Early Detection of Noise-Induced Hearing Loss

描述(由申请人提供)： 拟议的续签申请的总体目标是确定失真产品耳声发射(DPOAEs)的特征，最终将改进早期检测噪声性听力损失(NIHL)的临床方法，这是一种主要的感官残疾，尤其是退伍军人。为此，我们将在标准化噪声暴露前后，在兔身上获得两种特殊用途的DPOAE测量，我们称之为增强和残留DP-gram，以及相关的DPOAE水平/相位(L/P)图。这些DP图将测试这样一种概念，即当通过使用干扰音(IT)和矢量减法分离f2源和基源产生的DPOAE时，可以比使用普通标准DP图更敏感地识别DPOAE响应空间中的细微的噪声后变化。在我们之前的研究中，我们出人意料地(见初步研究)发现，兔子，以及可能其他常见的实验室物种，没有像人类一样从DPOAE频率位置(FDP)产生的反射发射。然而，令人费解的是，它们仍然表现出垂直相移带状，这是反射发射的一个基本特征。用抑制方法获得了在L/P空间内不同频率位置放置和不放置IT的DPOAE L/P图，证实了DPOAEs的基础耳蜗源的存在。这一基础来源被揭示为残存的DPOAE，即‘有-IT’和‘没有IT’的DPOAE L/P图之间的矢量差异。术语‘增强的’地图或DP-gram被创造来描述这些频率函数，当利用存在的IT时，在这种情况下，‘填充’或‘掩盖’损伤模式的真实范围的基本来源被移除。污染基底源的发现有望改变听力领域目前关于耳蜗产生DPOAE的基本过程的知识，并可能导致DPOAE测试的发展，该测试可以更灵敏地识别NIHL的发病阶段。这类测试对退伍军人也很有用，他们是临床患者，通常有严重的听力损失，因为较高级别的原音可以用来提高信噪比(SNR)，同时保持测试的灵敏度和频率特异性。将实现三个具体目标，以设计一种最佳的增强DPOAE测试并评估其在检测NIHL中的有效性。第一个目的是在使用第四音调的模拟NIHL条件下测试这样的假设，即可以确定各种原音级别组合的最佳IT级别，从而最有效地去除(抑制)污染的基本来源，而不影响f2 DPOAE来源。第二个特定目标测试优化的“增强”(f2源)和来自特定目标1的实验得到的剩余DP-gram(基础源)识别在暂时性和永久性NIHL条件下的兔耳蜗声损伤程度的能力。这里测试的假设是，增强的DP-gram将在噪声诱导的永久性阈值移位的兔中揭示出比标准DP-gram预测的更大的耳蜗病损。最后，第三个具体目标将测试由更高级别的原声诱发的增强DP-gram的能力，以发现患有NIHL的退伍军人中噪音受损的耳蜗区。这里研究的概念是，在预先存在听力损失的情况下，高水平原音将比使用优化的增强DP-gram的传统低水平原音更有用，因为随着原音水平的增加，去除了掩盖受损耳蜗区的基本来源。总之，联合实验将提供对DPOAEs产生的更完整的了解，这将允许创建一种有用的临床测试来诊断和监测NIHL的发展。

DESCRIPTION (provided by applicant): The overall goal of the proposed renewal application is to identify features of distortion product otoacoustic emissions (DPOAEs) that will eventually improve clinical methods for the early detection of noise-induced hearing loss (NIHL), which is a major sensory disability suffered by military veterans, in particular. Toward this end, two special-purpose DPOAE measures, which we have termed augmented and residual DP-grams, along with related DPOAE level/phase (L/P) maps will be obtained in rabbits before and after standardized noise- exposure episodes. These DP-grams will test the notion that subtle post-noise changes in the DPOAE response space can be more sensitively identified when the f2- and basal-source generated DPOAEs are isolated by the use of an interference tone (IT) and vector-subtraction methods than they can be by the common standard DP-gram. During our prior studies, we unexpectedly (see Preliminary Studies) discovered that rabbits, and likely other common laboratory species, do not have 'reflection emissions' arising from the DPOAE frequency place (fdp) as do humans. However, inexplicably, they still exhibit vertical phasing banding, which is a cardinal feature of reflection emissions. Using suppression methods to obtain DPOAE L/P maps with and without an IT placed at various frequency locations within the L/P space, the existence of a basal cochlear source of DPOAEs was established. This basal source was revealed as a residual DPOAE obtained as the vector difference between the 'with-IT' and 'without IT' DPOAE L/P maps. The term 'augmented' maps or DP- grams was coined to describe these frequency functions when obtained with the IT present in that, under this condition, the basal source that 'fills in' or 'masks' the true extent of the damage pattern is removed. The discovery of the contaminating basal source promises to modify the hearing field's current knowledge concerning the fundamental processes underlying DPOAE generation by the cochlea, and may also lead to the development of DPOAE tests that more sensitively identify the onset stages of NIHL. Such tests may also be useful in veterans, who are clinic patients, often with significant preexisting hearing losses, in that higher-level primary tones can be used to increase the signal-to-noise ratio (SNR), while maintaining the test's sensitivity and frequency specificity. Three specific aims will be achieved to devise an optimal augmented DPOAE test and to evaluate its utility in detecting NIHL. The first aim under simulated NIHL conditions using a 4th tone tests the hypothesis that an optimal IT level for various primary-tone level combinations can be identified that most effectively removes (suppresses) the contaminating basal source, without affecting the f2 DPOAE source. The second specific aim tests the ability of the optimized 'augmented' (f2 source) and residual DP-gram (basal source) resulting from the experiments of Specific Aim #1 to identify the extent of cochlear damage under both temporary and permanent NIHL conditions in rabbits. The hypothesis tested here is that the augmented DP- gram will reveal in rabbits with noise-induced permanent threshold shifts a larger cochlear lesion than predicted by standard DP-grams. Finally, the third specific aim will test the ability of augmented DP-grams elicited by higher-level primary tones to uncover noise-damaged cochlear regions in veterans with NIHL. The notion examined here is that high-level primary tones will be more useful under conditions of preexisting hearing loss than conventional low-level primaries using the optimized augmented DP-gram by removing basal sources that come into play to obscure damaged cochlear regions as primary-tone levels are increased. Together, the combined experiments will provide a more complete understanding of the generation of DPOAEs, which will permit the creation of a useful clinical test for diagnosing and monitoring the development of NIHL.