New neuroimaging methods for clinical neuroscience and neurological disorders

236 p.

Structural Integrity of the Contralesional Hemisphere Predicts Cognitive Impairment in Ischemic Stroke at Three Months

After stroke, white matter integrity can be affected both locally and distally to the primary lesion location. It has been shown that tract disruption in mirror's regions of the contralateral hemisphere is associated with degree of functional impairment. Fourteen patients suffering right hemispheric focal stroke (S) and eighteen healthy controls (HC) underwent Diffusion Weighted Imaging (DWI) and neuropsychological assessment. The stroke patient group was divided into poor (SP; n = 8) and good (SG; n = 6) cognitive recovery groups according to their cognitive improvement from the acute phase (72 hours after stroke) to the subacute phase (3 months post-stroke). Whole-brain DWI data analysis was performed by computing Diffusion Tensor Imaging (DTI) followed by Tract Based Spatial Statistics (TBSS). Assessment of effects was obtained computing the correlation of the projections on TBSS skeleton of Fractional Anisotropy (FA) and Radial Diffusivity (RD) with cognitive test results. Significant decrease of FA was found only in right brain anatomical areas for the S group when compared to the HC group. Analyzed separately, stroke patients with poor cognitive recovery showed additional significant FA decrease in several left hemisphere regions; whereas SG patients showed significant decrease only in the left genu of corpus callosum when compared to the HC. For the SG group, whole brain analysis revealed significant correlation between the performance in the Semantic Fluency test and the FA in the right hemisphere as well as between the performance in the Grooved Pegboard Test (GPT) and theTrail Making Test-part A and the FA in the left hemisphere. For the SP group, correlation analysis revealed significant correlation between the performance in the GPT and the FA in the right hemisphere.

A novel brain partition highlights the modular skeleton shared by structure and function

Elucidating the intricate relationship between brain structure and function, both in healthy and pathological conditions, is a key challenge for modern neuroscience. Recent progress in neuroimaging has helped advance our understanding of this important issue, with diffusion images providing information about structural connectivity (SC) and functional magnetic resonance imaging shedding light on resting state functional connectivity (rsFC). Here, we adopt a systems approach, relying on modular hierarchical clustering, to study together SC and rsFC datasets gathered independently from healthy human subjects. Our novel approach allows us to find a common skeleton shared by structure and function from which a new, optimal, brain partition can be extracted. We describe the emerging common structure-function modules (SFMs) in detail and compare them with commonly employed anatomical or functional parcellations. Our results underline the strong correspondence between brain structure and resting-state dynamics as well as the emerging coherent organization of the human brain.

Methods of patterning magnetic fields using bulk superconductors

High Temperature superconductors are able to carry very high current densities, and thereby sustain very high magnetic fields. There are many projects which use the first property and these have concentrated on power generation, transmission and utilization, however there are relatively few which are currently exploiting the ability to sustain high magnetic fields. There are two main reasons for this: high field wound magnets can and have been made from both BSCCO and YBCO but currently their cost is much higher than the alternative provided by low Tc materials such as Nb3Sn and NbTi. An alternative form of the material is the bulk form which can be magnetized to high fields and using flux pumping this can be done in situ. This paper explores some of the applications of bulk superconductors and describes methods of producing field patterns using the highly uniform magnetic fields required for MRI and accelerator magnets as the frame of reference. The patterns are not limited to uniform fields and it is entirely possible to produce a field varying sinusoidally in space such as would be required for a motor or a generator. The scheme described in this paper describes a dipole magnet such as is found in an accelerator magnet. The tunnel is 30 × 50 × 1000 mm and we achieve a uniformity of better than 200 ppm over the 1000 mm length and better than 1 ppm over the central 500 mm region. The paper presents results for both the overall uniformity and the integrated uniformity which is 302 ppm over the 1000 mm length. © 2010 IEEE.

Accurate real-time feedback of surface EMG during fMRI.

Real-time acquisition of EMG during functional MRI (fMRI) provides a novel method of controlling motor experiments in the scanner using feedback of EMG. Because of the redundancy in the human muscle system, this is not possible from recordings of joint torque and kinematics alone, because these provide no information about individual muscle activation. This is particularly critical during brain imaging because brain activations are not only related to joint torques and kinematics but are also related to individual muscle activation. However, EMG collected during imaging is corrupted by large artifacts induced by the varying magnetic fields and radio frequency (RF) pulses in the scanner. Methods proposed in literature for artifact removal are complex, computationally expensive, and difficult to implement for real-time noise removal. We describe an acquisition system and algorithm that enables real-time acquisition for the first time. The algorithm removes particular frequencies from the EMG spectrum in which the noise is concentrated. Although this decreases the power content of the EMG, this method provides excellent estimates of EMG with good resolution. Comparisons show that the cleaned EMG obtained with the algorithm is, like actual EMG, very well correlated with joint torque and can thus be used for real-time visual feedback during functional studies.

