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，例如包括特发性肺纤维化（IPF），包括特发性肺部疾病， 慢性阻塞性肺疾病（COPD）和急性病毒感染是主要领先的 全世界死亡的原因。由于空气污染，烟草吸烟的最近增加而使用 在美国，电子烟的生长迅速增长，导致慢性肺急剧增加 疾病。 IPF的特征是细胞外基质（ECM）增加，包括胶原蛋白， 在肺部内导致不可逆的肺部损伤。而高分辨率计算机断层扫描 （HRCT）通常用于诊断IPF。这种方法会产生较大的变化和错误 （高达50％），无法检测到早期肺纤维化。由于症状的存在 并非总是表明疾病类型，通常在更晚的阶段获得诊断。尽管 MRI的优势包括沉积深度穿透，缺乏电离辐射， 和高分辨率，由于MRI在肺成像中的应用非常具有挑战性 与其他组织相比，肺密度降低（低10倍） 与肺中的分子氧相互作用。因此，有一个紧迫的 未满足的医学需要开发非侵入性成像方法和对比剂 根据IPF的进展，检测肺纤维化的早期阶段和纤维化严重程度。