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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.

项目总结/文摘