Volumetric analysis of the aging auditory pathway using high resolution magnetic resonance histology

Eric Y Du; Briana K Ortega; Yuzuru Ninoyu; Robert W Williams; Gary P Cofer; James J Cook; Kathryn J Hornburg; Yi Qi; G Allan Johnson; Rick A Friedman

doi:10.3389/fnagi.2022.1034073

Volumetric analysis of the aging auditory pathway using high resolution magnetic resonance histology

Front Aging Neurosci. 2022 Nov 10:14:1034073. doi: 10.3389/fnagi.2022.1034073. eCollection 2022.

Authors

Affiliations

¹ Department of Otolaryngology-Head and Neck Surgery, University of California, San Diego, San Diego, CA, United States.
² Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center (UTHSC), Memphis, TN, United States.
³ Department of Radiology, Center for In Vivo Microscopy, Duke University Medical Center, Durham, NC, United States.

Abstract

Numerous shown consequences of age-related hearing loss have been unveiled; however, the relationship of the cortical and subcortical structures of the auditory pathway with aging is not well known. Investigations into neural structure analysis remain sparse due to difficulties of doing so in animal models; however, recent technological advances have been able to achieve a resolution adequate to perform such studies even in the small mouse. We utilize 12 members of the BXD family of recombinant inbred mice and aged separate cohorts. Utilizing novel magnetic resonance histology imaging techniques, we imaged these mice and generated high spatial resolution three dimensional images which were then comprehensively labeled. We completed volumetric analysis of 12 separate regions of interest specific to the auditory pathway brainstem nuclei and cortical areas with focus on the effect of aging upon said structures. Our results showed significant interstrain variation in the age-related effect on structure volume supporting a genetic influence in this interaction. Through multivariable modeling, we observed heterogenous effects of aging between different structures. Six of the 12 regions of interests demonstrated a significant age-related effect. The auditory cortex and ventral cochlear nucleus were found to decrease in volume with age, while the medial division of the medial geniculate nucleus, lateral lemniscus and its nucleus, and the inferior colliculus increased in size with age. Additionally, no sex-based differences were noted, and we observed a negative relationship between auditory cortex volume and mouse weight. This study is one of the first to perform comprehensive magnetic resonance imaging and quantitative analysis in the mouse brain auditory pathway cytoarchitecture, offering both novel insights into the neuroanatomical basis of age-related changes in hearing as well as evidence toward a genetic influence in this interaction. High resonance magnetic resonance imaging provides a promising efficacious avenue in future mouse model hearing loss investigations.

Keywords: BXD family; aging; auditory pathway; hearing; magnetic resonance imaging; neuroaging; neuroanatomy; volumetric 3D.