Novel MRI techniques for imaging cardiac fibrosis to improve clinical practice in patients with renal failure

用于心脏纤维化成像的新型 MRI 技术可改善肾衰竭患者的临床实践

• 批准号: 9116278
• 负责人: MORIEL VANDSBURGER
• 金额: $ 37.63万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9116278
• 关键词: Affect; Age; Agreement; American; Area; Biological Markers; Blood; Cardiac; Cardiovascular Diseases; Cause of Death; Chemicals; Chronic Kidney Failure; Cicatrix; Clinical; Clinical Research; Comorbidity; Contrast Media; Coronary Arteriosclerosis; Defibrillators; Development; Diagnostic; Diffuse; Disease; Edema; Equilibrium; Evaluation; Event; Fibrosis; Frequencies; Funding; Gadolinium; Gold; Health; Heart; Heart Hypertrophy; Heart failure; Hormones; Image; Image Enhancement; Imaging Techniques; Individual; Intraobserver Variability; Kentucky; Kidney Failure; Left ventricular structure; Link; Magnetic Resonance Imaging; Maps; Measurement; Measures; Methods; Monitor; Morbidity - disease rate; Motion; Myocardial Infarction; Non-Insulin-Dependent Diabetes Mellitus; PTH gene; Pathway interactions; Patients; Recruitment Activity; Relaxation; Renal function; Risk; Sensitivity and Specificity; Serum; Serum Markers; Signal Transduction; Slice; Structure; Testing; Therapeutic Intervention; Time; Tissues; Treatment Efficacy; Universities; Ventricular; Ventricular septum; Weight; Work; base; clinical practice; coronary fibrosis; density; design; extracellular; fibroblast growth factor 23; follow-up; gadolinium oxide; imaging modality; improved; mortality; non-invasive monitor; novel; novel therapeutics; peptide hormone; potential biomarker; standard of care; targeted treatment; therapeutic target

 DESCRIPTION (provided by applicant): Cardiovascular disease affects millions of Americans, with heart failure as a common endpoint. The development of cardiac fibrosis occurs early in cardiovascular disease, promotes heart failure, and provides arrhythmogenic substrate leading to increased frequency of adverse cardiac events and higher mortality. Cardiac magnetic resonance imaging (CMR) is routinely used to measure changes in ventricular structure and function with balanced steady state free precession (bSSFP) imaging. With intravenously delivered gadolinium contrast agents, late gadolinium enhancement (LGE) CMR is the clinical standard for identifying focal fibrosis and quantifying fibrotic burden, and when combined with mapping of T1-relaxation times can quantify diffuse fibrosis through measurement of increased extracellular volume fraction (ECV). In individuals with chronic kidney disease a strong link exists between cardiac fibrosis and adverse cardiac events, however LGE is contraindicated due to the danger of nephrogenic systemic fibrosis. Emerging studies suggest that specific circulating hormones and peptides may be biomarkers of cardiac fibrosis and potential therapeutic targets in chronic kidney disease. However, the inability to measure fibrosis in such patients represents a major gap to the discovery of potential biomarkers, and leaves most studies measuring cardiac hypertrophy as an insensitive surrogate of fibrosis. This proposal seeks to develop a gadolinium free MRI method to measure fibrotic burden via reduced magnetization transfer (MT) in areas fibrotic tissue. This method, termed 2-point bSSFP, exploits an endogenous contrast mechanism in bSSFP imaging to identify fibrotic and edematous tissue. The proposed aims will validate 2-point bSSFP against standard of care LGE and measurement of diffuse fibrosis through ECV mapping. Finally, comparison of fibrotic burden (measured with 2-point bSSFP) to blood chemical workup in CKD patients will examine the correlation between fibrosis and potential biomarkes. The successful completion of these aims will enable rapid and gadolinium free imaging of cardiac fibrosis over the entire heart. Further, correlation of cardiac fibrosis with blood serum biomarkers in chronic kidney disease patients can help identify potential therapeutic targets to halt or reverse fibrosis, the efficacy f which can be serially monitored using 2-point bSSFP.

 描述（由申请人提供）：心血管疾病影响着数百万美国人，心力衰竭是常见的终点。心脏纤维化的发展发生在心血管疾病的早期，促进心力衰竭，并提供致炎底物，导致不良心脏事件的频率增加和死亡率升高。心脏磁共振成像（CMR）通常用于通过平衡稳态自由进动（bSSFP）成像测量心室结构和功能的变化。使用静脉内输送的钆造影剂，晚期钆增强（LGE）CMR是识别局灶性纤维化和量化纤维化负荷的临床标准，当与T1弛豫时间标测结合时，可以通过测量细胞外容积分数（ECV）增加来量化弥漫性纤维化。在患有慢性肾脏疾病的个体中，心脏纤维化和不良心脏事件之间存在强烈的联系，然而，由于肾源性系统性纤维化的危险，LGE是禁忌的。新的研究表明，特定的循环激素和肽可能是心脏纤维化的生物标志物和慢性肾脏疾病的潜在治疗靶点。然而，无法测量此类患者的纤维化是发现潜在生物标志物的主要差距，并且使大多数测量心脏肥大的研究成为纤维化的不敏感替代品。该提案旨在开发一种无钆MRI方法，以通过减少纤维化组织区域中的磁化传递（MT）来测量纤维化负荷。该方法称为2点bSSFP，利用bSSFP成像中的内源性对比机制来识别纤维化和水肿组织。提出的目的将根据标准治疗LGE和通过ECV标测测量弥漫性纤维化来验证2点bSSFP。最后，将CKD患者的纤维化负荷（用2点bSSFP测量）与血液化学检查进行比较，将检查纤维化与潜在的纤维化之间的相关性。这些目标的成功完成将使整个心脏的心脏纤维化的快速和无钆成像成为可能。此外，慢性肾病患者中心脏纤维化与血清生物标志物的相关性可以帮助鉴定潜在的治疗靶标以停止或逆转纤维化，其功效可以使用2点bSSFP连续监测。