British Heart Foundation Centre of Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.
Contrast Media Mol Imaging. 2018 Oct 25;2018:9641527. doi: 10.1155/2018/9641527. eCollection 2018.
Manganese-enhanced MRI (MEMRI) has the potential to identify viable myocardium and quantify calcium influx and handling. Two distinct manganese contrast media have been developed for clinical application, mangafodipir and EVP1001-1, employing different strategies to mitigate against adverse effects resulting from calcium-channel agonism. Mangafodipir delivers manganese ions as a chelate, and EVP1001-1 coadministers calcium gluconate. Using myocardial T mapping, we aimed to explore chelated and nonchelated manganese contrast agents, their mechanism of myocardial uptake, and their application to infarcted hearts.
T mapping was performed in healthy adult male Sprague-Dawley rats using a 7T MRI scanner before and after nonchelated (EVP1001-1 or MnCl (22 mol/kg)) or chelated (mangafodipir (22-44 mol/kg)) manganese-based contrast media in the presence of calcium channel blockade (diltiazem (100-200 mol/kg/min)) or sodium chloride (0.9%). A second cohort of rats underwent surgery to induce anterior myocardial infarction by permanent coronary artery ligation or sham surgery. Infarcted rats were imaged with standard gadolinium delayed enhancement MRI (DEMRI) with inversion recovery techniques (DEMRI inversion recovery) as well as DEMRI T mapping. A subsequent MEMRI scan was performed 48 h later using either nonchelated or chelated manganese and T mapping. Finally, animals were culled at 12 weeks, and infarct size was quantified histologically with Masson's trichrome (MTC).
Both manganese agents induced concentration-dependent shortening of myocardial T values. This was greatest with nonchelated manganese, and could be inhibited by 30-43% with calcium-channel blockade. Manganese imaging successfully delineated the area of myocardial infarction. Indeed, irrespective of the manganese agent, there was good agreement between infarct size on MEMRI T mapping and histology (bias 1.4%, 95% CI -14.8 to 17.1 >0.05). In contrast, DEMRI inversion recovery overestimated infarct size (bias 11.4%, 95% CI -9.1 to 31.8 =0.002), as did DEMRI T mapping (bias 8.2%, 95% CI -10.7 to 27.2 =0.008). Increased manganese uptake was also observed in the remote myocardium, with remote myocardial ∆T inversely correlating with left ventricular ejection fraction after myocardial infarction (=-0.61, =0.022).
MEMRI causes concentration and calcium channel-dependent myocardial T shortening. MEMRI with T mapping provides an accurate assessment of infarct size and can also identify changes in calcium handling in the remote myocardium. This technique has potential applications for the assessment of myocardial viability, remodelling, and regeneration.
锰增强磁共振成像（MEMRI）具有识别存活心肌和量化钙流入和处理的潜力。已经开发出两种用于临床应用的不同锰对比剂，即锰螯合物和 EVP1001-1，它们采用不同的策略来减轻钙通道激动引起的不良反应。锰螯合物将锰离子作为螯合物输送，而 EVP1001-1 则共同给予葡萄糖酸钙。通过心肌 T 映射，我们旨在探索螯合和非螯合锰对比剂、它们的心肌摄取机制及其在梗死心脏中的应用。
在存在钙通道阻断剂（地尔硫卓（100-200 摩尔/千克/分钟）或氯化钠（0.9%））的情况下，使用 7T MRI 扫描仪在健康成年雄性 Sprague-Dawley 大鼠体内进行非螯合（EVP1001-1 或 MnCl2（22 摩尔/千克））或螯合（mangafodipir（22-44 摩尔/千克））锰基对比剂之前和之后，进行 T 映射。第二组大鼠接受手术通过永久性冠状动脉结扎或假手术诱导前壁心肌梗死。使用标准钆延迟增强磁共振成像（DEMRI）反转恢复技术（DEMRI 反转恢复）以及 DEMRI T 映射对梗死大鼠进行成像。48 小时后，使用非螯合或螯合锰进行后续 MEMRI 扫描并进行 T 映射。最后，动物在 12 周时被处死，并用 Masson 三色（MTC）对梗死面积进行组织学量化。
两种锰剂均诱导心肌 T 值的浓度依赖性缩短。非螯合锰的作用最大，钙通道阻断可抑制 30-43%。锰成像成功描绘了心肌梗死的区域。事实上，无论使用哪种锰剂，MEMRI T 映射和组织学上的梗死面积之间都有很好的一致性（偏差 1.4%，95%CI-14.8 至 17.1>0.05）。相比之下，DEMRI 反转恢复高估了梗死面积（偏差 11.4%，95%CI-9.1 至 31.8=0.002），DEMRI T 映射也是如此（偏差 8.2%，95%CI-10.7 至 27.2=0.008）。在远程心肌中也观察到锰摄取增加，远程心肌 ∆T 与心肌梗死后左心室射血分数呈负相关（=-0.61，=0.022）。
MEMRI 导致浓度和钙通道依赖性心肌 T 缩短。带 T 映射的 MEMRI 可提供梗死面积的准确评估，还可识别远程心肌中钙处理的变化。该技术具有评估心肌存活、重塑和再生的潜力。
