PET-MR Imaging of pulmonary fibrosis

项目总结/摘要 本项目的目标是使用定量PET-MR成像的肺部，以准确地量化分子 与肺纤维化相关的异常，以预测疾病进展，并提供早期 抗纤维化治疗是否可能有效的指示。特发性肺纤维化（IPF）是一种 进行性和最终致命的疾病，从诊断开始的中位生存期不到4年。 由于高度可变的临床过程和对致病性知之甚少， 机制等目前诊断和监测IPF的策略包括肺活检、肺功能检查， 测量整体肺功能和解剖成像工具，如高分辨率计算机断层扫描 （HRCT）。然而，这些方法在早期检测疾病、在任何时间确定疾病活动性的能力方面是有限的。 一个测量或监测治疗反应。分子成像可能是一种替代方法， 对检测早期纤维化更敏感，并可能能够区分新的、活动性纤维化和稳定性纤维化 疾病-迫切和未满足的临床需求。我们小组最近开发了一种I型胶原特异性正电子 发射断层扫描（PET）探头，68 Ga-CBP 8，在动物模型中显示可检测肺纤维化 在早期阶段，并能够监测治疗反应。该探头的初步数据在健康 志愿者和IPF患者证实，68 Ga-CBP 8在IPF肺中的摄取显著高于在正常肺中的摄取。 正常的肺该数据还显示，除了在具有纤维化的肺区域中的探针摄取， 通过HRCT确定，在放射学“正常”肺中存在额外的探针摄取区域，表明 探针可能对比HRCT更低水平的纤维化敏感和/或对疾病活动敏感，即 新形成的胶原蛋白。另一方面，磁共振成像（MRI）可以提供多个读数， 形态学生理学和功能。我们实验室使用动态对比增强MRI的初步数据 在健康对照和IPF受试者中的DCE-MRI结果表明，DCE参数可以区分异常与 正常肺，这些措施可以预测疾病的进展。肺的定量MRI-PET已经被 由于低质子密度和由于空气中的磁化率伪影导致的快速信号衰减， 组织界面进行MRI，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变化。然而，将这两种模式结合起来， 有很大的潜力来克服其中的一些限制。我们的中心假设是， 胶原积聚的成像将使我们能够捕获IPF患者持续肺损伤的程度， 使用胶原靶向PET的双模式成像方法，通过DCE-MRI增强， 准确检测疾病活动和治疗反应。

Project Summary/Abstract The goal of this project is to use quantitative PET-MR imaging of the lung to accurately quantify molecular abnormalities associated with pulmonary fibrosis, to predict disease progression, and to provide an early indication of whether anti-fibrotic therapy is likely to be effective. 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 (HRCT). Yet these methods are limited in their ability to detect disease early, determine disease activity at any one measure, 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. Our group recently developed a type I collagen-specific positron emission tomography (PET) probe, 68Ga-CBP8, which was shown in animal models to detect pulmonary fibrosis at an early stage and was capable of monitoring treatment response. Preliminary data with this probe in healthy volunteers and IPF patients demonstrated that 68Ga-CBP8 had significantly higher uptake in IPF lungs than in normal lungs. This data also showed that in addition to probe uptake in regions of lung with fibrosis as established by HRCT, there were additional areas of probe uptake in radiographically “normal” lung suggesting that the probe may be sensitive to lower levels of fibrosis than HRCT and/or sensitive to disease activity, i.e. newly formed collagen. Magnetic resonance imaging (MRI) on the other hand can provide multiple readouts of morphology, physiology, and function. Preliminary data from our lab using dynamic contrast enhanced-MRI (DCE-MRI) in healthy controls and IPF subjects indicated that DCE parameters can distinguish abnormal from normal lung, and that these measures may predict disease progression. Quantitative MRI-PET in lung 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. However, combining the two modalities holds great potential to overcome some of these limitations. Our central hypothesis is that non-invasive molecular imaging of collagen accumulation will allow us to capture the extent of ongoing lung injury in IPF patients and that a bi-modal imaging approach using collagen-targeted PET augmented by DCE-MRI will enable more accurate detection of disease activity and treatment response.