Ferumoxytol-Enhanced Cardiac MRI for Ischemic Heart Disease

项目摘要 缺血性心脏病(IHD)和慢性肾脏病(CKD)是常见的同床者，但IHD作为 这一人群的主要死因是诊断不足。尽管慢性肾脏病和肾后病变的患者 移植有最高的IHD风险，但对缺血负荷的可靠估计仍然是一个挑战。准确 缺血负荷的量化对临床治疗至关重要，因为侵入性干预可能 使肾功能恶化。在慢性肾脏病患者中，心血管事件发生率随着年龄的增加而显著增加 CKD分期。对比剂增强的心脏磁共振成像(MRI)因其缺失而备受关注 电离辐射及其提供高空间分辨率图像的固有能力。但灌注心脏核磁共振 对于缺血的定义依赖于第一次注射Gd，这存在固有的技术缺陷。 晚期Gd对活性的增强也依赖于Gd对比动力学。两者都较少 适合慢性肾脏病患者使用。在肾功能衰竭患者中，与Gd相关的肾源性系统 纤维化可能是致命的，最近，肾功能支持正常的患者的尸检结果 Gd在某些器官和组织中积聚。我们的目标是测试和验证一种无肾毒性的， 稳态心脏MRI策略，克服了Gd增强心脏MRI的许多缺点 检测可诱导的缺血和存活情况。我们以我们的集体经验为基础，使用阿魏酸甲酯增强剂 核磁共振和缺血性心脏病。因为阿魏酸甘油酯在肾损害患者中耐受性良好 有广泛的临床批准用于静脉治疗缺铁性贫血，如果被证明成功，我们的 稳态应激心脏MRI方法也可能在其他方面有应用价值。

Project Summary Ischemic heart disease (IHD) and chronic kidney disease (CKD) are frequent bedfellows, but IHD as the leading cause of death in this population is under-diagnosed. Although patients with CKD and post-renal transplant have the highest risk for IHD, reliable estimation of ischemic burden remains a challenge. Accurate quantification of ischemic burden is crucial for clinical management because invasive interventions may worsen kidney function. In patients with CKD, cardiovascular event rates increase significantly with increasing stage of CKD. Contrast-enhanced cardiac magnetic resonance imaging (MRI) is attractive due to the absence of ionizing radiation and its inherent ability to provide high spatial resolution images. But perfusion cardiac MRI for defining ischemia relies on the first-pass bolus of gadolinium, which has intrinsic technical shortcomings. Late gadolinium enhancement for viability is also dependent on gadolinium contrast kinetics. Both are less suitable for patients with CKD. In patients with renal failure, gadolinium-associated nephrogenic systemic fibrosis may be fatal and more recently, autopsy results in patients with normal kidney function support gadolinium accumulation in certain organs and tissues. Our goal is to test and validate a non-nephrotoxic, steady-state cardiac MRI strategy that overcomes many drawbacks of gadolinium-enhanced cardiac MRI to detect inducible ischemia and viability. We build upon our collective experience with ferumoxytol-enhanced MRI and ischemic heart disease. Because ferumoxytol is well-tolerated in patients with renal impairment and has broad clinical approval for intravenous treatment of iron deficiency anemia, if proven successful, our steady state stress cardiac MRI approach may also be valuable for other applications.