Novel Quantitative MRI Techniques for the Assessment of Cardiac Fibrosis without Gadolinium Contrast

项目总结/摘要 评估心脏纤维化的临床金标准是晚期钆增强（LGE）心脏 MRI（CMR），使用反转恢复T1加权序列，在植入后10至20分钟获得。 基于钆的造影剂（GBCA）的施用。尽管LGE CMR在临床上被广泛使用， 在心肌梗死、存活力和心肌病的评估中，存在关于GBCA的几个问题。 这些包括其与肾损害患者的肾源性系统性纤维化（NSF）的相关性; 一些患者对GBCA的过敏反应;最近，人们担心GBCA在大脑中蓄积。 因此，在不施用GBCA的情况下评估心肌纤维化的策略是非常期望的。 定量CMR技术作为识别心肌纤维化的替代方案已经受到关注， GBCA。天然T1映射已受到关注，研究表明其在各种心肌病中的实用性。 其主要缺点是其有限的灵敏度，其中所报道的纤维化引起的T1值的变化， 在一个小范围内。磁化传递（MT）成像是另一种已被研究的技术 通过MT比率（MTR），其是取决于采集参数的非定量度量。 尽管如此，它已经显示出与LGE的有希望的相关性，即使是通过简单的比率来实现， 使用不同的平衡SSFP序列参数采集的两个图像。T1ρ松弛映射，即 基于旋转帧弛豫，在微米到毫秒的尺度上绘制运动状态， 在猪模型中得到组织学证实，以及与体内LGE的相关性。 然而，它在心脏中的应用一直局限于连续波自旋锁制备， 磁场的不均匀性，并限制了它可以评估的大分子运动的范围。 在这个建议中，我们寻求开发新的定量CMR技术，以释放MT的全部潜力 成像和旋转帧松弛评估心肌纤维化。对于MT对比度，我们将扩展到 MTR和量化MT参数，提高灵敏度和重现性。对于旋转框架松弛，我们 将开发改进的量化技术，使用绝热T1 p和高阶弛豫的基础上， 在n阶旋转标架（TRAFFn）中沿Fictionary域的沿着松弛。这些方法将允许探测 大分子运动机制的广泛范围。我们关于MT或旋转标架松弛的想法 已经探索了用于对人类心肌进行成像的成像，但是它们的潜力已经在 其他解剖学该项目的成功完成有可能改变CMR的方式， 用于评估心肌纤维化，消除了GBCA给药的需要。

PROJECT SUMMARY/ABSTRACT The clinical gold standard for the assessment of cardiac fibrosis is late gadolinium enhancement (LGE) cardiac MRI (CMR), which is acquired using an inversion-recovery T1-weighted sequence, 10-to-20 minutes after the administration of a gadolinium-based contrast agent (GBCA). Though LGE CMR is widely used in the clinical assessment of myocardial infarction, viability and cardiomyopathies, there are several concerns about GBCA. These include its association with nephrogenic systemic fibrosis (NSF) in patients with renal impairment; allergic reactions to GBCA in some patients; and recently, concerns related to GBCA accumulation in the brain. Thus, strategies for assessing myocardial fibrosis without administering GBCA are highly desirable. Quantitative CMR techniques have received interest as alternatives for identifying myocardial fibrosis without GBCA. Native T1 mapping has received attention, with studies indicating its utility in various cardiomyopathies. Its main drawback has been its limited sensitivity, where the reported changes in T1 values from fibrosis has been in a small range. Magnetization transfer (MT) imaging is another technique that has been investigated through the MT ratio (MTR), which is a non-quantitative metric that depends on acquisition parameters. Nonetheless, it has shown promising correlation with LGE, even when implemented through a simple ratio of two images acquired with different balanced SSFP sequence parameters. T1ρ relaxation mapping, which is based on rotating frame relaxations, maps motional regimes in the micro-to-millisecond scale and has also shown promise, with histological confirmation in a swine model, as well as correlation with LGE in vivo. However, its use in the heart has been limited to continuous-wave spin-lock preparation, making it susceptible to magnetic field inhomogeneities, and limiting the range of macromolecular motion that it can assess. In this proposal, we seek to develop novel quantitative CMR techniques to unleash the full potential of MT imaging and rotating frame relaxation in assessing myocardial fibrosis. For MT contrast, we will extend beyond MTR and quantify MT parameters, improving sensitivity and reproducibility. For rotating frame relaxations, we will develop improved quantification techniques using adiabatic T1p, and higher order relaxations based on Relaxation Along a Fictitious Field in the rotating frame of rank n (TRAFFn). These methods will allow probing of a wide range of macromolecular motion regimes. Neither of our ideas on MT or rotating frame relaxation imaging have been explored for imaging the human myocardium, but their potential has been highlighted in other anatomies. Successful completion of this project has the potential to transform the way CMR is performed for the assessment of myocardial fibrosis, eliminating the need for GBCA administration.