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

 描述(申请人提供)：心血管疾病影响数以百万计的美国人，心力衰竭是共同的终点。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，并提供致心律失常的底物，导致不良心脏事件的频率增加和更高的死亡率。心脏磁共振成像(CMR)通常用于通过平衡稳态自由进动(BSSFP)成像来测量心脏结构和功能的变化。在静脉注射造影剂的情况下，晚期Gd增强(LGE)CMR是确定局灶性纤维化和量化纤维化负担的临床标准，当与T1松弛时间图相结合时，可以通过测量细胞外体积分数(ECV)来定量弥漫性纤维化。在慢性肾脏疾病患者中，心脏纤维化和不良心脏事件之间存在很强的联系，但由于存在肾源性全身纤维化的危险，LGE是禁忌。新的研究表明，特定的循环激素和多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，无法测量这类患者的纤维化是发现潜在生物标志物的一个重大差距，并使大多数测量心肌肥厚的研究成为纤维化的不敏感替代品。这项建议寻求开发一种不含Gd的MRI方法，通过减少纤维化组织中的磁化转移(MT)来测量纤维化负担。这种方法被称为两点bSSFP，利用bSSFP成像中的内源性对比机制来识别纤维化和水肿性组织。建议的AIMS将根据护理标准、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(用两点bSSFP测量)与血化学检查进行比较，将检验纤维化与潜在生物标志物之间的相关性。这些目标的成功完成将使整个心脏的心脏纤维化快速和无Gd成像成为可能。此外，慢性肾脏疾病患者的心脏纤维化与血清生物标志物的相关性有助于确定阻止或逆转纤维化的潜在治疗靶点，其疗效可以使用两点bSSFP进行连续监测。

 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.