Abstract:
Inner ear inflammation is considered a major contributor to the development of hearing loss. Yet most information is derived from acute animal studies and little is known about the progression of inflammatory disease in the living inner ear. To chronically study the inner ear we have developed acquisition methods for magnetic resonance imaging (MRI) of the cochlea and have reported dramatic changes in cochlear 1,2 vascular permeability with inflammation . Purpose: To better understand the etiology of inflammation we have studied the extent and time course of macrophage infiltration in the inflamed cochlea using ultrasmall superparamagnetic iron oxide particles (USPIOs). Methods: To induce cochlear inflammation guinea pigs (GPs, n=6) were sensitised by bacterial lipopolysaccharide (LPS,0.8mg/kg) followed 24 hours later by bilateral LPS intra-tympanic injection (30ìl) and intravenous injection of USPIOs (50mg/kg, P904,Guerbet research). One control animal was treated with saline. Anaesthetised GPs were scanned before LPS sensitization (baseline, n=5) and then at 2 days (n=4), 3 days (n=3), 4 days (n=1) and 7 days (n=2) after LPS sensitisation using a 4.7T MRI system. T2- weighted MR sequences were acquired to determine the signal intensity changes and spatial locations, and to calculate the transverse relaxation time(T2). Some animals were euthanized at 2 days for histology. Results: The signal intensity in perilymphatic spaces dropped (up to 8-fold) in some or all cochlear turns at 2 days, and then progressively increased the following days. T2 decreased at these locations, and the iron staining was observed in the perilymphatic spaces, modiolus and spiral ligament. Conclusion: These results reveal the recruitment of macrophages at the onset of cochlear inflammation, and suggest that MRI can characterize this process in the living cochlea.