Molecular Imaging of Gingipain Activity in Advanced Periodontitis

晚期牙周炎中 Gingipain 活性的分子成像

• 批准号: 10259849
• 负责人: Jesse Vincent Jokerst
• 金额: $ 19.01万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-09 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10259849
• 关键词: Acoustics; Alveolar Bone Loss; Alzheimer' s Disease; American; Amino Acids; Anatomy; Area; Bacteria; Basic Science; Biological Markers; Biology; Cardiology; Cardiovascular Diseases; Caring; Chemistry; Clinic; Clinical; Communicable Diseases; Contrast Media; Dangerousness; Data; Dental; Dentists; Diagnosis; Diagnostic; Disease; Early Diagnosis; Etiology; Exhibits; Gingiva; Gingival Crevicular Fluid; Health; Health Status; Healthcare; Hemorrhage; Housekeeping; Human; Image; Imaging Techniques; Immune; Immune response; In Situ; In Vitro; Infection; Inflammation; Intervention; Laboratories; Leadership; Link; Location; Long-Term Effects; Malignant Neoplasms; Maps; Measures; Microbial Biofilms; Microbiology; Modality; Molecular; Monitor; Optical Methods; Oral cavity; Oral health; Paper; Pathogenesis; Pathogenicity; Patient Monitoring; Patient Triage; Patient-Focused Outcomes; Peptide Hydrolases; Periodontal Diseases; Periodontal Pocket; Periodontitis; Play; Porphyromonas gingivalis; Positioning Attribute; Premature Birth; Problem Solving; Proteins; Publishing; Quality of life; Recombinants; Reporting; Research; Role; Saliva; Sampling; School Dentistry; Science; Sensitivity and Specificity; Signal Transduction; Spatial Distribution; Spectrum Analysis; Structure; Symptoms; Techniques; Testing; Time; Tissues; Tooth Loss; Tooth structure; Toothache; Translating; Triage; Trypsin; Ultrasonography; Work; absorption; base; bone loss; clinical care; compliance behavior; dysbiosis; gingipain; heart disease risk; improved; in vitro testing; in vivo; innovation; insight; materials science; molecular imaging; non-invasive imaging; novel; oral microbial community; oral microbiome; pathogen; pathogenic bacteria; photoacoustic imaging; response; routine care; skills; tool; treatment response; uptake

PROJECT SUMMARY This objective of this proposal is an activatable photoacoustic contrast agent to map and measure the gingipain proteases released by P. gingivalis during periodontitis. While P. gingvalis is easy to measure with PCR it cannot mapped in the mouth. Here, photoacoustic ultrasound will be used to report the quantity and location of gingipains released by P. gingivalis and improve diagnosis and response to therapy. We are motivated by studies showing that dental pain dramatically decreases quality of life but that nearly 50% of Americans have some form of periodontitis. Our rationale is that current approaches to monitoring oral health only measure the results and symptoms of gingipains (tooth loss, pocket depth, etc.). We argue that by imaging and measuring a molecular cause of periodontal disease—i.e., the gingipains secreted by P. gingivalis—new insights will be gained into the basic biology of this condition as well as better diagnostic and treatment-monitoring plans. This improved diagnostic insight will better guide therapy, and non-invasive imaging will increase patient compliance ultimately translating into earlier and better treatment of periodontitis. The workflow will include two parts: Aim 1 will build the contrast agent and validate it with recombinant gingipains, bacterial culture, and saliva from healthy subjects. Aim 2 will test the probe with gingival crevicular fluid (GCF) samples collected by Dr. Chen during routine cleanings. We will resuspend these samples and quantitate the gingipains using the probe validated in Aim 1. We hypothesize that the photoacoustic signal of our probe will increase linearly with gingipain concentration in vitro. We hypothesize that photoacoustic imaging can stratify GCF samples as a function of oral health status. This approach is innovative because this contrast agent will be the first molecular imaging technique for periodontal disease. It will detect disease prior to anatomical damage. As such, we will be able to map and measure the extent of pathogenic activity caused by P. gingivalis in the subgingival space in real time. It will also triage the disease in early stages. Current periodontal charting can only assess pocket depths and bleeding on probing, but detection of early- stage pathogenic activity will allow easy and inexpensive intervention to lower the clinical burden of periodontitis and improve patient outcomes. The clinical impact is a tool to detect early-stage changes in the oral microbiota to guide/monitor therapy. This technique could also answer questions about the impact of gingipains on inflammation, immune loading, pocket deepening, and alveolar bone loss in situ. We all well positioned to perform this work because of Dr. Jokerst’s skills in photoacoustic contrast media and Dr. Chen’s leadership position at the USC School of Dentistry; we have already published together on related research.

项目总结 这项提议的目标是一种可激活的光声造影剂，以映射和测量 牙龈假单胞菌在牙周炎过程中释放的牙龈痛蛋白。而P.gingvalis很容易用来测量 聚合酶链式反应它不能在嘴里映射。在这里，光声超声将被用来报告数量和 对牙龈假单胞菌释放的牙周疼痛进行定位，提高诊断和治疗反应。我们是 研究表明，牙痛会显著降低生活质量，但近50%的人 美国人有某种形式的牙周炎。我们的理由是，目前监测口腔健康的方法 只测量牙痛的结果和症状(牙齿脱落、口袋深度等)。我们认为，通过 成像和测量牙周病的分子病因--即由P. 牙周炎-将获得对这种疾病的基本生物学的新见解，以及更好的诊断和 治疗监测计划。这种改进的诊断洞察力将更好地指导治疗，而且是非侵入性的 成像将增加患者的依从性，最终转化为牙周炎的更早和更好的治疗。 该工作流程将包括两个部分：Aim 1将构建造影剂并用重组 牙周疼痛，细菌培养，以及健康受试者的唾液。目标2将测试带有牙龈沟的探头 陈博士在常规清洗过程中采集的液体(GCF)样本。我们将重新寄送这些样品并 使用在目标1中验证的探针对牙周疼痛进行定量。我们假设 在体外，我们的探针会随着牙周疼痛浓度的增加而线性增加。我们假设光声 成像可以根据口腔健康状况对GCF样本进行分层。这种方法是创新的，因为 这种造影剂将是第一个用于牙周疾病的分子成像技术。它将检测疾病 在解剖损伤之前。因此，我们将能够绘制和测量致病活动的程度 由牙龈下间隙中的P.givalis实时引起。它还将在早期阶段对疾病进行分类。 目前的牙周图只能评估牙袋深度和探诊时的出血，但早期- 阶段性致病活动将允许简单和廉价的干预措施，以减轻临床负担 牙周炎和改善患者的预后。临床影响是一种检测早期变化的工具 指导/监测治疗的口腔微生物区系。这项技术还可以回答有关 牙周疼痛、炎症、免疫负荷、牙槽窝加深和牙槽骨原位丢失。我们都很好 由于Jokerst博士在光声造影剂方面的技能和陈博士的 南加州大学牙科学院的领导职位；我们已经共同发表了相关研究。