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

基本信息

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
项目类别：
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

项目摘要

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 万患者在世界范围内，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，尽管每年花费 100,000 美元，并且对个别患者的疗效未知。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有力指标。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。间质屏障鳞片增厚，这提供了治疗的敏感和早期标志这导致需要更广泛的传播以及统一的获取和量化。我们的长期目标是广泛传播全面而快速的协议。（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。疾病并在开始后 3 个月内可视化治疗反应。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。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，以及 3) 部署和验证框架来识别活动性纤维化完成这些目标将 1) 提供跨扫描仪的标准化协议。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。方法是创新的，因为它建立在一种全新的方法上来探测系统的功能肺泡-毛细血管界面非常重要，因为它将使得广泛采用的方法得以推进。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。