Evaluation of HCC Response to Systemic Therapy with Quantitative MRI

定量 MRI 评估 HCC 对全身治疗的反应

• 批准号: 8821588
• 负责人: Bachir Taouli
• 金额: $ 53.01万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-02-05 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8821588
• 关键词: Algorithms; American; Angiogenesis Inhibitors; BAY 54-9085; Blood Vessels; Brain Neoplasms; Carbogen; Cellularity; Chemoembolization; Chronic Hepatitis C; Cirrhosis; Clinical; Country; Data; Data Quality; Development; Diffusion; Diffusion Magnetic Resonance Imaging; Disease Progression; Early treatment; Evaluation; Excision; Fibrosis; Gadolinium; Goals; Growth; Health; Health Care Costs; Histologic; Histopathology; Human; Hypoxia; Image; Incidence; Infection; Investigational Therapies; Keratin-19; Liver; Liver diseases; Liver parenchyma; Mammary Neoplasms; Measurement; Measures; Metastatic Neoplasm to the Liver; Methods; Modeling; Molecular; Molecular Target; Monitor; Morbidity - disease rate; Motion; Necrosis; Outcome; Oxygen; Pathway interactions; Patients; Perfusion; Perfusion Weighted MRI; Pharmaceutical Preparations; Play; Primary carcinoma of the liver cells; Prospective Studies; Prostatic Neoplasms; Quality Control; Reaction Time; Reproducibility; Research Personnel; Role; Source; Staging; Stimulus; System; Systemic Therapy; Techniques; Testing; Therapeutic; Training; Tumor Biology; Tumor Markers; United States; Validation; Vascular Endothelial Growth Factors; Weight; Work; angiogenesis; base; blood oxygen level dependent; blood perfusion; density; effective therapy; experience; gadolinium oxide; hypoxia inducible factor 1; imaging modality; improved; liver imaging; liver injury; mortality; non-invasive imaging; non-invasive system; novel; outcome forecast; research study; response; response marker; screening; tool; tumor; tumor progression; uptake

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.

描述(申请人提供)：美国的肝细胞癌的发病率最近有所增加。肝细胞癌是/将是巨大的医疗费用和发病率/死亡率的来源，通常在晚期肝损伤(晚期纤维化和肝硬变)的患者中发展。尽管成像在肝癌的筛查和分期中发挥了重要作用，但利用成像预测肝癌的分级、侵袭性、血管生成和缺氧的可能性尚未得到满足。此外，现在可用于治疗晚期肝癌的新的抗血管生成药物需要使用超出大小的新的成像标准。在这项建议中，我们想测试和验证基于先进扩散加权成像(体素内非相干运动扩散磁共振成像：IVIM DWI)、BOLD(血氧水平依赖)MRI和灌注加权成像(PWI，使用Gd对比)的非侵入性磁共振成像(MRI)方法，以作为肝细胞癌主要组织病理学特征(分级、侵袭性、血管生成和缺氧)的无创性标志物，并预测和评估肝癌对索拉非尼(已被批准用于晚期肝癌的全身药物)系统治疗的早期反应。我们还希望开发质量控制工具，以提高这些定量MRI指标的质量并减少变异性。根据我们最近的初步数据，我们认为DWI有可能预测肝癌的肿瘤分级和对局部治疗的反应；BOLD MRI和PWI可以用来量化肝癌的血管程度和缺氧(缺氧)，这是重要的肿瘤标志物，可以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的新的非侵入性算法来预测肝癌对索拉非尼的反应，并预测预后。这些方法可能成为测试新的抗血管生成药物和实验性治疗肝癌的有用工具，将使个体化治疗成为可能，并提供肝细胞癌患者的预后。鉴于美国日益加重的肝癌负担，这将是在肝癌和肝病方面取得的重大进展，并将在未来十年使大量美国人受益。