共查询到11条相似文献,搜索用时 0 毫秒
1.
Mark D. Meadowcroft BS James R. Connor PhD Michael B. Smith PhD Qing X. Yang PhD 《Journal of magnetic resonance imaging : JMRI》2009,29(5):997-1007
Purpose
To investigate the relationship between MR image contrast associated with beta‐amyloid (Aβ) plaques and their histology and compare the histopathological basis of image contrast and the relaxation mechanism associated with Aβ plaques in human Alzheimer's disease (AD) and transgenic APP/PS1 mouse tissues.Materials and Methods
With the aid of the previously developed histological coil, T‐weighted images and R parametric maps were directly compared with histology stains acquired from the same set of Alzheimer's and APP/PS1 tissue slices.Results
The electron microscopy and histology images revealed significant differences in plaque morphology and associated iron concentration between AD and transgenic APP/PS1 mice tissue samples. For AD tissues, T contrast of Aβ‐plaques was directly associated with the gradation of iron concentration. Plaques with significantly less iron load in the APP/PS1 animal tissues are equally conspicuous as the human plaques in the MR images.Conclusion
These data suggest a duality in the relaxation mechanism where both high focal iron concentration and highly compact fibrillar beta‐amyloid masses cause rapid proton transverse magnetization decay. For human tissues, the former mechanism is likely the dominant source of R relaxation; for APP/PS1 animals, the latter is likely the major cause of increased transverse proton relaxation rate in Aβ plaques. The data presented are essential for understanding the histopathological underpinning of MRI measurement associated with Aβ plaques in humans and animals. J. Magn. Reson. Imaging 2009;29:997–1007. © 2009 Wiley‐Liss, Inc. 相似文献2.
MRI assessment of neuropathology in a transgenic mouse model of Alzheimer's disease. 总被引:4,自引:0,他引:4
Joseph A Helpern Sang-Pil Lee Maria F Falangola Victor V Dyakin Adam Bogart Babak Ardekani Karen Duff Craig Branch Thomas Wisniewski Mony J de Leon Oliver Wolf Jacqueline O'Shea Ralph A Nixon 《Magnetic resonance in medicine》2004,51(4):794-798
The cerebral deposition of amyloid beta-peptide, a central event in Alzheimer's disease (AD) pathogenesis, begins several years before the onset of clinical symptoms. Noninvasive detection of AD pathology at this initial stage would facilitate intervention and enhance treatment success. In this study, high-field MRI was used to detect changes in regional brain MR relaxation times in three types of mice: 1). transgenic mice (PS/APP) carrying both mutant genes for amyloid precursor protein (APP) and presenilin (PS), which have high levels and clear accumulation of beta-amyloid in several brain regions, starting from 10 weeks of age; 2). transgenic mice (PS) carrying only a mutant gene for presenilin (PS), which show subtly elevated levels of Abeta-peptide without beta-amyloid deposition; and 3). nontransgenic (NTg) littermates as controls. The transverse relaxation time T(2), an intrinsic MR parameter thought to reflect impaired cell physiology, was significantly reduced in the hippocampus, cingulate, and retrosplenial cortex, but not the corpus callosum, of PS-APP mice compared to NTg. No differences in T(1) values or proton density were detected between any groups of mice. These results indicate that T(2) may be a sensitive marker of abnormalities in this transgenic mouse model of AD. 相似文献
3.
Borthakur A Gur T Wheaton AJ Corbo M Trojanowski JQ Lee VM Reddy R 《Journal of magnetic resonance imaging : JMRI》2006,24(5):1011-1017
PURPOSE: To demonstrate an MRI method for directly visualizing amyloid-beta (Abeta) plaques in the APP/PS1 transgenic (tg) mouse brain in vivo, and show that T1rho relaxation rate increases progressively with Alzheimer's disease (AD)-related pathology in the tg mouse brain. MATERIALS AND METHODS: We obtained in vivo MR images of a mouse model of AD (APP/PS1) that overexpresses human amyloid precursor protein, and measured T1rho via quantitative relaxometric maps. RESULTS: A significant decrease in T1rho was observed in the cortex and hippocampus of 12- and 18-month-old animals compared to their age-matched controls. There was also a correlation between changes in T1rho and the age of the animals. CONCLUSION: T1rho relaxometry may be a sensitive method for noninvasively determining AD-related pathology in APP/PS1 mice. 相似文献
4.
