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.

项目摘要/摘要 在过去的10年中，特发性肺纤维化（IPF）的患病率已翻了一番，达到约300万患者 全世界。它的预后比许多癌症都要糟，如果未经治疗，中位生存期为3 - 5年。 虽然IPF无法治愈，但新近可用的药物可以减慢肺功能下降〜50％ 安慰剂，尽管每年的费用为100,000美元，并且个人患者的效率不明。今天，IPF 临床护理和研究受到缺乏可以可靠评估其异质区域的工具的困扰 功能障碍可检测疾病并提供良好的治疗反应指标。对此 最后，我们开发了超极化（HP）129xE MRI，并证明它提供了快速，无创的​​3D 空间中遗传气体分布的功能评估及其在间质中的吸收（屏障） 组织）并转移到毛细血管红细胞（RBC）中。我们已经证明了它对微米的敏感性 间质屏障的比例比例增厚，这提供了敏感和早期的治疗标记 回复。这导致要求更广泛的传播和统一的获取和数量 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又快速的 （15分钟），非侵入性，鲁棒和敏感的MRI检查，用于纤维化肺部疾病。我们带来了高级HP 129XE MR采集和分析技术以及三个开创性的胸腔MRI专业知识的轨道记录 开发此应用程序的中心。这种更新的目的是优化对改变的敏感性 疾病，最大重复性，协调获取和分析并建立其物理和临床 解释。我们的核心假设是这些方法将使人们能够自信地检测治疗 疾病并在开始后的3个月内可视化治疗反应。拟议研究的理由 受到行业和学术伙伴的浓厚兴趣的驱动，即将批准FDA 129xE 通风MRI将加速采用。这是拟议的研究与NIH的任务有关 通过开发和加速生物医学技术来改善健康。我们的方法是 基于三个具体目的：1）在MRI平台上建立129XE指标的最佳可重复性，2） 建立统一的定量分析，3）部署和验证一个识别活性纤维化的框架 和治疗反应。这些目标的完成1）在扫描仪中提供标准化协议 平台，2）建立最大化可重复性的标准，3）提供所需的工具和框架 将129 XE MRI纳入进行性纤维化和最终临床护理的多中心试验中。提议 方法具有创新性，因为它建立在一种从根本上进行探测功能的新方法 肺泡毛细管界面。这很重要，因为它将能够采用宽度 我们对纤维化肺部疾病的理解，加速对新疗法的测试并改善患者护理。