Evaluation of HCC Response to Systemic Therapy with Quantitative MRI

描述（由申请人提供）：肝细胞癌（HCC）的发病率最近在美国有所增加。HCC是/将是巨大的医疗费用和发病率/死亡率的来源，通常发生在晚期肝损伤（晚期纤维化和肝硬化）患者中。尽管影像学在HCC筛查和分期中发挥着重要作用，但影像学预测HCC肿瘤分级、侵袭性、血管生成和缺氧的可能性尚不满足需求。此外，新的抗血管生成药物现在可用于治疗晚期HCC，需要使用新的成像标准，而不仅仅是尺寸。在本提案中，我们想测试和验证基于高级弥散加权成像（体素内非相干运动弥散MRI）的无创磁共振成像（MRI）方法：IVIM DWI)、BOLD（血氧水平依赖）MRI和灌注加权成像（PWI，使用钆造影剂）可作为HCC主要组织病理学特征（分级、侵袭性、血管生成和缺氧）的无创标志物，并可预测和评估HCC对索拉非尼（批准用于晚期HCC的全身药物）全身治疗的早期反应。我们还希望开发质量控制工具，以提高质量和减少这些定量MRI指标的可变性。基于我们最近的初步数据，我们认为DWI具有预测HCC肿瘤分级和HCC对局部治疗反应的潜力；BOLD MRI和PWI可用于量化HCC的血管供应程度和缺氧（缺氧），这是重要的肿瘤标志物，可作为索拉非尼反应的早期标志物。最终，我们希望验证一种基于多参数MRI的新型无创算法，以预测HCC对索拉非尼的反应，并预测预后。这些方法可以成为测试新的抗血管生成药物和肝细胞癌实验疗法的有用工具，将实现个体化治疗，并为肝细胞癌患者提供预后。鉴于美国HCC负担的增加，这将是HCC和肝脏疾病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): The incidence of hepatocellular carcinoma (HCC) has recently increased in the United States. HCC is/will be the source of enormous health care costs and morbidity/mortality, and generally develops in patients with advanced liver damage (advanced fibrosis and cirrhosis). Although imaging plays a major role in HCC screening and staging, the possibility of predicting HCC tumor grade, aggressiveness, angiogenesis and hypoxia with imaging are unmet needs. In addition, new antiangiogenic drugs now available to treat advanced HCC necessitate the use of new imaging criteria beyond size. In this proposal, we would like to test and validate non invasive magnet resonance imaging (MRI) methods based on advanced diffusion-weighted imaging (intravoxel incoherent motion diffusion MRI: IVIM DWI), BOLD (blood oxygen level dependent) MRI and perfusion-weighted imaging (PWI, using gadolinium contrast) to be used as non invasive markers of major histopathologic features of HCC (grade, aggressiveness, angiogenesis and hypoxia), and to predict and assess early response of HCC to systemic therapy with sorafenib (systemic drug approved for use in advanced HCC). We also would like to develop quality control tools to improve the quality and decrease variability of these quantitative MRI metrics. Based on our recent preliminary data, we believe that DWI has potential for predicting HCC tumor grade, and HCC response to locoregional therapy; and that BOLD MRI and PWI can be used to quantify degree of vascularity and lack of oxygen supply (hypoxia) in HCC, which are important tumor markers, and could be used as early markers of response to sorafenib. Ultimately, we are hoping to validate a novel non invasive algorithm based on multiparametric MRI to predict response of HCC to sorafenib, and to predict prognosis. These methods could become useful tools for testing new antiangiogenic drugs and experimental therapies in HCC, will enable individualized therapy, and provide prognosis in patients with HCC. This will be a highly significant progress in HCC and liver diseases given the increased burden of HCC in this country, and would benefit a large number of Americans over the next decade.