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

19F-MRI 心肌梗死后单核细胞迁移的时间动态

• 批准号: 492563001
• 负责人: Professor Dr. Michael Bock
• 金额: --
• 依托单位: Klinik für Kardiologie und Angiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/492563001?language=en
• 关键词: Temporal; dynamics; monocyte; migration; after

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.

心肌梗死（MI）后，单核细胞炎症和修复反应的失衡导致心肌损伤加重和组织修复不佳，从而导致患者长期预后不良。目前，研究了调节单核细胞迁移和对MI的反应以限制缺血性损伤并促进愈合的新的治疗策略。因此，临床上迫切需要开发和验证MI后单核细胞迁移和反应的新的体内读数作为心脏结局的潜在预后标志物，或表征新的免疫调节化合物的功效。19 F-MRI已成功应用于小动物研究MI后骨髓细胞的摄取和迁移，但只有少数报告已被用于人类大小的模型，如猪。将19 F MRI转移到大型动物中对于方法验证和临床应用的开发至关重要。在本研究项目中，19 F-MRI将在猪模型中实现，集中于MI期间脾脏的MRI，以检测骨髓细胞的排出，并评估早期炎症反应。对于猪的成像研究，将开发新的RF线圈，以实现猪脾脏中的高灵敏度19 F/1H图像采集，并将实施MRI采集方法，以通过纳入1H图像信息来克服非质子MRI中的低信噪比。使用这些仪器，首先用MRI可视化脾中用19 F纳米颗粒标记的骨髓细胞。将在介入性MRI引导下结合脾脏19 F MRI诱导MI。然后在MI期间监测19 F标记的骨髓细胞从脾脏中的排出，并检测血管紧张素转化酶抑制的排出抑制。带有标记的骨髓细胞的19 F-MRI具有作为预后标记物的潜力，并使用PFC载体翻译成人类，PFC载体已经被批准用于人类应用。