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（由适用提供）：诊断为特发性肺纤维化（IPF）的患者的预后非常差，平均生存时间仅为35.2个月。 IPF现在影响了100,000多名美国居民，其特征是肺气体屏障增厚和气体交换受损。不幸的是，即使为加速IPF开发疗法的努力，大多数临床试验都无法充分表征该疾病，其进展及其治疗反应而受到阻碍。现有的生物标志物要么太敏感，要么太侵入性，无法重复使用。我们打算通过引入全面的基于MRI的3D成像方法来解决这个问题，不仅可以识别区域疾病，还可以预测和观察区域治疗反应。我们的长期目标是对心肺功能各个方面的各个方面进行广泛部署非侵入性，高分辨率的定量MR成像，以改变IPF的管理方式。我们的方法探讨了结构和灌注的1H MR成像中的融合进展，并使用超极化的129 XE MR成像进行通风和气体交换。这项研究的目的是整合和优化这些结构和功能性MRI方法，并使用它们来识别区域扩散限制，并比标准方法早4次预测和观察治疗反应。我们的中心假设是，结构，通风，灌注和气体交换的结合成像将提供识别疾病前缘的手段，肺功能恢复仍然是可能的。拟议的研究的理由是，如果不是不可能使用全球指标来检测治疗反应，则需要3个非侵入性成像来可视化可回收区域。这是拟议的研究与NIH任务的那部分有关，该部分与通过开发和加速生物医学技术的应用来改善健康有关。在强大的初步数据的指导下，我们的方法基于三个具体目的：1）在两个中心为IPF建立全面的，定量的结构/功能MRI协议，2）2）通过合并GD灌注和129XE Exchange MRI和3）使用结构/功能MRI来监测IPF的治疗方法，以确定区域早期疾病。完成这些目标的完成1）建立具有成像IPF的优化方案的2个领导中心，2）确定能够可视化仍然可以响应治疗的扩散障碍区域的能力，3）3）3）在3个月内而不是1年内，而不是1年，而4）4）在治疗后的12个月内预测胜利，如传统测试所见。提出的方法具有创新性，因为它使用一项综合协议来衡量任何一种孤立的技术无法衡量的方法，并探讨了2个中心的专业知识，以加速发展并扩大这种罕见疾病的招聘池。拟议的研究很重要，因为它有可能开发关键的非侵入性功能成像生物标志物，这些功能成像生物标志物可以使IPF试验更快，患者较少，成本较低，并且成功的可能性更大。