MRI和PET心肌梗死小鼠模型
Summary
We describe how to perform MRI and PET imaging of the mouse heart. The protocol is tailored to assess treatment efficacy in models of myocardial infarction and heart failure.
Abstract
心肌梗死是导致死亡的，在西方世界的主要原因之一。小鼠心脏对人的心脏的相似性使得它用于测试新的治疗策略的理想模型。
体内磁共振成像（MRI）给出了心脏的美景无创性有明确的解剖细节，可用于精确功能评估。造影剂可提供组织活力的基本措施，但这些都是非特异性的。正电子发射断层扫描（PET）是一种补充技术，它是高度特异性的分子成像，但缺乏MRI的解剖细节。一起使用，这些技术提供了一个敏感，特异和定量工具，用于疾病和恢复心脏的治疗后的评估。
在本文中我们将介绍这些方法是如何在急性心肌梗死小鼠模型进行的。该程序描述ħERE被设计为假定的保护药物治疗的评估。我们使用磁共振成像测量收缩功能和心肌梗死面积与后期钆增强和PET与氟脱氧葡萄糖（FDG），以评估在梗死区的代谢功能。本文侧重于实用方面，如切片规划，准确的门，药物释放，图像分割，和多式联运配准。这里介绍的方法，可以实现良好的重复性和精度保持较高的吞吐量。
Introduction
In order to measure the efficacy of new treatment strategies for myocardial infarction (MI) in preclinical studies, the assessment of the acute stage as well as long-term outcome is required1. Methods such as histopathology, intracardiac catheters2, and ex vivo heart models3 are commonly used for preclinical studies in mice. It is impossible, however, to follow up treatment with ex vivo or highly invasive methods. Noninvasive measurement techniques as in vivo magnetic resonance imaging (MRI) and positron emission tomography (PET) allow longitudinal experimental designs for disease staging in single subjects. Cine-MRI is used to derive global functional parameters such as left ventricular mass (LVM), ejection fraction (EF) and cardiac output (CO). In addition, after the injection of a gadolinium contrast agent, due to impaired perfusion and washout in the infarction, tissue viability can be assessed with late gadolinium enhancement (LGE) MRI. Complementarily, PET offers a sensitive measure of radiolabeled molecules in order to assess tissue metabolism. The high accuracy of these techniques permits significant reductions in the number of animals required for testing new drugs targeting MI.
The PET and MRI procedures are involved, and without a carefully designed protocol reproducibility is hard to maintain. Procedures established in the clinic for patients require substantial modification for use in mice, due to their considerably faster heart rate and smaller dimensions of the heart4. There is wide variation between individual subjects, both at baseline and in response to induced injury, so a considerable number of mice are needed to establish treatment efficacy.
In this report, we describe our method for sequential PET/MRI imaging of the mouse heart. Both modalities use intravenous contrast agents, which are delivered through the tail vein. MRI consists of standard assessment with Cine-MRI5 with an optimal protocol for LGE as described in our previous work6. The entire MRI procedure lasts 30 min. We have obtained consistent fittings for the beds of our instruments so it is possible to transfer the animal on a platform with the same monitoring and anesthetic delivery apparatus between the machines. The PET scan lasts 45 min with in situ injection once the scan is started. The final step is to measure the parameters from both MRI and PET images following coregistration.
Protocol
Representative Results
Discussion
PET/MRI is a comprehensive measurement method for the noninvasive and longitudinal evaluation of systolic function, tissue viability and specific metabolic markers in mouse models of myocardial infarction. Here we have described a protocol for performing MRI and PET sequentially, where coregistration is simplified by the transfer of the same bed between systems. This strategy, also adopted by manufacturers of clinical systems11, does not require a combined PET/MRI scanner and can be performed with standard equ…
Divulgations
The authors have nothing to disclose.
Acknowledgements
We are grateful for funding from the British Heart Foundation to TK and to the UK Medical Research Council for a postgraduate research studentship to GB.
Materials
| Material name | Company | Catalogue number | Comments |
| Gadovist | Bayer Schering Pharma | PL 00010/0535 | |
| FDG | IBA Molecular | ||
| Equipment | |||
| Material name | Company | Catalog number | Comments |
| Bruker BioSpec 47/40 | Bruker | ||
| Bruker mouse bed | Bruker | This bed includes tubing for anesthesia delivery and scavenging. | |
| 12 cm diameter birdcage transmitter | Bruker | T5346 | |
| 2 cm diameter surface coil receiver | Bruker | T7027 | |
| Red Dot Neonatal monitoring electrodes | 3M | P/N: 2330 | |
| Monitoring equipment | SA Systems | The monitoring kit includes respiratory pillow and rectal probe for temperature measurements. | |
| Anesthesia equipment | General Anesthetic Services | ||
| Induction box | Vet Tech Solutions LTD | ||
| Cambridge split-magnet PET/MRI scanner | University of Cambridge | A custom built PET/MRI scanner22 was used to perform the PET, its PET performance similar to an F120 micropet scanner23 | |
| Segment software | Medviso, Lund University | Freely available | |
| SPM-mouse | University of Cambridge | Freely available |
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