-MRS）表现及其临床意义;探讨脑胶质瘤的1H-MRS特点与其病理级别相关性.方法 搜集经临床手术、病理证实的脑胶质瘤病例49例,按照WHO诊断标准分成两组：低级别脑胶质瘤组、高级别脑胶质瘤组.所有患者在术前行1H-MRs检查,均在MR非增强成像的基础上获得.使用Philips Achieva 1.5T超导磁共振扫描仪,单体素或多体素扫描,点分辨法,检测不同区域代谢物变化.结果 脑胶质瘤的1H-MRS表现：肌酸（Cr）轻度下降,N-乙酰天门冬氨酸（NAA）显著下降,胆碱（Cho）显著增高.低、高级别脑胶质瘤的肿瘤组织与对侧止常脑组织的NAA、Cho、NAA/Cr、NAA/Cho值存在显著性差异（P〈0.05）;低级别和高级别脑胶质瘤的肿瘤组织的NAA/Cr、NAA/Cho值存在显著性差异（P〈0.05）.脑胶质瘤的NAA/Cho、Cho/Cr、NAA/Cr值与病理级别相关,其中NAA/Cho和NAA/Cr值反映肿瘤级别较稳定;NAA/Cr、NAA/Cho值呈负相关关系,Cho/Cr值呈正相关关系.结论 ：1H-MRS结合MKI能提高脑胶质瘤术前诊断的准确性.1H-MRS能对胶质瘤进行分级,反映胶质瘤代谢特性以及肿瘤生长潜能.     

磁共振波谱成像结合扩散加权成像在脑胶质瘤及脑转移瘤鉴别诊断中的意义

目的:评估磁共振波谱成像(Proton Magnetic Resonance Spectroscopy,1H-MRS)联合磁共振扩散加权成像(Diffusion Weighted Imaging,DWI)在鉴别脑胶质瘤及孤立的脑转移瘤中的作用。方法:应用3.0T磁共振扫描仪,对临床手术确诊及组织病理学诊断证实的49例脑肿瘤患者(35例多形性胶质母细胞瘤,14例脑转移瘤)进行常规磁共振成像、磁共振波谱成像及磁共振扩散加权成像,并并对获得的数据进一步测量瘤内及瘤周区的代谢比、N-乙酰天门冬氨酸(NAA)、胆碱(Cho)、肌酸(Cr)值以及表观弥散系数(ADC值),分析两肿瘤组之间不同参数的统计学差异。此外,我们研究了感兴趣区域(ROI)的大小对肿瘤区域的病变扩散性能潜在影响。结果:胶质母细胞瘤瘤周N-乙酰天门冬氨酸(NAA)、肌酸(Cr),胆碱(Cho)/Cr,Cho/NAA和r CBV显著高于颅内转移瘤(P0.05);ADC值在两肿瘤组之间无显著差异(P0.05)。结论:在瘤周区1H-MRS有助于鉴别胶质母细胞瘤与单发的脑转移瘤。在瘤内扩散性的定量特性依赖ROI大小的设置。     

Spleen Dynamic Contrast-Enhanced Magnetic Resonance Imaging as a New Method for Staging Liver Fibrosis in a Piglet Model

Objective

To explore spleen hemodynamic alteration in liver fibrosis with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and to determine how to stage liver fibrosis with spleen DCE-MRI parameters.

Materials and Methods

Sixteen piglets were prospectively used to model liver fibrosis staged by liver biopsy, and underwent spleen DCE-MRI on 0, 5th, 9th, 16th and 21st weekend after modeling this disease. DCE-MRI parameters including time to peak (TTP), positive enhancement integral (PEI), maximum slope of increase (MSI) and maximum slope of decrease (MSD) of spleen were measured, and statistically analyzed to stage this disease.

Results

Spearman''s rank correlation tests showed that TTP tended to increase with increasing stages of liver fibrosis (r = 0.647, P<0.001), and that PEI tended to decrease from stage 0 to 4 (r = −0.709, P<0.001). MSD increased slightly from stage 0 to 2 (P>0.05), and decreased from stage 2 to 4 (P<0.05). MSI increased from stage 0 to 1, and decreased from stage 1 to 4 (all P>0.05). Mann-Whitney tests demonstrated that TTP and PEI could classify fibrosis between stage 0 and 1–4, between 0–1 and 2–4, between 0–2 and 3–4, or between 0–3 and 4 (all P<0.01). MSD could discriminate between 0–2 and 3–4 (P = 0.006), or between 0–3 and 4 (P = 0.012). MSI could not differentiate between any two stages. Receiver operating characteristic analysis illustrated that area under receiver operating characteristic curve (AUC) of TTP was larger than of PEI for classifying stage ≥1 and ≥2 (AUC = 0.851 and 0.783, respectively). PEI could best classify stage ≥3 and 4 (AUC = 0.903 and 0.96, respectively).

