MR biomarkers of noise-induced hearing loss - studies of neurodegeneration, connectivity and neurotransmitter metabolism in the central auditory system of the mouse

部分或完全听力损失通常伴随着各种心理声学现象，如耳鸣、听觉过敏、噪音辨别力受损或言语理解力下降。因此，详细调查导致进行性听力损失的潜在机制至关重要。近年来，噪声损伤不仅对耳蜗周围结构产生影响，而且对大脑听觉处理结构的生理和解剖也产生显著影响。拟议项目的总体目标是开发和组织学验证神经退行性和神经可塑性过程的非侵入性成像生物标志物，使用噪声创伤引起的听力损失作为模型疾病。将开发实验和临床适用的预测模型，用于推导基于磁共振成像（MRI）的神经病理学变化和相应的功能测量。该项目的设计将使其结果可以转移到其他神经退行性过程，例如脑血管疾病或痴呆症。使用非侵入性MRI连续多次记录小鼠中枢听觉系统中噪声诱导的病理生理过程。为此，将使用基于体素的形态测量（VBM）研究神经退行性过程，通过扩散张量成像（DTI）绘制结构连接性变化，并通过听觉中脑和丘脑的质子磁共振波谱（1H-MRS）分析抑制性和兴奋性传递中突触可塑性的调制。对于每次MR检查，将对这些脑结构的组织进行处理，以进行神经变性（细胞和神经元染色）、轴突投射（神经丝染色）和突触活动（抑制性和兴奋性囊泡神经递质转运蛋白的表示）的免疫组织化学研究。使用线性模型，非侵入性MRI在噪声创伤后的组织学和功能结果方面的价值将被定性和定量分析。拟议项目的研究结果将作为开发新型基于MR的噪声诱导创伤患者诊断工具的基础。

Partial or complete hearing loss is often accompanied by various psychoacoustic phenomena such as tinnitus, hyperacusis, impaired discrimination in noise, or a reduced speech comprehension. Therefore, detailed investigations of the underlying mechanisms leading to progressive hearing loss are of utmost importance. In recent years, it has become increasingly evident that noise trauma not only has an impact on peripheral cochlear structures but also causes prominent effects on the physiology and anatomy of auditory processing structures in the brain. The overarching goal of the proposed project is to develop and histologically validate noninvasive imaging biomarkers of neurodegenerative and neuroplastic processes using noise trauma-induced hearing loss as a model disease. Experimentally and clinically applicable prediction models for the derivation of neuropathological changes and corresponding functional measures based on Magnetic Resonance Imaging (MRI) will be developed. The project will be designed in a way that results can be transferred to other neurodegenerative processes, e.g. in cerebrovascular diseases or dementia. Noise-induced pathophysiological processes in the central auditory system of the mouse will be recorded at several consecutive times using non-invasive MRI. To this end, neurodegenerative processes will be investigated using voxel-based morphometric measurements (VBM), changes in structural connectivity will be mapped by diffusion tensor imaging (DTI) and modulation of synaptic plasticity in inhibitory and excitatory transmission will be analyzed by proton magnetic resonance spectroscopy (1H-MRS) in the auditory midbrain and thalamus. For each MR examination, tissue of these brain structures will be processed for immunohistochemical studies of neurodegeneration (cell and neuronal staining), axonal projections (staining of neurofilaments) and synaptic activity (representation of inhibitory and excitatory vesicular neurotransmitter transporter). Using linear models, the value of non-invasive MRI in terms of histological and functional outcome after noise trauma will be both qualitatively and quantitatively analyzed. The findings of the proposed project will serve as a basis for the development of novel MR-based diagnostic tools of noise-induced trauma in patients.