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  • Article: MR Microscopy of Human Amyloid-β Deposits: Characterization of Parenchymal Amyloid, Diffuse Plaques, and Vascular Amyloid.
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    ABSTRACT: Cerebral deposits of amyloid-β peptides (Aβ) form the neuropathological hallmarks of Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). In the brain, Aβ can aggregate as insoluble fibrils present in amyloid plaques and vascular amyloid, or as diffuse plaques consisting of mainly non-fibrillar Aβ. Previously, magnetic resonance imaging (MRI) has been shown to be capable of detecting individual amyloid plaques, not only via the associated iron, but also Aβ itself has been suggested to be responsible for a decrease in the image intensity. In this current study we aim to investigate the MRI properties of the different cerebral Aβ deposits including diffuse plaques and vascular amyloid. Postmortem 60-μm-thick brain sections of AD, CAA, and Down's syndrome patients, known to contain Aβ, were studied. High resolution T2*- and T2-weighted MRI scans and quantitative relaxation maps were acquired using a microcoil on a Bruker 9.4T MRI system. Specific MRI characteristics of each type of Aβ deposit were examined by co-registration of the MRI with Congo Red and Aβ-immunostainings of the same sections. Our results show that only fibrillar Aβ, present in both vascular and parenchymal amyloid, induced a significant change in T2* and T2 values. However, signal changes were not as consistent for all of the vessels affected by CAA, irrespective of possible dyshoric changes. In contrast, the non-fibrillar diffuse plaques did not create any detectable MRI signal changes. These findings are relevant for the interpretation and further development of (quantitative) MRI methods for the detection and follow-up of AD and CAA.
    Journal of Alzheimer's disease: JAD 01/2013; · 3.74 Impact Factor
  • Article: Longitudinal Monitoring of Sex-Related in vivo Metabolic Changes in the Brain of Alzheimer's Disease Transgenic Mouse Using Magnetic Resonance Spectroscopy.
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    ABSTRACT: Epidemiological studies indicate that the incidence of Alzheimer's disease (AD) is higher in women than in men. There is evidence that changes in metabolites in the brain associated with the development of AD are present earlier than structural brain changes. The effect of sex on the metabolic profile during the development of AD has not yet been studied. In this study we longitudinally monitored and compared in vivo metabolic changes in male and female AβPPswe, PSEN1dE9 transgenic mice brains using magnetic resonance spectroscopy. Our results show a lower level of glutamate as well as of N-acetylaspartate (NAA) in transgenic mice. The decline in NAA with age was more apparent in female mice. The level of taurine was higher in female mice and showed a faster decline over time. In conclusion, our study is the first to suggest that changes in the metabolic profile during AD development are influenced by sex.
    Journal of Alzheimer's disease: JAD 01/2013; · 3.74 Impact Factor
  • Article: MRI artifacts in human brain tissue after prolonged formalin storage.
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    ABSTRACT: For the interpretation of magnetic resonance imaging (MRI) abnormalities in brain pathology, often ex vivo tissue is used. The purpose of this study was to determine the pathological substrate of several distinct forms of MR hypointensities that were found in formalin-fixed brain tissue with amyloid-beta deposits. Samples of brain cortex were scanned using effective transverse relaxation time-weighted protocols at several resolutions on a 9.4 T MRI scanner. High resolution MRI showed large coarse hypointensities throughout the cortical gray and white matter, corresponding to macroscopic discolorations and microscopic circumscribed areas of granular basophilic neuropil changes, without any further specific tissue reactions or amyloid-beta related pathology. These coarse MRI hypointensities were identified as localized areas of absent neuropil replaced by membrane/myelin sheath remnants using electron microscopy. Interestingly, the presence/absence of these tissue alterations was not related to amyloid deposits, but strongly correlated to the fixation time of the samples in unrefreshed formalin. These findings show that prolonged storaged of formalin fixed brain tissue results in subtle histology artifacts, which show on MRI as hypointensities that on first appearance are indistinguishable from genuine brain pathology. This indicates that postmortem MRI should be interpreted with caution, especially if the history of tissue preservation is not fully known.
    Magnetic Resonance in Medicine 02/2011; 65(6):1750-8. · 2.96 Impact Factor
  • Article: High-field MRI of single histological slices using an inductively coupled, self-resonant microcoil: application to ex vivo samples of patients with Alzheimer's disease.
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    ABSTRACT: A simple inductively coupled microcoil has been designed to image tissue samples placed on a microscope slide, samples which can subsequently be stained histologically. As the exact same tissue is used for MRI and histology, the two data sets can be compared without the need for complicated image registration techniques. The design can be integrated into any MRI system using existing commercial hardware. Compared with a commercial 25-mm-diameter birdcage, the signal-to-noise ratio was increased by a factor of 3.8, corresponding to an approximate 15-fold reduction in the data acquisition time. An example is shown of ex vivo samples from patients with Alzheimer's disease, in which the coregistration of highly sensitive iron staining and amyloid-β deposits is confirmed. Copyright © 2010 John Wiley & Sons, Ltd.
    NMR in Biomedicine 10/2010; 24(4):351-7. · 3.21 Impact Factor
  • Article: net.researchgate.refind.jaxb.schema.dblp.I@4fc6258b
    BMC Bioinformatics. 01/2010; 11:67.

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