Conclusion

Spleen DCE-MRI has potential to monitor spleen hemodynamic alteration and classify liver fibrosis stages.     

A Simplified Newton Method for Computing the Factor Loadings in Maximum Likelihood Factor Analysis

A simplified Newton iteration scheme for computation of factor loadings in maximum likelihood factor analysis is described. It operates in the space of factor loadings and avoids eigenvalue problems. From this, a comparatively small computational effort results. Besides of the case of positive unique variances, also the Heywood case is considered, where some unique variances vanish. The ability of the proposed method is demonstrated in three examples, results and iteration process are compared with data given in literature.     

Responsive Mn(II) complexes for potential applications in diagnostic Magnetic Resonance Imaging

The investigation of new Mn(II)-based MRI/Molecular Imaging probes responsive to the enzyme tyrosinase for potential diagnostic applications is herein described. The expression of the enzyme tyrosinase, an oxidoreductase, is up-regulated in melanoma cancer cells. Three novel ligands (L₁, L₂ and L₃) were designed as modified acyclic polyaminocarboxylate chelates by introducing an l-tyrosine residue in place of an aminoacetate unit. The corresponding Mn(II) complexes were fully characterised by ¹H NMR relaxometric techniques in aqueous media. The responsive activity towards the expression of tyrosinase was then assessed by monitoring the ¹H 1/T₁ relaxivity changes during incubation experiments in buffered solutions containing tyrosinase at different concentrations and in B16F10 melanoma cell homogenate. New insight on the mechanism of action of these systems was gained by measuring the magnetic field dependence of the relaxivity and ESR spectra of the incubated solutions. The systems developed showed responsive activity to tyrosinase with a relaxation enhancement spanning from 50% (MnL₁) to 350% (MnL₃) which augurs well for the development of diagnostic probes to detect melanoma cancer.     

A Logic Programming and Expert Statistical Systems Approach for Tissue Characterization in Magnetic Resonance Imaging

The main research goal has been to evaluate significant factors affecting the in vivo magnetic resonance imaging (MRI) parameters T, T, T₂, and ¹H density. This approach differs significantly from other such projects in that the experimental data analysis is being performed while concurrently developing automated, computer-aided analysis software for such MRI tissue parameters. In the experimental portion of the project, statistical analyses, and a heuristic minimum/maximum discriminant analysis algorithm have been explored. Both methods have been used to classify tissue types from 1.5 Tesla transaxial MR images of the human brain. The developing program, written in the logic programming language Prolog, is similar in a number of ways to many existing expert systems now in use for other medical applications; inclusion of the underlying statistical data base and advanced statistical analyses is the main differentiating feature of the current approach. First results indicate promising classification accuracy of various brain tissues such as gray and white matter, as well as differentiation of different types of gray matter and white matter (e.g.: caudate-nucleus vs. thalamus, both representatives of gray matter; and, cortical white matter vs. internal capsule as representative of white matter). Taking all four tissue types together, the percentage of correct classifications ranges from 73 to 87%.     

抗人精子蛋白17磁性纳米探针靶向的卵巢癌体内外磁共振成像

用MRI(magnetic resonance imaging)技术探索连接抗人精子蛋白17单克隆抗体(anti-Sp17 mAb)的磁性纳米探针对体外培养及动物体内Sp17+卵巢癌的靶向性。将anti-Sp17mAb连接到表面包覆壳聚糖的超顺磁性氧化铁纳米颗粒上,制成磁性纳米探针anti-Sp17-MNP,用作MRI阴性对比剂。将磁性纳米探针与Sp17+和Sp17-培养的肿瘤细胞共育,进行一系列体外磁共振成像实验。荷瘤小鼠尾静脉注射磁性纳米颗粒,用7T磁共振仪在体成像,观察肿瘤部位的信号变化,并用普鲁士蓝染色肿瘤组织切片,观察有无铁粒子聚集。体外MRI数据显示,anti-Sp17-MNP与细胞靶向结合,并与细胞共育2 h后,Sp17+HO-8910的T2*信号强度比Sp17-HepG2低2倍;anti-Sp17-MNP对肿瘤细胞的靶向作用可被重组人Sp17阻断。7T磁共振仪对动物在体肿瘤成像结果显示,感兴趣区因磁性纳米探针靶向聚集而导致信号降低,并经组织切片普鲁士蓝染色证实。本研究结果表明,用anti-Sp17抗体和新的合成路线制备的纳米探针具有用作MR对比剂进行分子成像的潜能。     

单位点孢子体-配子体互作模型中不育基因的位置和效应的估计方法

水稻籼粳亚种间杂交F1通常表现为高度不育,这种不育性的一种遗传学解释称为单位点孢子体-配子体互作模型.为了研究这种不育性,提出了一种统计方法,可以估计单位点孢子体-配子体互作模型中不育基因位点的位置和效应.该方法利用回交群体中呈现异常分离的标记位点,用最大似然法对不育基因与标记位点之间的重组率和雌配子存活率进行估计.由于所依据的是非连续变异的遗传标记的分离,而不是连续分布的配子育性指标,因此可以避免由育性直接估计所带来的重组率结果的不稳定.     

