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Improvements in a Mouse Model of Alzheimer's Disease Through SOD2 Overexpression are Due to Functional and Not Structural Alterations. SOD2过表达对阿尔茨海默病小鼠模型的改善是功能性而非结构性改变所致
Pub Date : 2012-03-29 DOI: 10.4137/MRI.S9352
Brittany R Bitner, Carlos J Perez-Torres, Lingyun Hu, Taeko Inoue, Robia G Pautler

Oxidative stress and mitochondrial dysfunction have been implicated in the pathogenesis of Alzheimer's disease. We and others have shown that over expression of the mitochondrial antioxidant superoxide dismutase 2 (SOD-2) can improve many of the pathologies in the Tg2576 mouse model of Alzheimer's disease that harbors the Swedish mutation in the amyloid precursor protein. However, it is not clear if these improvements are due to functional improvements or structural/anatomical changes. To answer this question, we used diffusion tensor imaging (DTI) to assess the structural integrity of white matter tracts in the control mice, Tg2576 mouse and Tg2576 mice over expressing SOD-2. We observed minimal differences in diffusion parameters with SOD-2 over expression in this model indicating that the improvements we previously reported are due to functional changes and not any alterations to the white matter tractography.

氧化应激和线粒体功能障碍与阿尔茨海默病的发病机制有关。我们和其他人已经证明,过度表达线粒体抗氧化剂超氧化物歧化酶 2(SOD-2)可以改善携带瑞典淀粉样前体蛋白突变的 Tg2576 阿尔茨海默病小鼠模型的许多病理症状。然而,目前还不清楚这些改善是由于功能改善还是由于结构/解剖变化。为了回答这个问题,我们使用弥散张量成像(DTI)来评估对照组小鼠、Tg2576 小鼠和过度表达 SOD-2 的 Tg2576 小鼠白质束的结构完整性。在该模型中,我们观察到 SOD-2 过度表达时的扩散参数差异极小,这表明我们之前报告的改善是由于功能性变化,而不是白质束成像的任何改变。
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引用次数: 0
Detection of Amide and Aromatic Proton Resonances of Human Brain Metabolites Using Localized Correlated Spectroscopy Combined with Two Different Water Suppression Schemes. 结合两种不同的水抑制方案的局部相关光谱法检测人脑代谢物的酰胺和芳香质子共振
Pub Date : 2010-06-15 DOI: 10.4137/MRI.S4739
Rajakumar Nagarajan, Saadallah Ramadan, M Albert Thomas

The purpose of the study was to demonstrate the J-coupling connectivity network between the amide, aliphatic, and aromatic proton resonances of metabolites in human brain using two-dimensional (2D) localized correlated spectroscopy (L-COSY). Two different global water suppression techniques were combined with L-COSY, one before and another after localizing the volume of interest (VOI). Phantom solutions containing several cerebral metabolites at physiological concentrations were evaluated initially for sequence optimization. Nine healthy volunteers were scanned using a 3T whole body MRI scanner. The VOI for 2D L-COSY was placed in the right occipital white/gray matter region. The 2D cross and diagonal peak volumes were measured for several metabolites such as N-acetyl aspartate (NAA), creatine (Cr), free choline (Ch), glutamate/glutamine (Glx), aspartate (Asp), myo-inositol (mI), GABA, glutathione (GSH), phosphocholine (PCh), phosphoethanolamine (PE), tyrosine (Tyr), lactate (Lac), macromolecules (MM) and homocarnosine (Car). Using the pre-water suppression technique with L-COSY, the above mentioned metabolites were clearly identifiable and the relative ratios of metabolites were calculated. In addition to detecting multitude of aliphatic resonances in the high field region, we have demonstrated that the amide and aromatic resonances can also be detected using 2D L-COSY by pre water suppression more reliably than the post-water suppression.

