Investigation of sandwiched gadolinium(III) complexes with tungstosilicates as potential MRI contrast agents

Two gadolinium-sandwiched complexes with tungstosilicates, K-13[Gd(SiW11O39)(2)] (Gd(SiW11)(2)) and K11H6[Gd2O3(SiW9O34)(2)] (Gd-3(SiW9)(2)), have been investigated by in vitro and in vivo experiments as potential contrast agents for magnetic resonance imaging (MRI). T-1-relaxivity of Gd(SiW11)(2)was 6.59 mM(-1) . s(-1) in aqueous solution and 6.85 mM(-1) . s(-1) in 0.725 mmol . L-1 bovine serum albumin solution at 25degreesC and 9.39 T, respectively. The corresponding T-1-relaxivity of Gd-3(SiW9)(2) was 12.6 and 19.3 mM(-1) . s(-1) per Gd, respectively. MRI for Sprague-Dawley rats showed longer and more remarkable enhancement in rat liver after i.v. injection of these two complexes: 39.4 +/- 3.9% and 57.4 +/- 11.6% within the first 30 min after injection, 31.2 +/- 2.6% and 39.9 +/- 7.6% in the next 60 min for Gd(SiW11)(2) and Gd-3(SiW9)(2) at doses of 0.081 and 0.084 mmol Gd/kg, respectively. Our preliminary in vitro and in vivo study indicates that Gd(SiW11)(2) and Gd-3(SiW9)(2) are favorable candidates for hepatic contrast agents for MRI. However, the two complexes exhibit higher acute toxicity and need to be modified and studied further before clinical use.

Gadolinium heteropoly complex K-17[Gd(P2W17O61)(2)] as a potential MRI contrast agent

Gadolinium heteropoly complex K-17[Gd(P2W17O61)(2)] has been evaluated by in vitro and in vivo experiments as a potential contrast agent for magnetic resonance imaging (MRI). The thermal analysis and conductivity study indicate that this complex has good thermal stability and wide pH stability range. The T-1 relaxivity is 7.59 mM(-1) s(-1) in aqueous solution and 7.97 mM(-1) s(-1) in 0.725 mmol l(-1) bovine serum albumin (BSA) solution at 25degreesC and 9.39 T, respectively. MR imaging of three male Sprague-Dawley rats showed remarkable enhancement in rat liver after intravenous injection, which persisted longer than with Gd-DTPA. The signal intensity increased by 57.1 +/- 16.9% during the whole imaging period at 0.082 mmol kg(-1) dose. Our preliminary in vitro and in vivo studies indicate that K-17[Gd(P2W17O61)(2)] is a potential liver-specific MRI contrast agent.

Comparison between GdDTPA and two gadolinium polyoxometalates as potential MRI contrast agents

Two gadolinium polyoxometalates, Gd2P2W18O62 and K-15[(GdO)(3)(PW9O34)(2)], have been evaluated by in vivo as well as in vitro experiments as the candidates of tissue-specific magnetic resonance imaging (MRI) contrast agents. T-1-relaxivities of 28.4 mM(-1)-s(-1) for Gd2P2W18O62 and 11.2 mM(-1)-s(-1) for K-15[(GdO)(3)(PW9O34)(2)] (400 MHz, 25 degreesC) were higher than that of the commercial MRI contrast agent (GdDTPA). Their relaxivities in bovine serum albumin and human serum transferrin were also reported. The favorable liver-specific contrast enhancement and renal excretion capability in in vivo MRI with Sprague-Dawley rats after i.v. administration of K-15[(GdO)(3)(PW9O34)(2)] was demonstrated. In vivo and in vitro assay showed that K-15[(GdO)(3)(PW9O34)(2)] is a promising liver-specific MRI contrast agent. However, Gd2P2W18O62 did not show the favorable quality in vivo as expected from its high relaxivity in vitro, which was attributed to low bioavailability, indicating that it is of limited value as tissue-specific MRI contrast agent.

