Department of Ophthalmology, Visual, and Anatomical Sciences, Wayne State University School of Medicine, Detroit, Michigan, USA.
John D. Dingell Veteran Affairs Medical Center, Detroit, Michigan, USA.
Sci Rep. 2019 Nov 7;9(1):16265. doi: 10.1038/s41598-019-52439-4.
Effective personalized therapeutic treatment for hearing loss is currently not available. Cochlear oxidative stress is commonly identified in the pathogenesis of hearing loss based upon findings from excised tissue, thus suggesting a promising druggable etiology. However, the timing and site(s) to target for anti-oxidant treatment in vivo are not clear. Here, we address this long-standing problem with QUEnch-assiSTed Magnetic Resonance Imaging (QUEST MRI), which non-invasively measures excessive production of free radicals without an exogenous contrast agent. QUEST MRI is hypothesized to be sensitive to noise-evoked cochlear oxidative stress in vivo. Rats exposed to a loud noise event that resulted in hair cell loss and reduced hearing capability had a supra-normal MRI R1 value in their cochleae that could be corrected with anti-oxidants, thus non-invasively indicating cochlear oxidative stress. A gold-standard oxidative damage biomarker [heme oxidase 1 (HO-1)] supported the QUEST MRI result. The results from this study highlight QUEST MRI as a potentially transformative measurement of cochlear oxidative stress in vivo that can be used as a biomarker for improving individual evaluation of anti-oxidant treatment efficacy in currently incurable oxidative stress-based forms of hearing loss.
目前尚无有效的个性化听力损失治疗方法。基于切除组织的研究结果，耳蜗氧化应激通常被认为是听力损失发病机制中的一个重要因素，因此提示了一种有前途的可治疗病因。然而，体内抗氧化治疗的时间和靶点尚不清楚。在这里，我们使用 QUEnch-assiSTed 磁共振成像（QUEST MRI）解决了这一长期存在的问题，该方法无需外源性对比剂即可非侵入性地测量自由基的过度产生。假设 QUEST MRI 对体内噪声诱发的耳蜗氧化应激敏感。在经历了导致毛细胞损失和听力下降的强噪声事件后，暴露于强噪声中的大鼠耳蜗的 MRI R1 值高于正常水平，而抗氧化剂可以纠正这种异常，从而非侵入性地指示耳蜗氧化应激。一种金标准的氧化损伤生物标志物[血红素加氧酶 1（HO-1）]支持 QUEST MRI 的结果。这项研究的结果强调了 QUEST MRI 作为一种潜在的变革性测量方法，可以用于评估体内耳蜗氧化应激，作为改善目前无法治愈的基于氧化应激的听力损失患者个体化评估抗氧化治疗效果的生物标志物。