这项研究的目的是利用二维(2D)局部相关光谱(L-COSY)来展示人脑中代谢物的酰胺、脂肪族和芳香族质子共振之间的 J 耦合连接网络。两种不同的全局水抑制技术与 L-COSY 相结合,一种在感兴趣体积(VOI)定位之前,另一种在感兴趣体积定位之后。首先对含有多种生理浓度脑代谢物的模型溶液进行了评估,以优化序列。使用 3T 全身磁共振成像扫描仪对九名健康志愿者进行了扫描。二维 L-COSY 的 VOI 位于右枕部白质/灰质区域。测量了几种代谢物的二维交叉峰和对角峰体积,如天冬氨酸 N-乙酰(NAA)、肌酸(Cr)、游离胆碱(Ch)、谷氨酸/谷氨酰胺(Glx)、天冬氨酸(Asp)、肌酸(Myc)、谷氨酸/谷氨酰胺(Glx)、天门冬氨酸(Asp)、肌醇(mI)、GABA、谷胱甘肽(GSH)、磷胆碱(PCh)、磷乙醇胺(PE)、酪氨酸(Tyr)、乳酸(Lac)、大分子(MM)和高肌肽(Car)。利用 L-COSY 的水前抑制技术,上述代谢物可以清晰地识别出来,并计算出代谢物的相对比率。除了在高场区检测到大量脂肪族共振外,我们还证明了利用二维 L-COSY 的水前抑制技术检测酰胺和芳香族共振比水后抑制更为可靠。
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引用次数: 0
Increased Human Wildtype Tau Attenuates Axonal Transport Deficits Caused by Loss of APP in Mouse Models. 在小鼠模型中,增加人类野生型Tau可减弱APP缺失引起的轴突运输缺陷。
Pub Date : 2010-01-01 DOI: 10.4137/mri.s5237
Karen D B Smith, Erica Peethumnongsin, Han Lin, Hui Zheng, Robia G Pautler

Amyloid precursor protein (APP) is implicated in axonal elongation, synaptic plasticity, and axonal transport. However, the role of APP on axonal transport in conjunction with the microtubule associated protein tau continues to be debated. Here we measured in vivo axonal transport in APP knockout mice with Manganese Enhanced MRI (MEMRI) to determine whether APP is necessary for maintaining normal axonal transport. We also tested how overexpression and mutations of tau affect axonal transport in the presence or absence of APP. In vivo axonal transport reduced significantly in the absence of functional APP. Overexpression of human wildtype tau maintained normal axonal transport and resulted in a transient compensation of axonal transport deficits in the absence of APP. Mutant R406Wtau in combination with the absence of APP compounded axonal transport deficits and these deficits persisted with age. These results indicate that APP is necessary for axonal transport, and overexpression of human wildtype tau can compensate for the absence of APP at an early age.

淀粉样前体蛋白(APP)与轴突伸长、突触可塑性和轴突运输有关。然而,APP与微管相关蛋白tau在轴突运输中的作用仍存在争议。在这里,我们用锰增强MRI (MEMRI)测量APP敲除小鼠体内轴突运输,以确定APP是否对维持正常轴突运输是必要的。我们还测试了在APP存在或不存在的情况下,tau的过表达和突变如何影响轴突运输。在没有功能性APP的情况下,体内轴突运输显著减少。人类野生型tau的过表达维持了正常的轴突运输,并在APP缺失的情况下对轴突运输缺陷进行了短暂的补偿。突变体R406Wtau与APP缺失结合,复合了轴突运输缺陷,这些缺陷随着年龄的增长而持续存在。这些结果表明APP是轴突运输所必需的,人类野生型tau的过表达可以弥补早期APP的缺失。
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引用次数: 28
DANCING WITH THE ELECTRONS: TIME-DOMAIN AND CW IN VIVO EPR IMAGING. 与电子共舞:时域和连续波在体电磁共振成像。
Pub Date : 2008-09-24 DOI: 10.4137/mri.s1131
Sankaran Subramanian, Murali C Krishna

The progress in the development of imaging the distribution of unpaired electrons in living systems and the functional and the potential diagnostic dimensions of such an imaging process, using Electron Paramagnetic Resonance Imaging (EPRI), is traced from its origins with emphasis on our own work. The importance of EPR imaging stems from the fact that many paramagnetic probes show oxygen dependent spectral broadening. Assessment of in vivo oxygen concentration is an important factor in radiation oncology in treatment-planning and monitoring treatment-outcome. The emergence of narrow-line trairylmethyl based, bio-compatible spin probes has enabled the development of radiofrequency time-domain EPRI. Spectral information in time-domain EPRI can be achieved by generating a time sequence of T(2)* or T(2) weighted images. Progress in CW imaging has led to the use of rotating gradients, more recently rapid scan with direct detection, and a combination of all the three. Very low field MRI employing Dynamic Nuclear polarization (Overhauser effect) is also employed for monitoring tumor hypoxia, and re-oxygenation in vivo. We have also been working on the co-registration of MRI and time domain EPRI on mouse tumor models at 300 MHz using a specially designed resonator assembly. The mapping of the unpaired electron distribution and unraveling the spectral characteristics by using magnetic resonance in presence of stationary and rotating gradients in indeed 'dancing with the (unpaired) electrons', metaphorically speaking.

