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

项目摘要/摘要 临床上评估心肌纤维化的金标准是晚期Gd增强(Lge)心脏 磁共振成像(CMR)，使用反转恢复T1加权序列，在10至20分钟后采集 注射一种基于Gd的造影剂(GBCA)。虽然LGE CMR在临床上有广泛的应用 评估心肌梗死、存活能力和心肌病，对GBCA有几点担忧。 这些包括它与肾损伤患者的肾源性系统性纤维化(NSF)的关系； 一些患者对GBCA的过敏反应；最近，与GBCA在大脑中积累有关的担忧。 因此，在不使用GBCA的情况下评估心肌纤维化的策略非常可取。 定量CMR技术作为识别心肌纤维化的替代技术受到了人们的关注 GBCA。自然T1定位已受到关注，研究表明其在各种心肌病中的应用。 它的主要缺点是灵敏度有限，报道的纤维化导致的T1值变化 一直在一个小范围内。磁化转移(MT)成像是另一种已被研究的技术 通过MT比率(MTR)，这是一个依赖于采集参数的非定量指标。 尽管如此，它已经显示出与LGE的良好相关性，即使通过简单的 用不同平衡SSFP序列参数采集的两幅图像。T1ρ松弛映射，这是 基于旋转框架松弛，绘制了从微秒到毫秒尺度的运动状态图，还 在猪模型上的组织学证实，以及在活体内与LGE的相关性，显示了前景。 然而，它在心脏中的使用仅限于连续波自旋锁制剂，使其变得敏感 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。 在这个提议中，我们试图开发新的定量CMR技术来释放MT的全部潜力 影像和旋转框架松弛在评价心肌纤维化中的作用。对于MT对比度，我们将扩展到 MTR和量化MT参数，提高灵敏度和重复性。对于旋转框架放松，我们 将开发改进的量化技术，使用绝热T1p和基于以下条件的更高阶弛豫 在阶为n的旋转标架(TRAFFn)中沿虚场松弛。这些方法将允许探测 广泛的大分子运动机制。我们对MT和旋转框架松弛的看法都不是 成像技术已被探索用于人体心肌成像，但其潜力已在 其他的解剖结构。该项目的成功完成有可能改变CMR的方式 进行心肌纤维化评估，不再需要GBCA治疗。

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.