Quantitative MRI-PET Imaging of Pulmonary Fibrosis

肺纤维化的定量 MRI-PET 成像

• 批准号: 10269911
• 负责人: Iris Yuwen Zhou
• 金额: $ 15.96万
• 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 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10269911
• 关键词: Address; Air; Algorithms; Animal Model; Animals; Binding; Biometry; Biopsy; Blood; Blood Vessels; Breathing; Cardiovascular Diseases; Chest; Clinical; Clinical Trials; Clinical Trials Design; Collagen; Collagen Type I; Data; Deposition; Diagnosis; Diagnostic radiologic examination; Disease; Disease Progression; Fibrosis; Freezing; Functional disorder; Gallium; Goals; Grant; High Resolution Computed Tomography; Human; Image; Image Analysis; Imaging Device; Individual; Label; Lead; Lung; Magnetic Resonance; Magnetic Resonance Imaging; Maps; Measurement; Measures; Mentors; Metabolism; Methods; Modeling; Molecular; Molecular Abnormality; Monitor; Morphologic artifacts; Morphology; Motion; Oncology; Outcome; Output; Pathogenicity; Patient Care; Patients; Phase; Photons; Physics; Physiology; Positron-Emission Tomography; Predisposition; Process; Prognosis; Protocols documentation; Protons; Pulmonary Fibrosis; Pulmonary function tests; Radial; Research; Research Proposals; Sampling; Scheme; Selection for Treatments; Services; Signal Transduction; Stable Disease; Structure of parenchyma of lung; Techniques; Therapeutic Effect; Therapeutic Intervention; Time; Tissues; Training; Translating; Variant; Writing; X-Ray Computed Tomography; anatomic imaging; attenuation; base; blood fractionation; career; contrast enhanced; contrast imaging; density; design; drug development; first-in-human; healthy volunteer; human disease; idiopathic pulmonary fibrosis; imaging approach; improved; in vivo; indium-bleomycin; injured; lung imaging; lung injury; molecular imaging; nervous system disorder; novel; novel therapeutic intervention; optimal treatments; programs; pulmonary function; quantitative imaging; respiratory; segmentation algorithm; simulation; skills; treatment response; uptake

Project Summary/Abstract The goal of this project is to develop and implement a 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 course 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. Our central hypothesis is that non- invasive MR-aided PET imaging of collagen accumulation will allow us to capture the extent of ongoing lung injury in IPF patients and thus service as a viable disease activity measure. 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 in 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 artefacts 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.

项目摘要/摘要 该项目的目的是开发和实施MR-PET肺成像工具，以准确量化 与肺纤维化有关的分子异常。特发性肺纤维化（IPF）是一种进步 最终是致命疾病，其中位生存率从诊断开始不到4年。治疗 由于临床高度可变，并且理解致病机制，因此期权仍然受到限制。 当前诊断和监测IPF的策略包括肺活检，肺功能测试，以测量全局 肺功能和解剖成像工具，例如高分辨率计算机断层扫描。但是这些方法 他们早日检测疾病，确定疾病活动，提供准确的预后或 监视治疗反应。分子成像可能是一种更敏感的替代方法 检测早期纤维化，并可能能够区分新的活性纤维化与稳定疾病 - 紧急 和未满足的临床需求。推进定量成像工具确定IPF疾病活动的能力 将改善患者护理并促进急需的药物开发。我们的核心假设是非 胶原蛋白积累的侵入性MR-ADED PET成像将使我们能够捕获持续的肺 IPF患者的损伤，因此作为可行的疾病活动措施服务。磁共振（MR）成像 可以提供多种形态学，生理学，代谢和分子过程的读数，而正电子 排放断层扫描（PET）对询问病理生物学具有独家敏感性。高级先生和宠物 技术对肿瘤学，心血管疾病和神经系统疾病产生了重大影响。然而， 由于质子密度低和快速信号，它们在肺成像中的应用在历史上受到限制 由于MRI的气体组织接口处的敏感性伪像衰减，而宠物量化仍然受到挑战 由于呼吸运动，光子衰减和组织，空气和血液分数的区域变化。最近， 我们开发了一个标记为胶原蛋白结合PET探针进行纤维化成像的镀凝剂（GA）-68。离体测量 在博来霉素受伤的纤维化肺中的摄取比对照组高5倍。但是，都体内动物 最初的人类研究显示，宠物信号差异为35-40％。这个差异突出了 运动定量中运动，衰减和部分体积校正的重要性。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 启用了诸如平行成像，超短期时间的超短期时间（UTE）和旋转阶段编码 肺的高级质子MR成像。那个简单的MR-PET有望改善PET定量 通过使用空间和临时关联的MR信息以纠正运动，部分体积和照片 衰减效果。利用成像和敏感胶原蛋白靶向探针的技术进步， 该建议旨在建立MR-PET肺成像工具，以准确量化胶原蛋白的沉积 IPF患者的肺进行精确评估疾病活动。