An evaluation of gadolinium polyoxornetalates as possible MRI contrast agent

Two gadolinium polyoxometalates, K9GdW10O36 and K-11 [Gd(PW11O39)(2)], have been evaluated both in vivo and in vitro as candidates for tissue-specific MRI contrast agents. T-1-relaxivities of 6.89 mM(-1) . s(-1) for K9GdW10O36 and 5.27 mM(-1) . s(-1) for K-11[Gd(PW11O39)(2)] are slightly higher than that of the commercial MRI contrast agent (Gd-DTPA). Both compounds bind with bovine serum albumin and human serum transferrin and favorable liver-specific contrast enhancement in in vivo MRI with Sprague-Dawley rats after i.v. administration has been demonstrated. Imaging studies demonstrate that the two agents have a long residence time, showing MR signal enhancement in the liver for more than 40 min, longer than commercially available contrast agents. In vivo and in vitro assays showed that GdW10 and Gd(PW11)(2) are promising liver-specific MRI contrast agents and GdW10 may be used in the diagnosis of the pathological state. However, with the higher acute toxicity, the two gadolinium polyoxometalates need to be modified and studied further before clinical use.

NMR studies of Gd(DTPA-BIN) in human serum albumin solution

Stable gadolinium complexes, such as Gd(DTPA) and Gd(DOTA), are usually used as the contrast agents for magnetic resonance imaging(MRI). Reported here are the enhanced relaxation properties of a novel gadolinium complex, diethylene-triaminopentaacetate Lis (isoniazid) [Gd(DTPA-BIN)], in aqueous and in human serum albumin(HSA) solution, which indicates that (1) two Gd(DTPA-BIN) can integrate non-covalently with one HSA with an equilibrium constant of 0. 02 mmol(-2) . L-2 ; (2) the relaxivities are 3. 28 and 4. 92 mmol(-1) . L . s(-1) for the free Gd(DTPA-BIN) and the [Gd(DTPA-BIN)](2), HSA conjugator, respectively; (3) the rotational correlation time of protein conjugator is notably higher than that of the free complex, The above results may imply that Gd(DTPA-BIN) has a higher tissue selectivity than that of its parent Gd(DTPA).

Synthesis and solvent enhanced relaxation property of water-soluble endohedral metallofullerenols

Gadolinium fullerenols, as novel and potential contrast agents for magnetic resonance imaging, were synthesized, which showed excellent efficiency in enhancing water proton relaxation with a relaxivity of 47.0+/-1.0 mM(-1).s(-1).

H-1 NMR Titration Studies of Two Novel DTPA Derivatives

Polyaminopolycarboxylate gadolinium (III) complexes have been studied intensively in recent years because of their potential uses as contrast agents for magnetic resonance imaging (MHI)([1]). The research interests are mainly focussed on Gd3+ complexes of DTPA, DOTA and their various derivatives. Four kinds of Gd3+ complexes can be used presently in clinical MRI, which are GD(DTPA)([2]), Gd(DOTA)([3]), Gd(DTPA-BMA)([4]) and Gd(HP-DO3A)([5]). Here report two new DTPA bis (amide) derivatives-diethylenetriaminepentaacetic acid-N, N ''-bis (dimethylamide) (DTPA-BDMA) and -bis (diethylamide) (DTPA-BDEA).

稀土化合物的一种新用途(上)——核磁共振成像(MRI)用造影剂

磁共振成像(Magnetic Resonance Imaging简称MRI)是近十几年来发展起来的一种新的医疗诊断手段,与x-射线计算机断层扫描(Computed Tomography简称x-CT)相比,具有明显的优点,如对脑部、腹腔部、椎间盘组织等的病变有较高的灵敏度。同时,由于磁场和射频电波对人体健康的损害远远小于x-CT产生的x-射线,因此,MRI法已成为当前

