Visualization of acute focal lesions in rats with experimental autoimmune encephalomyelitis by magnetic nanoparticles, comparing different MRI sequences including phase imaging

Abstract

To compare the sensitivity and specificity of phase imaging (PI) with other magnetic resonance imaging (MRI) methods in lesion detection in rats with experimental autoimmune encephalomyelitis (EAE), as an animal model for multiple sclerosis (MS). EAE was induced in rats (n = 14) by subcutaneous (s.c.) injection of myelin basic protein (MBP) and complete Freund's adjuvant (CFA). Control animals (n = 4) were given an s.c. injection of phosphate-buffered saline mixed with CFA. The development of local inflammatory processes, demyelinations, and blood-brain barrier (BBB) disruptions were monitored over 7 weeks in a 4.7T animal scanner by T1-, T2-, T2*-weighted images, magnetization transfer, and PI in the presence or absence of very small superparamagnetic iron oxide particles (VSOP) and confirmed by immunostaining using CD31, CD68, MBP, and albumin antibodies and Gallyas silver staining. EAE rats developed time-dependent local inflammations and BBB disruptions but no clear demyelinizations. In histological stainings these processes were trackable as accumulations of phagocytic monocytes and extravasal albumin. In MRI without application of VSOP inflammatory processes were not detectable. MRI in the presence of VSOP revealed inflammatory processes by the appearance of hypointense spots (hs). The specificity of PI to detect hs was similar to T1- and T2*-weighted images The calculated sensitivity was less than in corresponding T2*-weighted images. The diagnostic use of PI without VSOP as contrast agent to detect lesions is not recommended at field strength of 4.7T or lower.