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）是常见的同床异梦，但IHD作为 这一人群的主要死因是诊断不足。尽管CKD和肾后性肾病患者 移植后缺血性心脏病的风险最高，但可靠估计缺血负荷仍然是一个挑战。准确 缺血负荷的定量对于临床管理是至关重要的，因为侵入性干预可能 肾功能恶化。在CKD患者中，心血管事件发生率随着 CKD阶段。对比增强心脏磁共振成像（MRI）是有吸引力的，由于缺乏 电离辐射及其提供高空间分辨率图像的固有能力。但是心脏灌注磁共振成像 用于定义缺血依赖于钆的首过推注，其具有固有的技术缺陷。 晚期钆增强的活力也依赖于钆对比动力学。两者都比较少 适合CKD患者。在肾衰竭患者中，钆相关性肾源性系统性 纤维化可能是致命的，最近，尸检结果显示，患者的肾功能正常 某些器官和组织中的钆积累。我们的目标是测试和验证一种无肾毒性， 稳态心脏MRI策略克服了钆增强心脏MRI的许多缺点， 检测可诱导的缺血和活力。我们建立在我们的集体经验与ferumoxytol增强 MRI与缺血性心脏病由于ferumoxytol在肾损害患者中耐受性良好， 已经广泛的临床批准静脉治疗缺铁性贫血，如果证明成功，我们的 稳态应力心脏MRI方法对于其它应用也是有价值。

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.