Application of 3.0 Tesla Magnetic Resonance Imaging for Diagnosis in the Orthotopic Nude Mouse Model of Pancreatic Cancer

The aim of this study was to successfully establish an orthotopic murine model using two different human pancreatic adenocarcinoma cell lines and to propose a 3.0 tesla MRI protocol for noninvasive characterization of this model. SW1990 and MIAPaca-2 tumor cells were injected into the pancreas of BALB/C nu/nu mice. Tumor growth rate and morphological information were assessed by 3.0 tesla MRI (T1WI, T2WI and DCE-MRI) and immunohistology. Proliferation of SW1990 was significantly faster than that of MIAPaca-2 (P=0.000), but MIAPaca-2 mice had a significantly shorter survival than SW1990 mice (41 days and 44 days respectively, P=0.027). MRI could reliably monitor tumor growth in both cell lines: the tumors exhibiting a spherical growth pattern showed a high-intensity signal, and the SW1990 group developed significantly larger tumors compared with the MIAPaCa-2 group. There were no statistical differences between the two groups in which tumor size was assessed using electronic calipers and an MRI scan (P=0.680). Both tumors showed a slow gradual enhancement pattern. Immunohistochemistry demonstrated tumor tissues showing high expression of Ki-67. This model closely mimics human pancreatic cancer and permits monitoring of tumor growth and morphological information by noninvasive 3.0 tesla MRI studies reducing the number of mice required.     

磁共振弥散加权成像及ADC值对鼻咽癌颅底放疗疗效的评价价值

目的:探讨磁共振弥散加权成像(DWI)及表观扩散系数(ADC)值在鼻咽癌颅底放疗中的临床价值。方法:收集我院于2013年6月~2014年6月复查的40例鼻咽癌患者,分别于放疗前及放疗结束12个月以后对所有患者行常规核磁共振成像(MRI)及DWI检查,测量放疗前、后ADC值,根据影像学检查以及临床诊断结果分为复发组(n=5)及未复发组(n=35)。结果:复发组放疗前ADC值为(0.797±0.031)×10~(-3)mm~2/s,与未复发组放疗前ADC值(0.805±0.028)×10~(-3)mm~2/s比较,差异无统计学意义(P0.05)。复发组放疗结束12个月以后ADC值为(1.097±0.091)×10~(-3)mm~2/s,与未复发组放疗结束12个月以后ADC值(1.705±0.128)×10~(-3)mm~2/s比较,差异有统计学意义(P0.05)。结论:DWI作为一种新兴的磁共振成像技术,对于鼻咽癌颅底放疗疗效的评价具有重要价值,通过DWI对ADC值的测量,可有效的预测患者预后是否良好。     

Hemocyanin gene family evolution in spiders (Araneae), with implications for phylogenetic relationships and divergence times in the infraorder Mygalomorphae

Hemocyanins are multimeric copper-containing hemolymph proteins involved in oxygen binding and transport in all major arthropod lineages. Most arachnids have seven primary subunits (encoded by paralogous genes a–g), which combine to form a 24-mer (4 × 6) quaternary structure. Within some spider lineages, however, hemocyanin evolution has been a dynamic process with extensive paralog duplication and loss. We have obtained hemocyanin gene sequences from numerous representatives of the spider infraorders Mygalomorphae and Araneomorphae in order to infer the evolution of the hemocyanin gene family and estimate spider relationships using these conserved loci. Our hemocyanin gene tree is largely consistent with the previous hypotheses of paralog relationships based on immunological studies, but reveals some discrepancies in which paralog types have been lost or duplicated in specific spider lineages. Analyses of concatenated hemocyanin sequences resolved deep nodes in the spider phylogeny and recovered a number of clades that are supported by other molecular studies, particularly for mygalomorph taxa. The concatenated data set is also used to estimate dates of higher-level spider divergences and suggests that the diversification of extant mygalomorphs preceded that of extant araneomorphs. Spiders are diverse in behavior and respiratory morphology, and our results are beneficial for comparative analyses of spider respiration. Lastly, the conserved hemocyanin sequences allow for the inference of spider relationships and ancient divergence dates.