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.

项目总结/文摘