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

描述（由申请人提供）：在未来几年内，美国慢性丙型肝炎病毒感染（HCV）的发病率预计会增加，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/将是巨大的卫生保健费用和发病率/死亡率的来源。 大多数肝病学家仍然依赖于新诊断为HCV的患者的肝活检结果，这使得能够评估肝损伤（纤维化和炎症）。肝活检具有局限性，包括成本、侵入性、患者接受度差、有限的采样、观察者间的变异性，并且难以重复。 迫切需要非侵入性测试来更大规模地捕获肝损伤的程度。这些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先进扩散（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的组合具有检测纤维化和肝硬化的潜力，具有极好的准确性，同时能够覆盖整个肝脏。为了提高MRI的诊断性能，我们希望建立和验证基于先进的功能性MRI指标（扩散和灌注）的预测模型。如果得到验证，这种新型的非侵入性算法不仅可以减少肝活检的数量，而且可以在抗病毒治疗更有效时早期诊断肝纤维化，并能够对肝脏进行全面评估（评估肝硬化，门脉高压和肝细胞癌）。 这可以显着降低护理成本，可以成为一个有用的工具，用于测试新的抗纤维化和抗病毒药物在丙型肝炎病毒，并可用于跟踪患者检测进展为肝硬化。这将是肝脏疾病的一个非常重要的进展，因为HCV在这个国家的负担增加，并将在未来十年内使大量美国人受益。 公共卫生相关性：丙型肝炎病毒感染（HCV）患者发生肝瘢痕（纤维化）的风险很高，最终有可能发生肝硬化和肝癌，可能需要肝移植。我们希望开发无创的先进MRI技术（扩散和动态对比增强MRI）来评估HCV的肝损害程度。这些技术相结合可以达到检测肝纤维化的高诊断性能;并且可以减少必要的肝活检的数量，这些活检具有风险并且仅对肝脏的一小部分进行采样。

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.