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

描述（由申请人提供）：预计未来几年美国慢性丙型肝炎病毒感染（HCV）的发病率将增加，随后肝损伤的风险增加，包括纤维化和肝硬化，最终可能导致肝细胞癌和需要肝移植的终末期肝病。这种疾病是/将是巨大的保健费用和发病率/死亡率的来源。大多数肝病学家仍然依靠新诊断的HCV患者的肝活检结果来评估肝损伤（纤维化和炎症）。肝活检有局限性，包括成本、侵入性、患者接受度差、采样有限、观察者之间的可变性以及难以重复。目前迫切需要非侵入性检测，以在更大范围内捕捉肝损伤的程度。这些方法将在患者和肝病学家中获得更多的认可。在本提案中，我们希望测试和验证基于高级扩散（体素内非相干运动扩散MRI: IVIM DW-MRI）和动态对比增强MRI （DCE-MRI）的无创磁共振成像（MRI）方法，用于检测HCV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的结合具有检测纤维化和肝硬化的潜力，准确度很高，同时能够覆盖整个肝脏。为了提高MRI的诊断性能，我们想建立并验证一个基于高级功能MRI指标（扩散和灌注）的预测模型。如果得到验证，这种新的非侵入性算法不仅可以减少肝活检的次数，而且可以在抗病毒治疗更有效的情况下更早地诊断肝纤维化，并可以对肝脏进行全面评估（评估肝硬化、门脉高压和肝细胞癌）。这可以显著降低护理成本，可以成为测试丙型肝炎病毒抗纤维化和抗病毒药物的有用工具，并可用于跟踪患者以检测肝硬化进展。鉴于美国丙肝病毒负担的增加，这将是肝病方面的一个非常重大的进展，并将在未来十年使大量美国人受益。

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.