石油二次运移机理物理模拟研究

Oil and gas migration is very important for theoretical hydrocarbon geology study and exploration practice, but related research is weak. Physical simulation is a main method to study oil migration. Systematic experiments were done to quantitatively describe the migration patterns, path characters and oil saturation by adjusting the possible dynamic factors respectively. The following conclusions were drawn. 1. Darcy velocity and pore throat diameter were calculated according to seepage cross-sectional area and glass beads arrangement. With such normalized Darcy velocity and pore throat diameter, the date from one and two dimensional experiments can be reasonably drawn in two phase diagrams. It is found that the migration pattern can be identified using only one dimensionless number L which is defined as the ration of capillary number and Bond number. 2. Oil saturated in the pores between glass beads was used as calibration and oil saturation in the path was measured by magnetic resonance imaging. The results show that oil saturation in the center of migration path can reach 100%, is higher than oil saturation in the edge of migration path. 3. Percolation backbone during secondary oil migration was identified experimentally using Hele-Shaw cell. The backbone formed mainly because of the spatial variation of the cluster conductivity caused by oil saturation heterogeneity, main resistant force change, and path shrinkage and snap-off. Percolation backbone improves hydrocarbon migration efficiency and is a favorable factor for reservoir forming. 4. In the three dimensional filling models, the thickness of the secondary migration path is mall. It is only 2.5cm even for the piston pattern. Inclination of the model is the main influencing factor of the secondary path width.

阿片药物依赖的神经机制---内侧前额叶与药物的心理依赖

Mental dependence, characterized by craving and impulsive seeking behavior, is the matter of intensive study in the field of drug addiction. The mesolimbic dopamine system has been suggested to play an important role in rewarding of drugs and relapse. Although chronic drug use can induce neuroadaptations of the mesolimbic system and changes of drug reinforcement, these mechanisms cannot fully account for the craving and the compulsive drug-using behavior of addicts. Acknowledging the reinforcement effects of drugs, most previous studies have studied the impact of environmental cues and conditioned learning on addiction behavior, often using established classical or operant conditioning model. These studies, however, paid little attention to the role of cognitive control and emotion in addiction. These mental factors that are believed to have an important influence on conditioned learning. The medial prefrontal cortex (mPFC) has close anatomic and functional connections with the mesolimbic dopamine system. A number of the cognitive neurological studies demonstrate that mPFC is involved in motivation, emotional regulation, monitoring of responses and other executive functions. Thus we speculated that the function of abnormality in mPFC following chronic drug use would cause related to the abnormal behavior in addicts including impulse and emotional changes. In the present study of a series of experiments, we used functional magnetic resonance imaging to examine the hemodynamic response of the mPFC and related circuits to various cognitive and emotional stimuli in heroin addicts and to explore the underlying dopamine neuromechnism by microinjection of tool drugs into the mPFC in laboratory animals. In the first experiment, we found that heroin patients, relative to the normal controls, took a much shorter time and committed more errors in completing the more demanding of cognitive regulation in the reverse condition of the task, while the neural activity in anterior cingulate cortex (ACC) was attenuated. In the second experiment, the scores of the heroin patients in self-rating depression scale (SDS) and Self-rating anxiety scale (SAS) were significantly higher than the normal controls and they rated the negative pictures more aversive than the normal controls. Being congruent with the behavioral results, hemodynamic response to negative pictures showed significant difference between the two groups in bilateral ventral mPFC (VMPFC), amygdala, and right thalamus. The VMPFC of patients showed increased activation than normal controls, whereas activation in the amygdala of patients was weaker than that in normal subjects. Our third experiment showed that microinjection of D1 receptor agonist SKF38393 into the mPFC of rats decreased hyperactivity, which was induced by morphine injection, in contrast, D1 receptor antagonist SCH23390 increased the hyperactivity, These findings suggest: (1) The behavior and neural activity in ACC of addicts changed in chronic drug users. Their impulsive behavior might result from the abnormal neural activity in the mPFC especially the ACC. (2) Heroine patients were more depress and anxiety than normal controls. The dysfunction of the mPFC---amygdala circuit of heroine addicts might be related to the abnormal emotion response. (3) Dopamine in the mPFC has an inhibitory effect on morphine induced behavior. The hyperactivity induced by chronic morphine was reduced by dopamine increase with D1 receptor agonist, confirm the first experiment that the neuroadaption of mPFC system induced by chronic morphine administration appears to be the substrate the impulse behavior of drug users.

