Magnetic Resonance Imaging of Amyloid Plaques in Transgenic Mice

Wadghiri, Youssef Zaim; Sigurdsson, Einar M.; Wısnıewskı, Thomas; Turnbull, Daniel H.

doi:10.1385/1-59259-874-9:365

Cited by 11 publications

(9 citation statements)

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“…This finding was not replicated in another study that reported the dark spots to be vascular structures [168]. Later studies in ex-vivo transgenic mouse brain specimens confirmed that plaques could be imaged at 7 T [169][170][171][172] (Fig. 8).…”

Section: Other Mri Techniquesmentioning

confidence: 88%

Magnetic resonance imaging of Alzheimer’s disease

et al. 2006

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A modern challenge for neuroimaging techniques is to contribute to the early diagnosis of neurodegenerative diseases, such as Alzheimer's disease (AD). Early diagnosis includes recognition of pre-demented conditions, such as mild cognitive impairment (MCI) or having a high risk of developing AD. The role of neuroimaging therefore extends beyond its traditional role of excluding other conditions such as neurosurgical lesions. In addition, early diagnosis would allow early treatment using currently available therapies or new therapies in the future. Structural imaging can detect and follow the time course of subtle brain atrophy as a surrogate marker for pathological processes. New MR techniques and image analysis software can detect subtle brain microstructural, perfusion or metabolic changes that provide new tools to study the pathological processes and detect pre-demented conditions. This review focuses on markers of macro- and microstructural, perfusion, diffusion and metabolic MR imaging and spectroscopy in AD.

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Section: Other Mri Techniquesmentioning

confidence: 88%

Magnetic resonance imaging of Alzheimer’s disease

et al. 2006

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“…However, the 20 hr imaging time used in this study is not feasible for in vivo studies. Because the chemical constituents of senile plaques affect MRI signal, a small proportion of mature plaques with high levels of iron have been detected ex vivo and in vivo without contrast agents in old transgenic mice by μMRI (Borthakur et al, 2006; Braakman et al, 2006; Helpern et al, 2004; Jack et al, 2004; Lee et al, 2004; Meadowcroft et al, 2009; Sigurdsson et al, 2008; Vanhoutte et al, 2005; Wadghiri et al, 2005). However, this method is not specific for amyloid plaques and detects other iron-containing structures, such as remnants of old hemorrhages and calcification.…”

Section: Introductionmentioning

confidence: 99%

Detection of amyloid plaques targeted by USPIO-Aβ1–42 in Alzheimer's disease transgenic mice using magnetic resonance microimaging

et al. 2011

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Amyloid plaques are one of the pathological hallmarks of Alzheimer's disease (AD). The visualization of amyloid plaques in the brain is important to monitor AD progression and to evaluate the efficacy of therapeutic interventions. Our group has developed several contrast agents to detect amyloid plaques in vivo using magnetic resonance microimaging (μMRI) in AD transgenic mice, where we used intra-carotid mannitol to enhance blood brain barrier (BBB) permeability. In the present study, we used ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, chemically coupled with Aβ 1-42 peptide to detect amyloid deposition along with mannitol for in vivo μMRI by femoral intravenous injection. A 3D gradient multi-echo sequence was used for imaging with a 100 μm isotropic resolution. The amyloid plaques detected by T2*-weighted μMRI were confirmed with matched histological sections. Furthermore, two different quantitative analyses were used. The region of interest-based quantitative measurement of T2* values showed contrast injected APP/PS1 mice had significantly reduced T2* values compared to wild-type mice. In addition, the scans were examined with voxel-based morphometry (VBM) using statistical parametric mapping (SPM) for comparison of contrast injected AD transgenic and wild-type mice. The regional differences seen in VBM comparing USPIO-Aβ1-42 injected APP/PS1 and wild type mice correlated with the amyloid plaque distribution histologically, contrasting with no differences between the two groups of mice without contrast agent injection in regions of the brain with amyloid deposition. Our results demonstrated that both approaches were able to identify the differences between AD transgenic mice and wild type mice, after injected with USPIO-Aβ1-42. The feasibility of using less invasive intravenous femoral injections for amyloid plaque detection in AD transgenic mice facilitates using this method for longitudinal studies in the pathogenesis of AD.

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“…We and others have previously shown the successful use of gadolinium labeled A␤ peptides to target amyloid plaques in transgenic AD model mice (Poduslo et al, 2002Sigurdsson et al, 2004c;Wadghiri et al, 2003Wadghiri et al, , 2005. This approach for labeling amyloid lesions takes advantage of the high affinity binding A␤ peptides have to other A␤ peptides (Jarrett and Lansbury, 1993;Wadghiri et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

A non-toxic ligand for voxel-based MRI analysis of plaques in AD transgenic mice

Sigurdsson

Wadghiri

Mosconi

et al. 2008

Neurobiology of Aging

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Amyloid plaques are a characteristic feature in Alzheimer's disease (AD). A novel non-toxic contrast agent is presented, Gd-DTPA-K6A␤1-30, which is homologous to A␤, and allows plaque detection in vivo. MRI was performed on AD model mice and controls prior to and following intracarotid injection with Gd-DTPA-K6A␤1-30 in mannitol solution, to transiently open the blood-brain barrier. A gradient echo T2 * -weighted sequence was used to provide 100 m isotropic resolution with imaging times of 115 min. The scans were examined with voxel-based analysis (VBA) using statistical parametric mapping, for un-biased quantitative comparison of ligand-injected mice and controls. The results indicate that: (1) Gd-DTPA-K6A␤1-30 is an effective, non-toxic, ligand for plaque detection when combined with VBA (p ≤ 0.01-0.001), comparing pre and post-ligand injection scans. (2) Large plaques can be detected without the use of a contrast agent and this detection co-localizes with iron deposition. (3) Smaller, earlier plaques require contrast ligand for MRI visualization. Our ligand when combined with VBA may be useful for following therapeutic approaches targeting amyloid in transgenic mouse models.

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Magnetic Resonance Imaging of Amyloid Plaques in Transgenic Mice

Cited by 11 publications

References 1 publication

Magnetic resonance imaging of Alzheimer’s disease

Magnetic resonance imaging of Alzheimer’s disease

Detection of amyloid plaques targeted by USPIO-Aβ1–42 in Alzheimer's disease transgenic mice using magnetic resonance microimaging

A non-toxic ligand for voxel-based MRI analysis of plaques in AD transgenic mice

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