Innovations in Monitoring Ototoxic Changes using DPOAEs

Maintaining quality of life in patients undergoing chemotherapy is becoming increasingly important with increasing life expectancy. Preserving hearing in patients undergoing chemotherapy with ototoxic agents is critical to quality of life. Chemotherapeutic treatment with cisplatin is highly effective against many types of cancer; however, it is well established that cisplatin can produce cochlear damage initially evident and most prominent at frequencies above 8 kHz (corresponding to the cochlear base). Prevention is most effective when ototoxic changes in the cochlea are detected early. Distortion-product otoacoustic emissions (DPOAEs) offer a convenient and noninvasive clinical tool to detect this change. Such a tool may be the only approach available for evaluation of auditory function in young children and/or patients too sick to be evaluated with ¡°gold-standard¡± behavioral audiometry. In current clinical practice DPOAEs are measured over a limited frequency range (typically ¡Ü 6-8 kHz) when the earliest ototoxic effects on cochlear physiology are known to occur at the cochlear base sensitive to the highest audible frequencies. In this proposal we deploy three innovations that will radically change the clinical application of DPOAEs in detecting small changes in cochlear function. First, we utilize a revolutionary new sound delivery and measurement probe being developed by the team at Northwestern University in collaboration with our engineering partners at Etymotic Research to deliver high-quality signals up to 20 kHz. Current probe designs are limited in their effective bandwidth to 6 or 8 kHz. Second, we utilize modern calibration techniques implemented in an automated calibrator invented by Jonathan Siegel (Patent Pending 13/471,941) to accurately deliver the desired signal levels at the patient¡¯s eardrum. Third, we use a new stimulus paradigm that changes the frequency relationship between the two stimulus tones in keeping with local cochlear mechanics in different regions of the cochlea. We present preliminary data showing significantly greater DPOAE amplitudes using our hardware, calibration technique, and cochlea-driven stimulus paradigm as compared to those obtained using traditional methods. In this proposal we examine the efficacy of these innovations for early detection of ototoxic changes. This research translates current knowledge of cochlear mechanics related to DPOAE generation into a sensitive clinical tool critical to hearing conservation. While the scope of the proposal is limited to ototoxicity monitoring, the results will be relevant to many other applications where accurate monitoring of cochlear status is important.