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

使用新型蛋白质造影剂进行精密 MRI，用于肺纤维化的早期检测和分期

• 批准号: 10760794
• 负责人: Jenny J. Yang
• 金额: $ 29.88万
• 依托单位: INLIGHTA BIOSCIENCES, LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10760794
• 关键词: Acute; Affinity; Air Pollution; Animal Model; Binding; Biology; Biopsy; Cause of Death; Chronic Obstructive Pulmonary Disease; Chronic lung disease; Clinical; Clinical Research; Clinical Trials; Collagen; Contrast Media; Deposition; Detection; Development; Diagnosis; Diagnostic Procedure; Disease; Disease Progression; Early Diagnosis; Effectiveness; Exhibits; Extracellular Matrix; Fibrosis; Goals; High Resolution Computed Tomography; Histologic; Human; Image; Impairment; Interobserver Variability; Interstitial Lung Diseases; Ionizing radiation; Ions; Lung; Lung diseases; Lung nodule; Magnetic Resonance Imaging; Medical; Metals; Methodology; Methods; Modeling; Molecular; Monitor; Noise; Operative Surgical Procedures; Oxygen; Pathologic; Patient Care; Patients; Pattern; Penetration; Phase; Physiological; Proteins; Public Health; Pulmonary Fibrosis; Radiation; Reporting; Research; Resistance; Resolution; Safety; Sensitivity and Specificity; Severities; Small Business Technology Transfer Research; Specificity; Staging; Stains; Statistical Data Interpretation; Symptoms; Testing; Tissue Sample; Tissues; Tobacco smoking behavior; Variant; Virus Diseases; X-Ray Computed Tomography; antifibrotic treatment; clinical application; comorbidity; density; design; dosage; drug discovery; effective therapy; electronic cigarette use; experience; high risk; idiopathic pulmonary fibrosis; imaging capabilities; imaging detection; in vivo; in vivo imaging; lung imaging; lung injury; metal poisoning; mouse model; non-invasive imaging; novel; particle; phase 2 study; pre-clinical; quantitative imaging; soft tissue; translational potential; treatment response; treatment strategy

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.

概括 肺部疾病，例如间质性肺病，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病因 全世界的死亡原因。最近由于空气污染、吸烟和使用烟草的增加 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，包括胶原蛋白、 进入肺部，造成不可逆的肺部损伤。虽然高分辨率计算机断层扫描 (HRCT) 通常用于诊断 IPF。该方法会产生较大的变化和误差 （高达 50%）并且无法检测早期肺纤维化。由于症状的存在 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 MRI 的优点，包括沉积深度穿透、缺乏电离辐射、 和高分辨率，MRI 在肺部成像中的应用一直非常具有挑战性，因为 与其他组织相比，肺部密度降低（低 10 倍），并且受到以下限制： 与肺部分子氧的广泛偶极相互作用。因此，迫切需要 开发无创成像方法和造影剂的未满足的医疗需求 检测肺纤维化的早期阶段，并根据 IPF 的进展对纤维化严重程度进行分期。