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。唾液的产生和/或分泌受损会对言语、味觉和吞咽产生重大影响，并导致患牙病的风险增加。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）是放射治疗的一种令人衰弱的副作用。口干症的临床评估涉及基于患者或基于医生的分级系统，这些系统是主观的，容易出现错误和变异，传统的口腔造影和闪烁扫描方法可以客观评估唾液腺功能障碍，但要么是侵入性的，要么是侵入性的。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益处。提议利用光声成像（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。考虑到血流和唾液产生之间的关系，我们发现基于 PAI 的血流动力学评估可以作为一种方法。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。饱和度与血管分布的功率多普勒超声测量有良好的相关性。放疗后 24 小时，血管对味觉刺激的反应显着降低，表明唾液腺存在早期辐射引起的血管损伤。基于这些初步观察，本应用将检验以下中心假设： PAI 可用于体内唾液腺功能和辐射引起的唾液腺损伤的非侵入性评估。我们建议检查 PAI 在小型（目标 1）和大型动物唾液腺成像中的潜力。 （目标 2）模型，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）。