Accurate, Needle-Free, MRI-based Detection of Ischemic Heart Disease without Contrast Agents

无需造影剂即可通过 MRI 进行准确、无针、基于 MRI 的缺血性心脏病检测

• 批准号: 9981378
• 负责人: Rohan Dharmakumar
• 金额: $ 81.59万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-24 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9981378
• 关键词: Address; Adenosine; Affect; Algorithmic Analysis; American; Ammonia; Angioplasty; Animal Model; Animals; Brain; Breathing; Carbon Dioxide; Cardiac; Cardiovascular system; Caring; Cause of Death; Cessation of life; Clinical; Contrast Media; Coronary Artery Bypass; Coronary Stenosis; Coronary artery; Data; Detection; Development; Disease; Disease Surveillance; Early Intervention; Electrocardiogram; End stage renal failure; Event; Exercise; Face; Functional Magnetic Resonance Imaging; Funding; General Population; Gold; Heart; Hospitalization; Hypercapnia; Image; Impairment; Injectable; Intravenous; Ionizing radiation; Ions; Ischemia; Kinetics; Magnetic Resonance Imaging; Maps; Measurement; Medical; Methods; Microvascular Dysfunction; Motion; Myocardial; Myocardial Ischemia; Myocardium; Needles; Operative Surgical Procedures; Oxygen; Partial Pressure; Patients; Perfusion; Pharmacology; Physiological; Positron-Emission Tomography; Press Releases; Prevalence; Publishing; Radial; Radiation; Reporting; Resolution; Risk; Safety; Science; Sensitivity and Specificity; Severities; Signal Transduction; Statistical Algorithm; Stimulus; Stress; Stress Tests; Testing; Thallium Myocardial Perfusion Imaging Stress Test; Time; Translating; Translations; United States; United States National Institutes of Health; Validation; base; blood oxygen level dependent; cardiovascular risk factor; clinically relevant; clinically significant; clinically translatable; compliance behavior; computer framework; coronary vasodilator; cost effective; high risk; image processing; improved; insight; mortality; prevent; prognostic value; prospective; reconstruction; research clinical testing; single photon emission computed tomography; targeted imaging

PROJECT SUMMARY Ischemic heart disease (IHD) is the leading cause of death in the United States. It emanates from narrowing of coronary arteries (CAD) and/or development of microvascular dysfunction culminating in myocardial ischemia – a condition where the oxygen demand of the myocardium is far in excess of the available supply. IHD accounts for more than 1 in 3 deaths and >1 million hospitalizations each year in the US. The extent and severity of myocardial ischemia has been shown to provide incremental prognostic value over standard clinical variables across the spectrum of presentation of patients with IHD. Long-established (SPECT or PET) and more recently established (e.g., first pass-perfusion MRI) methods are routinely used to gather this information. In spite of their capabilities, these methods have key limitations – they expose the patients to either ionizing radiation or exogenous contrast agents, which carry risks to the patients. This is particularly a critical problem in at least half a million patients with end-stage renal disease (ESRD) in the US. In ESRD patients, annual ischemia testing is needed since the risk of cardiovascular mortality is > 10-fold greater than in the general population. Hence there is an unmet and growing need for safe and reliable assessment of myocardial ischemia in all patients, and is most pressing in ESRD patients, whose prevalence in the US is on the rise. Blood-Oxygen-Level-Dependent (BOLD) Cardiac MRI (CMR) is a potential alternative to standard clinical methods since it is free of ionizing radiation and exogenous contrast media. It also has the capability to provide physiological insight into the disease based on measurements of impaired oxygen supply, and not from surrogate metrics (wall motion, ECG changes, or contrast kinetics). Over the past two decades, the technical capabilities of BOLD CMR have led to clinical testing. However, limitations in reliability (sensitivity, specificity and accuracy) remain a major impediment for widespread clinical use of BOLD CMR. To overcome the reliability limitations of BOLD CMR, in a previous R01 funding (2013 to 2017), we hypothesized that repeat stimulations of the heart, analogous to brain activation studies using BOLD MRI (brain fMRI), could improve the reliability of BOLD CMR. Subsequently, we went onto demonstrate that (i) a targeted change in arterial partial pressure of CO2 (PaCO2) can be a potent non-invasive vasoactive stimulus; and a (ii) high-resolution, whole heart BOLD CMR at 3T with repeat PaCO2 stimulation of the heart, when combined with a statistical framework, can reliably detect BOLD signal changes in large, healthy, animals. To successfully translate the promising impact of this BOLD CMR approach into the clinical arena, further advances and validation will be required. This proposal aims to continue the successful advancement of this BOLD CMR approach towards clinical feasibility so that it can enable a truly noninvasive and cost-effective ischemia testing that is free of ionizing radiation, exogenous contrast agents, intravenous pharmacological agents or even needles. Thus, this proposal is a critical step towards advancing the care of a large segment of IHD patients in the US.

项目概要 缺血性心脏病（IHD）是美国的主要原因。它源自于缩小 冠状动脉（CAD）和/或微血管功能障碍的发展最终导致心肌缺血 – 心肌的需氧量远远超过可用供应的情况。内出血 在美国，每年有超过三分之一的人死亡，超过 100 万人住院。范围和 与标准临床相比，心肌缺血的严重程度已被证明可提供增量的预后价值 IHD 患者表现范围内的变量。历史悠久（SPECT 或 PET）和 最近建立的（例如，首次灌注 MRI）方法通常用于收集这些信息。 尽管有这些能力，这些方法还是有关键的局限性——它们使患者暴露在电离环境中 放射线或外源性造影剂会给患者带来风险。这是一个特别关键的问题 在美国，至少有 50 万终末期肾病 (ESRD) 患者。在 ESRD 患者中，每年 需要进行缺血测试，因为心血管死亡的风险比一般情况高 10 倍以上 人口。因此，对安全可靠的心肌评估的需求尚未得到满足且不断增长。 所有患者都会出现缺血，其中 ESRD 患者最为紧迫，其患病率在美国呈上升趋势。 血氧水平依赖性 (BOLD) 心脏 MRI (CMR) 是标准临床的潜在替代方案 方法，因为它不含电离辐射和外源性造影剂。它还有能力提​​供 对疾病的生理洞察是基于对氧气供应受损的测量，而不是通过 替代指标（室壁运动、心电图变化或对比动力学）。近二十年来，技术 BOLD CMR 的功能已进入临床测试。然而，可靠性的局限性（敏感性、特异性 和准确性）仍然是 BOLD CMR 广泛临床应用的主要障碍。为了克服 由于 BOLD CMR 的可靠性局限性，在之前的 R01 资助（2013 年至 2017 年）中，我们假设重复 类似于使用 BOLD MRI（脑 fMRI）进行的大脑激活研究，刺激心脏可以改善 BOLD CMR 的可靠性。随后，我们继续证明（i）动脉血流有针对性的改变 CO2 分压 (PaCO2) 可以是一种有效的非侵入性血管活性刺激；和（ii）高分辨率， 3T 时的全心 BOLD CMR，重复 PaCO2 刺激心脏，并结合统计数据 框架，可以可靠地检测大型健康动物的大胆信号变化。要想成功翻译 这种大胆的 CMR 方法对临床领域的有希望的影响，进一步的进展和验证将是 必需的。该提案旨在继续成功推进这种大胆的 CMR 方法，以实现 临床可行性，使其能够实现真正的无创且具有成本效益的缺血测试，并且无需 电离辐射、外源性造影剂、静脉注射药物甚至针头。因此，这个 该提案是推进美国大部分 IHD 患者护理的关键一步。