共查询到20条相似文献，搜索用时 15 毫秒
1.
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
2.
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
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.
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
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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
8.
Susan K. Lemieux PhD Carrie A. Smith‐Bell BS Jered R Wells BA Nnadozie M. Ezerioha Jeffrey S. Carpenter MD D. Larry Sparks PhD Bernard G. Schreurs PhD 《Journal of magnetic resonance imaging : JMRI》2010,32(2):306-314
Purpose:
To test the hypothesis that narrowing of cranial blood vessels in cholesterol‐fed rabbits is a function of the duration of the high cholesterol diet. Such neurovascular changes, caused by elevated serum cholesterol, are linked to stroke and Alzheimer's disease risk.Materials and Methods:
Four groups of New Zealand White rabbits were studied. Six were fed a normal diet, 19 were fed a 2% cholesterol diet with 0.12 ppm copper in the drinking water for 8 weeks, 10 weeks, or 12 weeks. Time‐of‐flight (TOF) MR angiography (MRA) at 3 Tesla was used to measure arterial diameters in 11 vessels. Previously published data for amyloid β‐peptide (Aβ) accumulation in the brains measured postmortem were correlated to vessel diameters. Ventricular volumes of rabbits were measured on group‐averaged data.Results:
Several vessel diameters decreased with cholesterol diet duration. The posterior communicating arteries showed the largest significant effect. Aβ accumulation was inversely correlated with arterial diameter. Ventricular volumes between the normal diet and 12 weeks cholesterol‐fed groups were not significantly different.Conclusion:
Reduction in vessel diameter of medium‐sized vessels but not large vessels was measured in these hypercholesterolemic rabbits. The vessel diameter narrowing and cortical Aβ deposition occurred before measurable ventricular enlargement. J. Magn. Reson. Imaging 2010;32:306–314. © 2010 Wiley‐Liss, Inc. 相似文献9.
Clifford R. Jack Michael Garwood Thomas M. Wengenack Bret Borowski Geoffrey L. Curran Joseph Lin Gregor Adriany Olli H. J. Grhn Roger Grimm Joseph F. Poduslo 《Magnetic resonance in medicine》2004,52(6):1263-1271
One of the cardinal pathologic features of Alzheimer's disease (AD) is the formation of senile, or amyloid, plaques. Transgenic mice have been developed that express one or more of the genes responsible for familial AD in humans. Doubly transgenic mice develop \"human-like\" plaques, providing a mechanism to study amyloid plaque biology in a controlled manner. Imaging of labeled plaques has been accomplished with other modalities, but only MRI has sufficient spatial and contrast resolution to visualize individual plaques noninvasively. Methods to optimize visualization of plaques in vivo in transgenic mice at 9.4 T using a spin echo sequence based on adiabatic pulses are described. Preliminary results indicate that a spin echo acquisition more accurately reflects plaque size, while a T2* weighted gradient echo sequence reflects plaque iron content, not plaque size. In vivo MRI-ex vivo MRI-in vitro histologic correlations are provided. Histologically verified plaques as small as 50 microm in diameter were visualized in living animals. To our knowledge this work represents the first demonstration of noninvasive in vivo visualization of individual AD plaques without the use of a contrast agent. 相似文献
10.
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
11.
B. Douglas Ward MS Zhilin Wu PhD Wenjun Li BS Malgorzata Franczak MD Jennifer L. Jones MS Piero G. Antuono MD Shi‐Jiang Li PhD 《Journal of magnetic resonance imaging : JMRI》2011,34(4):764-773
Purpose:
To identify the neural correlates of cognitive improvement in mild Alzheimer's disease (AD) subjects following 12 weeks of donepezil treatment.Materials and Methods:
Resting‐state functional connectivity magnetic resonance imaging (R‐fMRI) was used to measure the hippocampal functional connectivity (HFC) in 14 mild AD and 18 age‐matched normal (CN) subjects. AD subjects were scanned at baseline and after donepezil treatment. CN subjects were scanned only at baseline as a reference to identify regions correlated or anticorrelated to the hippocampus. Before each scan, participants underwent cognitive, behavioral, and functional assessments.Results:
After donepezil treatment, neural correlates of cognitive improvement measured by Mini‐Mental State Examination scores were identified in the left parahippocampus, dorsolateral prefrontal cortex (DLPFC), and inferior frontal gyrus. Improvement in AD Assessment Scale‐cognitive subscale scores correlated with the HFC changes in the left DLPFC and middle frontal gyrus. Stronger recovery in the network connectivity was associated with cognitive improvement.Conclusion:
R‐fMRI may provide novel insights into the brain's responses to AD treatment in clinical pharmacological trials, and also may predict clinical response. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc. 相似文献12.
