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一个组成部分，对于维持口腔健康至关重要。唾液产生和/或分泌受损会对言语、味觉和吞咽产生重大影响，并导致龋齿和口腔感染的风险增加。在头颈癌患者中，唾液腺功能障碍是放射治疗（RT）的常见并发症之一。口干症（严重口干）是放疗的一种使人衰弱的副作用，会对这些患者的生活质量产生不利影响。口干症的临床评估涉及基于患者或基于医生的分级系统，该系统是主观的并且容易出错和可变。传统的唾液照相和闪烁照相方法可以客观评估唾液腺功能障碍，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、可靠且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效益。在此应用中，我们建议利用光声成像（PAI），这是一种相对较新的成像技术，可以对唾液腺结构和功能进行非侵入性评估。鉴于血流量和唾液产生之间的关系，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。为了支持这一假设，我们实验室进行的初步研究表明，PAI 可以检测体内味觉刺激后唾液腺血流动力学的变化。基于 PAI 的氧饱和度测量值的变化与功率多普勒超声检查的血管分布测量值显示出良好的相关性。放疗后 24 小时，血管对味觉刺激的反应显着降低，提示唾液腺有早期辐射引起的血管损伤。基于这些初步观察，该应用将测试以下中心假设：PAI 可用于唾液腺功能和体内辐射引起的唾液腺损伤的非侵入性评估。我们建议在小型（目标 1）和大型动物（目标 2）模型中检查 PAI 用于唾液腺成像的潜力，并在健康人类志愿者和接受放射治疗的头颈癌患者中进行试点研究（目标 3）。