Magnetic Targeting of Gadolinium Contrast to Enhance MRI of the Inner Ear in Endolymphatic Hydrops.

OBJECTIVES: 1. Determine the feasibility and efficiency of local magnetic targeting delivery of gadolinium (Gad) contrast to the inner ear in rodents. 2. Assess any potential ototoxicity of magnetic targeting delivery of Gad in the inner ear. 3. Study the utility of magnetic targeting delivery of Gad to visualize and quantify endolymphatic hydrops (EH) in a transgenic mouse model. STUDY DESIGN: Controlled in vivo animal model study. METHODS: Paramagnetic Gad was locally delivered to the inner ear using the magnetic targeting technique in both rat and mouse models. Efficiency of contrast delivery was assessed using magnetic resonance imaging (MRI). Ototoxicity of Gad was examined with histology of the cochlea and functional audiological tests. The Phex mouse model was used to study EH, hearing loss, and balance dysfunction. Magnetic targeting delivery of Gad contrast was used in the Phex mouse model to visualize the effects of EH using MRI. RESULTS: Magnetic targeting improved the delivery of Gad to the inner ear and the technique was reproducible in both rat and mouse models. The delivery method did not result in microstructural damage or any significant hearing loss in a normal animal. Magnetic targeting of Gad in the Phex mouse model allowed detailed visualization and quantification of EH. CONCLUSION: This study provided the first evidence of the effectiveness and efficiency of the local magnetic targeting delivery of gadolinium contrast to the inner ear and its application to the visualization and quantification of EH. Laryngoscope, 133:914-923, 2023.

Local magnetic delivery of adeno-associated virus AAV2(quad Y-F)-mediated BDNF gene therapy restores hearing after noise injury.

Moderate noise exposure may cause acute loss of cochlear synapses without affecting the cochlear hair cells and hearing threshold; thus, it remains "hidden" to standard clinical tests. This cochlear synaptopathy is one of the main pathologies of noise-induced hearing loss (NIHL). There is no effective treatment for NIHL, mainly because of the lack of a proper drug-delivery technique. We hypothesized that local magnetic delivery of gene therapy into the inner ear could be beneficial for NIHL. In this study, we used superparamagnetic iron oxide nanoparticles (SPIONs) and a recombinant adeno-associated virus (AAV) vector (AAV2(quad Y-F)) to deliver brain-derived neurotrophic factor (BDNF) gene therapy into the rat inner ear via minimally invasive magnetic targeting. We found that the magnetic targeting effectively accumulates and distributes the SPION-tagged AAV2(quad Y-F)-BDNF vector into the inner ear. We also found that AAV2(quad Y-F) efficiently transfects cochlear hair cells and enhances BDNF gene expression. Enhanced BDNF gene expression substantially recovers noise-induced BDNF gene downregulation, auditory brainstem response (ABR) wave I amplitude reduction, and synapse loss. These results suggest that magnetic targeting of AAV2(quad Y-F)-mediated BDNF gene therapy could reverse cochlear synaptopathy after NIHL.

Acquired cholesteatoma in children following congenital cholesteatoma surgery.

OBJECTIVES: To determine the incidence of severe atelectatic otitis media and acquired cholesteatoma (AC) in children treated for congenital cholesteatoma (CC). METHODS: Retrospective chart review of 15 children who underwent primary surgery for CC over a 15 year period by a single surgeon. RESULTS: The mean postoperative follow up was 3.1 years. Significant tympanic retraction occurred in 6 children, included a retraction pocket that required T-tube insertion (3), and AC requiring tympanomastoid surgery (3). There was no complication related to retraction pocket in 9 children however 2 developed residual disease. In comparing the two groups, those with and without subsequent significant tympanic retraction, both groups had similar gender, age, extent of CC (median Potsic grade of 2), bone erosion, and surgical technique. Differences were noted in air-bone gap at presentation (PTA 32.4 and 17.25), otitis media with effusion in the contralateral ear (3/6 and 1/9), smaller mastoid volume ratio compared with the contralateral ear (0.74 and 1.21), and longer average timing for second surgery (14.8 months and 8 months). CONCLUSIONS: Acquired middle ear disease, including cholesteatoma, can follow surgical removal of CC, and long term follow up of all patients is required. Factors at initial evaluation indicative of risk of AC include a significant air-bone gap, otitis media with effusion in the contralateral ear and a smaller mastoid cavity ratio. The use of composite grafts at the time of CC surgery should be considered. Additionally, our findings suggest that the mastoid volume plays a causative role in the development of AC.