Increasing top-down suppression from prefrontal cortex facilitates tactile working memory

Navigated transcranial magnetic stimulation (TMS) combined with diffusion-weighted magnetic resonance imaging (DW-MRI) and tractography allows investigating functional anatomy of the human brain with high precision. Here we demonstrate that working memory (WM) processing of tactile temporal information is facilitated by delivering a single TMS pulse to the middle frontal gyrus (MFG) during memory maintenance. Facilitation was obtained only with a TMS pulse applied to a location of the MFG with anatomical connectivity to the primary somatosensory cortex (S1). TMS improved tactile WM also when distractive tactile stimuli interfered with memory maintenance. Moreover, TMS to the same MFG site attenuated somatosensory evoked responses (SEPs). The results suggest that the TMS-induced memory improvement is explained by increased top-down suppression of interfering sensory processing in S1 via the MFG-S1 link. These results demonstrate an anatomical and functional network that is involved in maintenance of tactile temporal WM. (C) 2009 Elsevier Inc. All rights reserved.

新型靶向性磁共振成像造影剂的合成及性质研究

磁共振成像(magnetic resonance imaging, MRI)以其分辨率高、对人体无电离辐射损伤、多参数成像等优点而得到迅速发展和广泛应用。目前，MRI已从单一形态学向分子影像学的深度发展，对医学临床和医学研究产生了巨大影响。为了提高病变部位与正常组织间信号的对比度，约30%~40%的诊断需要使用磁共振成像造影剂。它是一类能缩短成像时间、提高成像对比度和清晰度、显示组织器官功能状态的诊断用药。下一代磁共振成像造影剂的设计目标将集中在对特定组织或器官具有选择性或靶向性、高弛豫性能和减少用药剂量等方面。本论文在此领域的研究内容可归纳如下： (1) 以多糖为载体的MRI造影剂 设计合成了阿拉伯半乳聚糖修饰的Gd-DTPA配合物(Gd-DTPA-CMAG-An)和葡聚糖修饰的Gd-DTPA配合物(Gd-DTPA-CMDn-Cyst)。通过体外弛豫时间测试和体内磁共振成像实验研究了Gd-DTPA-CMAG-An弛豫性能、器官选择性、体内滞留时间和代谢情况，结合体外稳定性综合评价了其应用于临床的可能性。研究结果表明，Gd-DTPA-CMAG-An配合物在水溶液中弛豫性能为Gd-DTPA的1.4倍左右，Gd-DTPA-CMAG-A2对肝脏信号的增强效果是Gd-DTPA的2.0倍左右，并且能在较长时间内产生良好稳定的增强效果。这与肝脏表面的去唾液酸糖蛋白受体的专一性识别有关。Gd-DTPA-CMAG-A2良好的肝脏选择性和肾脏代谢能力，有望成为有前景的肝脏选择性造影剂。通过小鼠MRI实验初步评价了Gd-DTPA-CMDn-Cyst配合物造影剂对血管信号的增强作用。Gd-DTPA-CMD4-Cyst对血管产生了良好的增强效果，并且能在较长时间内对血管产生良好稳定的增强，从而有充分的时间优化成像窗口获得理想的成像效果。但造影剂在体内的分布和代谢是一个非常复杂的过程，Gd-DTPA-CMD4-Cyst在血液中的滞留情况及能否用于血管造影仍需进一步的实验证实。 (2) MnNaY 型分子筛作为胃肠道MRI造影剂 离子交换法制备了Mn2+交换的NaY分子筛MnNaY，从对造影剂的一般要求出发，对其酸性水溶液中的稳定性和离子交换选择性、体外弛豫性能和体内成像等方面进行研究，并对器官的选择性及体内滞留时间和代谢情况进行了分析，从而对其应用于临床的可能性进行了探讨。研究结果表明，MnNaY悬浮液能长时间在较低的酸性条件下保持良好的稳定性，其弛豫效率高于目前临床所用造影剂Gd-DTPA，随Mn2+的含量在NaY分子筛中的增加(3.2%~5.2%)，弛豫效率反而降低。MnNaY (3.2% Mn)对胃部具有良好的增强效果，并且能在较长时间内产生良好稳定的增强效果，有利于获得理想的成像效果。它是一种比较好的潜在口服胃肠道造影剂。 (3) 甘草酸为载体的MRI造影剂 合成了甘草酸为载体的配合物GL-(A-Gd-DTPA)3，对其体外弛豫性能和体内成像等方面进行了研究，结果表明，其在水中的弛豫效率约为目前临床所用造影剂Gd-DTPA的1.4倍，体内成像表明它能在较长时间内对大鼠肝脏产生良好稳定的增强效果，这是由于肝(实质)细胞膜表面存在GL和GA受体，Gd-DTPA 以GL为载体后具有良好的趋肝性与肝细胞靶向性。 (4) 中性的Gd-DTPA双酰胺衍生物 合成了两种中性的Gd-DTPA双酰胺衍生物Gd-DTPA-BBA和Gd-DTPA-BtBA，其弛豫效率与Gd-DTPA相近，对肝脏和肾脏具有较好的增强效果，由于这两种配合物均为电中性化合物，这样配合物溶液的渗透压值与血液的渗透压值较接近，可能更易为生物体所接受。

