Use of advanced imaging techniques to improve diagnostic methods for ARDS

使用先进的成像技术改进 ARDS 的诊断方法

• 批准号: 9199441
• 负责人: ROBERT SCOTT HARRIS
• 金额: $ 67.74万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9199441
• 关键词: Address; Adult Respiratory Distress Syndrome; Affect; Biological Markers; Biology; Blood Tests; Catheterization; Cessation of life; Clinical; Clinical Research; Complication; Critical Illness; Cytokine Receptors; Data; Detection; Diagnosis; Diagnostic; Diagnostic Procedure; Diagnostic radiologic examination; Diagnostic tests; Echocardiography; Edema; Enrollment; Ensure; Etiology; Functional disorder; Gases; Goals; Half-Life; Heart failure; Human; Image; Imaging Techniques; Imaging technology; Immune Tolerance; Impairment; Inflammation; Inflammatory; Kinetics; Lead; Lung; Lung Inflammation; Lymphoma; Measures; Methods; Modeling; Modernization; Patient Selection; Patients; Phenotype; Plant Roots; Plasma; Play; Positron-Emission Tomography; Problem Solving; Process; Pulmonary Edema; Pulmonary Inflammation; Research; Research Personnel; Respiratory Failure; Role; Scanning; Sepsis; Skin Cancer; Specificity; Syndrome; Techniques; Technology; Testing; Tracer; Trauma; United States; Ventricular Remodeling; Water; Work; X-Ray Computed Tomography; accurate diagnosis; animal data; clinical Diagnosis; coronary fibrosis; diagnostic biomarker; effective therapy; fluorodeoxyglucose; human data; human subject; imaging biomarker; improved; in vivo; innovation; lung imaging; malignant breast neoplasm; mortality; novel; novel marker; portability; public health relevance; research study; success; tomography; uptake

DESCRIPTION (provided by applicant): The goal of this five-year project is to use advanced imaging and biomarker techniques to improve strategies for diagnosing the Acute Respiratory Distress Syndrome (ARDS). ARDS is a common complication of critical illnesses such as sepsis, and affects over 200,000 patients annually in the United States. ARDS mortality exceeds 30%. As yet, few effective therapies have been found. A major reason for this lack of progress is the difficulty in accurately diagnosing ARDS, leading to difficulty in studying potentil treatments. ARDS is characterized by inflammation-induced pulmonary edema that leads to severe respiratory failure. However, other conditions such as heart failure (HF) may also cause respiratory failure and pulmonary edema despite having very different pathophysiologic causes, and therefore different treatments. Traditional diagnostic methods include clinical criteria and radiography, which have proven to lack precision in distinguishing ARDS from other illnesses. Recent advances in imaging have demonstrated that lung inflammation and lung edema can be quantified with Computed Tomography/Positron Emission Tomography (PET/CT) scanning, by measuring uptake of 18F-fluorodeoxyglucose uptake (18F-FDG) and 15O-water activity (H215O). A combination of these methods might have potential for improving the diagnosis of ARDS, but has not yet been studied in humans. This project will adapt PET/CT methods to provide functional in vivo lung imaging, with the goal of distinguishing between patients with pulmonary edema due to ARDS and those with pulmonary edema due to HF. This would enable treatment targeted to the underlying biology of the patient's illness, and would help ensure that patients of the appropriate phenotype are enrolled into ARDS clinical studies. This project will also utilize these results to develop a plasma biomarker test for this diagnostic purpose. Specifically, levels of soluble ST2 (sST2), a cytokine receptor that has been studied as novel biomarker of immune tolerance, and which plays a role in myocardial fibrosis and remodeling, will be validated for detection of pulmonary inflammation as demonstrated by PET/CT imaging. Specific aims of the project are as follows: SPECIFIC AIM 1: We will perform PET/CT imaging of critically ill patients to compare lung inflammation (18F- FDG) and pulmonary edema (H215O) in ARDS vs. HF, and compare these with a novel model using 18F-FDG data alone to quantify inflammation and edema. We hypothesize that PET/CT imaging will enable separation of subjects into diagnostic groups according to underlying pulmonary inflammation and edema. SPECIFIC AIM 2: We will test the relationship between lung inflammation and novel biomarker sST2. We hypothesize that plasma concentration of sST2 can be used as a surrogate for imaging to detect lung inflammation, and thus can enable diagnostic separation of subjects according to the presence of this process.

描述（由申请人提供）：这个为期五年的项目的目标是使用先进的成像和生物标志物技术，以改善诊断急性呼吸窘迫综合征（ARDS）的策略。急性呼吸窘迫综合征（ARDS）是败血症等危重疾病的常见并发症，在美国每年影响超过20万例患者。ARDS死亡率超过30%。迄今为止，有效的治疗方法还很少被发现，缺乏进展的一个主要原因是难以准确诊断ARDS，导致难以研究有效的治疗方法。 急性呼吸窘迫综合征的特征是炎症引起的肺水肿，导致严重的呼吸衰竭。然而，其他疾病，如心力衰竭（HF）也可能导致呼吸衰竭和肺水肿，尽管有非常不同的病理生理原因，因此不同的治疗。传统的诊断方法包括临床标准和放射学检查，这些方法已被证明在区分ARDS与其他疾病方面缺乏准确性。 成像的最新进展已经证明，肺部炎症和肺水肿可以用计算机断层扫描/正电子发射断层扫描（PET/CT）扫描通过测量18F-氟脱氧葡萄糖摄取（18F-FDG）和15 O-水活性（H215 O）的摄取来量化。这些方法的组合可能有潜力改善ARDS的诊断，但尚未在人类中进行研究。 本项目将调整PET/CT方法，以提供功能性体内肺成像，目的是区分ARDS所致肺水肿患者和HF所致肺水肿患者。这将使治疗能够针对患者疾病的潜在生物学，并将有助于确保患者 合适的表型被纳入ARDS临床研究。该项目还将利用这些结果开发用于该诊断目的的血浆生物标志物检测。具体而言，将验证可溶性ST 2（sST 2）（一种细胞因子受体，已被研究为免疫耐受的新型生物标志物，并在心肌纤维化和重塑中发挥作用）的水平，以检测肺部炎症，如PET/CT成像所示。该项目的具体目标如下：具体目标1：我们将对危重患者进行PET/CT成像，以比较ARDS与HF中的肺部炎症（18F-FDG）和肺水肿（H215 O），并将这些与单独使用18F-FDG数据的新模型进行比较，以量化炎症和水肿。我们假设PET/CT成像能够根据潜在的肺部炎症和水肿将受试者分为诊断组。具体目标2：我们将测试肺部炎症与新生物标志物sST 2之间的关系。我们假设sST 2的血浆浓度可以用作成像的替代物以检测肺部炎症，并且因此可以根据该过程的存在来实现受试者的诊断分离。