## 1 Introduction
### Advancing Distortion Product Otoacoustic Emission (DPOAE) Paradigms
Currently, DPOAE stimulus level and ratio sweeps have predominantly been used for research and have not translated to regular clinical practice. However, there is evidence that signs of ototoxic damage may be demonstrated with the use of advanced DPOAE techniques before the traditional frequency sweep at frequencies \(<\)8 kHz [33]. In the case of level sweeps, f\({}_{1}\) and f\({}_{2}\) frequencies are held constant, as is the ratio between them, and stimulus level is increased until a measurable DPOAE is recorded. Level sweeps are recordedas input-output (I/O) functions, which are examined to determine a detection threshold. A detection threshold can be defined as the first level of the stimulus that produces a measurable DPOAE (typically, 6 dB signal-to-noise ratio or SNR) and results in continued growth as stimulus levels are further increased. Increasing the stimulus level can be done by increasing the levels of the two tones, L\({}_{1}\) and L\({}_{2}\), together (either L\({}_{1}\) = L\({}_{2}\) or when the difference between L\({}_{1}\) and L\({}_{2}\) is consistent), or by holding one constant and increasing the other until a present DPOAE is observed [31]. In general, holding the L\({}_{2}\) constant and increasing the L\({}_{1}\) shows greater growth and overall larger DPOAE levels are measured when L\({}_{1}\) is greater than L\({}_{2}\) regardless of which level is varied [28; 31]. In a study of patients receiving tobramycin (an ototoxic aminoglycososide antibiotic) where detection thresholds for frequencies \(\leq\)8 kHz were examined, changes in DPOAE detection threshold were observed before clinically significant changes in the audiometric thresholds as well as before changes in the DPOAE frequency sweep paradigm (current clinical standard) [33]. In this study, detection thresholds were examined at f\({}_{2}\) frequencies of 4.3 and 8.5 kHz and changes in the higher of the two frequencies occurred sooner than changes at the lower frequency for patients receiving antibiotics. Additionally, all subjects that received any dose of tobramycin demonstrated elevated DPOAE detection thresholds when compared to the healthy control subjects [33] suggesting that detection thresholds are sensitive to even slight ototoxic damage. This study highlights that DPOAE detection thresholds may be more useful for monitoring the first signs of change within the cochlea as a result of ototoxic damage even at more traditional frequency ranges (closer to 8 kHz). As mentioned previously, DPOAE detection thresholds vary depending on which stimulus levels are varied (both together, or one constant while the other is varied). Because the study examining detection thresholds for ototoxic monitoring focused on frequencies \(\leq\)8 kHz, it is important to note that DPOAE detection thresholds at high frequencies have been shown to respond in a similar manner as DPOAEs at frequencies \(\leq\)8 kHz [28; 31]. Thus, since changes in detection thresholds as a result of ototoxic damage are seen first in the 8 kHz region when looking at frequencies \(\leq\)8 kHz and detection thresholds can be measured at higher frequencies, detection thresholds at high frequencies (\(>\)8 kHz) may be even more telling of insults to the cochlea as a result of ototoxic damage than high frequency DPOAE frequency sweeps, especially as they have been shown to be repeatable in a patient population [30]. DPOAE ratio sweeps also were sensitive to ototoxic damage [33]. The levels of both stimulus tones (L\({}_{1}\) and L\({}_{2}\)) are held constant in this paradigm, as is one of the stimulus tone frequencies (f\({}_{1}\) or f\({}_{2}\)), while the other stimulus tone is swept across frequencies, changing the ratio between the frequencies (f\({}_{2}\)/f\({}_{1}\)). This paradigm uses the phase of the distortion product (2f\({}_{1}\)-f\({}_{2}\)) that travels from the cochlea to the ear canal to calculate the travel time of the DPOAE [21; 28; 29].