核磁共振技术在生物医学及临床评价中的应用--磁共振成像造影剂及稀土的生物效应研究

近年来，随着高场傅里叶变换核磁共振波谱仪灵敏度的提高、分辨率的增加、化学位移的扩展、多脉冲实验技术的发展以及计算机技术的不断进步，使NMR技术和MRI技术在生物和医学领域的应用有了飞速的发展。论文工作围绕新型MRI造影剂的研制和稀土对动物体液代谢产物的影响及作用，进行了较系统的研究。合成了四种稀土配合物：K_(11)[Gd(PW_(11)o_(39)]_2]、K_9GdW_(10)O_(36)、Gd_2(P_2W_(18)O_(62)、K_(15)[(GdO)_3(PW_9O_(34)_2]和四种中性的多竣多胺类稀土配合物：Gd(DTPA-BDEA）、Gd(DTPA-BDMA)、Gd(DTPA-BIN)和Gd(cyclic-DTPA-1,2-pn),从对造影剂临床应用的一般要求出发，对其进行了表征和溶解性、稳定性及体外的弛豫实验，指出它们是潜在的较好的MRI造影剂。在此基础上，通过大鼠体内的MRI实验考察了／又种造影剂侯选化合物的体内弛豫效率、选择性及体内滞留时间和代谢情况，并与目前临床普遍运用的造影剂GdDTPA进行了比较。并结合动物急性毒性实验(LD_(50)测定）对其进行综合评价，且对其应用于临床的可能性进行了探讨。结果表明，K_(11)[Gd(PW_(11)O_(39)_2]、K_9GdW_(10)O_(36)、K_(15)[GdO)_3(PW_9O_(34)_2]和Gd(DTPA-BDMA), Gd(DTPA-BIN), Gd(cyclic-DTPA-1,2-pn)是良好的具有肝脏选择性的MRI造影剂，K_(15)[(GdO_3(PW_9O_(34)_2]、Gd(cyclic-DTPA-1,2-pn)Gd(DTPA-BDMA)具有良好的肾脏代谢性能，另外KgGdW10036有可能对病理状态的诊断有一定的作用。首次运用高分辨'H NMR技术，检测了大鼠长期服用不同剂量硝酸斓(0,0.05, 0.2, 2.0, 10, 20 mg/kg体重）和农用稀土微肥常乐(La203: 30.48%, Ce02: 54.67,Pr6011: 6.05%, Nd203: 8.8%) (0, 0.1, 0.2, 2.0, 10, 20 mg/kg体重）后血清及尿液中的代谢物如柠檬酸、酮体、肌酸酚、二甲胺、二甲基甘氨酸、TMAO、氨基酸和乳酸、唬拍酸、牛磺酸等的浓度、物种的变化，并用ICP-MS法测定了长期口服常乐后大鼠各组织及脏器中的稀土含量，并结合一些生化指标的测试，对稀土在体内与细胞、组织和器官的作用机理及在动物体内的积累、排泄和远期毒性进行了有意义的探讨。结果表明，高剂量稀土在体内长期作用，可能导致动物肝脏和肾脏特定部位（如肾小管、'肾乳头、肝脏线粒体）受到选择性的损伤，且损害程度与剂量成正比关系。并发现，不同的稀土离子在体内有不同的作用方式，不同的稀土离子在体内有不同的代谢和累积速率，而且动物对稀土的毒性可能有一个适应过程。低剂量稀土对代谢没有明显影响，并建议了一个较安全剂量，但仍需对稀土的农用安全性进行进一步研究。

