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 ....

Protocol

All components of this study were carried out in accordance with the UK Animals (Scientific Procedures) Act, 1986, and with the approval of the University of Cambridge Ethical Review Panel.

1. Animal Preparation

1. Induce infarcts with a surgical intervention^7,8. For measuring at the acute stage, perform imaging 24 hr after intervention.
2. Prepare a thin syringe tubing for drug delivery with a 25 G needle at one extremity and a syringe with a 25 G needle at the other end. The length of the line should be enough to allow the injection from outside the magnet’s bore (approximately 1.5 m).
3. Prepa....

Results

One of the advantages of using MRI is that a longitudinal design can be used in order to stage disease. This is especially important when evaluating novel compounds, as the time course of effect may not be known. Variations in heart volumes due to the disease progression in the same animal are shown in Figure 4. The figure clearly shows the effects of remodeling post myocardial infarction.

Correct slice geometry is crucial for the success of a cardiac MRI experiment. Represent.......

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.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Gadovist	Bayer Schering Pharma	PL 00010/0535
FDG	IBA Molecular
Equipment
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