利用电子顺磁共振成像(EPRI)对生命系统中不成对电子的分布以及这种成像过程的功能和潜在诊断维度进行成像的进展,从其起源追溯,重点是我们自己的工作。EPR成像的重要性源于这样一个事实,即许多顺磁探针显示出氧依赖的光谱展宽。体内氧浓度的评估是放射肿瘤学治疗计划和监测治疗结果的重要因素。窄线四烷基甲基基生物相容性自旋探针的出现使射频时域EPRI的发展成为可能。时域EPRI中的光谱信息可以通过生成T(2)*或T(2)加权图像的时间序列来实现。连续波成像技术的进步导致了旋转梯度成像、最近的直接检测快速扫描以及三者的结合。采用动态核极化(Overhauser效应)的极低场MRI也被用于监测肿瘤体内缺氧和再氧合。我们也一直在使用特殊设计的谐振器组件对300 MHz的小鼠肿瘤模型进行MRI和时域EPRI的共同配准。打个比方说,在静止和旋转梯度存在的情况下,利用磁共振绘制不成对电子分布的映射并揭示光谱特征,实际上是“与(不成对的)电子共舞”。
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引用次数: 10
Gender Differences in Musculoskeletal Lipid Metabolism as Assessed by Localized Two-Dimensional Correlation Spectroscopy. 用局部二维相关光谱评估肌肉骨骼脂质代谢的性别差异。
Pub Date : 2008-09-03
S Sendhil Velan, Nicholas Said, Kartik Narasimhan, Cyrus Papan, Ali Bahu, John Austin Vargo, Raymond R Raylman, M Albert Thomas, Vazhaikkurichi M Rajendran, Richard G Spencer, Stephen E Alway

Gender differences in lipid metabolism are poorly understood and difficult to study using conventional approaches. Magnetic resonance spectroscopy (MRS) permits non-invasive investigation of lipid metabolism. We employed novel two-dimensional MRS techniques to quantify intramyocellular (IMCL) and extramyocellular (EMCL) lipid compartments and their degree of unsaturation in normal weight adult male and female subjects. Using muscle creatine (Cr) for normalization, a statistically significant (p < 0.05) increase in IMCL/Cr (7.8 ± 1.6) and EMCL/Cr (22.5 ± 3.6) for female subjects was observed (n=8), as compared to IMCL/Cr (5.9 ± 1.7) and EMCL/Cr (18.4 ± 2.64) for male subjects. The degree of unsaturation within IMCL and EMCL was lower in female subjects, 1.3 ± 0.075 and 1.04 ± 0.06, respectively, as compared to that observed in males (n=8), 1.5 ± 0.08 and 1.12 ± 0.03, respectively (p < 0.05 male vs female for both comparisons). We conclude that certain salient gender differences in lipid metabolism can be assessed noninvasively by advanced MRS approaches.

