## 1 Introduction
### Advancing Distortion Product Otoacoustic Emission (DPOAE) Paradigms  
Distortion product otoacoustic emissions (DPOAEs) offer a noninvasive, objective approach to monitor cochlear health. DPOAEs can be recorded in the ear canal in response to two simultaneous pure tones (f\({}_{1}\) and f\({}_{2}\), f\({}_{1}\) < f\({}_{2}\)) at frequencies mathematically related to the stimulus frequencies [23]. The response that is the largest level in humans and most commonly used in the clinic for detection of hearing loss is the 2f\({}_{1}\)-f\({}_{2}\) DPOAE [24]. DPOAEs in clinical practice provide a frequency-specific snapshot of overall outer hair cell function with measurements at a few stimulus frequency pairs per octave and using standard stimulus parameters (level of f\({}_{1}\)/f\({}_{2}\) of 65/55 dB SPL, stimulus ratio (f\({}_{2}\)/f\({}_{1}\)) of 1.22; f\({}_{2}\) frequencies 1-8 kHz). DPOAE measurements have long been employed in clinical practice to distinguish between normal and impaired hearing, and more specifically, cochlear function (e.g., [25]). DPOAEs have been leveraged for ototoxic monitoring approaches such that DPOAE measurements consistently demonstrate earlier signs of ototoxic damage at the same frequencies when compared to conventional (1-8 kHz) behavioral hearing thresholds (e.g., [2; 7; 26]). It has also been demonstrated that higher frequency (\(>\)8 kHz) information is most valuable for timely detection of cochlear dysfunction and specifically utilizing high-frequency DPOAEs [16; 27]. Furthermore, the feasibility of measuring DPOAEs beyond 8 kHz has been demonstrated across a range of ages (10 to 65 years) with normal-hearing [21] as well as repeatable over time in healthy, young, normal-hearing adults and in a patient population not exposed to ototoxic medications during monitoring [28; 29; 30]. Studies have demonstrated that higher frequency (up to 16 kHz) DPOAE measurements can provide more insight into changes in cochlear physiology that may be utilized in clinical management [21]. Clinically, at frequencies of \(\leq\)8 kHz, DPOAEs are measured by changing the frequencies of f\({}_{1}\) and f\({}_{2}\), while keeping the ratio between them and the levels (L\({}_{1}\) and L\({}_{2}\)) constant and recording the level of the response (in dB). This frequency sweep can be completed across a wide frequency range with greater distance between frequencies tested (commonly referred to as a \"gross\" frequency sweep) or across a more concentrated frequency range with smaller distances between frequencies tested (commonly referred to as a \"concentrated\" frequency sweep) [31]. There is the possibility that DPOAEs at lower frequencies (\(\leq\)8 kHz) have characteristics that differ from those at higher frequencies due to differences in the underlying physiology at the base and apex of the cochlea (see review [32]). However, a study by [PERSON] and [PERSON] [28] demonstrated that DPOAEs measured at high frequencies were comparable up to about 10 kHz as those measured in the lower frequency range. That said, DPOAEs at higher frequencies, while still measurable, were lower in level than those at 10 kHz and below [28]. Although not quite as repeatable as in the lower frequencies (\(\leq\)8 kHz), high-frequency DPOAE frequency sweeps have been shown to be repeatable in normal-hearing adults [29] and a patient population not receiving ototoxic medications during monitoring [30]. This suggests that high-frequency DPOAEs are potentially a very powerful tool for ototoxic monitoring. Although frequency sweep DPOAEs are the most often used, and can be measured reliably at high frequencies, there are two other DPOAE paradigms that could provide a more sensitive look into potential damage to the cochlea as a result of ototoxic medications. Specifically, these paradigms are stimulus level sweeps and ratio sweeps which are used to determine detection thresholds and group delay values, respectively [7; 21; 28; 31; 33].