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 行政补充将帮助 PI 在完成护理工作的同时保持工作效率 责任并实现母 K25 项目开发和实施 MR-PET 肺的目标 成像工具可准确量化与肺纤维化相关的分子异常。特发性 肺纤维化 (IPF) 是一种进行性且最终致命的疾病，中位生存期不到 4 年 从诊断时起。由于临床过程高度可变且效果不佳，治疗选择仍然有限 了解致病机制。目前诊断和监测 IPF 的策略包括肺活检、 测量整体肺功能的肺功能测试，以及高分辨率等解剖成像工具 计算机断层扫描。然而，这些方法在早期检测疾病、确定疾病的能力方面受到限制。 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，并且可能能够区分新的、 稳定疾病引起的活动性纤维化——紧迫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) 成像可以提供形态学、生理学、 代谢和分子过程，而正电子发射断层扫描 (PET) 提供了精湛的灵敏度 询问病理学。先进的 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。然而，它们在肺部成像中的应用已经 历史上由于质子密度低和空气中磁化率伪影导致的信号快速衰减而受到限制 MRI 的组织界面，而 PET 定量由于呼吸运动、光子 组织、空气和血液成分的衰减和区域差异。最近，我们开发了镓(Ga)-68 用于纤维化成像的标记胶原蛋白结合 PET 探针。离体测量显示摄取量高出 5 倍 与对照组相比，博来霉素损伤的纤维化肺中的效果更好。然而，动物体内研究和首次人体研究均表明 PET 信号差异为 35-40%。这种差异凸显了运动、衰减和部分运动的重要性 PET 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，例如并行成像、超 短回波时间 (UTE) 和旋转相位编码使得先进的肺部质子 MR 成像成为可能。 因此，同步 MR-PET 有望通过使用空间和时间上的数据来改进 PET 定量。 关联 MR 信息以校正运动、部分体积和光子衰减效应。利用 成像技术的进步和敏感的胶原蛋白靶向探针，该提案旨在建立一个 MR-PET 肺部成像工具可准确量化 IPF 患者肺部胶原蛋白沉积，以实现精确定量 疾病活动评估。