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In vivo micro magnetic resonance imaging signal changes in scrapie infected mice
Marcin Sadowski1, Cheuk Ying Tang, Juan Gilberto Aguinaldo
1Department of Neurology, New York University School of Medicine, 550 First Avenue, New York 10016, USA.
Abstract:
Signal abnormalities on magnetic resonance imaging (MRI) T2-weighted images (T2WI) have been described in patients with Creutzfeldt-Jakob disease; however, the pathology underlying these findings remains to be fully described. We investigated the time-course of signal alterations in a murine model of prion disease using in vivo 9.4 Tesla micro magnetic resonance imaging (muMRI). The topography of muMRI signal changes was correlated with the accumulation of proteinase resistant PrP(Sc) in corresponding brain sections. Increased signal intensity on T2WI was observed in the septum and in the hippocampus of presymptomatic mice 120 days post infection (dpi). Mildly symptomatic animals (150 dpi) and animals with apparent neurological deficit (180 dpi) had a greater increase of signal intensity on T2WI in the septum and the hippocampus; in addition, abnormalities in the cortex and in the thalamus were found. Neuropathological evaluation demonstrated accumulation of PrP(Sc) and astrogliosis but only minimal or no spongiform changes in structures where abnormal signal was detected. These observations suggest that early pathological changes related to the accumulation of PrP(Sc) may be detectable in presymptomatic subjects using MRI systems with higher magnetic field strength.
Insights
High-field magnetic resonance imaging (MRI) can detect early prion disease pathology in presymptomatic mice. This study correlates T2-weighted image signal changes with proteinase-resistant PrP(Sc) accumulation, revealing detectable changes before symptoms appear.
Area of Science:
- Neuroscience
- Biomedical Imaging
- Prion Disease Research
Background:
- Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disorder.
- Signal abnormalities on T2-weighted MRI are known in CJD, but underlying pathology is unclear.
- Prion diseases involve the accumulation of abnormal prion protein (PrPSc).
Purpose of the Study:
- To investigate the temporal and topographical evolution of MRI signal alterations in a mouse model of prion disease.
- To correlate MRI findings with the accumulation of PrPSc and other neuropathological changes.
- To assess the utility of high-field microMRI for early detection of prion disease pathology.
Main Methods:
- In vivo 9.4 Tesla micro magnetic resonance imaging (muMRI) was used to monitor signal changes over time in mice infected with prions.
- T2-weighted images (T2WI) were analyzed for signal intensity alterations.
- Brain sections were examined neuropathologically to correlate MRI findings with PrPSc deposition and astrogliosis.
Main Results:
- Increased T2WI signal intensity was observed in the septum and hippocampus of presymptomatic mice (120 days post-infection).
- Signal abnormalities expanded to the cortex and thalamus in symptomatic mice (150-180 days post-infection).
- Neuropathology revealed PrPSc accumulation and astrogliosis, with minimal spongiform changes in affected areas.
Conclusions:
- Early pathological changes in prion disease, including PrPSc accumulation, are detectable using high-field MRI in presymptomatic stages.
- High-field muMRI can reveal signal abnormalities in specific brain regions prior to the onset of overt neurological symptoms.
- These findings suggest MRI's potential for early diagnosis and monitoring of prion diseases.