Quantitative Estimation of Periodontal Inflammation and Tissue Destruction with High-Resolution Ultrasound-Based Imaging - Admin Supp

摘要（来自父母补助金申请） 牙周炎是由细菌感染引起，并伴随宿主炎症反应的一种主要疾病， 牙齿脱落影响6500万美国成年人的福利越来越多的证据表明牙周炎也是 与全身健康有关，主要是通过一个共同的联系，炎症。因此，诊断和 牙周炎的治疗将潜在地改善总体健康。目前的临床措施 牙周炎的主要诊断方法是目测和“探诊出血（BOP）"。不幸的是， 对检测疾病活动性主观且不敏感。炎症亚临床体征的靶向成像，例如 增加的血管分布、间质液和组织损失等，将有助于精确诊断和及时 非侵入性地在椅旁治疗这种疾病。一些定量超声生物标志物， 例如后向散射、弹性、彩色血流和能量多普勒在医学中已被广泛研究， 近年来，已被公认为用于评估特定身体器官的炎症。他们 将是客观测量牙周炎症的潜在候选者。微型尺寸（16.2 mm）， 高成像分辨率（~60 µm）超声探头原型是由我们的团队专门开发的， 在受限的口腔中，并且已经被验证用于精确地成像牙周组织。其准备好 用于收集上述定量超声的市售超声系统 参数推动这一建议的假设是，可以使用非侵入性和定量超声 估计牙周炎症的程度/范围，最终可能导致早期发现 牙周附着和骨丢失。本建议的目的有两个：（1）建立定量的 基于超声的成像生物标记，即，B模式（定量超声，QUS）、组织应变以及 使用具有已知特性的体模进行血液体积分数，以及（2）对以下各项进行相关性测试 确定所述非侵入性超声成像生物标志物和所述非侵入性超声成像生物标志物之间的炎症程度/严重性， 侵入性组织学/分子生物学，使用已建立的临床前猪模型。圆满成果 这项研究将导致新的，客观的和精确的超声生物标志物，可以估计， 牙周炎的严重性/程度。随后，检测疾病活动的可预测性 将通过纵向临床前和人体研究单独和共同进行评价。最后， 我们打算制定常规口腔护理的临床指南和临床成像方案，以缓解 牙周炎的巨大负担影响了数百万美国成年人。

ABSTRACT (from parent grant application) Periodontitis, initiated by bacterial infection and compounded by host inflammatory response, is a leading cause of tooth loss affecting welfare of 65 million US adults. Mounting evidence suggests periodontitis is also associated with systemic health, mostly through a common link, inflammation. Therefore, diagnosis and treatment of periodontal inflammation would potentially improve general health. Current clinical measures of periodontal inflammation are visual inspection and “bleeding on probing (BOP)”. Unfortunately, they are subjective and insensitive to detect disease activity. Targeted imaging of subclinical signs of inflammation, e.g. increased vascularity, interstitial fluid and tissue loss, etc., would shed light on precise diagnosis and timely treatment of this deliberating disease non-invasively at chairside. Some quantitative ultrasound biomarkers, e.g. backscatter, elasticity, color flow, and power Doppler have been investigated extensively in medicine in recent years and have been recognized as validated for evaluating inflammation of specific body organs. They would be potential candidates to measure periodontal inflammation objectively. A miniature sized (16.2 mm), high-imaging resolution (~60 µm) ultrasound probe prototype was developed by our group specifically for use in the constrainted oral cavity and has been validated for accurately imaging periodontal tissues. It is ready for use on a commercially available ultrasound system for collecting the above-mentioned quantitative ultrasound parameters. The hypothesis driving this proposal is that non-invasive and quantitative ultrasound can be used to estimate degree/extent of periodontal inflammation that could eventually lead to early detection of periodontal attachment and bone loss. The aims of this proposal are two folds: (1) Establish quantitative ultrasound based imaging biomarkers, i.e., B-mode (Quantitative Ultrasound, QUS), tissue strain as well as fractional blood volume using phantoms with known properties and (2) Perform correlation testing for determining inflammation extent/severity between the non-invasive ultrasound imaging biomarkers and the invasive histology/molecular biology, using an established preclinical porcine model. Successful outcomes of this investigation will lead to novel, objective and precise ultrasound biomarkers that can estimate severity/extent of periodontal inflammation. Subsequently, the predictability of detecting disease activity individually and collectively will be evaluated through longitudinal preclinical and human studies. Ultimately, we intend to develop clinical guidelines and a clinical imaging protocol for routine oral care to alleviate the tremendous burden of periodontitis affecting millions of US adults.