Development of a Novel Diagnostic Test for Pulmonary Embolism Based on Artificial Intelligence and Spectral Analysis of Blood

基于人工智能和血液光谱分析的新型肺栓塞诊断测试的开发

• 批准号: 10081921
• 负责人: Jeremy Ford Huckins
• 金额: $ 29.97万
• 依托单位: BIOCOGNIV INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10081921
• 关键词: Accident and Emergency department; Acute; Address; Adult; Affect; Age; Angiography; Area; Artificial Intelligence; Autopsy; Biological Assay; Biological Markers; Blood; Blood Proteins; Blood Tests; Blood coagulation; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Chest Pain; Creatine Kinase MB Isoenzyme; Data; Data Set; Decision Making; Deep Vein Thrombosis; Development; Diagnosis; Diagnostic; Diagnostic tests; Dyspnea; Emergency Department patient; Evaluation; Fibrin fragment D; Goals; Gold; Hospitals; Image; Immunoassay; Intravenous; Ionizing radiation; Life; Lower Extremity; Lung; Machine Learning; Measures; Medical center; Methodology; Methods; Modeling; Multicenter Studies; Myocardial Infarction; Myoglobin; Patient Care; Patient Triage; Patients; Performance; Perfusion; Phase; Physicians; Plasma; Population; Predictive Value; Process; Pulmonary Embolism; ROC Curve; Radiation; Risk; Sampling; Scanning; Seizures; Sensitivity and Specificity; Shortness of Breath; Specificity; Standardization; Symptoms; Syncope; Test Result; Testing; Training; Travel; Troponin I; Universities; Validation; Venous system; Vermont; X-Ray Computed Tomography; base; clinical care; cost; cost effective; data modeling; improved; inflammatory marker; instrumentation; molecular marker; novel; novel diagnostics; patient safety; performance tests; point of care; standard of care; targeted biomarker; ventilation

Pulmonary Embolism (PE) is a potentially life-threatening condition that affects adults of all ages yet can present with a myriad of symptoms, ranging from chest pain to shortness of breath, syncope, or seizure. Currently, physicians can assess for this condition with a blood test (D-dimer) which has high sensitivity but very poor specificity, thus resulting in a larger number of false positives. Alternatively, or in the case of a positive D-dimer, computed tomography pulmonary angiography (CTPA) or ventilation-perfusion (VQ) scan can be used, both of which are expensive and expose the patient to a significant amount of ionizing radiation. To develop a more specific blood test for PE, Biocogniv will apply state-of-the-art artificial intelligence (AI) to aggregate analysis of existing blood biomarkers measured on two commercially available multiplex immunoassay platforms, one of which is currently used in hospital labs. A sufficiently accurate, rapid and cost-effective test could be broadly applied (i.e., like troponin-I for myocardial infarction) to reduce overuse of CT, simplify ED decision making, and reduce the number of deaths from unrecognized PE. In this proposed Phase I single center study, Biocogniv will collaborate with the University of Vermont Medical Center (UVMMC) to demonstrate proof-of-concept for diagnosing PE in emergency department (ED) patients for whom there is sufficient concern for PE to warrant a D-dimer test as part of routine clinical care. Specific Aim I is to collect blood from 225 emergency department (ED) patients at UVMMC who were suspected of having PE (including 75 patients that are confirmed to have PE by CTPA), and analyze the blood plasma with quantitative immunoassays to create training and validation datasets for AI analysis. Immunoassays will be comprised of a set of 6 rapid FDA-cleared chemiluminescent immunoassays performed in parallel, and a 20-plex bead-based immunoassay panel targeting known cardiovascular and inflammatory markers associated with acute PE. Specific Aim II is to develop AI data models for two pretest populations—all D-dimer tested patients and just D-dimer positive patients—for bead-based and point-of-care immunoassay datasets (analyzed separately), then evaluate the performance of each data model on a subset of blood plasma data withheld for validation. As part of the evaluation of AI data model performance, the potential impact of study size on data model accuracy will be simulated by plotting specificity as a function of training sample number to show that adding more samples can improve test results. The performance of each approach (i.e., AI methodology applied to a given immunoassay panel for a given pretest population) will be compared and used to plan a Phase II multi-center study and to identify and attract a suitable instrumentation partner. Biocogniv’s end goal is to develop a rapid, highly specific and sensitive FDA cleared test for PE that will become the standard of care for initial diagnosis and triage of patients with potential pulmonary embolism, disrupting the $2B/year D-Dimer market and improving ED patient care.

肺栓塞 (PE) 是一种可能危及生命的疾病，影响所有年龄段的成年人，但 出现多种症状，从胸痛到气短、晕厥或癫痫发作。 目前，医生可以通过血液检测（D-二聚体）来评估这种情况，该检测具有很高的敏感性，但 特异性非常差，从而导致大量假阳性。 D-二聚体阳性、计算机断层扫描肺血管造影 (CTPA) 或通气灌注 (VQ) 扫描可以 两种方法都很昂贵并且使患者暴露于大量的电离辐射下。 Biocogniv 将应用最先进的人工智能 (AI) 来开发针对 PE 的更具体的血液测试 对两种市售多重检测仪上测量的现有血液生物标志物进行聚合分析 免疫分析平台，其中之一目前在医院实验室中使用，足够准确、快速和可靠。 可以广泛应用具有成本效益的测试（即，如肌钙蛋白-I 用于心肌梗塞），以减少过度使用 CT，简化急诊室的决策，并减少因未识别的肺栓塞而导致的死亡人数。 在这项拟议的第一阶段单中心研究中，Biocogniv 将与佛蒙特大学医学院合作 中心 (UVMMC) 将展示诊断急诊科 (ED) 患者 PE 的概念验证 对于那些对 PE 有足够关注的人，需要将 D-二聚体测试作为常规临床护理的一部分。 目标 I 是从 UVMMC 225 名疑似患有以下疾病的急诊科 (ED) 患者采集血液 患有PE（其中75名经CTPA证实患有PE的患者），并用 定量免疫分析将为人工智能分析创建训练和验证数据集。 包括一组 6 项经 FDA 批准的并行进行的快速化学发光免疫测定，以及 针对已知心血管和炎症相关标志物的 20 重微珠免疫测定组合 具体目标 II 是为两个预测试人群（所有 D-二聚体进行测试）开发 AI 数据模型。 患者和 D-二聚体阳性患者 - 用于基于微珠和护理点免疫分析数据集 （单独分析），然后评估每个数据模型在血浆数据子集上的性能 作为人工智能数据模型性能评估的一部分，研究的潜在影响。 将通过绘制特异性作为训练样本数的函数来模拟数据模型准确性的大小 表明添加更多样本可以提高每种方法（即人工智能）的性能。 将比较和使用应用于给定预测试群体的给定免疫测定组的方法 计划第二阶段多中心研究并确定和吸引合适的仪器合作伙伴。 Biocogniv 的最终目标是开发一种快速、高度特异性和灵敏的 FDA 批准的 PE 测试，该测试将 成为潜在肺栓塞患者初步诊断和分诊的护理标准， 扰乱每年 20 亿美元的 D-二聚体市场并改善 ED 患者护理。