Assessment of Myocardial Fibrosis in Mice Using a T2*-Weighted 3D Radial Magnetic Resonance Imaging Sequence

BackgroundMyocardial fibrosis is a common hallmark of many diseases of the heart. Late gadolinium enhanced MRI is a powerful tool to image replacement fibrosis after myocardial infarction (MI). Interstitial fibrosis can be assessed indirectly from an extracellular volume fraction measurement using contrast-enhanced T1 mapping. Detection of short T2* species resulting from fibrotic tissue may provide an attractive non-contrast-enhanced alternative to directly visualize the presence of both replacement and interstitial fibrosis.ObjectiveTo goal of this paper was to explore the use of a T2*-weighted radial sequence for the visualization of fibrosis in mouse heart.MethodsC57BL/6 mice were studied with MI (n = 20, replacement fibrosis), transverse aortic constriction (TAC) (n = 18, diffuse fibrosis), and as control (n = 10). 3D center-out radial T2*-weighted images with varying TE were acquired in vivo and ex vivo (TE = 21 μs-4 ms). Ex vivo T2*-weighted signal decay with TE was analyzed using a 3-component model. Subtraction of short- and long-TE images was used to highlight fibrotic tissue with short T2*. The presence of fibrosis was validated using histology and correlated to MRI findings.ResultsDetailed ex vivo T2*-weighted signal analysis revealed a fast (T2*fast), slow (T2*slow) and lipid (T2*lipid) pool. T2*fast remained essentially constant. Infarct T2*slow decreased significantly, while a moderate decrease was observed in remote tissue in post-MI hearts and in TAC hearts. T2*slow correlated with the presence of diffuse fibrosis in TAC hearts (r = 0.82, P = 0.01). Ex vivo and in vivo subtraction images depicted a positive contrast in the infarct co-localizing with the scar. Infarct volumes from histology and subtraction images linearly correlated (r = 0.94, Pin vivo post-MI and TAC hearts revealed significant T2* shortening due to fibrosis, in agreement with the ex vivo results. However, in vivo contrast on subtraction images was rather poor, hampering a straightforward visual assessment of the spatial distribution of the fibrotic tissue.

背景：心肌纤维化(Myocardial fibrosis)是多种心脏疾病的常见标志性病理特征。晚期钆增强MRI(Late gadolinium enhanced MRI)是用于成像心肌梗死(Myocardial infarction, MI)后替代性纤维化的有效影像学手段。间质性纤维化可通过对比增强T1映射(T1 mapping)获取细胞外容积分数(extracellular volume fraction)实现间接评估。针对纤维化组织产生的短T2*物质进行检测，有望成为无需对比剂即可直接可视化替代性与间质性纤维化的理想替代方案。
目的：本研究旨在探索T2*加权径向序列(T2*-weighted radial sequence)在小鼠心脏纤维化可视化中的应用价值。
方法：本研究纳入C57BL/6小鼠，分为三组：心肌梗死组（n=20，对应替代性纤维化）、主动脉缩窄组(transverse aortic constriction, TAC，n=18，对应弥漫性纤维化)以及对照组（n=10）。分别在活体与离体状态下采集不同回波时间(TE)的3D中心向外径向T2*加权图像（TE范围为21 μs~4 ms）。采用三组分模型分析离体状态下T2*加权信号随TE的衰减规律。通过短TE与长TE图像相减，可凸显携带短T2*特征的纤维化组织。采用组织病理学方法验证纤维化的存在，并与MRI成像结果进行相关性分析。
结果：详细的离体T2*加权信号分析显示，存在快弛豫（T2*fast）、慢弛豫（T2*slow）以及脂质（T2*lipid）三个信号组分池。T2*fast基本保持稳定。梗死区域的T2*slow显著降低，而心肌梗死后小鼠的远端心肌组织以及主动脉缩窄小鼠的心肌组织均出现中度降低。在主动脉缩窄小鼠中，T2*slow与弥漫性纤维化的存在显著相关（r=0.82，P=0.01）。离体与活体的相减图像均显示，梗死区域与瘢痕组织共定位且呈现阳性对比。组织病理学测量的梗死体积与相减图像得到的梗死体积呈线性相关（r=0.94，原文此处P值表述不完整）。活体心肌梗死与主动脉缩窄小鼠的心肌组织均因纤维化出现显著的T2*缩短，与离体实验结果一致。然而，活体相减图像的对比度较差，难以直接可视化评估纤维化组织的空间分布。