Liver Parametric PET

肝脏参数 PET

基本信息

批准号：
10263281
负责人：
Guobao Wang
金额：
$ 54.52万
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：
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/10263281
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 Liver diseases Lobular Magnetic Resonance Elastography Magnetic Resonance Imaging Malignant neoplasm of liver Measures Methodology Methods Modality Modeling Nature Organ Outcome Patients Performance 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 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 uptake

项目摘要

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.

项目概要非酒精性脂肪肝 (NAFLD) 影响着美国大约三分之一的总人口国家。非酒精性脂肪性肝炎 (NASH) - NAFLD 的一种更严重的形式 - 5-10% 的 NAFLD 会出现这种情况患有肝脏炎症的患者（即美国有 5-1000 万人）脂肪变性。区分 NASH 与单纯性肝脂肪变性对于 NAFLD 患者的管理至关重要，因为 NASH 与加速进展为终末期肝病（肝衰竭和肝癌）有关与单纯性脂肪肝相比，肝脏相关死亡率要高得多。虽然无创成像方法已已被开发用于量化肝脏脂肪和肝纤维化，因此对新的成像方法来检测的需求尚未得到满足和分级肝脏炎症。该项目的目标是开发一种正电子发射断层扫描（PET）方法实现肝脏炎症的无创评估和 NASH 诊断。使用广泛可访问的放射性示踪剂 18F-氟脱氧葡萄糖 (FDG)，我们提出了一种使用动态扫描的肝脏参数 PET 方法和示踪动力学建模。我们假设通过肝脏参数 PET 测量的葡萄糖转运可以准确表征 NASH 背后的肝脏炎症。实现这一目标的一个主要挑战技术认为，肝脏是一个独特的器官，具有肝动脉和门静脉双重血液供应，需要双血输入函数（DBIF）的知识来进行动力学建模，这在国内很难获得人体 PET 研究。我们的前期工作通过开发一种新颖的方法解决了这一技术挑战优化衍生的 DBIF 建模方法。通过改进的动力学模型，我们在飞行员中发现临床研究表明血液到组织的葡萄糖转运速率 K1 与组织学肝脏密切相关炎症等级。该提案的重点是进一步开发和优化肝脏的方法参数 PET 并验证其评估肝脏炎症和诊断患者 NASH 的有效性患有 NAFLD。具体来说，我们将（1）开发肝脏参数化PET技术方法； (2) 评价葡萄糖转运率 K1 作为肝脏炎症有效且独特的 PET 生物标志物； (3) 联合肝参数 PET 结合 CT 或 MR 方法进行多参数 NASH 诊断； (4)缩短肝脏扫描时间参数化 PET 从一小时到十五分钟。这些具体目标的综合成果将是一个新的 18F-FDG PET 用于肝脏炎症评估以及检测和验证的技术能力和验证 NASH 分级。所提出的方法将填补肝脏炎症无创评估的关键空白脂肪肝疾病。该项目的成功完成有可能对临床产生深远的影响 NAFLD 患者的管理和新 NASH 治疗的临床试验。