Precision MRI with a Novel Protein Contrast Agent for Early Detection and Staging of Lung Fibrosis

摘要 肺部疾病，如间质性肺疾病，包括特发性肺纤维化(IPF)， 慢性阻塞性肺疾病(COPD)和急性病毒感染是主要的 全球范围内的死因。最近由于空气污染的增加，吸烟是和使用的 电子烟在美国迅速增长，导致慢性肺病急剧增加 疾病。IPF的特点是细胞外基质(ECM)增加，包括胶原， 在肺内，造成不可逆转的肺损伤。而高分辨率计算机断层扫描 (HRCT)是诊断IPF的常用方法。这种方法会产生较大的偏差和误差 (高达50%)，并且无法检测到早期肺纤维化。就像症状的出现 并不总是表明疾病类型，诊断通常是在更晚的阶段获得的。尽管 磁共振成像的优点包括沉积深度穿透，无电离辐射， 和高分辨率，MRI在肺部成像中的应用一直是非常具有挑战性的，因为 与其他组织相比，肺的密度降低(低10倍)， 在肺中与分子氧广泛的偶极相互作用。因此，有一个迫在眉睫的 开发非侵入性成像方法和造影剂以满足未满足的医疗需求 检测肺纤维化的早期阶段，并根据IPF的进展来判断纤维化的严重程度。

Summary Lung diseases, such as interstitial lung diseases including idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), and acute viral infection are major leading causes of death worldwide. The recent increase due to air pollution, tobacco smoking is and use of E-cigarettes has grown rapidly in the US contributing to a sharp increase in chronic lung diseases. IPF is characterized by increased extracellular matrix (ECM), including collagen, within the lung, causing irreversible lung damage. While high-resolution computed tomography (HRCT) is commonly used to diagnose IPF. This method can produce large variation and error (up to 50%) and is unable to detect early-stage lung fibrosis. As the presence of symptoms does not always indicate disease type, diagnosis is usually obtained at a much later stage. Despite the advantages of MRI, which includes deposition depth penetration, lack of ionizing radiation, and high resolution, the application of MRI to lung imaging has been very challenging due to reduced (10x lower) density of the lungs compared to other tissues and limitations from extensive dipolar interactions with molecular oxygen in the lungs. Therefore, there is a pressing unmet medical need to develop noninvasive imaging methodologies and contrast agents to detect early stages of lung fibrosis, and stage fibrosis severity based on progression of IPF.