Non-invasive assessment of salivary gland function: Translational Studies

唾液腺功能的无创评估：转化研究

• 批准号: 9082643
• 负责人: Mukund Seshadri
• 金额: $ 39.23万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-15 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9082643
• 关键词: Address; Adverse effects; Affect; Animals; Biological; Biology; Blood Vessels; Blood flow; Citric Acid; Clinical; Clinical Research; Clinical assessments; Complex; Contrast Media; Data Set; Deglutition; Dental caries; Development; Evaluation; FRAP1 gene; Functional disorder; Head and Neck Cancer; Hemoglobin; Hour; Human Volunteers; Hybrids; Hyperemia; Image; Imaging Techniques; Injury; Laboratories; Lead; Magnetic Resonance Imaging; Maintenance; Measures; Melanins; Methods; Modeling; Monitor; Mus; New Zealand; Optics; Oral; Oral health; Oryctolagus cuniculus; Oxygen; Pathway interactions; Patients; Perception; Perfusion; Phase; Physicians; Physiology; Pilot Projects; Production; Quality of life; Radiation; Radiation Monitoring; Radiation therapy; Radio; Radioisotopes; Radioprotection; Reading; Research; Risk; Saliva; Salivary Gland Neoplasms; Salivary Glands; Signal Transduction; Speech; Structure; Symptoms; System; Taste Perception; Technology; Testing; Therapeutic; Tissues; Ultrasonography; Water; Xerostomia; base; clinical application; head and neck cancer patient; healthy volunteer; hemodynamics; image guided; imaging modality; in vivo; interest; non-invasive imaging; novel; optical imaging; oral infection; photoacoustic imaging; public health relevance; research clinical testing; response; saliva secretion; translational study; tumor

 DESCRIPTION (provided by applicant): Saliva is an integral component of oral physiology and critical for the maintenance of oral health. Impaired production and/or secretion of saliva can have a significant impact on speech, taste and swallowing and lead to increased risk of dental caries and oral infection. In patients with head and neck cancer, salivary gland dysfunction is one of the common complications of radiation therapy (RT). Xerostomia (severe dry mouth) is a debilitating side-effect of RT that adversely affects quality of life in these patients. Clinical evaluation of xerostomia involves patient-based or physician-based grading systems that are subjective and prone to error and variability. Conventional sialographic and scintigraphic methods allow for objective evaluation of salivary gland dysfunction but are either invasive or require the use of radioisotopes and are therefore not ideal for longitudinal assessment in patients. Development of a cheap, reliable, and easy to use non-invasive imaging method for salivary gland imaging could therefore be of immense clinical benefit. In this application, we propose to utilize photoacoustic imaging (PAI), a relatively new imaging technique that allows for non-invasive assessment of salivary gland structure and function. Given the relationship between blood flow and saliva production, we hypothesize that PAI-based hemodynamic assessment can serve as a reliable read-out of salivary gland function in vivo. In support of this hypothesis, preliminary studies conducted in our laboratory have shown that PAI can detect changes in salivary gland hemodynamics following gustatory stimulation in vivo. Changes in PAI-based measures of oxygen saturation showed good correlation with power Doppler sonography measures of vascularity. Vascular response to gustatory stimulation was significantly reduced 24 hours following RT suggestive of early radiation-induced vascular injury of salivary glands. Building on these preliminary observations, this application will test the central hypothesis that PAI can be used for non-invasive assessment of salivary gland function and radiation-induced salivary gland injury in vivo. We propose to examine the potential of PAI for salivary gland imaging in small (Aim 1) and large animal (Aim 2) models, conduct a pilot study (Aim 3) in healthy human volunteers and head and neck cancer patients undergoing radiation treatment.

 描述（由申请人提供）：唾液是口腔生理学的组成部分，对维持口腔健康至关重要。唾液的产生和/或分泌受损会对言语、味觉和吞咽产生显著影响，并导致龋齿和口腔感染的风险增加。头颈部恶性肿瘤放射治疗后，唾液腺功能障碍是常见的并发症之一。口干症（严重口干）是RT的一种使人衰弱的副作用，对这些患者的生活质量产生不利影响。口腔干燥症的临床评价涉及基于患者或基于医生的分级系统，这些系统是主观的，容易出现错误和变化。传统的涎腺造影和唾液腺造影方法可以客观评价唾液腺功能障碍，但要么是侵入性的，要么需要使用放射性同位素，因此对于患者的纵向评估并不理想。因此，开发一种廉价、可靠、易于使用的非侵入性唾液腺成像方法可能具有巨大的临床益处。在这个应用中，我们建议利用光声成像（派），一个相对较新的成像技术，允许非侵入性评估唾液腺的结构和功能。考虑到血流和唾液分泌之间的关系，我们假设基于PAI的血流动力学评估可以作为体内唾液腺功能的可靠读数。在支持这一假设，在我们的实验室进行的初步研究表明，派可以检测唾液腺血流动力学的变化后，味觉刺激在体内。以PAI为基础的血氧饱和度测量值的变化与能量多普勒超声测量的血管分布具有良好的相关性。RT后24小时，对味觉刺激的血管反应显著降低，提示早期放射诱导的唾液腺血管损伤。基于这些初步观察，本申请将测试派可用于无创评估唾液腺功能和放射诱导的唾液腺损伤的体内中心假设。我们建议在小动物（目标1）和大动物（目标2）模型中检查派用于唾液腺成像的潜力，在健康人类志愿者和接受放射治疗的头颈癌患者中进行初步研究（目标3）。