48 research outputs found

    The apparent mechanical effect of isolated amyloid‐β and α‐synuclein aggregates revealed by multi‐frequency MRE

    No full text
    International audienceSeveral biological processes are involved in dementia, and fibrillar aggregation of misshaped endogenous proteins appears to be an early hallmark of neurodegenerative disease. A recently developed means of studying neurodegenerative diseases is magnetic resonance elastography (MRE), an imaging technique investigating the mechanical properties of tissues. Although mechanical changes associated with these diseases have been detected, the specific signal of fibrils has not yet been isolated in clinical or preclinical studies. The current study aims to exploit the fractal‐like properties of fibrils to separate them from nonaggregated proteins using a multi‐frequency MRE power law exponent in a phantom study. Two types of fibril, α‐synuclein (α‐Syn) and amyloid‐β (Aβ), and a nonaggregated protein, bovine serum albumin, used as control, were incorporated in a dedicated nondispersive agarose phantom. Elastography was performed at multiple frequencies between 400 and 1200 Hz. After 3D‐direct inversion, storage modulus (G'), phase angle (ϕ), wave speed and the power law exponent (y) were computed. No significant changes in G' and ϕ were detected. Both α‐Syn and Aβ inclusions showed significantly higher y values than control inclusions ( P = 0.005) but did not differ between each other. The current phantom study highlighted a specific biomechanical effect of α‐Syn and Aβ aggregates, which was better captured with the power law exponent derived from multi‐frequency MRE than with single frequency‐derived parameters

    The apparent mechanical effect of isolated amyloid‐β and α‐synuclein aggregates revealed by multi‐frequency MRE

    No full text
    International audienceSeveral biological processes are involved in dementia, and fibrillar aggregation of misshaped endogenous proteins appears to be an early hallmark of neurodegenerative disease. A recently developed means of studying neurodegenerative diseases is magnetic resonance elastography (MRE), an imaging technique investigating the mechanical properties of tissues. Although mechanical changes associated with these diseases have been detected, the specific signal of fibrils has not yet been isolated in clinical or preclinical studies. The current study aims to exploit the fractal‐like properties of fibrils to separate them from nonaggregated proteins using a multi‐frequency MRE power law exponent in a phantom study. Two types of fibril, α‐synuclein (α‐Syn) and amyloid‐β (Aβ), and a nonaggregated protein, bovine serum albumin, used as control, were incorporated in a dedicated nondispersive agarose phantom. Elastography was performed at multiple frequencies between 400 and 1200 Hz. After 3D‐direct inversion, storage modulus (G'), phase angle (ϕ), wave speed and the power law exponent (y) were computed. No significant changes in G' and ϕ were detected. Both α‐Syn and Aβ inclusions showed significantly higher y values than control inclusions (P = 0.005) but did not differ between each other. The current phantom study highlighted a specific biomechanical effect of α‐Syn and Aβ aggregates, which was better captured with the power law exponent derived from multi‐frequency MRE than with single frequency‐derived parameters

    MRI coupled with clinically-applicable iron oxide nanoparticles reveals choroid plexus involvement in a murine model of neuroinflammation

    No full text
    International audienceChoroid plexus (ChPs) are involved in the early inflammatory response that occurs in many brain disorders. However, the activation of immune cells within the ChPs in response to neuroinflammation is still largely unexplored in-vivo. There is therefore a crucial need for developing imaging tool that would allow the non-invasive monitoring of ChP involvement in these diseases. Magnetic resonance imaging (MRI) coupled with superparamagnetic particles of iron oxide (SPIO) is a minimally invasive technique allowing to track phagocytic cells in inflammatory diseases. Our aim was to investigate the potential of ultrasmall SPIO (USPIO)-enhanced MRI to monitor ChP involvement in-vivo in a mouse model of neuroinflammation obtained by intraperitoneal administration of lipopolysaccharide. Using high resolution MRI, we identified marked USPIO-related signal drops in the ChPs of animals with neuroinflammation compared to controls. We confirmed these results quantitatively using a 4-points grading system. Ex-vivo analysis confirmed USPIO accumulation within the ChP stroma and their uptake by immune cells. We validated the translational potential of our approach using the clinically-applicable USPIO Ferumoxytol. MR imaging of USPIO accumulation within the ChPs may serve as an imaging biomarker to study ChP involvement in neuroinflammatory disorders that could be applied in a straightforward way in clinical practice
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