Scrapie infection investigated by magnetic resonance imaging and Fourier transform infrared microscopy

Abstract

Magnetic resonance imaging (MRI) and Fourier transform infrared (FTIR) microscopy were used to investigate disease progression in hamsters infected with scrapie. T2 MR images of the brain were acquired every 2 weeks starting 19 days post-injection (dpi). No significant difference was observed between normal and scrapie-infected hamsters early in the disease, but hyperintense T2 signals were observed in the hippocampus of all infected animals starting 33 dpi. Such hyperintensity was never observed in control animals. At 47 days post-infection all animals were asymptomatic. The hyperintensity progressed from the hippocampus of one hemisphere to both sides by 61 dpi. Infected and control animals were sacrificed at 48 and 62 days post-infection and the brains removed for Western blot and FTIR microscopic analysis. Low-resolution spectral mapping (∼100 μm) was performed on the hippocampus of infected, control and sham animals. Some similarities and differences were observed in the infrared spectra arising from both grey and white matter of the hippocampus in control animals, a result expected considering the natural biochemical variability found in biological tissues. It reflects normal variations in tissue composition and also in thickness. The degree of variability between spectra was greater in grey and white matter from infected animals. However, using standard infrared microscopy it was not possible to identify reproducible differences in spectra of grey or white matter from control and scrapie-infected hamsters, most likely due to limitations in spatial resolution. To confirm this hypothesis, regions of the hippocampus were re-investigated using a 64×64 element MCT focal-plane array detector, with an effective spatial resolution of approximately 7 μm. Using such high spatial resolution subtle differences could be observed in the amide I band.