MRI and PET in Mouse Models of Myocardial Infarction
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
Myocardial infarction is one of the leading causes of death in the Western world. The similarity of the mouse heart to the human heart has made it an ideal model for testing novel therapeutic strategies.
In vivo magnetic resonance imaging (MRI) gives excellent views of the heart noninvasively with clear anatomical detail, which can be used for accurate functional assessment. Contrast agents can provide basic measures of tissue viability but these are nonspecific. Positron emission tomography (PET) is a complementary technique that is highly specific for molecular imaging, but lacks the anatomical detail of MRI. Used together, these techniques offer a sensitive, specific and quantitative tool for the assessment of the heart in disease and recovery following treatment.
In this paper we explain how these methods are carried out in mouse models of acute myocardial infarction. The procedures described here were designed for the assessment of putative protective drug treatments. We used MRI to measure systolic function and infarct size with late gadolinium enhancement, and PET with fluorodeoxyglucose (FDG) to assess metabolic function in the infarcted region. The paper focuses on practical aspects such as slice planning, accurate gating, drug delivery, segmentation of images, and multimodal coregistration. The methods presented here achieve good repeatability and accuracy maintaining a high throughput.
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…
Divulgaciones
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 |
Referencias
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