Non-invasive assessment of salivary gland function: Translational Studies

 描述(申请人提供)：唾液是口腔生理学不可或缺的组成部分，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，涎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，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以患者为基础或以医生为基础的分级系统，这些系统是主观的，容易出错和变异性。传统的唾液腺造影术和放射性核素造影术可以客观地评估唾液腺功能障碍，但它们要么是侵入性的，要么需要使用放射性同位素，因此不适合于患者的纵向评估。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会带来巨大的临床益处。在这项应用中，我们建议利用光声成像(PAI)，这是一种相对较新的成像技术，允许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。为了支持这一假说，我们实验室进行的初步研究表明，PAI可以在体内检测味觉刺激后唾液腺血流动力学的变化。以PAI为基础的血氧饱和度测量的变化与能量多普勒超声血管测量显示出良好的相关性。血管对味觉刺激的反应在放疗后24小时显著降低，提示早期放射诱导的唾液腺血管损伤。在这些初步观察的基础上，这一应用将检验核心假设，即PAI可用于体内唾液腺功能和辐射诱导的唾液腺损伤的非侵入性评估。我们建议在小(Aim 1)和大动物(Aim 2)模型中检验PAI用于唾液腺成像的潜力，并在健康的人类志愿者和接受放射治疗的头颈癌患者中进行一项先导研究(Aim 3)。

 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.