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In This Article

  • Summary
  • Abstract
  • Introduction
  • Protocol
  • Results
  • Discussion
  • Disclosures
  • Acknowledgements
  • Materials
  • References
  • Reprints and Permissions

Summary

Here, we present an experimental imaging protocol for the quantification of cardiac function and morphology using high-resolution positron emission tomography/computed tomography for small animals. Both mice and rats are considered, discussing the different requirements of computed tomography contrast agents for the two species.

Abstract

Positron emission tomography (PET) and computed tomography (CT) are among the most employed diagnostic imaging techniques, and both serve in understanding cardiac function and metabolism. In preclinical research, dedicated scanners with high sensitivity and high spatio-temporal resolution are employed, designed to cope with the demanding technological requirements posed by the small heart size and very high heart rates of mice and rats. In this paper, a bimodal cardiac PET/CT imaging protocol for experimental mouse and/or rat models of cardiac diseases is described, from animal preparation and image acquisition and reconstruction to image processing and visualization.

In particular, the 18F-labeled fluorodeoxyglucose ([18F]FDG)-PET scan allows for the measurement and visualization of glucose metabolism in the different segments of the left ventricle (LV). Polar maps are convenient tools to display this information. The CT part consists of a time-resolved 3D reconstruction of the entire heart (4D-CT) using retrospective gating without electrocardiography (ECG) leads, allowing the morphofunctional evaluation of the LV and the subsequent quantification of the most important cardiac function parameters, such as ejection fraction (EF) and stroke volume (SV). Using an integrated PET/CT scanner, this protocol can be executed within the same anesthesia induction without the need to reposition the animal between different scanners. Hence, PET/CT can be seen as a comprehensive tool for the morphofunctional and metabolic evaluation of the heart in several small animal models of cardiac diseases.

Introduction

Small animal models are extremely important for the advancement of the understanding of cardiovascular diseases1,2. Non-invasive, diagnostic imaging tools have revolutionized the way we look at cardiac function in the last decades, both in clinical and preclinical settings. As far as small animal models of cardiac diseases are concerned, specific imaging tools have been developed with very high spatiotemporal resolution. Thus, such instruments can match the need for accurate quantification of the relevant metabolic and kinetic myocardial parameters on the very small and very fast-moving hearts of mice and rats....

Protocol

Animal experiments were performed in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the International Guidelines on Handling of Laboratory Animals, demanded by the European Directive (Directive 86/609/EEC of 1986 and Directive 2010/63/UE) and Italian laws (D.Lgs. 26/2014).

1. Setup of the PET/CT imaging protocols and workflow

NOTE: The protocol presented here is specifically designed for cardiac imaging of mouse models. Working with rats might imply some modifications to the actual protocol, mainly because of the bigger size of the animal (roughly 10x....

Results

In this section, typical results are shown for both PET and CT analysis following the procedures described so far. Figure 6 shows the results of the automatic myocardial and LV cavity segmentation of the [18F]FDG PET scan of a control (healthy) CD-1 mouse. Even though the right ventricle is not always visible in the reconstructed images, the orientation axes based on the DICOM header can be used to correctly discriminate the interventricular septum from the other LV walls, as requ.......

Discussion

The protocol presented in this paper focuses on a typical experimental procedure for translational cardiovascular research on small animal models of cardiac injury by using high-resolution PET/CT imaging. The presented results are indicative of the high quantitative and qualitative value of PET and Cine-CT images, providing both functional and structural information of the whole heart regarding its glucose metabolism, shape, and the dynamics of its contraction. Moreover, all the images obtained are 3D, time-resolved, and.......

Disclosures

Daniele Panetta received grants for the R&D of micro-CT instrumentation from Inviscan Sas.

Acknowledgements

This research was supported in part by the JPI-HDHL-INTIMIC "GUTMOM" Project: Maternal obesity and cognitive dysfunction in the offspring: Cause-effect role of the GUT MicrobiOMe and early dietary prevention (project no. INTIMIC-085, Italian Ministry of Education, University and Research Decree no. 946/2019).

....

Materials

NameCompanyCatalog NumberComments
0.9% sterile salineFresenius Kabi0.9% sodium chloride for injection
1025L Physiological MonitoringSmall Animal InstrumentsPhysiological monitoring system for small animal imaging
5 mL syringesArtsanaSyringes with needle for injection of PET tracer
Atomlab 500Else NuclearPET Dose calibrator
Atrium softwareInviscanVersion 1.5.5PET/CT operating software
Butterfly cathetersDelta Med27.5 G needle
Carimas softwareTurku PET CenterVersion 2.10Image analysis software
Fenestra VCMedilumineLipid emulsion iodinated contrast agent for small animals
Heat lampHeat lamp with clamp and switch
Insulin syringesArtsanaSyringes with needle for injection of CT CA
Iomeron 400 mgI/mLBraccoIomeprol, vascular contrast agent
IRIS PET/CTInviscanPET/CT scanner for small animals
IsofluraneZoetisInhalation anesthetic, 250 mL
OneTouch GlucometerJohnson&Johnson MedicalGlucose meter kit
Osirix MD softwarePixmeoVersion 11Image analysis software
OxygenAir liquideCompressed gas
Rectal probe for 1025LSmall Animal InstrumentsRectal probe with cable for SAII 1025L systems
Respiratory sensor for 1025LSmall Animal InstrumentsRespiratory pillow with tubings for SAII 1025L systems
TJ-3A syringe pumpLongerMotorized syringe pump for CT CA injection

References

  1. Zaragoza, C. Animal models of cardiovascular diseases. Journal of Biomedicine and Biotechnology. 2011, 497841 (2011).
  2. Russell, J. C., Proctor, S. D. Small animal models of car....

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