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: 9064201
• 负责人: Bastiaan Driehuys
• 金额: $ 74.71万
• 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 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9064201
• 关键词: Address; Affect; Alveolar; Anatomy; Area; Biological Markers; Biomedical Technology; Biopsy; Blood capillaries; Blood gas; Breathing; Cardiopulmonary; Cessation of life; Chest; Chronic lung disease; Clinical; Clinical Trials; Data; Defect; Detection; Development; Diagnosis; Diffuse; Diffusion; Disease; Disease Progression; Environmental air flow; Fibrosis; Functional Imaging; Functional Magnetic Resonance Imaging; Gases; Goals; Hamman-Rich syndrome; Health; High Resolution Computed Tomography; Image; Impairment; Investigational Therapies; Laboratories; Lung; Magnetic Resonance Imaging; Mean Survival Times; Measurable; Measures; Methods; Mission; Modality; Monitor; Multicenter Trials; New Agents; Outcome; Patient Recruitments; Patients; Perfusion; Process; Protocols documentation; Protons; Pulmonary Gas Exchange; Pulmonary function tests; Rare Diseases; Recording of previous events; Recovery; Regional Disease; Research; Resolution; Respiratory physiology; Site; Staging; Structure; Techniques; Testing; Therapeutic; Thick; Three-Dimensional Imaging; Time; United States National Institutes of Health; Work; base; capillary; cost; design; experience; imaging biomarker; imaging modality; improved; innovation; interstitial; lung imaging; non-invasive imaging; novel therapeutics; outcome forecast; response; success; therapy development; treatment response

 DESCRIPTION (provided by applicant): The prognosis for patients diagnosed with idiopathic pulmonary fibrosis (IPF) is very poor, with a mean survival time of only 35.2 months. IPF now affects more than 100,000 US residents and is characterized by thickening of the pulmonary blood-gas barrier and impaired gas exchange. Unfortunately, even as efforts to develop therapies for IPF accelerate, most clinical trials are stymied by the inability to adequately characterize the disease, its progression, and its therapeutic response. Existing biomarkers are either too insensitive or too invasive for repeat use. We intend to address this problem by introducing a comprehensive MRI-based 3D imaging approach to not only identify regional disease, but to predict and observe regional therapeutic response. Our long-term goal is to broadly deploy non-invasive, high-resolution, quantitative MR imaging of all aspects of cardiopulmonary function to change the way IPF is managed. Our approach exploits the converging progress in 1H MR imaging of structure and perfusion, with hyperpolarized 129Xe MR imaging of ventilation and gas exchange. The objective of this study is to integrate and optimize these structural and functional MRI approaches and use them to identify regional diffusion limitation, and predict and observe therapeutic response 4 times earlier than standard methods can. Our central hypothesis is that combined imaging of structure, ventilation, perfusion and gas exchange, will provide the means to identify the leading edge of disease, where recovery of lung function remains possible. The rationale for the proposed research is that therapeutic response is difficult if not impossible to detect using global metrics and thus, 3 non-invasive imaging is needed to visualize recoverable areas. Thus, the proposed research is relevant to that part of the NIH Mission that pertains to improving health by developing and accelerating the application of biomedical technologies. Guided by strong preliminary data, our approach is based on three Specific Aims: 1) Establish a comprehensive, quantitative structure/function MRI Protocol for IPF at two centers, 2) Identify regional early- stage disease by combining Gd perfusion and 129Xe exchange MRI, and 3) Use structure/function MRI to monitor progression and response to therapy in IPF. Completion of these aims will 1) set up 2-leading centers with an optimized protocol for imaging IPF, 2) establish the ability to visualize regions of diffusion impairment that can still respond to therapy, 3) observe therapeutic response within 3 months instead of 1 year, and 4) predict outcomes at 12 months post therapy as seen by conventional tests. The proposed approach is innovative because it uses a comprehensive protocol to measure what cannot be measured by any one technique in isolation, and exploits the expertise of 2 centers to accelerate development and expand the recruitment pool for this rare disease. The proposed research is significant because it has the potential to develop the key noninvasive functional imaging biomarkers that can enable IPF trials to be conducted faster, with fewer patients, at lower cost and with greater likelihood for success.

 描述（申请人提供）：诊断为特发性肺纤维化（IPF）的患者预后非常差，平均生存时间仅为35.2个月。IPF现在影响超过100，000名美国居民，其特征是肺血气屏障增厚和气体交换受损。不幸的是，即使在努力开发IPF治疗方法的同时，大多数临床试验仍因无法充分表征疾病、其进展及其治疗反应而受阻。现有的生物标志物要么太不敏感，要么太具侵入性，无法重复使用。我们打算通过引入一种全面的基于MRI的3D成像方法来解决这个问题，不仅可以识别局部疾病，而且可以预测和观察局部治疗反应。我们的长期目标是广泛部署心肺功能各个方面的无创、高分辨率、定量MR成像，以改变IPF的管理方式。我们的方法利用了结构和灌注的1H MR成像与通气和气体交换的超极化129 H MR成像的融合进展。本研究的目的是整合和优化这些结构和功能MRI方法，并使用它们来识别区域扩散限制，预测和观察治疗反应比标准方法早4倍。我们的中心假设是，结构、通气、灌注和气体交换的组合成像将提供识别疾病前沿的手段，其中肺功能恢复仍然是可能的。拟议研究的基本原理是，使用全局指标检测治疗反应是困难的（如果不是不可能的话），因此，需要3非侵入性成像来可视化可恢复区域。因此，拟议中的研究与NIH使命的一部分有关，即通过发展和加速生物医学技术的应用来改善健康。在强有力的初步数据的指导下，我们的方法基于三个特定目标：1）在两个中心建立针对IPF的全面的定量结构/功能MRI方案，2）通过结合Gd灌注和129交换MRI来识别局部早期疾病，以及3）使用结构/功能MRI来监测IPF的进展和对治疗的反应。这些目标的实现将：1）建立2个领先的研究中心，采用优化的IPF成像方案; 2）建立对治疗仍有反应的弥散损害区域进行可视化的能力; 3）在3个月而不是1年内观察治疗反应; 4）预测治疗后12个月的结局，如常规检查所示。所提出的方法是创新的，因为它使用了一个全面的协议来测量无法通过任何一种技术孤立地测量的东西，并利用2个中心的专业知识来加速开发和扩大这种罕见疾病的招募库。这项拟议的研究意义重大，因为它有可能开发关键的非侵入性功能成像生物标志物，使IPF试验能够更快地进行，患者更少，成本更低，成功的可能性更大。