脂质代谢的性别差异尚不清楚,很难用常规方法进行研究。磁共振波谱(MRS)允许无创调查脂质代谢。我们采用了新的二维磁共振技术来定量正常体重的成年男性和女性的细胞内(IMCL)和细胞外(EMCL)脂质室及其不饱和程度。用肌酸(Cr)归一化,女性受试者IMCL/Cr(7.8±1.6)和EMCL/Cr(22.5±3.6)升高(n=8),男性受试者IMCL/Cr(5.9±1.7)和EMCL/Cr(18.4±2.64),差异有统计学意义(p < 0.05)。女性受试者IMCL和EMCL的不饱和程度分别为1.3±0.075和1.04±0.06,低于男性(n=8)、1.5±0.08和1.12±0.03(男女比较均p < 0.05)。我们的结论是,脂质代谢的某些显著性别差异可以通过先进的MRS方法无创地评估。
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引用次数: 0
Gender Differences in Musculoskeletal Lipid Metabolism as Assessed by Localized Two-Dimensional Correlation Spectroscopy. 用局部二维相关光谱评估肌肉骨骼脂质代谢的性别差异。
Pub Date : 2008-09-03 DOI: 10.4137/MRI.S958
S. Velan, Nicholas Said, Kartik Narasimhan, C. Papan, A. Bahu, J. Vargo, R. Raylman, M. Thomas, V. Rajendran, R. Spencer, S. Alway
Gender differences in lipid metabolism are poorly understood and difficult to study using conventional approaches. Magnetic resonance spectroscopy (MRS) permits non-invasive investigation of lipid metabolism. We employed novel two-dimensional MRS techniques to quantify intramyocellular (IMCL) and extramyocellular (EMCL) lipid compartments and their degree of unsaturation in normal weight adult male and female subjects. Using muscle creatine (Cr) for normalization, a statistically significant (p < 0.05) increase in IMCL/Cr (7.8 ± 1.6) and EMCL/Cr (22.5 ± 3.6) for female subjects was observed (n=8), as compared to IMCL/Cr (5.9 ± 1.7) and EMCL/Cr (18.4 ± 2.64) for male subjects. The degree of unsaturation within IMCL and EMCL was lower in female subjects, 1.3 ± 0.075 and 1.04 ± 0.06, respectively, as compared to that observed in males (n=8), 1.5 ± 0.08 and 1.12 ± 0.03, respectively (p < 0.05 male vs female for both comparisons). We conclude that certain salient gender differences in lipid metabolism can be assessed noninvasively by advanced MRS approaches.
脂质代谢的性别差异尚不清楚,很难用常规方法进行研究。磁共振波谱(MRS)允许无创调查脂质代谢。我们采用了新的二维磁共振技术来定量正常体重的成年男性和女性的细胞内(IMCL)和细胞外(EMCL)脂质室及其不饱和程度。用肌酸(Cr)归一化,女性受试者IMCL/Cr(7.8±1.6)和EMCL/Cr(22.5±3.6)升高(n=8),男性受试者IMCL/Cr(5.9±1.7)和EMCL/Cr(18.4±2.64),差异有统计学意义(p < 0.05)。女性受试者IMCL和EMCL的不饱和程度分别为1.3±0.075和1.04±0.06,低于男性(n=8)、1.5±0.08和1.12±0.03(男女比较均p < 0.05)。我们的结论是,脂质代谢的某些显著性别差异可以通过先进的MRS方法无创地评估。
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引用次数: 8
Role of Magnetic Resonance in Understanding the Pathogenesis of Hepatic Encephalopathy. 磁共振在了解肝性脑病发病机制中的作用。
Pub Date : 2008-01-01 DOI: 10.4137/mri.s973
A Huda, R K Gupta, N Rajakumar, M A Thomas

A spectrum of neuropsychiatric abnormalities caused by portosystemic venous shunting occurs in hepatic encephalopathy (HE) patients with or without liver dysfunction. It is not completely clear how the astrocyte swelling leads to glial-neuronal dysfunction, and how the symptoms are manifested in HE. A major goal of this work is to review the current status of information available from the existing magnetic resonance (MR) modalities including MR imaging (MRI) and MR Spectroscopy (MRS) as well as other modalities in the understanding the pathogenesis of HE. First, we discuss briefly neuron-histopathology, neurotoxins, neuropsychological and neurophysiological tests. A short review on the progress with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) is then presented. In the remaining part of the manuscript, the following topics pertinent to understanding the pathogenesis of HE are discussed: MRI, diffusion tensor imaging (DTI), one-dimensional MRS based single- and multi-voxel based spectroscopic imaging techniques and two-dimensional MRS.

无论有无肝功能异常,肝性脑病(HE)患者都会出现门静脉分流引起的一系列神经精神异常。目前尚不完全清楚星形胶质细胞肿胀是如何导致神经胶质细胞功能障碍的,以及 HE 的症状是如何表现出来的。这项研究的一个主要目标是回顾现有磁共振(MR)模式(包括磁共振成像(MRI)和磁共振波谱(MRS))以及其他模式在了解 HE 发病机制方面的信息现状。首先,我们简要讨论神经组织病理学、神经毒素、神经心理学和神经生理学测试。然后简要回顾了单光子发射计算机断层扫描(SPECT)和正电子发射断层扫描(PET)的进展。手稿的其余部分讨论了以下与了解 HE 发病机制相关的主题:核磁共振成像(MRI)、弥散张量成像(DTI)、基于单体和多体素光谱成像技术的一维 MRS 和二维 MRS。
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引用次数: 0
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Magnetic resonance insights
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