Quantitative MRI-PET Imaging of Pulmonary Fibrosis

肺纤维化的定量 MRI-PET 成像

• 批准号: 10769999
• 负责人: Iris Yuwen Zhou
• 金额: $ 5.29万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-25 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10769999
• 关键词: Administrative Supplement; Air; Animals; Binding; Biopsy; Cardiovascular Diseases; Clinical; Clinical Trials; Collagen; Deposition; Diagnosis; Disease; Early Diagnosis; Fibrosis; Gallium; Goals; High Resolution Computed Tomography; Image; Imaging Device; Label; Lung; Magnetic Resonance; Magnetic Resonance Imaging; Measurement; Measures; Metabolism; Methods; Molecular; Molecular Abnormality; Monitor; Morphologic artifacts; Morphology; Motion; Oncology; Outcome; Parents; Pathogenicity; Patient Care; Patients; Phase; Photons; Physiology; Positron-Emission Tomography; Predisposition; Process; Productivity; Prognosis; Protons; Pulmonary Fibrosis; Pulmonary function tests; Rotation; Signal Transduction; Stable Disease; Techniques; Time; Tissues; Variant; anatomic imaging; attenuation; blood fractionation; caregiving; contrast imaging; density; drug development; fibrotic lung; first-in-human; idiopathic pulmonary fibrosis; improved; in vivo; indium-bleomycin; injured; lung imaging; molecular imaging; nervous system disorder; novel therapeutic intervention; pulmonary function; quantitative imaging; respiratory; simulation; treatment response; uptake

Abstract The administrative supplement will help the PI to maintain productivity while fulfilling her caregiving responsibilities and achieve the goal of the parent K25 project to develop and implement an MR-PET lung imaging tool to accurately quantify molecular abnormalities associated with pulmonary fibrosis. Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease with a median survival of less than 4 years from the time of diagnosis. The treatment options remain limited due to highly variable clinical courses and poorly understood pathogenic mechanisms. Current strategies to diagnose and monitor IPF include lung biopsy, pulmonary function tests that measure global lung function, and anatomic imaging tools such as high-resolution computed tomography. Yet these methods are limited in their ability to detect disease early, determine disease activity, provide accurate prognosis or monitor the therapeutic response. Molecular imaging may be an alternative approach that is more sensitive to detect early fibrosis and potentially capable of distinguishing new, active fibrosis from stable disease – urgent and unmet clinical needs. Advancing the capacity of quantitative imaging tools to determine IPF disease activity would improve patient care and facilitate much-needed drug development. Magnetic resonance (MR) imaging can provide multiple readouts of morphology, physiology, metabolism, and molecular processes, while positron emission tomography (PET) offers exquisite sensitivity to interrogate pathobiology. Advanced MR and PET techniques have had major impacts on oncology, cardiovascular diseases, and neurological disorders. However, their application to lung imaging has been historically limited because of low proton density and the fast signal decay due to susceptibility artifacts at air- tissue interfaces for MRI, while PET quantification remains challenging due to respiratory motion, photon attenuation, and regional variations in tissue, air, and blood fractions. Recently, we developed a gallium(Ga)-68 labeled collagen-binding PET probe for fibrosis imaging. Ex vivo measurement showed a 5-fold higher uptake in bleomycin-injured fibrotic lungs than controls. However, both in vivo animal and first-in-human studies showed a PET signal difference of 35-40%. This discrepancy highlights the importance of motion, attenuation, and partial volume correction in PET quantification. Our preliminary simulation results show that attenuation and motion correction substantially increase the imaging contrast. Recent technical advances such as parallel imaging, ultra- short time to echo (UTE), and rotating phase encoding have enabled advanced proton MR imaging of the lung. Thus, simultaneous MR-PET promises to improve PET quantification by using the spatially and temporally correlated MR information to correct for motion, partial volume, and photon attenuation effects. Capitalizing on the technical advances in imaging and the sensitive collagen-targeted probe, this proposal aims to establish an MR-PET lung imaging tool to accurately quantify collagen deposition in the lung of IPF patients for precise assessment of disease activity.

抽象的 行政补充剂将帮助PI在履行照料的同时保持生产力 责任并实现家长K25项目的目标，以开发和实施MR-PET肺 成像工具，以准确量化与肺纤维化相关的分子异常。特发性 肺纤维化（IPF）是一种进行性疾病，最终是致命疾病，中位生存期不到4年 从诊断开始。由于高度可变的临床课程，治疗方案仍然有限 了解致病机制。当前诊断和监测IPF的策略包括肺活检， 肺功能测试测量全局肺功能和解剖成像工具（例如高分辨率） 计算机断层扫描。然而，这些方法的早期检测能力受到限制，确定疾病 活性，提供准确的预后或监测治疗反应。分子成像可能是 替代方法对检测早期纤维化更敏感，并有可能区分新的方法 稳定疾病的主动纤维化 - 紧急且未满足的临床需求。提高定量能力 确定IPF疾病活动的成像工具将改善患者护理并促进急需的药物 发展。磁共振（MR）成像可以提供多种形态学，生理学的读数， 代谢和分子过程，而正电子发射断层扫描（PET）对 质疑病理学。高级MR和PET技术对肿瘤学产生了重大影响， 心血管疾病和神经系统疾病。但是，它们在肺成像中的应用是 历史上由于质子密度较低和由于空气上的敏感性伪像而导致的快速信号衰变而有限 MRI的组织界面，而PET定量由于呼吸运动而挑战 衰减以及组织，空气和血液分数的区域变化。最近，我们开发了炮（GA）-68 标记的胶原结合PET探针进行纤维化成像。离体测量显示出高5倍 在博来霉素受伤的纤维化肺中，肺比对照组。但是，显示了体内动物和人类第一研究 宠物信号差为35-40％。这种差异突出了运动，衰减和部分的重要性 宠物定量中的体积校正。我们的初步模拟结果表明衰减和运动 校正大大增加了成像对比度。最近的技术进步，例如平行成像，超级成像 回声（UTE）和旋转相编码的短时间使肺的高级质子MR成像。 这是简单的MR-PET有望通过使用空间和临时使用该PET定量 将MR信息相关联，以纠正运动，部分体积和光子衰减效果。大写 成像和敏感胶原蛋白靶向探针的技术进步，该提议旨在建立一个 MR-PET肺成像工具可准确量化IPF患者肺中的胶原蛋白沉积 评估疾病活动。