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: 10390384
• 负责人: Bastiaan Driehuys
• 金额: $ 68.3万
• 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/10390384
• 关键词: 3-Dimensional; Adoption; Alveolar; Biological Markers; Biomedical Technology; Blood capillaries; COVID-19; Cessation of life; Chest; Chronic; Chronic Obstructive Pulmonary 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; Techniques; Technology; Testing; Time; Tissues; Transplantation; Treatment Efficacy; United States National Institutes of Health; Vendor; Work; X-Ray Computed Tomography; base; clinical care; clinical decision-making; cohort; cost; experience; fibrotic lung disease; functional disability; functional status; idiopathic pulmonary fibrosis; improved; individual patient; innovation; interest; interstitial; nintedanib; normal aging; novel; novel strategies; novel therapeutics; outcome prediction; physiologic model; programs; public health relevance; pulmonary function; pulmonary function decline; pulmonary vascular disorder; reconstruction; 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.

项目总结/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300万例患者 国际吧它的预后比许多癌症更差，如果不治疗，中位生存期为3-5年。 虽然IPF无法治愈，但新的可用药物可以使肺功能下降的速度相对于 安慰剂，尽管每年的费用为10万美元，并且在个体患者中的疗效未知。今天，IPF 临床护理和研究因缺乏能够可靠评估其异质性区域的工具而受到阻碍 功能障碍，以检测疾病，并提供积极的治疗反应的强大指标。本 最后，我们已经开发出超极化（HP）129 MRI，并显示它提供快速，非侵入性，3D 对吸入气体在空气空间中的分布及其在屏障中的吸收进行功能评估 组织）并转移到毛细血管红细胞（RBC）。我们已经证明了它对微米的敏感性- 间质屏障的规模增厚，这提供了一个敏感的和早期的治疗标志物， 反应这导致要求更广泛地传播和统一获取和量化 最大化可重复性的协议。我们的长期目标是广泛传播一个全面而迅速的 (15分钟），非侵入性，稳健，灵敏的MRI检查纤维化肺疾病。我们带来了先进的HP 129 MR采集和分析技术以及三个开创性的胸部MRI专业知识的跟踪记录 开发了这个应用程序的中心。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，这些方法将使可靠的检测可治疗的 疾病和可视化治疗反应在3个月内开始。拟议研究的理由 是由行业和学术合作伙伴的强烈兴趣推动的， 这将加速MRI的普及。因此，拟议的研究与NIH的使命有关， 通过发展和加速应用生物医学技术来改善健康状况。我们的做法是 基于三个特定目标：1）在MRI平台上建立129个MRI指标的最佳可重复性，2） 建立协调的定量分析，以及3）部署并验证识别活动性纤维化的框架 和治疗反应。这些目标的完成将1）使整个扫描仪的标准化协议可用 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129 MRI纳入进行性纤维化的多中心试验，并最终纳入临床护理。拟议 方法是创新的，因为它是建立在一个从根本上新的方法来探索的功能， 肺泡-毛细血管界面这是重要的，因为它将使广泛采用的方法，以促进 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。