基于可复制性的独立成分分析——应用于功能磁共振成像数据

This dissertation systematically depicted and improved the application of Independent Component Analysis (ICA) to Functional Magnetic Resonance Imaging (fMRI), following the logic of verification, improvement, extension, and application. The concept of “reproducibility” was the philosophy throughout its four concluded studies. In the “verification” study, ICA was applied to the resting-state fMRI data, verified the resultant components with reproducibility, and examined the consistency of the results from ICA and traditional “seed voxel” method. At the meantime, the limitation of ICA application on fMRI data analysis was presented. In the “improvement” study, an improved ICA algorithm based on reproducibility, RAICAR, was developed to aid some of the limitations of ICA application. RAICAR was able to rank ICA components by reproducibility, determine the number of reliable components, and obtain more stable results. RAICAR provided useful tools for validation and interpretation of ICA results. In the “extension” study, RAICAR as well as the concept of “reproducibility” was extended to multi-subject ICA analysis, and gRAICAR algorithm was developed. gRAICAR allows some variation across subjects, examining common components among subjects. gRAICAR is also capable to detect potential subject grouping on some components. It is a new way for exploratory group analysis on fMRI. In the “application” study, two newly developed methods, RAICAR and gRAICAR, were used to investigate the effect of early music training on the brain mechanism of memory and learning. The results showed brain mechanism difference in memory retrieval and learning process between two groups of subjects. This study also verified the usefulness and importance of the new methods.

心算年老化的认知心理机制及功能磁共振成像研究

Mechanisms underlying cognitive psychology and cerebral physiological of mental arithmetic with increasing are were studied by using behavioral methods and functional magnetic resonance imaging (fMRI). I. Studies on mechanism underlying cognitive psychology of mental arithmetic with increasing age These studies were accomplished in 172 normal subjects ranging from 20 to 79 years of age with above 12 years of education (Mean = 1.51, SD = 1.5). Five mental arithmetic tasks, "1000-1", "1000-3", "1000-7", "1000-13", "1000-17", were designed with a serial calculation in which subjects sequentially subtracted the same prime number (1, 3, 7, 13, 17) from another number 1000. The variables studied were mental arithmetic, age, working memory, and sensory-motor speed, and four studies were conducted: (1) Aging process of mental arithmetic with different difficulties, (2) mechanism of aging of mental arithmetic processing. (3) effects of working memory and sensory-motor speed on aging process of mental arithmetic, (4) model of cognitive aging of mental arithmetic, with statistical methods such as MANOVA, hierarchical multiple regression, stepwise regression analysis, structural equation modelling (SEM). The results were indicated as following: Study 1: There was an obvious interaction between age and mental arithmetic, in which reaction time (RT) increased with advancing age and more difficult mental arithmetic, and mental arithmetic efficiency (the ratio of accuracy to RT) deceased with advancing age and more difficult mental arithmetic; Mental arithmetic efficiency with different difficulties decreased in power function: Study 2: There were two mediators (latent variables) in aging process of mental arithmetic, and age had an effect on mental arithmetic with different difficulties through the two mediators; Study 3: There were obvious interactions between age and working memory, working memory and mental arithmetic; Working memory and sensory-motor speed had effects on aging process of mental arithmetic, in which the effect of working memory on aging process of mental arithmetic was about 30-50%, and the effect of sensory-motor speed on aging process of mental arithmetic was above 35%. Study 4: Age, working memory, and sensory-motor speed had effects on two latent variables (factor 1 and factor 2), then had effects on mental arithmetic with different difficulties through factor 1 which was relative to memory component, and factor 2 which relative to speed component and had an effect on factor 1 significantly. II. Functional magnetic resonance imaging study on metal arithmetic with increasing age This study was accomplished in 14 normal right-handed subjects ranging from 20 to 29 (7 subjects) and 60 to 69 (7 subjects) years of age by using functional magnetic resonance imaging apparatus, a superconductive Signa Horizon 1.5T MRI system. Two mental arithmetic tasks, "1000-3" and "1000-17", were designed with a serial calculation in which subjects sequentially subtracted the same prime number (3 or 17) from another number 1000 silently, and controlling task, "1000-0", in which subjects continually rehearsed number 1000 silently, was regarded as baseline, based on current "baseline-task" OFF-ON subtraction pattern. Original data collected by fMRI apparatus, were analyzed off-line in SUN SPARC working station by using current STIMULATE software. The analytical steps were composed of within-subject analysis, in which brain activated images about mental arithmetic with two difficulties were obtained by using t-test, and between-subject analysis, in which features of brain activation about mental arithmetic with two difficulties, the relationship between left and right hemisphere during mental arithmetic, and age differences of brain activation in young and elderly adults were examined by using non-parameter Wilcoxon test. The results were as following:

PROTRACTED HYPOFRACTIONATED RADIOTHERAPY for GRAVES' OPHTHALMOPATHY: A PILOT STUDY of CLINICAL and RADIOLOGIC RESPONSE

Purpose: To evaluate the clinical and radiologic response of patients with Graves' ophthalmopathy given low-dose orbital radiotherapy (RT) with a protracted fractionation.Methods and Materials: Eighteen patients (36 orbits) received orbital RT with a total dose of 10 Gy, fractionated in 1 Gy once a week over 10 weeks. of these, 9 patients received steroid therapy as well. Patients were evaluated clinically and radiologically at 6 months after treatment. Clinical response assessment was carried out using three criteria: by physical examination, by a modified clinical activity score, and by a verbal questionnaire considering the 10 most common signs and symptoms of the disease. Radiologic response was assessed by magnetic resonance imaging.Results: Improvement in ocular pain, palpebral edema, visual acuity, and ocular motility was observed in all patients. Significant decrease in symptoms such as tearing (p < 0.001) diplopia (p = 0.008), conjunctival hyperemia (p = 0.002), and ocular grittiness (p = 0.031) also occurred. Magnetic resonance imaging showed decrease in ocular muscle thickness and in the intensity of the T2 sequence signal in the majority of patients. Treatments were well tolerated, and to date no complications from treatment have been observed. There was no statistical difference in clinical and radiologic response between patients receiving RT alone and those receiving RT plus steroid therapy.Conclusion: RT delivered in at a low dose and in a protracted scheme should be considered as a useful therapeutic option for patients with Graves' ophthalmopathy. (C) 2012 Elsevier Inc.

Rough set feature selection and rule induction for prediction of malignancy degree in brain glioma

X. Wang, J. Yang, R. Jensen and X. Liu, 'Rough Set Feature Selection and Rule Induction for Prediction of Malignancy Degree in Brain Glioma,' Computer Methods and Programs in Biomedicine, vol. 83, no. 2, pp. 147-156, 2006.

LA Size in Former Elite Athletes

A recent meta-analysis by Iskandar et al. (1) nicely showed that endurance athletes have larger left atrial (LA) diameters compared with control subjects. Yet only 9 of 54 studies included in their analysis reported LA volume values corrected for body surface area (BSA). In fact, few studies have determined LA volume in young athletes, and, to the best of our knowledge, no study has reported this variable in older athletes. This is an important question given the growing debate about the potential deleterious effects of long-term strenuous endurance exercise on the human heart, notably the higher risk of atrial fibrillation (AF), a condition for which both atrial dilation and the normal aging process are thought to be potential causative mechanisms (2). Thus, we aimed to assess the long-term consequences of endurance exercise on LA volume in athletes who were highly competitive at younger ages and are still active. To this end, we compared BSA-corrected LA volumes determined with late gadolinium enhancement magnetic resonance imaging (LGE-MRI) in former elite endurance athletes and sedentary control subjects.