Detection of amyloid plaques in mouse models of Alzheimer's disease by magnetic resonance imaging. 总被引:4,自引:0,他引:4
Jiangyang Zhang Paul Yarowsky Marcia N Gordon Giovanni Di Carlo Sanjay Munireddy Peter C M van Zijl Susumu Mori 《Magnetic resonance in medicine》2004,51(3):452-457
We performed three-dimensional, high-resolution magnetic resonance imaging (MRI) of fixed mouse brains to determine whether MRI can detect amyloid plaques in transgenic mouse models of Alzheimer's disease. Plaque-like structures in the cortex and hippocampus could be clearly identified in T2-weighted images with an image resolution of 46 microm x 72 microm x 72 microm. The locations of plaques were confirmed in coregistration studies comparing MR images with Congo red-stained histological results. This technique is quantitative, less labor-intensive compared to histology, and is free from artifacts related to sectioning process (deformation and missing tissues). It enabled us to study the distribution of plaques in the entire brain in 3D. The results of this study suggest that this method may be useful for assessing treatment efficacy in mouse models of Alzheimer's disease (AD). 相似文献
5.
Sang-Pil Lee Maria F Falangola Ralph A Nixon Karen Duff Joseph A Helpern 《Magnetic resonance in medicine》2004,52(3):538-544
The visualization of beta-amyloid plaque deposition in brain, a key feature of Alzheimer's disease (AD), is important for the evaluation of disease progression and the efficacy of therapeutic interventions. In this study, beta-amyloid plaques in the PS/APP transgenic mouse brain, a model of human AD pathology, were detected using MR microscopy without contrast reagents. beta-Amyloid plaques were clearly visible in the cortex, thalamus, and hippocampus of fixed brains of PS/APP mice. The distribution of plaques identified by MRI was in excellent agreement with those found in the immunohistological analysis of the same brain sections. It was also demonstrated that image contrast for beta-amyloid plaques was present in freshly excised nonfixed brains. Furthermore, the detection of beta-amyloid plaques was achieved with a scan time as short as 2 hr, approaching the scan time considered reasonable for in vivo imaging. 相似文献
6.
Braakman N Matysik J van Duinen SG Verbeek F Schliebs R de Groot HJ Alia A 《Journal of magnetic resonance imaging : JMRI》2006,24(3):530-536
PURPOSE: To assess the development of beta-amyloid (Abeta) plaques in the brain with age in the transgenic mouse model of Alzheimer's disease (AD) pathology by in vivo magnetic resonance microimaging (microMRI). MATERIALS AND METHODS: Live transgenic mice (Tg2576) and nontransgenic littermates (control) were studied at regular intervals between the ages of 12 and 18 months. Plaques were visualized using a T(2)-weighted rapid acquisition with relaxation enhancement (RARE) sequence. Changes in T(2) relaxation times were followed using a multislice multiecho (MSME) sequence. Plaque load and numerical density in MR images were calculated using SCIL image software. RESULTS: Abeta plaques were clearly detected with the T(2)-weighted RARE sequence in the hippocampal and cortical regions of the brain of Tg2576 mice but not in control mice. Following the plaque development in the same animals with age showed that plaque area, number, and size increased markedly, while T(2) relaxation time showed a decreasing trend with age. CONCLUSION: These results demonstrate that microMRI is a viable method for following the development of Abeta plaques in vivo, and suggest that this method may be feasible for assessing the effect of therapeutic interventions over time in the same animals. 相似文献
7.
Nadine El Tannir El Tayara Andreas Volk Benoît Delatour 《Magnetic resonance in medicine》2007,58(1):179-184
Amyloid deposits are one of the hallmarks of Alzheimer's disease (AD), one of the most devastating neurodegenerative disorders. In transgenic mice modeling Alzheimer's pathology, the MR transverse relaxation time (T(2)) has been described to be modulated by amyloidosis. This modification has been attributed to the age-related iron deposition that occurs within the amyloid plaques of old animals. In the present study, young APP/PS1 transgenic mice without histochemically detectable iron in the brain were specifically studied. In vivo measurements of T(2) in the hippocampus, at the level of the subiculum, were shown to reflect the density of amyloid plaques. This suggests that T(2) variations can be induced solely by aggregated amyloid deposits in the absence of associated histologically-detectable iron. Thus T(2) from regions with high amyloid load, such as the subiculum, is particularly well suited for following plaque deposition in young animals, i.e., at the earliest stages of the pathological process. 相似文献
8.
