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: 10201743
• 负责人: Rohan Dharmakumar
• 金额: $ 80.04万
• 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 2021-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10201743
• 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.

项目摘要 缺血性心脏病（IHD）是美国死亡的主要原因。它从狭窄的 冠状动脉（CAD）和/或微血管功能障碍的发育高潮在心肌缺血中 - 心肌的氧气需求远远超过可用供应的条件。 IHD 在美国，每年占三分之一的死亡人数和> 100万次住院。程度和程度 心肌缺血的严重程度已被证明可提供与标准临床相比的增量预后价值 跨IHD患者表现范围的变量。长期建立的（SPECT或PET）和 最近建立的（例如，第一个通过通行MRI）通常用于收集此信息。 尽管具有功能，这些方法仍具有关键局限性 - 它们使患者暴露于电离 辐射或外源性对比剂，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50万名终末期肾脏疾病（ESRD）的患者中。在ESRD患者中，每年 需要缺血测试，因为心血管死亡率的风险比一般大于10倍 人口。因此，对心肌的安全和可靠评估的需求尚未满足和越来越多 所有患者的缺血性，并且在美国的患病率上升的ESRD患者中最紧迫。 血氧基水平依赖性（BOLD）心脏MRI（CMR）是标准临床的潜在替代品 方法因为它不含电离辐射和外源性对比介质。它还具有提供的能力 基于氧气供应受损的测量，对疾病的生理见解，而不是 替代指标（壁运动，心电图变化或对比动力学）。在过去的二十年中，技术 大胆CMR的功能导致了临床测试。但是，可靠性的限制（敏感性，特异性 准确的）仍然是BOLD CMR宽度临床使用的主要障碍。克服 BOLD CMR的可靠性限制，在先前的R01资金（2013年至2017年）中，我们假设重复 使用BOLD MRI（脑FMRI）类似于大脑激活研究的心脏刺激可以改善 大胆CMR的可靠性。随后，我们继续证明（i）动脉的有针对性变化 二氧化碳（PACO2）的部分压力可能是潜在的非侵入性血管活性刺激。和（ii）高分辨率， 当与统计结合使用时，全心CMR在3T处，重复对心脏的重复刺激心脏刺激 框架可以可靠地检测出大型健康动物的大胆信号变化。成功翻译 这种大胆的CMR方法对临床领域的有希望的影响，进一步的进步和验证将是 必需的。该提案旨在继续成功地发展这种大胆的CMR方法 临床可行性，因此它可以实现真正的无创和成本效益的缺血测试 电离辐射，外源对比剂，静脉注射药物甚至针头。那，这个 提案是促进美国大部分IHD患者护理的关键一步。