Liver Parametric PET

肝脏参数 PET

• 批准号: 10456875
• 负责人: Guobao Wang
• 金额: $ 53.84万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10456875
• 关键词: Acute; Address; Adult; Affect; Biological Markers; Biopsy; Blood; Blood flow; Cicatrix; Cirrhosis; Clinic; Clinical; Clinical Management; Clinical Research; Clinical Trials; Complement; Computer Simulation; Data; Development; Diagnosis; Effectiveness; Fatty Liver; Fatty acid glycerol esters; Fibrosis; General Population; Glucose Transporter; Goals; Gold; Hepatic; Hepatic artery; Histologic; Hour; Human; Image; Imaging Techniques; Individual; Inflammation; Kinetics; Knowledge; Liver; Liver Failure; Liver Fibrosis; Lobular; Magnetic Resonance Elastography; Magnetic Resonance Imaging; Malignant neoplasm of liver; Measures; Methodology; Methods; Modality; Modeling; Nature; Organ; Outcome; Patients; Performance; Persons; Pharmaceutical Preparations; Phase II/III Trial; Phase III Clinical Trials; Portal vein structure; Positron-Emission Tomography; Protons; Reporting; Risk; Scanning; Sensitivity and Specificity; Standardization; Techniques; Testing; Time; Tissues; Tracer; Translations; United States; Validation; Vascular blood supply; Work; chronic liver disease; chronic liver inflammation; clinical application; cohort; density; effectiveness evaluation; end stage disease; end stage liver disease; fatty liver disease; fluorodeoxyglucose; fluorodeoxyglucose positron emission tomography; glucose metabolism; glucose transport; imaging biomarker; imaging modality; improved; innovation; kinetic model; liver biopsy; liver inflammation; liver injury; mortality; non-alcoholic fatty liver disease; non-invasive imaging; nonalcoholic steatohepatitis; noninvasive diagnosis; novel; novel therapeutics; public health relevance; radiotracer; simple steatosis; uptake

PROJECT SUMMARY Nonalcoholic fatty liver disease (NAFLD) affects approximately one-third of the general population in the United States. Nonalcoholic steatohepatitis (NASH) - a more severe form of NAFLD - develops in 5-10% of NAFLD patients (i.e., 5-10 million people in the US) with the hallmark of hepatic inflammation in the setting of hepatic steatosis. Differentiation of NASH from simple hepatic steatosis is vital for patient management in NAFLD as NASH is associated with accelerated progression into end-stage liver diseases (liver failure and liver cancer) and with much higher liver-related mortality than the simple fatty liver. While noninvasive imaging methods have been developed to quantify liver fat and liver fibrosis, there is an unmet need for new imaging methods to detect and grade liver inflammation. The goal of this project is to develop a positron emission tomography (PET) method to enable noninvasive assessment of liver inflammation and NASH diagnosis. Using the widely accessible radiotracer 18F-fluorodeoxyglucose (FDG), we propose a liver parametric PET method using dynamic scanning and tracer kinetic modeling. We hypothesize that glucose transport measured by liver parametric PET can accurately characterize the liver inflammation underlying NASH. One major challenge with enabling this technique is that the liver is a unique organ with dual blood supplies from the hepatic artery and portal vein, requiring the knowledge of dual-blood input function (DBIF) for kinetic modeling, which is difficult to obtain in human PET studies. Our preliminary work has addressed this technical challenge by developing a novel optimization-derived DBIF modeling approach. With improved kinetic modeling, we have discovered in a pilot clinical study that the blood-to-tissue glucose transport rate K1 was strongly associated with histological liver inflammation grades. The focus of this proposal is to further develop and optimize the methodology of liver parametric PET and validate its effectiveness for assessing liver inflammation and diagnosing NASH in patients with NAFLD. More specifically, we will (1) develop the technical method of liver parametric PET; (2) Evaluate glucose transport rate K1 as an effective and unique PET biomarker of liver inflammation; (3) Combine liver parametric PET with CT or MR methods for multiparametric NASH diagnosis; (4) Shorten the scan time of liver parametric PET from one hour to fifteen minutes. The integrated outcome of these specific aims will be a new technical capability and validation of 18F-FDG PET for liver inflammation assessment and for detecting and grading NASH. The proposed method will fill the critical gap for noninvasive assessment of liver inflammation in fatty liver disease. Successful completion of this project has the potential to profoundly impact the clinical management of NAFLD patients and clinical trials of new NASH treatments.

项目摘要 非酒精性脂肪肝疾病（NAFLD）影响了美国大约三分之一的普通人群 国家。非酒精性脂肪性肝炎（NASH）（一种更严重的NAFLD形式）在5-10％的NAFLD中发展 患者（即美国5-1亿人）在肝的情况下具有肝发炎的标志 脂肪变性。 NASH与简单肝脂肪变性的区分对于NAFLD的患者管理至关重要 NASH与加速发展为末期肝病（肝癌和肝癌）有关 与简单的脂肪肝相比，与肝脏相关的死亡率要高得多。而无创成像方法具有 开发以量化肝脂肪和肝纤维化，未满足检测的新成像方法 和肝脏炎症。该项目的目的是开发正电子发射断层扫描（PET）方法 能够对肝脏炎症和NASH诊断进行无创评估。使用广泛访问的 radiotracer 18F-氟脱氧葡萄糖（FDG），我们使用动态扫描提出了一种肝参数PET方法 和示踪动力学建模。我们假设通过肝参数PET测量的葡萄糖转运可以 准确地表征了NASH潜在的肝脏炎症。实现这一目标的一个主要挑战 技术是肝脏是一种独特的器官，具有肝动脉和门静脉的双血液供应， 需要了解双血输入函数（DBIF）进行动力学建模，这很难在 人类宠物研究。我们的初步工作通过开发小说来应对这一技术挑战 优化衍生的DBIF建模方法。随着动力学建模的改进，我们在飞行员中发现了 临床研究表明，血到组织的葡萄糖转运率K1与组织学肝密切相关 炎症等级。该建议的重点是进一步发展和优化肝脏的方法论 参数宠物并验证其评估肝炎和诊断患者NASH的有效性 与nafld。更具体地说，我们将（1）开发肝参数PET的技术方法； （2）评估 葡萄糖转运率K1是肝脏炎症的有效且独特的宠物生物标志物； （3）结合肝脏 具有CT或MR方法的参数PET用于多参数NASH诊断； （4）缩短肝脏的扫描时间 参数宠物从一小时到十五分钟。这些特定目标的综合结果将是一个新的 18F-FDG PET的技术能力和验证用于肝发炎评估以及检测和检测 给纳什分级。提出的方法将填补无创评估肝炎的关键空白 脂肪肝病。该项目的成功完成有可能深刻影响临床 NAFLD患者的管理和新NASH治疗的临床试验。