Fluorescence Lifetime Imaging (FLIm): a method to evaluate colon inflammation in vivo

荧光寿命成像（FLIm）：一种体内评估结肠炎症的方法

• 批准号: 10511983
• 负责人: Alba Alfonso-Garcia
• 金额: $ 19.94万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10511983
• 关键词: Abscess; Adult; Agonist; Animal Model; Animals; Antibiotic Therapy; Antibiotics; Applications Grants; Autopsy; Biochemical; Biological Assay; Biopsy; Caliber; Characteristics; Chronic; Clinical; Colon; Colonic inflammation; Colonoscopy; Colorectal; Communicable Diseases; Contrast Media; Data; Diagnosis; Disease; Disease Progression; Disease model; Dysplasia; Early Diagnosis; Endoscopy; Energy Metabolism; Environment; Epithelial; Exhibits; Female; Fiber; Fistula; Fluorescence; Funding; Gastrointestinal Diseases; Gastrointestinal tract structure; Glycolysis; Goals; High Fat Diet; Histopathology; Hour; Human; Hypoxia; Image; Imaging Device; Imaging Techniques; Immune response; In Situ; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Inflammatory Response; Intervention; Intestines; Knock-out; Knockout Mice; Label; Laboratories; Lateral; Length; Link; Magnetic Resonance; Malignant Neoplasms; Mediating; Medical; Metabolic; Metabolism; Methods; Modality; Modeling; Monitor; Motion; Mus; NADH; Nutritional; Operative Surgical Procedures; Optics; Outcome; Oxygen; PPAR gamma; Pathogenesis; Patients; Perforation; Personal Satisfaction; Pharmacology; Process; Property; Quality of life; Recording of previous events; Research; Research Project Grants; Resolution; Side; Speed; Statistical Data Interpretation; Streptomycin; Structure; Study models; Symptoms; Technology; Testing; Thick; Time; Tissues; Translating; United States; Visual; Visualization; Wild Type Mouse; X-Ray Computed Tomography; base; cofactor; dietary; dysbiosis; fluorescence lifetime imaging; gastrointestinal; gastrointestinal imaging; health care service utilization; host microbiota; human imaging; image processing; imaging modality; imaging probe; in vivo; in vivo fluorescence; in vivo imaging; intestinal epithelium; male; microbiome; microbiota; novel; novel imaging technology; operation; optical fiber; oxidation; patient prognosis; physical conditioning; response; tool; treatment response

PROJECT SUMMARY/ABSTRACT Inflammatory bowel disease (IBD) is an umbrella term for gastrointestinal (GI) diseases where chronic inflammation and its sequelae significantly impact a patient’s physical health, quality of life, and healthcare utilization. Early diagnosis of GI inflammation could prompt earlier medical intervention with a direct impact on patient’s prognosis and quality of life. There is a need for novel methods capable of detecting early and low- grade GI inflammation. The goal of this proposal is to demonstrate the feasibility of fluorescence lifetime imaging (FLIm) for detecting early colorectal inflammation in vivo. Without requiring exogenous labeling agents, FLIm is sensitive to changes in cellular metabolism, which is altered at the onset of inflammatory processes. Our specific aims focus on establishing FLIm as a research tool to quantify and monitor inflammation at the tissue level using the in vivo murine colon as a model. In Aim 1 we will (sub-aim 1.1) fabricate a side-viewing endoscopic probe for nondestructive, in situ, and in vivo intraluminal imaging of the full length of the colon and (sub-aim 1.2) show that FLIm is sensitive to epithelial metabolism using wild-type and PPAR-g knockout mice treated with antibiotic (streptomycin) to generate transient dysbiosis and with 5-ASA to protect against antibiotic effects. In Aim 2 we will test the relevance of FLIm for detecting early inflammatory changes with a model that recapitulates aspects of pre-IBD (high-fat diet and antibiotics). Using image processing and statistical analysis, we will validate the FLIm parameters with histopathology and biochemical assays (H&E, tissue hypoxia, intracellular lactate, NAD+/NADH, ADP/ATP, PDH activity) performed after necropsy (n = 6 animals/group for both male and female mice). The broad range of inflammatory responses generated with this study will demonstrate the sensitivity of FLIm as a research tool for label-free, nondestructive, in vivo intraluminal detecting and monitoring the host response to GI inflammation. Results from this research are expected to provide convincing preliminary data for subsequent R01-type research grant applications that build on the proposed concept. The long-term goal of the PI is to establish FLIm as a nondestructive and label-free, in situ and in vivo, mesoscopic imaging modality to study 1) pathogenesis and treatment of GI inflammation over time, 2) the host-microbiota relationship with pharmacological and dietary changes, and 3) to translate this approach into a clinical tool for in vivo endoscopic imaging of the human GI tract. We anticipate that the applications of the proposed implementation of FLIm range from early detection of inflammatory and infectious diseases and cancer to the close monitoring of pharmacological and nutritional treatments on the GI tract.

项目摘要/摘要 炎症性肠病（IBD）是胃肠道（GI）疾病的雨伞术语 炎症及其后遗症显着影响患者的身体健康，生活质量和医疗保健 利用率。胃肠道炎症的早期诊断可能会促使早期的医疗干预，直接影响 患者的预后和生活质量。需要能够检测早期和低 - 的新方法 GI级炎症。该建议的目的是证明荧光寿命成像的可行性 （FLIM）用于在体内检测早期结直肠炎。不需要外源标记剂，Flim是 对细胞代谢的变化敏感，在炎症过程的开始时会改变。 我们的具体目的是建立FLIM作为量化和监视注入的研究工具 使用体内鼠结肠作为模型的组织水平。在AIM 1中，我们将（sub-aim 1.1）制造侧视图 内窥镜探针，用于非损坏，原位和体内腔内成像的全长度，并在体内成像。 （sub-aim 1.2）表明FLIM使用野生型和PPAR敲除小鼠对上皮代谢敏感 用抗生素（链霉素）治疗以产生短暂性营养不良，并用5-ASA预防抗生素 效果。在AIM 2中，我们将测试FLIM在检测早期炎症变化与模型中的相关性 概括了前IBD（高脂饮食和抗生素）的各个方面。使用图像处理和统计分析， 我们将使用组织病理学和生化测定法（H＆E，组织缺氧，，验证FLIM参数， 在尸检后进行的细胞内缝合液，NAD+/NADH，ADP/ATP，PDH活性）（n = 6个动物/组。 雄性和雌性小鼠）。这项研究产生的广泛炎症反应将 证明FLIM作为无标记，无损，体内腔内检测的敏感性 并监视宿主对胃肠道炎症的反应。 预计这项研究的结果将为随后的R01型提供令人信服的初步数据 研究赠款应用于拟议概念。 PI的长期目标是建立FLIM 作为无损和无标记的原位和体内的无标记，介观像研究方式1）发病机理 随着时间的流逝，胃肠道炎症的治疗，2）宿主 - 微生物群与药物和饮食的关系 变化，3）将这种方法转化为用于人GI体内内窥镜成像的临床工具 道。我们预计拟议实施FLIM的应用范围从早期发现 炎症和传染病以及癌症，以密切监测药理和营养 胃肠道的治疗。