Wu Yijen L, Ye Qing, Sato Kazuya, Foley Lesley M, Hitchens T Kevin, Ho Chien
Pittsburgh NMR Center for Biomedical Research and the Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
JACC Cardiovasc Imaging. 2009 Jun;2(6):731-41. doi: 10.1016/j.jcmg.2009.01.013.
We sought to use cardiac magnetic resonance (CMR) to establish sensitive and reliable indexes for noninvasive detection of acute cardiac allograft rejection.
Appropriate surveillance for acute allograft rejection is vitally important for graft survival. The current gold standard for diagnosing and staging rejection after organ transplantation is endomyocardial biopsy, which is not only invasive but also prone to sampling errors. The motivation of this study is to establish a CMR-based alternative that is noninvasive and sensitive for early detection of allograft rejection before irreversible damage occurs.
We employed a noninvasive 2-pronged approach to detect acute cardiac allograft rejection using a rodent working heart and lung transplantation model. We used CMR to detect immune-cell infiltration at sites of rejection by monitoring the accumulation of dextran-coated ultra-small superparamagnetic-iron-oxide-labeled immune cells (in particular macrophages) in vivo. Simultaneously, we used CMR tagging and strain analysis to detect regional myocardial function loss resulting from acute rejection.
Immune cells infiltration, mainly macrophages and monocytes, could be identified with CMR by in vivo labeling with ultra-small superparamagnetic-iron-oxide. Our data show that immune-cell infiltration in cardiac allograft rejection was highly heterogeneous. Thus, it is not surprising to find inconsistencies between rejection and endomyocardial biopsy results because of the limited number and small samples available. Tagged CMR and strain analysis showed that, as with immune-cell infiltration, ventricular functional loss was also heterogeneous. Although changes in global systolic function were generally not observed until the later stages of rejection, our data revealed that a functional index derived from local strain analysis correlated well with rejection grades, which may be a more sensitive parameter for detecting early rejection.
CMR is noninvasive and provides a 3-dimensional, whole-heart perspective of the rejection status, potentially allowing more reliable detection of acute allograft rejection.
我们试图利用心脏磁共振成像（CMR）建立用于无创检测急性心脏移植排斥反应的敏感且可靠的指标。
对急性移植排斥反应进行适当监测对于移植物存活至关重要。目前器官移植后排斥反应诊断和分期的金标准是心内膜心肌活检，它不仅具有侵入性，而且容易出现抽样误差。本研究的目的是建立一种基于CMR的替代方法，该方法无创且对在不可逆损伤发生之前早期检测移植排斥反应敏感。
我们采用一种无创的双管齐下方法，利用啮齿动物工作心肺移植模型检测急性心脏移植排斥反应。我们使用CMR通过监测体内葡聚糖包被的超小超顺磁性氧化铁标记的免疫细胞（特别是巨噬细胞）的积累来检测排斥部位的免疫细胞浸润。同时，我们使用CMR标记和应变分析来检测急性排斥反应导致的局部心肌功能丧失。
通过超小超顺磁性氧化铁体内标记，CMR可识别免疫细胞浸润，主要是巨噬细胞和单核细胞。我们的数据表明，心脏移植排斥反应中的免疫细胞浸润高度异质性。因此，由于可用样本数量有限且样本较小，排斥反应与心内膜心肌活检结果之间存在不一致并不奇怪。标记的CMR和应变分析表明，与免疫细胞浸润一样，心室功能丧失也是异质性的。虽然直到排斥反应后期才普遍观察到整体收缩功能的变化，但我们的数据显示源自局部应变分析的功能指标与排斥反应分级密切相关，这可能是检测早期排斥反应更敏感的参数。
CMR是无创的，可提供排斥反应状态的三维全心脏视角，有可能更可靠地检测急性移植排斥反应。
