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PET, SPECT, CT, and MRI in Mouse Cardiac Phenotyping: An Overview

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  • Abstract
  • Table of Contents
  • Figures
  • Literature Cited

Abstract

 

This overview first summarizes the last decade of continuous developments and improvements in pre?clinical imaging methods that are now essential tools for in vivo evaluation of cardiac morphology and function in living mice, involving nuclear emission of labeled molecules (micro?PET and micro?SPECT) and electromagnetic wave interactions with biological tissues (micro?CT and micro?MRI). In the following, and for better understanding, the basic physical principles and specific technical innovations of the aforementioned imaging methods are reviewed. Specificity, sensitivity, and spatial and temporal resolutions, together with the corresponding advantages and weaknesses of each method are then discussed, and cardiac image?acquisition protocols and illustrative examples are given for each modality. Emerging hybrid cardiac imaging is also presented and illustrated. Then, recent biological insights provided by mouse cardiac imaging are presented. Finally, imaging strategies in mouse cardiac phenotyping involving the aforementioned methods, adding metabolic and molecular information to morphological data, are emphasized and discussed. Curr. Protoc. Mouse Biol. 2:129?144 © 2012 by John Wiley & Sons, Inc.

Keywords: pre?clinical imaging; phenotyping; mouse models; cardiology; PET; SPECT; CT; MRI

     
 
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Table of Contents

  • 1: Introduction: A Short Historical Perspective on In Vivo Microimaging of Mouse Cardiac Morphology and Function Using PET, SPECT, CT, and MRI
  • 2: Pre‐Clinical Imaging Background Physics and Examples of Mouse Cardiac Imaging Protocols and Results
  • 3: Cardiac Hybrid Imaging in the Mouse
  • 4: New Biological Insights Provided by Mouse Cardiac Imaging
  • Conclusion
  • Literature Cited
  • Figures
     
 
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Materials

 
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Figures

  •   Figure 1. Example of gated‐imaging PET protocol. (A ) Time‐activity curves (mean ± SEM) illustrating the lower glucose uptake of the myocardium of a high‐fat‐diet mouse group compared to the standard chow control group (SEM has been determined according to the mouse population). (B ) Micro‐PET imaging device (yap‐PET, ISE srl, Migliarino Pisano, Pisa Italy) showing the opposite detectors and an anesthetized mouse inside the imaging cell. (C ) Set of contiguous micro‐PET ungated axial slices of the mouse thorax showing, clearly and at one time point, the [18 F]FDG uptake by the mouse myocardium (arrow).
    View Image
  •   Figure 2. Example of gated‐imaging SPECT protocol. (A ) 16 time bins of a mid‐ventricular short axis slice, extracted from the micro‐SPECT 3D set of healthy mouse cardiac perfusion images using the eXplore speCZT Vision 120 imaging device, showing end diastole (images 1 and 16) and end systole (image 8) of left and right ventricular wall perfusion. (B ) left ventricular volume curve and corresponding ejection fraction (EF) value based on the formula EF = (EDV‐ESV)/EDV.
    View Image
  •   Figure 3. General view of (A ), the dedicated small animal MRI at 1.5 T (OPTImouse 1.5; http://www.rs2d.com), and (B ) the micro‐SPECT/CT (eXplore speCZT Vision 120) in our lab. The two imaging devices are in close proximity, without any interference between them, allowing easily sequential multimodality acquisition procedures like SPECT/MRI by simply translating the air‐warmed and nonmagnetic imaging cell with the anesthetized mouse from one system to the other.
    View Image
  •   Figure 4. Example of gated imaging CT protocol. (A ) End diastole and (B ) end systole left and right mid ventricular micro‐CT (eXplore speCZT Vision 120) images of myocardium in healthy mouse in three orthogonal planes extracted from the isotropic 3D set of acquired images, showing several anatomic details. (C ) Left ventricular volume curve and corresponding ejection fraction (EF) value based on the formula (EF = [EDV‐ESV]/EDV).
    View Image
  •   Figure 5. Example of MRI imaging protocol. Ungated T1‐weighted contiguous axial slices (1 mm thickness, in plane pixel size of 250 × 250 µm2 ) through the thorax of a healthy mouse acquired with a small‐animal dedicated MRI device (OPTImouse 1.5; http://www.rs2d.com) showing the ventricular anatomy clearly.
    View Image
  •   Figure 6. Example of hybrid SPECT/MRI cardiac imaging. Micro‐SPECT/MRI image fusion showing healthy mouse whole‐body contiguous coronal slices. [99m Tc]sestamibi SPECT tissue perfusion (heart) and tracer metabolic elimination routes (liver, gall bladder and digestive tract, kidneys) are represented in color superimposed on the MRI T1‐weighted mouse anatomy in gray. Left ventricle wall perfusion and gall bladder are easily visible. Both sets of isotropic 3D images were acquired sequentially with the micro‐SPECT (eXplore speCZT Vision 120) and the 1.5 T micro‐MRI (OPTImouse 1.5; http://www.rs2d.com). Total acquisition time of both sets of images including the transfer of the animal in the imaging cell was 40 min.
    View Image

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