Novel Biomedical Imaging Systems for Diagnosing Hearing Loss

用于诊断听力损失的新型生物医学成像系统

• 批准号: 10669250
• 负责人: Robert D Frisina
• 金额: $ 17.19万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10669250
• 关键词: Active Biological Transport; Age; Age Months; Aging; Animal Model; Animals; Atrophic; Auditory; Autopsy; BALB/cJ Mouse; Binding; Biological; Biological Markers; Biological Process; Biomedical Engineering; Blood flow; Bone neoplasms; Brain; Bulla; Bumetanide; CBA/CaJ Mouse; Cadaver; Cell Death; Cells; Characteristics; Clinical; Cochlea; Cochlear duct; Complication; Development; Diagnosis; Diagnostic; Diffuse; Diffusion; Discipline of Nuclear Medicine; Dose; Elderly; Endolymph; Etiology; Event; Exhibits; FDA approved; Future; Gamma Cameras; Gamma Rays; Gene Expression; Generations; Half-Life; Hearing; Heart; Hepatobiliary; Hot Spot; Human; Image; Imaging Techniques; Injections; Intervention; Ion Channel; Ions; Label; Labyrinth; Lateral; Liquid substance; Maintenance; Mammals; Measurement; Measures; Medical; Medicine; Methodology; Methods; Microelectrodes; Miraluma; Molecular; Movement; Mus; Na(+)-K(+)-Exchanging ATPase; Nature; Neoplasm Metastasis; Nerve Degeneration; Neurodegenerative Disorders; Operative Surgical Procedures; Organ; Ouabain; Pathogenesis; Pathology; Patients; Persons; Pharmaceutical Preparations; Photons; Physiological; Positron-Emission Tomography; Presbycusis; Procedures; Protocols documentation; Radial; Radiation; Radioactive; Radioactive Tracers; Radionuclide Imaging; Radiopharmaceuticals; Reporting; Research; Resolution; Risk Factors; Rodent; Roentgen Rays; Scanning; Science; Sensorineural Hearing Loss; Sensory Disorders; Signal Transduction; Source; Stria Vascularis; Study models; Techniques; Technology; Testing; Thallium; Therapeutic Intervention; Thyroid Gland; Time; Tissues; Tracer; Validation; X-Ray Computed Tomography; age related; aging population; analog; biomedical imaging; blood perfusion; clinical diagnosis; clinical risk; clinically relevant; detection method; dosage; enzyme activity; experimental study; feasibility testing; hearing impairment; heart visualization; human subject; imaging modality; imaging system; in vivo; innovation; longitudinal animal study; longitudinal human study; magnetic field; molecular imaging; normal hearing; novel; nuclear imaging; permanent hearing loss; prevent; radiotracer; screening; single photon emission computed tomography; symporter; targeted treatment; temporal measurement; tumor; two-dimensional; voltage; wireless; young adult

Age-related hearing loss (ARHL) is the predominant sensory disorder and neurodegenerative condition of our aged population. Currently, it is difficult or impossible to diagnose the exact etiology of ARHL, or other types of hearing loss in a particular patient clinically. This makes effective medical interventions for hearing loss quite challenging now, and indeed, there are no FDA-approved medical treatments to prevent or treat sensorineural hearing loss. The endocochlear potential (EP), also known as the “cochlear battery”, is the voltage difference between the endolymph of scala media and the surrounding fluids of the other two cochlear scalae. The EP results from the high K+ and low Na+ concentrations in the endolymph due to movement of K ions up a voltage and concentration gradient by specialized cells of the stria vascularis of the cochlear lateral wall. This voltage difference is critical for normal functioning of the inner ear, and good hearing. There are reports from animal model studies demonstrating the significance of the EP for hearing, and how it declines in the aging cochlea, with downstream effects on other cochlear pathologies as well. However, for human diagnoses, there is no clinical method available for EP measurements. Post-mortem EP measurements in human cadavers, for research purposes, are also not feasible, as mammals lose the EP immediately after they die. Currently, a surgical approach for rodents – exposing the bulla and cochlea, and measuring the EP using a microelectrode, is the gold standard for EP measurement in animal models. However, this approach cannot be utilized in humans due to its invasive characteristics, causing both permanent loss of hearing and surrounding tissue damage, while also being terminal in nature for rodents. This complication makes longitudinal human studies impossible, thus, hindering the firm establishment of strial atrophy and EP reduction as a predominant clinical risk factor in ARHL and other types of hearing impairment. Therefore, there is a compelling need to develop an in vivo, wireless EP measurement technique that could be utilized for human subjects. The primary aim of this project is to develop a dependable EP measurement methodology using current nuclear and molecular imaging methods in which a dilute radiotracer can be used to characterize K+ activity within the inner ear. The proposed research has a unique potential to revolutionize the diagnostic and treatment possibilities for hearing loss clinically. We combine biomedical engineering and imaging, with hearing sciences, animal model techniques and neuroengineering to achieve this translational breakthrough for hearing impaired persons.

年龄相关性听力损失（ARHL）是我们人类主要的感觉障碍和神经退行性疾病 老年人口。目前，很难或不可能诊断 ARHL 或其他类型的确切病因 临床上特定患者的听力损失。这使得针对听力损失的有效医疗干预措施相当有效 现在充满挑战，事实上，没有 FDA 批准的药物来预防或治疗感音神经性 听力损失。耳蜗内电位（EP），也称为“耳蜗电池”，是电压差 位于中阶的内淋巴与另外两个耳蜗阶的周围液体之间。欧洲议会 由于 K 离子向上移动而导致内淋巴中的高 K+ 和低 Na+ 浓度 以及耳蜗侧壁血管纹特殊细胞的浓度梯度。这个电压 差异对于内耳的正常功能和良好的听力至关重要。有动物报道称 模型研究证明了 EP 对听力的重要性，以及它如何在老化的耳蜗中衰退， 对其他耳蜗病变也有下游影响。然而，对于人类诊断来说，没有 可用于 EP 测量的临床方法。人体尸体死后 EP 测量， 出于研究目的，也不可行，因为哺乳动物死后会立即失去 EP。目前，一个 啮齿类动物的手术方法 – 暴露大泡和耳蜗，并使用微电极测量 EP， 是动物模型中 EP 测量的黄金标准。然而，这种方法不能用于 由于其侵入性特征，人类会导致听力和周围组织的永久性丧失 损害，同时对于啮齿动物来说也是致命的。这种并发症使得纵向人体研究 不可能，因此阻碍了纹状体萎缩和 EP 减少作为主要临床治疗的牢固确立 ARHL 和其他类型听力障碍的危险因素。因此，迫切需要开发一种 体内无线 EP 测量技术可用于人类受试者。此举的主要目的 该项目旨在利用当前的核和分子技术开发可靠的 EP 测量方法 成像方法，其中稀释的放射性示踪剂可用于表征内耳内的 K+ 活动。这 拟议的研究具有彻底改变听力诊断和治疗可能性的独特潜力 临床上的损失。我们将生物医学工程和成像与听力科学、动物模型相结合 技术和神经工程为听力障碍者实现这一转化突破。