新型选择性磁共振成像造影剂的设计、合成及性质

近年来，随着磁共振血管造影（magnetic resonance angiography，MRA）、功能磁共振成像（fuectional MRI）、灌注磁共振成像中erfusion MRI）、扩散加权磁共振成像（diffusion weigllted MRI）等新M班技术的发展和在临床诊断应用中的普及，磁共振成像造影剂的研究和开发已经成为一个日益重要的研究领域。其中大分子造影剂由于具有弛豫效率高、在血池中停留时间长及可能的组织、器官选择性等特点更是受到MRI造影剂研究者的广泛关注。论文工作围绕新型MRI造影剂的研制进行了较系统的研究，主要实验结果归纳如下：（1）以天然多糖为载体的M斑造影剂设计合成了四种天然多糖修饰的Gd-DTPA配合物：AG-（Gd-DTPA）n、PQPS-（Gd-DTPA）n、GAPS-（Gd-DTPA）n和EAPS-（Gd-DTPA）。通过体外弛豫时间测试和体内磁共振成像实验研究其弛豫性能、器官选择性、体内滞留时间和代谢情况，结合体外稳定性和溶血性综合评价了其应用于临床的可能性。研究结果表明，不同类型多糖Gd-DTPA配合物在水溶液中弛豫性能相近，为Gd-DTPA的1.5-2.0倍，对肝脏信号的增强效果是Gd-DTPA的3.0倍左右，并且能在较长时间内产生稳定良好的增强效果。肝脏信号的增强效果随多糖Gd-DTPA配合物分子量的增加基本呈现出升高趋势，表明分子量影响其肝脏分布，分子量越大越易于在肝脏积累。其中，AG-（GdDTPA）n表现出了良好的肝脏选择性和肾脏代谢性能，有望成为有前景的肝脏选择性造影剂。而EAPS-（Gd-DTPA）n在肾脏中的代谢速率较慢，这一特性在磁共振血管造影及灌注磁共振成像的研究中极有帮助。（2）稀土杂多配合物M班造影剂设计合成了三种夹心型稀土杂多配合物：K13［Gd（Siw11O39）］、K11H6［Gd3O3（SiWgO34）2］及K17［Gd（PZW17O61）2］，通过体外弛豫性能、稳定性、溶血性及体内急性毒性、磁共振成像实验，对其体外体内的增强效果和安全性进行了较全面的评价。K13［Gd（SIWllO39）2］和K17〔Gd（PZwl7o61）2］在水溶液中的弛豫效率略高于Gd-DTPA，而K11H6［Gd3O3（SiW9O34）2］在水溶液中的弛豫效率是Gd-DTPA的3.5倍左右。磁共振成像实验表明：K13［Gd（SIWll。动2］、K11H6［Gd3O3（siwgo34）2」和K17［Gd（P ZwI7o61）2］对肝脏产生的增强效果分别为Gd-DTPA的1.5、2.5和3.5倍左右，对肾脏的增强效果不及Gd-DTPA。通过与磷钨杂多配合物的比较发现，具有相同构型的稀土杂多配合物对肝脏和肾脏产生的增强效果相近，肝脏信号增强的顺序为Gd（凡wl7）2＞Gd3（XW9）2＞Gd（XW11）2，肾脏信号增强的顺序为Gd3（XW9）2≈Gd（XW11）2＞Gd（X2W17）2。总体来说，稀土杂多配合物在体内的分布和代谢是由其构型、离子大小、所带负电荷等因素决定的，受结构中的杂原子影响不大。

One-pot green synthesis of biocompatible arginine-stabilized magnetic nanoparticles

A green one-step approach has been developed for the synthesis of amino-functionalized magnetite nanoparticles. The synthesis was accomplished by simply mixing FeCl2 with arginine under ambient conditions. It was found that the Fe2+/arginine molar ratio, reaction duration and temperature greatly influence the size, morphology and composition of magnetic nanoparticles. The arginine-stabilized magnetic nanoparticles were characterized by transmission electron microscopy, x-ray diffraction, x-ray photoelectron spectroscopy, thermogravimetric analysis, and Fourier transform infrared spectroscopy techniques.

