title: Human audiometric thresholds do not predict specific cellular damage in the inner ear.
abstract: As otology enters the field of gene therapy and human studies commence, the question arises whether audiograms - the current gold standard for the evaluation of hearing function - can consistently predict cellular damage within the human inner ear and thus should be used to define inclusion criteria for trials. Current assumptions rely on the analysis of small groups of human temporal bones post mortem or from psychophysical identification of cochlear "dead regions" in vivo, but a comprehensive study assessing the correlation between audiometric thresholds and cellular damage within the cochlea is lacking.
  
  
  
  A total of 131 human temporal bones from 85 adult individuals (ages 19-92 years, median 69 years) with sensorineural hearing loss due to various etiologies were analyzed. Cytocochleograms - which quantify loss of hair cells, neurons, and strial atrophy along the length of the cochlea - were compared with subjects' latest available audiometric tests prior to death (time range 5 h-22 years, median 24 months). The Greenwood function and the equivalent rectangular bandwidth were used to infer, from cytocochleograms, cochlear locations corresponding to frequencies tested in clinical audiograms. Correlation between audiometric thresholds at clinically tested frequencies and cell type-specific damage in those frequency regions was examined by calculating Spearman's correlation coefficients.
  
  
  
  Similar audiometric profiles reflected widely different cellular damage in the cochlea. In our diverse group of patients, audiometric thresholds tended to be more influenced by hair cell loss than by neuronal loss or strial atrophy. Spearman's correlation coefficient across frequencies was at most 0.7 and often below 0.5, with 1.0 indicating perfect correlation.
  
  
  
  Audiometric thresholds do not predict specific cellular damage in the human inner ear. Our study highlights the need for better non- or minimally-invasive tools, such as cochlear endoscopy, to establish cellular-level diagnosis and thereby guide therapy and monitor response to treatment.
authors.affiliation: Eaton Peabody Laboratories, Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, 243 Charles St, Boston, MA 02141, United States; Department of Otolaryngology, Harvard Medical School, 25 Shattuck St, Boston, MA 02115, United States; Department of Otolaryngology, Vienna General Hospital, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. Electronic address: lukas_landegger@meei.harvard.edu.
authors.forename: Lukas D
authors.initials: LD
authors.lastname: Landegger
authors.affiliation: Optics Laboratory, School of Engineering, Swiss Federal Institute of Technology Lausanne (EPFL), BM 4102 (Bâtiment BM), Station 17, 1015 Lausanne, Switzerland. Electronic address: demetri.psaltis@epfl.ch.
authors.forename: Demetri
authors.initials: D
authors.lastname: Psaltis
authors.affiliation: Eaton Peabody Laboratories, Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, 243 Charles St, Boston, MA 02141, United States; Department of Otolaryngology, Harvard Medical School, 25 Shattuck St, Boston, MA 02115, United States; Harvard Program in Speech and Hearing Bioscience and Technology, 260 Longwood Avenue, Boston, MA 02115, United States. Electronic address: konstantina_stankovic@meei.harvard.edu.
authors.forename: Konstantina M
authors.initials: KM
authors.lastname: Stankovic
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001299:Audiometry / Q000379:methods*; D001309:Auditory Threshold; D003051:Cochlea / Q000473:pathology; D007758:Ear, Inner / Q000473:pathology*; D005260:Female; D006198:Hair Cells, Auditory / Q000473:pathology; D006319:Hearing Loss, Sensorineural / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D013136:Spiral Ganglion / Q000473:pathology; D013316:Stria Vascularis / Q000473:pathology; D013701:Temporal Bone / Q000473:pathology; D055815:Young Adult
keywords: Audiometric thresholds; Cytocochleograms; Hair cells; Human temporal bones; Spiral ganglion neurons; Stria vascularis