Quantitative MRI-PET Imaging of Pulmonary Fibrosis

摘要 行政副刊将帮助私人助理在履行照顾职责的同时保持生产力。 负责并实现母公司K25项目开发和实施MR-PET肺的目标 精确量化与肺纤维化相关的分子异常的成像工具。特发性 肺纤维化(Ipf)是一种进行性的、最终致命的疾病，中位生存期不到4年。 从确诊之时起。由于高度可变的临床病程和糟糕的治疗方案，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， 测量全球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，这些方法在及早发现疾病、确定疾病 活动，提供准确的预后或监测治疗反应。分子成像可能是一种 另一种方法对检测早期纤维化更敏感，并有可能区分新的、 来自稳定期疾病的活动性纤维化--紧急和未得到满足的临床需求。提升数量化能力 确定IPF疾病活动性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、生理、 代谢和分子过程，而正电子发射断层扫描(PET)提供了对 审问病理生物学。先进的磁共振和正电子发射计算机断层扫描技术对肿瘤学产生了重大影响， 心血管疾病和神经疾病。然而，它们在肺部成像中的应用一直是 由于低质子密度和由于空气中磁化率伪影而导致的快速信号衰减，历史上受到限制- MRI的组织界面，虽然由于呼吸运动、光子、PET量化仍然具有挑战性 衰减，以及组织、空气和血液成分的区域差异。最近，我们开发了一种镓(Ga)-68 用于纤维化成像的标记胶原结合的PET探针。体外测量显示摄取率增加了5倍 在博莱霉素损伤的纤维化肺中的作用明显高于对照组。然而，活体动物研究和第一次人类研究都表明 PET信号差35-40%。这种差异突出了运动、衰减和偏移的重要性 正电子发射计算机断层扫描定量中的体积校正我们的初步模拟结果表明，衰减和运动 校正大大提高了成像对比度。最新的技术进步，如并行成像，超 短时间回波(UTE)和旋转相位编码使先进的质子磁共振肺部成像成为可能。 因此，同步MR-PET有望通过使用空间和时间上的 关联MR信息以校正运动、部分体积和光子衰减效应。利用 在成像和敏感的胶原靶向探针方面的技术进展，这项提议旨在建立一种 MR-PET肺成像工具准确定量特发性肺纤维化患者肺内胶原沉积 对疾病活动性的评估。

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.