Facile coprecipitation to synthesize water-soluble amine-capped magnetite nanoparticles

Water solubility and surface functionalization of magnetic nanoparticles are crucial for bioapplication.[1]In this study,we presented a facile coprecipitation approach to synthesize lysine stabilized Fe3O4 nanoparticles.Lysine functionalized magnetite nanoparticles show an excellent colloidal stability of ＞20h.The as-synthesized magnetite nanoparticles have abundant amine groups on their surface which provide convenient sites for covalent linking of biological macromolecules.We believe that these amine-functionalized magnetic nanoparticles can be potentially used in fields such as magnetic bio-separation,immunoassay,MRI,and targeted drug delivery.

夹心型锰杂多配合物作为磁共振成像造影剂的研究

以两种夹心型锰杂多配合物K10[Mn4(PW9O34)2]·22H2O和Na16[Mn4(H2O)2(P2W15O56)2]·53H2O作为研究对象,采用元素分析和红外光谱对其结构进行了表征,测试其在水中、牛血清白蛋白及运铁蛋白溶液中的弛豫效率,并进行了大鼠活体成像实验.结果表明,这两种锰杂多配合物的弛豫效率高于或接近于目前临床常用的造影剂Gd-DTPA,对肝脏和肾脏MRI信号具有良好的增强效果,是比较好的潜在磁共振成像造影剂候选化合物.

Mn(II)-monosubstituted polyoxometalates as candidates for contrast agents in magnetic resonance imaging

Two mono-substituted manganese polyoxometalates, K6MnSiW11O39 (MnSiW11) and K8MnP2W17O61 (MnP2W17), have been evaluated by in vivo and in vitro experiments as the candidates of potential tissue-specific contrast agents for magnetic resonance imaging (MRI). T-1-relaxivities of 12.1 mM(-1) s(-1) for MnSiW11 and 4.7 mM(-1) s(-1) for MnP2W17 (400 MHz, 25 degrees C) were higher than or similar to that of the commercial MRI contrast agent (GdDTPA). Their relaxivities in BSA and hTf solutions were also reported. After administration of MnSiW11 and MnP2W17 to Wistar rats, MR imaging showed longer and remarkable enhancement in rat liver and favorable renal excretion capability. The signal intensity increased by 74.0 +/- 4.9% for the liver during the whole imaging period (90 min) and by 67.2 +/- 5.3% for kidney within 20-70 min after injection at 40 +/- 3 mu mol kg(-1) dose for MnSiW11. MnP2W17 induced 71.5 +/- 15.1%. enhancement for the liver in 10-45 min range and 73.1 +/- 3.2% enhancement for kidney within 5-40 min after injection at 39 +/- 3 mu mol kg(-1) dose. In vitro and in vivo study showed MnSiW11 and MnP2W17 being favorable candidates as the tissue-specific contrast agents for MRI.

Study of alpha-, beta- and gamma-cyclodextrin/C-60 supramolecular complexes: Influence of the cavity dimension toward the host-guest complexes

Herein we report the spectroscopic, electrochemical, TEM and DLS characterizations Of C-60 supramolecular inclusion complexes with alpha-, beta- and gamma-cyclodextrins prepared using anionic C-60. The results indicate that the cyclodextrin itself has little effect on the encapsulated C-60 or on the properties of the inclusion complex. Instead, the cyclodextrin has a significant influence on the aggregation behavior of individual complex in aqueous solution, which in turn affects the property of the supramolecular complex of cyclodextrin and C-60 greatly, As the cavity dimension of cyclodextrin becomes smaller as it changes from gamma-CD to beta-CD, and finally to alpha-CD, it is observed that more aggregation occurs for the corresponding inclusion complex in aqueous solution.

Arabinogalactan as a carrier for contrast agent in magnetic resonance imaging

Arabinogalactan-Gd-DTPA was synthesized by the reaction of diethylenetriaminepenta-acetic acid (DTPA) bisanhydride with polysaccharide in dry DMSO and characterized by FTIR, elemental analysis and ICP-AES. Its stability was investigated by competition with Ca2+, EDTA, DTPA. The t(1)-relaxivity is 8.06 mmol(-1) . L . s(-1) in D2O, 8.48 mmol(-1) . L . s(-1) in 0.725 mmol . L-1 BSA, respectively. t(1)-weighted MR imaging of rat kidney and liver showed a remarkable enhancement post injection of Arabinogalactan-Gd-DTPA. The results indicate that the arabinogalactan-Gd-DTPA is a potential contrast agent for MRI.