Michael J. House Timothy G. St. Pierre Kris V. Kowdley Thomas Montine James Connor John Beard Jose Berger Narendra Siddaiah Eric Shankland Lee‐Way Jin 《Magnetic resonance in medicine》2007,57(1):172-180
Iron accumulates in the Alzheimer's disease (AD) brain and is directly associated with β‐amyloid pathology. The proton transverse relaxation rate (R2) has a strong linear relationship with iron concentrations in healthy brain tissue; however, an independent test of this relationship has not been extended to AD brain tissue. In this study in vitro single spin‐echo (SE) measurements were made on tissue samples from four human AD brains using a 4.7T MRI research scanner. R2 values were calculated for 14 cortical and subcortical gray matter (GM) and white matter (WM) regions. Atomic absorption spectroscopy was used to measure iron concentrations in the corresponding excised brain regions. Significant positive linear correlations were observed between R2 values and iron concentrations in GM regions assessed across individual tissue samples and data averaged by brain region. With the use of a predictive model for R2, a threshold iron concentration of 55 μg Fe/g wet tissue was determined above which R2 appears to be dominated by the affects of iron in AD brain tissue. High‐field MRI may therefore be a useful research tool for assessing brain iron changes associated with AD. Magn Reson Med 57:172–180, 2007. © 2006 Wiley‐Liss, Inc. 相似文献
13.
Ryan Chamberlain Denise Reyes Geoffrey L. Curran Malgorzata Marjanska Thomas M. Wengenack Joseph F. Poduslo Michael Garwood Clifford R. Jack Jr. 《Magnetic resonance in medicine》2009,61(5):1158-1164
One of the hallmark pathologies of Alzheimer's disease (AD) is amyloid plaque deposition. Plaques appear hypointense on T2‐weighted and T‐weighted MR images probably due to the presence of endogenous iron, but no quantitative comparison of various imaging techniques has been reported. We estimated the T1, T2, T, and proton density values of cortical plaques and normal cortical tissue and analyzed the plaque contrast generated by a collection of T2‐weighted, T‐weighted, and susceptibility‐weighted imaging (SWI) methods in ex vivo transgenic mouse specimens. The proton density and T1 values were similar for both cortical plaques and normal cortical tissue. The T2 and T values were similar in cortical plaques, which indicates that the iron content of cortical plaques may not be as large as previously thought. Ex vivo plaque contrast was increased compared to a previously reported spin‐echo sequence by summing multiple echoes and by performing SWI; however, gradient echo and SWI were found to be impractical for in vivo imaging due to susceptibility interface–related signal loss in the cortex. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
14.
Michael J House Timothy G St Pierre Catriona McLean 《Magnetic resonance in medicine》2008,60(1):41-52
We measured proton magnetic longitudinal (R(1)) and transverse (R(2)) relaxation rates at 1.4T, iron concentrations, water contents, and amyloid plaque densities in postmortem brain tissue samples from three Alzheimer's disease (AD), two possible AD, and five control subjects. Iron concentrations and R(1) were significantly higher in the temporal cortex region of our AD group compared to the controls. Frequency analyses showed that the observed trends of higher iron, R(1), and R(2) in AD gray matter regions were statistically significant. Simple regression models indicated that for AD and control gray matter the iron concentrations and water contents have significant linear correlations with R(1) and R(2). Multiple regression models based on iron concentrations and water contents were highly significant for all groups and tissue types and suggested that the effects of iron become more important in determining R(1) and R(2) in the AD samples. At 1.4T R(1) and R(2) are strongly affected by water content and to a lesser extent by variations in iron concentrations. The AD plaque density did not correlate with iron concentrations, water contents, R(1), or R(2), suggesting that increases in AD brain iron are not strongly related to the accumulation of amyloid plaques. 相似文献
15.
Takashi Yoshiura Futoshi Mihara Atsuo Tanaka Tomoyuki Noguchi Osamu Togao Yasuo Kuwabara Hiroshi Honda 《Magnetic resonance in medicine》2005,54(2):455-459
Previous studies have shown that diffusion‐weighted imaging (DWI) is useful for detecting microstructural degradation of neuronal tissue in neurodegenerative diseases. Mapping of cortical degeneration by DWI is potentially useful, but is extremely difficult, mainly because of the partial volume effect resulting from the surrounding cerebrospinal fluid (CSF). In this study a novel method to map and display the cortical damage in neurodegenerative diseases using DWI is proposed. Instead of measuring the cortical diffusivity, the diffusivity of white matter directly beneath the cortex, where neuronal fibers enter or exit the overlying cortex, was measured and mapped onto the cortical surface. The map was viewed in a form of three‐dimensional (3D) rendering. Patients with Alzheimer's disease (AD) showed cortical damage in the temporal and parietal cortices, and a patient with frontotemporal dementia showed damage in the frontal lobe, consistent with the typical topographical distribution of histopathological cortical damage in each of these diseases. The results suggest that subcortical diffusivity closely reflects cortical damage, and that the current mapping technique is a promising tool for evaluating neurodegenerative diseases. Magn Reson Med 54:455–459, 2005. © 2005 Wiley‐Liss, Inc. 相似文献
16.
