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)是慢性胃肠道(GI)疾病的总称 炎症及其后遗症严重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促使更早的医学干预，直接影响 患者的预后和生活质量。需要新的方法能够检测早期和低水平的- 胃肠道炎症分级。这项提议的目的是论证荧光寿命成像的可行性。 (FLIM)用于活体检测早期结直肠炎症。不需要外源标签剂，Flim是 对细胞代谢的变化很敏感，这种变化在炎症过程开始时就会改变。 我们的具体目标集中在建立FLIM作为一种研究工具，以量化和监测炎症 以在体小鼠结肠为模型的组织水平。在目标1中，我们将(子目标1.1)制作侧视图 用于无损、原位和活体肠腔内成像的内窥镜探头 (子目标1.2)使用野生型和PPAR-g基因敲除小鼠显示FLIM对上皮代谢敏感 用抗生素(链霉素)治疗产生一过性生物失调，并用5-ASA预防抗生素 效果。在目标2中，我们将使用一个模型来测试FLIM对于检测早期炎症变化的相关性 概括了IBD前期的几个方面(高脂肪饮食和抗生素)。利用图像处理和统计分析， 我们将通过组织病理学和生化分析(H&E，组织缺氧， 细胞内乳酸、NAD+/NADH、ADP/ATP、PDH活性)(n=6动物/组 雄鼠和雌鼠)。这项研究产生的广泛的炎症反应将 展示了作为无标记、无损、活体腔内检测的研究工具的敏感性 以及监测宿主对胃肠道炎症的反应。 这项研究的结果有望为后续的R01型提供令人信服的初步数据 以拟议概念为基础的研究资助申请。国际和平研究所的长期目标是建立电影 作为一种无损的、无标记的、原位和活体的介观成像手段，用于研究1)发病机制 以及随时间推移对胃肠道炎症的治疗，2)宿主-微生物区系与药理和饮食的关系 改变，以及3)将这种方法转化为临床工具，用于活体内窥镜成像人类胃肠道 一条小路。我们预计，拟议的FLIM实施的应用范围从早期检测到 炎症性和感染性疾病和癌症要密切监测药理和营养 胃肠道的治疗。