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.

项目总结