Mohammad Haris PhD Erin McArdle BS Matthew Fenty BS Anup Singh PhD Christos Davatzikos PhD John Q. Trojanowski MD PhD Elias R. Melhem MD Christopher M. Clark MD Arijitt Borthakur PhD 《Journal of magnetic resonance imaging : JMRI》2009,29(5):1008-1012
Purpose
To evaluate the T1rho (T1ρ) MRI relaxation time in hippocampus in the brain of Alzheimer's disease (AD), mild cognitive impairment (MCI), and control, and to determine whether the T1ρ shows any significant difference between these cohorts.Materials and Methods
With informed consent, AD (n = 49), MCI (n = 48), and age‐matched control (n = 31) underwent T1ρ MRI on a Siemens 1.5T Scanner. T1ρ values were automatically calculated from the left and right hippocampus region using in‐house developed software. Bonferroni post‐hoc multiple comparisons was performed to compare the T1ρ value among the different cohorts.Results
Significantly higher T1ρ values were observed both in AD (P = 0.000) and MCI (P = 0.037) cohorts compared to control; also, the T1ρ in AD was significantly high over (P = 0.032) MCI. Hippocampus T1ρ was 13% greater in the AD patients than control, while in MCI it was 7% greater than control. Hippocampus T1ρ in AD patients was 6% greater than MCI.Conclusion
Higher hippocampus T1ρ values in the AD patients might be associated with the increased plaques burden. A follow‐up study would help to determine the efficacy of T1ρ values as a predictor of developing AD in the control and MCI individuals. J. Magn. Reson. Imaging 2009;29:1008–1012. © 2009 Wiley‐Liss, Inc. 相似文献17.
18.
A L Janke G de Zubicaray S E Rose M Griffin J B Chalk G J Galloway 《Magnetic resonance in medicine》2001,46(4):661-666
This work describes the development of a model of cerebral atrophic changes associated with the progression of Alzheimer's disease (AD). Linear registration, region-of-interest analysis, and voxel-based morphometry methods have all been employed to elucidate the changes observed at discrete intervals during a disease process. In addition to describing the nature of the changes, modeling disease-related changes via deformations can also provide information on temporal characteristics. In order to continuously model changes associated with AD, deformation maps from 21 patients were averaged across a novel z-score disease progression dimension based on Mini Mental State Examination (MMSE) scores. The resulting deformation maps are presented via three metrics: local volume loss (atrophy), volume (CSF) increase, and translation (interpreted as representing collapse of cortical structures). Inspection of the maps revealed significant perturbations in the deformation fields corresponding to the entorhinal cortex (EC) and hippocampus, orbitofrontal and parietal cortex, and regions surrounding the sulci and ventricular spaces, with earlier changes predominantly lateralized to the left hemisphere. These changes are consistent with results from post-mortem studies of AD. 相似文献
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Gunter JL Shiung MM Manduca A Jack CR 《Journal of magnetic resonance imaging : JMRI》2003,18(1):16-24
PURPOSE: To systematically compare two techniques for measuring brain atrophy rates from serial magnetic resonance imaging (MRI) studies. MATERIALS AND METHODS: Using the separation in atrophy rate between cohorts of cognitively normal elderly subjects and patients with Alzheimer's disease (AD) as the gold standard, we evaluated 1) different methods of computing volume change; 2) different methods for steps in image preprocessing-intensity normalization, alignment mask used, and bias field correction; 3) the effect of MRI acquisition hardware changes; and 4) the sensitivity of the method to variations in initial manual volume editing. For each of the preceding evaluations, measurements of whole-brain and ventricular atrophy rates were calculated. RESULTS: In general, greater separation between the clinical groups was seen with ventricular rather than whole-brain measures. Surprisingly, neither the use of bias field correction nor a major hardware change between the scan pairs affected group separation. CONCLUSION: Atrophy rate measurements from serial MRI are candidates for use as surrogate markers of disease progression in AD and other dementing neurodegenerative disorders. The final method has excellent precision and accurately captures the expected biology of AD-arguably the two most important features if this technique is to be used as a biomarker of disease progression. 相似文献