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: 10539635
• 负责人: Robert D Frisina
• 金额: $ 21.91万
• 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 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10539635
• 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; Cardiac; Cell Death; Cells; Characteristics; Clinical; Cochlea; Cochlear duct; Complication; Development; Diagnosis; Diagnostic; Diffuse; Discipline of Nuclear Medicine; Dose; Elderly; Endolymph; Etiology; Event; Exhibits; FDA approved; Future; Gamma Cameras; Gamma Rays; Gene Expression; Generations; Gold; Half-Life; Hearing; Heart; Hepatobiliary; Hot Spot; Human; Image; Imaging Techniques; Injections; Intervention; Ion Channel; Ions; Label; Labyrinth; Lateral; Lead; Liquid substance; Maintenance; Mammals; Measurement; Measures; Medical; 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; Reading; Reporting; Research; Resolution; Risk Factors; Rodent; Roentgen Rays; Scanning; Science; Sensorineural Hearing Loss; Sensory Disorders; Signal Transduction; Source; Stria Vascularis; Study models; Techniques; Testing; Thallium; Therapeutic Intervention; Thyroid Gland; Time; Tissues; Tracer; Validation; X-Ray Computed Tomography; age related; aging population; analog; base; biomedical imaging; blood perfusion; clinical diagnosis; clinical risk; clinically relevant; dosage; enzyme activity; experimental study; feasibility testing; hearing impairment; 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; 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.

听觉相关性听力损失（ARHL）是我们的主要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ARHL的确切病因。 在临床上，特定患者的听力损失。这使得听力损失的有效医疗干预相当 现在具有挑战性，事实上，没有FDA批准的药物治疗来预防或治疗感觉神经性 听力损失耳蜗内电位（EP），也被称为“耳蜗电池”，是电压差 中阶的内淋巴和其他两个耳蜗阶的周围液体之间。的EP 由于K离子向上移动电压，导致内淋巴中的高K+和低Na+浓度 和浓度梯度由耳蜗外侧壁的血管纹的特化细胞。该电压 差异对于内耳的正常功能和良好的听力至关重要。有报道称， 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下降， 对其他耳蜗病变也有下游影响。然而，对于人类诊断， 可用于EP测量的临床方法。人尸体的死后EP测量， 研究目的，也是不可行的，因为哺乳动物在死亡后立即失去EP。现时 啮齿动物的手术方法-暴露大泡和耳蜗，并使用微电极测量EP， 是动物模型中EP测量的金标准。但是，这种方法不能用于 由于其侵入性特征，导致永久性听力损失和周围组织 损害，同时也是终端性质的啮齿动物。这种复杂性使得纵向人类研究 不可能，因此，阻碍了脊髓萎缩和EP减少作为主要临床 ARHL和其他类型听力障碍的危险因素。因此，迫切需要制定一项 可以用于人类受试者体内无线EP测量技术。其主要目的是 项目是开发一个可靠的EP测量方法，利用目前的核和分子 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+活性。的 拟议中的研究具有革命性的听力诊断和治疗可能性的独特潜力 临床损失我们将联合收割机生物医学工程和影像学与听力科学、动物模型 技术和神经工程学来为听力受损的人实现这一翻译突破。