Detection of Liver Fibrosis Using IVIM Diffusion and DCE MRI in HCV

描述(申请人提供)：预计在未来几年内，美国慢性丙型肝炎病毒感染(丙型肝炎病毒)的发病率会增加，随之而来的是肝脏损伤的风险增加，包括纤维化和肝硬变，最终可能导致肝细胞癌和终末期肝脏疾病，需要肝移植。这种疾病是/将是巨大的医疗费用和发病率/死亡率的来源。大多数肝病学家仍然依赖于新诊断为丙型肝炎病毒的患者的肝活检结果，这使得评估肝脏损伤(纤维化和炎症)成为可能。肝活检具有局限性，包括成本、侵袭性、患者接受性差、采样有限、观察者间的可变性以及难以重复。迫切需要非侵入性检测来捕捉更大规模的肝脏损伤程度。这些将在患者和肝病专家中获得更多的接受。在这项建议中，我们想测试和验证基于高级扩散(体素内非相干运动扩散磁共振成像：IVIM DW-MRI)和动态对比增强磁共振成像(DCE-MRI)的无创磁共振成像(MRI)方法，以检测丙型肝炎患者的纤维化和肝硬化。根据我们最近的初步数据，我们认为IVIM DW-和DCE-MRI的结合在检测纤维化和肝硬变方面具有极高的准确性，同时能够覆盖整个肝脏。为了提高MRI的诊断性能，我们希望建立并验证一个基于先进的功能性MRI指标(弥散和灌注)的预测模型。如果得到验证，这种新的非侵入性算法不仅将减少肝脏活检的次数，而且还可以在抗病毒治疗更有效的时候更早地诊断肝纤维化，并能够对肝脏进行全面评估(以评估是否有肝硬变、门脉高压和肝细胞癌)。这可以显著降低护理成本，可以成为测试新的抗纤维化和抗病毒药物在丙型肝炎病毒中的有用工具，并可以用于跟踪患者检测进展为肝硬变。鉴于丙型肝炎病毒在美国日益加重的负担，这将是肝病方面的一项非常重要的进展，并将在未来十年使大量美国人受益。 公共卫生相关性：丙型肝炎病毒感染(丙型肝炎病毒)患者发展为肝脏瘢痕(纤维化)的风险很高，最终有可能患上肝硬变和肝癌，可能需要肝移植。我们希望开发无创的先进磁共振成像技术(扩散和动态增强磁共振成像)来评估丙型肝炎病毒肝损害的程度。这些技术结合在一起，可以达到检测肝纤维化的高诊断性能；并可以减少必要的肝活组织检查的次数，因为这种检查有风险，只对一小部分肝脏进行采样。

DESCRIPTION (provided by applicant): There is an expected increased incidence of chronic hepatitis C virus infection (HCV) in the Unites States within the next years, with subsequent increased risks of liver damage, including fibrosis and cirrhosis, which may eventually lead to hepatocellular carcinoma and end-stage liver disease requiring liver transplantation. This disease is/will be the source of enormous health care costs and morbidity/mortality. Most hepatologists still rely on liver biopsy findings in patients newly diagnosed with HCV, which enables the assessment of liver damage (fibrosis and inflammation). Liver biopsy has limitations, including cost, invasiveness, poor patient acceptance, limited sampling, inter-observer variability and is difficult to repeat. Non invasive tests to capture the extent of liver damage at a larger scale are urgently needed. These will gain more acceptance among patients and hepatologists. In this proposal, we would like to test and validate non invasive magnetic resonance imaging (MRI) methods based on advanced diffusion (intravoxel incoherent motion diffusion MRI: IVIM DW-MRI) and dynamic contrast-enhanced MRI (DCE-MRI) for the detection of fibrosis and cirrhosis in HCV patients. Based on our recent preliminary data, we believe that the combination of IVIM DW- and DCE-MRI has potential for detection of fibrosis and cirrhosis with excellent accuracy, while enabling coverage of the whole liver. In order to improve the diagnostic performance of MRI, we would like to build and validate a predictive model based on advanced functional MRI metrics (diffusion and perfusion). If validated, this novel non invasive algorithm will not only decreases the number of liver biopsies, but also enable earlier diagnosis of liver fibrosis when antiviral treatment is more effective, and enable a comprehensive evaluation of the liver (to assess for cirrhosis, portal hypertension and hepatocellular cancer). This could significantly reduce the cost of care, could become a useful tool for testing new antifibrogenic and antiviral drugs in HCV, and could be used to follow patients for detection of progression to cirrhosis. This will be a highly significant progress in liver diseases given the increased burden of HCV in this country, and would benefit a large number of Americans over the next decade. PUBLIC HEALTH RELEVANCE: Patients with hepatitis C virus infection (HCV) are at high risk of developing liver scarring (fibrosis), with ultimate risks of cirrhosis and liver cancer that may require liver transplant. We would like to develop non invasive advanced MRI techniques (diffusion and dynamic contrast-enhanced MRI) to assess the degree of liver damage in HCV. These techniques combined could reach high diagnostic performance for detection of liver fibrosis; and could decrease the number of necessary liver biopsies, which have risks and sample only a small portion of the liver.