Daniel J. Stuckey Carolyn A. Carr Damian J. Tyler Ellen Aasum Kieran Clarke 《Magnetic resonance in medicine》2008,60(3):582-587
The aim of this study was to determine whether high‐temporal‐resolution (HTR) cardiac cine‐MRI could be used to identify subtle alterations in contractility and diastolic function in rodent models of disease. Following standard 45‐min in vivo MRI measurements of left ventricular (LV) volumes, a single mid‐ventricular slice was selected for 3‐min HTR imaging. Cavity volume was measured every 2.4 ms, yielding approximately 60 images through the cardiac cycle. From these images, peak ejection and filling rates were calculated and two separate filling phases (comparable with the early (E) and late (A) phases of a Doppler echocardiogram) were identified during diastole. Repeated HTR imaging of the same animals on sequential days indicated reproducibility of E′/A′ ratios of 11%. In chronically infarcted rat hearts, HTR imaging revealed lower peak ejection rates (PERs), peak early filling rates (E′) and E′/A′ ratios, and higher peak late filling rates (A′) than in sham‐operated rats. Diabetic db/db mouse hearts had the same function as controls when using standard cine‐MRI, yet HTR imaging identified significantly lower PERs, early filling rates and E′/A′ ratios in diabetic mouse hearts. In conclusion, the HTR MRI technique revealed changes in function that were below the limits of detection of standard cine‐MRI. Magn Reson Med 60:582–587, 2008. © 2008 Wiley‐Liss, Inc. 相似文献
9.
G Vanhoutte I Dewachter P Borghgraef F Van Leuven A Van der Linden 《Magnetic resonance in medicine》2005,53(3):607-613
Transgenic mice overexpressing the London mutant of human amyloid precursor protein (APP[V717I]) in neurons develop amyloid plaques in the brain, thus demonstrating the most prominent neuropathological hallmark of Alzheimer's disease. In vivo 3D T2*-weighted MRI on these mice (24 months of age) revealed hypointense brain inclusions that affected the thalamus almost exclusively. Upon correlating these MRI observations with a panel of different histologic staining techniques, it appeared that only plaques that were positive for both thioflavin-S and iron were visible on the MR images. Numerous thioflavin-S-positive plaques in the cortex that did not display iron staining remained invisible to MRI. The in vivo detection of amyloid plaques in this mouse model, using the intrinsic MRI contrast arising from the iron associated with the plaques, creates an unexpected opportunity for the noninvasive investigation of the longitudinal development of the plaques in the same animal. Thus, this work provides further research opportunities for analyzing younger APP[V717I] mouse models with the knowledge of the final outcome at 24 months of age. 相似文献
10.
Sytske H. Moolenaar Gudrun Ghlich‐Ratmann Udo F.H. Engelke Manfred Spraul Eberhard Humpfer Peter Dvortsak Thomas Voit Georg F. Hoffmann Christa Brutigam Andr B. van Kuilenburg Albert van Gennip Peter Vreken Ron A. Wevers 《Magnetic resonance in medicine》2001,46(5):1014-1017
In this work, NMR investigations that led to the discovery of a new inborn error of metabolism, beta-ureidopropionase (UP) deficiency, are reported. 1D (1)H-NMR experiments were performed using a patient's urine. 3-Ureidopropionic acid was observed in elevated concentrations in the urine spectrum. A 1D (1)H-(1)H total correlation spectroscopy (TOCSY) and two heteronuclear 2D NMR techniques (heteronuclear multiple bond correlation (HMBC) and heteronuclear single-quantum correlation (HSQC)) were used to identify the molecular structure of the compound that caused an unknown doublet resonance at 1.13 ppm. Combining the information from the various NMR spectra, this resonance could be assigned to 3-ureidoisobutyric acid. These observations suggested a deficiency of UP. With 1D (1)H-NMR spectroscopy, UP deficiency can be easily diagnosed. The (1)H-NMR spectrum can also be used to diagnose patients suffering from other inborn errors of metabolism in the pyrimidine degradation pathway. 相似文献