Quantitative MRI-PET Imaging of Pulmonary Fibrosis

肺纤维化的定量 MRI-PET 成像

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要该项目的目标是开发和实施 MR-PET 肺部成像工具，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）是一种进行性的疾病。并最终导致致命疾病，自诊断之日起中位生存期不到 4 年。由于临床病程高度可变且致病机制了解甚少，选择仍然有限。当前诊断和监测 IPF 的策略包括肺活检、测量整体肺功能的测试肺功能和解剖成像工具，如高分辨率计算机断层扫描，但这些方法。早期发现疾病、确定疾病活动性、提供准确预后或的能力有限监测治疗反应可能是一种更敏感的替代方法。检测早期纤维化，并有可能区分新的活动性纤维化和稳定的疾病 - 紧急提高定量成像工具确定 IPF 疾病活动度的能力。将改善患者护理并促进急需的药物开发。胶原蛋白积累的侵入性 MR 辅助 PET 成像将使我们能够捕获正在进行的肺部病变的范围 IPF 患者的损伤，因此可作为可行的疾病活动测量。可以提供形态学、生理学、新陈代谢和分子过程的多种读数，而正电子发射断层扫描 (PET) 为研究病理学提供了极高的灵敏度。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。由于质子密度低和信号快，它们在肺部成像中的应用历来受到限制由于 MRI 空气-组织界面处的磁化率伪影而导致衰变，而 PET 定量仍然具有挑战性由于呼吸运动、光子衰减以及组织、空气和血液成分的区域变化，最近，我们开发了一种用于纤维化成像的镓 (Ga)-68 标记胶原蛋白结合 PET 探针。与对照组相比，博莱霉素损伤的纤维化肺的摄取量高出 5 倍。首次人体研究显示 PET 信号差异为 35-40%，这一差异凸显了这一点。我们的初步模拟中运动、衰减和部分体积校正的重要性。结果表明，衰减和运动校正大大提高了成像对比度。并行成像、超短回波时间 (UTE) 和旋转相位编码等进步使得因此，同步 MR-PET 有望改善 PET 定量。通过使用空间和时间相关的 MR 信息来校正运动、部分体积和光子利用成像技术的进步和敏感的胶原蛋白靶向探针，该提案旨在建立一种 MR-PET 肺部成像工具，以准确量化肺部胶原沉积 IPF 患者的肺部，用于精确评估疾病活动度。