Temporal dynamics of monocyte migration after myocardial infarction with 19F-MRI

心肌梗死（MI）后，单核细胞的炎症和修复反应失衡，导致心肌损伤加重，组织修复不佳，导致患者长期预后恶化。目前，研究人员正在研究新的治疗策略，通过调节单核细胞的迁移和对心肌梗死的反应来限制缺血性损伤并促进愈合。因此，临床迫切需要开发和验证心肌梗死后单核细胞迁移和反应的新的体内读数，作为心脏预后的潜在预后标志物，或表征新的免疫调节化合物的功效。19F-MRI已经成功地应用于小动物研究心肌梗死后骨髓细胞的摄取和迁移，但在猪等人体大小的模型中使用19F-MRI的报道很少。将19F MRI转移到大型动物身上对于方法验证和临床应用的发展至关重要。在本研究项目中，将在猪模型中实现19F-MRI，集中于心肌梗死期间的脾脏MRI，以检测骨髓细胞的分泌，并评估早期炎症反应。对于猪的成像研究，将开发新的射频线圈，在猪的脾脏中实现高灵敏度的19F/1H图像采集，并实施MRI采集方法，通过结合1H图像信息来克服非质子MRI的低信噪比。使用这些仪器，首先在MRI上显示脾脏中被19F纳米颗粒标记的骨髓细胞。在介入MRI引导下结合脾19F MRI诱导心肌梗死。在心肌梗死期间，将监测19F标记的骨髓细胞从脾脏的分泌情况，并检测血管紧张素转换酶抑制的分泌情况。19F-MRI标记髓细胞具有预后标记和PFC载体转化为人类的潜力，PFC载体已被批准用于人类应用。

After myocardial infarction (MI), the imbalance of the monocytes’ inflammatory and reparative response leads to aggravated myocardial damage and suboptimal tissue repair which results in worse long-term patient outcomes. Currently, novel therapeutic strategies are investigated that modulate monocyte migration and response to MI to limit ischemic damage and promote healing. Thus, there is an urgent clinical need to develop and validate new in vivo readouts of monocyte migration and response after MI as a potential prognostic marker of cardiac outcomes, or to characterize the efficacy of new immune-modulating compounds. 19F-MRI has successfully been applied in small animals to study myeloid cell uptake and migration after MI, but only few reports are published where 19F-MRI has been used in human-size models such as pigs. The transfer of 19F MRI into large animals is crucial for both the method validation and the development of clinical applications. In this research project 19F-MRI will be realized in a pig model concentrating on MRI of the spleen during MI to detect myeloid cell egress, and assess early inflammatory responses. For the imaging studies in pigs new RF coils will be developed that enable highly sensitive 19F/1H image acquisitions in the spleen of a pig, and MRI acquisition methods will be implemented to overcome the low signal-to-noise ratio in non-proton MRI by incorporating 1H image information. With these instruments, at first myeloid cells in the spleen that are labeled with 19F nano¬particles will be visualized with MRI. MI will be induced under interventional MRI guidance in combination with 19F MRI of the spleen. The egress of 19F labeled myeloid cells from the spleen will then be monitored during MI, and egress inhibition by Angiotensin-converting enzyme inhibition will be tested. 19F-MRI with labeled myeloid cells has the potential of a prognostic marker and translation into humans using PFC carriers, which are already approved for human application.