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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要炎症性肠病（IBD）是慢性胃肠道（GI）疾病的总称。炎症及其后遗症会严重影响患者的身体健康、生活质量和医疗保健胃肠道炎症的早期诊断可以促进早期医疗干预，从而直接影响患者的预后和生活质量需要能够早期和低水平检测的新方法。该提案的目的是证明荧光寿命成像的可行性。 (FLIm) 用于检测体内早期结直肠炎症，无需外源标记剂。对细胞代谢的变化敏感，细胞代谢在炎症过程开始时发生改变。我们的具体目标是建立 FLIm 作为量化和监测炎症的研究工具在目标 1 中，我们将（子目标 1.1）制作一个侧视模型。用于对全长结肠进行无损、原位和体内腔内成像的内窥镜探头（子目标 1.2）使用野生型和 PPAR-g 敲除小鼠表明 FLIm 对上皮代谢敏感用抗生素（链霉素）治疗以产生短暂的生态失调，并用 5-ASA 治疗以防止抗生素的影响在目标 2 中，我们将使用一个模型来测试 FLIm 检测早期炎症变化的相关性。使用图像处理和统计分析概括 IBD 前期（高脂肪饮食和抗生素）的各个方面。我们将通过组织病理学和生化（H&E、组织测定缺氧、尸检后进行细胞内乳酸、NAD+/NADH、ADP/ATP、PDH 活性）（n = 6 只动物/组雄性和雌性小鼠）。本研究产生的广泛炎症反应将。证明 FLIm 作为无标记、无损体内管腔内检测研究工具的灵敏度并监测宿主对胃肠道炎症的反应。这项研究结果有望为后续R01型提供令人信服的初步数据基于所提议概念的研究资助申请 PI 的长期目标是建立 FLIm。作为一种无损、无标记、原位和体内介观成像方式来研究 1) 发病机制以及随着时间的推移胃肠道炎症的治疗，2）宿主-微生物群与药理学和饮食的关系变化，以及 3) 将这种方法转化为人类胃肠道体内内窥镜成像的临床工具我们预计所提议的 FLIm 实施的应用范围包括早期检测。炎症和传染病以及癌症的药理和营养密切监测胃肠道治疗。