Functional activity mapping of rat auditory pathway after intratympanic manganese administration

In the present study, we report a new method of manganese enhanced magnetic resonance imaging (MEMRI) using intratympanic (IT) manganese administration. We explore Mn²⁺ uptake from the middle ear cavity into the cochlea through mechanically gated ion channels of the hair cell and also functional auditory tract tracing without the use of excessive auditory stimuli for a long time period outside the scanner. After manganese administration in animals with normal hearing and unilateral deafness, T1-weighted MR images were obtained for up to 48 h with a 3.0 T MR imager. In normal rats, the mean signal-to-noise ratio (SNR) at each region of interest on the auditory pathway was significantly higher in the IT injection group than in the intraperitoneal (IP) injection group (P<0.05). Furthermore, the cochlea showed Mn²⁺ signal enhancement only in the IT injection group. In unilateral deafness rats, the IT injection of Mn²⁺ into the deaf-side middle ear cavity demonstrated signal enhancement in the cochlea but not in other auditory structures without axonal transport of Mn²⁺ along the auditory pathway. On the other hand, the IT injection of Mn²⁺ into the normal-side middle ear cavity demonstrated that the mean SNRs at the cochlea, cochlear nucleus, superior olivary complex, lateral lemniscus and inferior colliculus were significantly higher in the ipsilateral auditory pathway than in the contralateral pathway (P<0.05). For the IP injection group, the mean SNRs at each auditory structure, except the cochlea, increased bilaterally. In conclusion, the present work demonstrated the potential advantages of a new IT MEMRI over conventional systemic injection strategies in that (i) the functional auditory tract tracing initiated by the hair cell function is possible and (ii) the axonal transport of Mn²⁺ ions by trans-synaptic activity is possible without auditory stimulation for a long time period outside MR scanner.