Using MRI To Visualize Regional Therapy Response In Idiopathic Pulmonary Fibrosis

使用 MRI 可视化特发性肺纤维化的局部治疗反应

• 批准号: 10211015
• 负责人: Bastiaan Driehuys
• 金额: $ 72.89万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-06 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10211015
• 关键词: 3-Dimensional; Adoption; Alveolar; Biological Markers; Biomedical Technology; Blood capillaries; COVID-19; Cessation of life; Chest; Chronic; Chronic Obstructive Airway Disease; Cicatrix; Clinical; Clinical Research; Detection; Development; Diagnosis; Diffuse; Disease; Disease Progression; Dose; Erythrocytes; Fibrosis; Functional Magnetic Resonance Imaging; Gases; Goals; Health; Hospitalization; Image; Impairment; Individual; Industry; Inhalation; Intervention Trial; Lung; Lung diseases; Magnetic Resonance Imaging; Malignant Neoplasms; Measurement; Measures; Methods; Mission; Modality; Monitor; Multicenter Studies; Multicenter Trials; Outcome; Pathology; Patient Care; Patients; Pattern; Pharmaceutical Preparations; Phenotype; Physiological; Pirfenidone; Placebos; Positioning Attribute; Prevalence; Prognosis; Property; Protocols documentation; Publishing; Pulmonary function tests; Reader; Research; Site; Standardization; Structure; Techniques; Technology; Testing; Time; Tissues; Transplantation; Treatment Efficacy; United States National Institutes of Health; Vascular Diseases; Vendor; Work; X-Ray Computed Tomography; base; clinical care; clinical decision-making; cohort; cost; experience; functional disability; functional status; idiopathic pulmonary fibrosis; improved; individual patient; innovation; interest; interstitial; normal aging; novel; novel strategies; novel therapeutics; outcome prediction; physiologic model; programs; public health relevance; pulmonary function; pulmonary function decline; reconstruction; response; side effect; therapeutic biomarker; therapeutic development; tool; treatment response; uptake; ventilation

Project Summary/Abstract The prevalence of Idiopathic pulmonary fibrosis (IPF) has doubled in the past 10 years to ~3 million patients worldwide. It has a prognosis worse than for many cancers, and, if untreated, has a median survival of 3–5 years. While IPF has no cure, newly available medications can slow the rate lung function decline by ~50% relative to placebo, albeit at a cost of $100,000 per year, and with unknown efficacy in individual patients. Today, IPF clinical care and research are stymied by a lack of tools that can reliably assess its heterogeneous regional functional impairment to detect disease and provide robust indicators of positive therapeutic response. To this end, we have developed hyperpolarized (HP) 129Xe MRI and shown it to provide rapid, non-invasive, 3D functional assessment of inhaled gas distribution in the airspaces, as well as its uptake in the interstitium (barrier tissues) and transfer to the capillary red blood cells (RBCs). We have demonstrated its sensitivity to micron- scale thickening of the interstitial barrier and that this provides a sensitive and early marker of therapeutic response. This has led to demands for wider dissemination and harmonized acquisition and quantification protocols that maximize repeatability. Our long-term goal is to broadly disseminate a comprehensive, yet rapid (15 min), non-invasive, robust, and sensitive MRI exam for fibrotic lung disease. We bring advanced HP 129Xe MR acquisition and analysis techniques and a track-record of thoracic MRI expertise from three pioneering centers that have developed this application. The objective of this renewal is to optimize sensitivity to changing disease, maximize repeatability, harmonize acquisition and analysis and establish its physiological and clinical interpretation. Our central hypothesis is that this these methods will enable confident detection of treatable disease and visualize therapeutic response within 3 months of initiation. The rationale for the proposed research is driven by strong interest from both industry and academic partners, and impending FDA approval for 129Xe ventilation MRI that will accelerate adoption. Thus, the proposed research is relevant to the NIH Mission of improving health by developing and accelerating the application of biomedical technologies. Our approach is based on three Specific Aims: 1) Establish optimal repeatability of 129Xe metrics across MRI platforms, 2) Establish harmonized quantitative analysis, and 3) Deploy and validate a framework to identify active fibrosis and therapy response. Completion of these aims will 1) make available standardized protocols across scanner platforms, 2) establish standards that maximize repeatability, and 3) provide the tools and framework needed to incorporate 129Xe MRI into multi-center trials for progressive fibrosis and ultimately, clinical care. The proposed approach is innovative because it is built on a fundamentally new approach to probe the functioning of the alveolar-capillary interface. It is significant because it will enable widespread adoption of methods to advance our understanding of fibrotic lung disease, accelerate testing of novel therapies, and improve patient care.

项目概要/摘要 特发性肺纤维化 (IPF) 的患病率在过去 10 年中翻了一番，达到约 300 万患者 全世界。它的预后比许多癌症都要差，如果不治疗，中位生存期为 3-5 年。 虽然 IPF 无法治愈，但新推出的药物可以将肺功能下降速度减缓约 50%（相对于 IPF） 安慰剂，尽管每年的费用为 100,000 美元，并且对个别患者的疗效未知。今天，IPF 由于缺乏能够可靠评估其异质区域的工具，临床护理和研究受到阻碍 功能障碍检测疾病并提供积极治疗反应的可靠指标。对此 最后，我们开发了超极化 (HP) 129Xe MRI，并证明它可以提供快速、非侵入性的 3D 吸入气体在空域中的分布及其在间质（屏障）中的吸收的功能评估 组织）并转移至毛细血管红细胞（RBC）。我们已经证明了它对微米的敏感性 间质屏障鳞片增厚，这提供了治疗的敏感和早期标志 回复。这导致了对更广泛传播以及统一采集和量化的需求 最大化可重复性的协议。我们的长期目标是广泛传播全面而快速的信息 （15 分钟）针对纤维化肺部疾病的非侵入性、稳健且灵敏的 MRI 检查。我们带来先进的HP 129Xe MR 采集和分析技术以及三位先驱的胸部 MRI 专业知识记录 开发此应用程序的中心。此次更新的目的是优化对变化的敏感性 疾病，最大限度地提高可重复性，协调采集和分析并建立其生理和临床 解释。我们的中心假设是，这些方法将能够可靠地检测可治疗的 疾病并在开始后 3 个月内可视化治疗反应。拟议研究的理由 受到行业和学术合作伙伴的强烈兴趣以及 FDA 即将批准 129Xe 的推动 通气 MRI 将加速采用。因此，拟议的研究与 NIH 的使命相关 通过开发和加速生物医学技术的应用来改善健康。我们的方法是 基于三个具体目标：1) 跨 MRI 平台建立 129Xe 指标的最佳可重复性，2) 建立统一的定量分析，3) 部署和验证框架来识别活动性纤维化 和治疗反应。完成这些目标将 1) 跨扫描仪提供标准化协议 平台，2) 建立最大化可重复性的标准，以及 3) 提供所需的工具和框架 将 129Xe MRI 纳入进行性纤维化的多中心试验以及最终的临床护理中。拟议的 方法是创新的，因为它建立在一种全新的方法上来探索 肺泡-毛细血管界面。这很重要，因为它将使得广泛采用方法来推进 我们对纤维化肺病的了解，加速新疗法的测试，并改善患者护理。