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Monitoring of Cardiac Remodeling in a Mouse Model of Pressure-Overload Left Ventricular Hypertrophy with [18F]FDG MicroPET

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Abstract

Purpose

This study aims to analyze the left ventricular function parameters, scar load, and hypertrophy in a mouse model of pressure-overload left ventricular (LV) hypertrophy over the course of 8 weeks using 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) micro-positron emission tomography (microPET) imaging.

Procedures

LV hypertrophy was induced in C57BL/6 mice by transverse aortic constriction (TAC). Myocardial hypertrophy developed after 2–4 weeks. ECG-gated microPET scans with [18F]FDG were performed 4 and 8 weeks after surgery. The extent of fibrosis was measured by histopathologic analysis. LV function parameters and scar load were calculated using QGS®/QPS®. LV metabolic volume (LVMV) and percentage injected dose per gram were estimated by threshold-based analysis.

Results

The fibrotic tissue volume increased significantly from 4 to 8 weeks after TAC (​1.67 vs. 3.91  mm3; P = 0.044). There was a significant increase of the EDV (4 weeks: 54 ± 15 μl, 8 weeks: 79 ± 32 μl, P < 0.01) and LVMV (4 weeks: 222 ± 24 μl, 8 weeks: 276 ± 52 μl, P < 0.01) as well as a significant decrease of the LVEF (4 weeks: 56 ± 17 %, 8 weeks: 44 ± 20 %, P < 0.01). The increase of LVMV had a high predictive value regarding the amount of ex vivo measured fibrotic tissue (R = 0.905, P < 0.001). The myocardial metabolic defects increased within 4 weeks (P = 0.055) but only moderately correlated with the fibrosis volume (R = 0.502, P = 0.021). The increase in end-diastolic volume showed a positive correlation with the fibrosis at 8 weeks (R = 0.763, P = 0.017).

Conclusions

[18F]FDG-PET is applicable for serial in vivo monitoring of the TAC mouse model. Myocardial hypertrophy, the dilation of the left ventricle, and the decrease in LVEF could be reliably quantified over time, as well as the developing localized scar. The increase in volume over time is predictive of a high fibrosis load.

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Acknowledgements

A part of this work originated from the doctoral thesis of Nick L. Beetz.

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Author notes

  1. Stefan Brunner and Sebastian Lehner contributed equally.

Authors and Affiliations

  1. Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany

    Andrei Todica, Lisa Günther, Mathias J. Zacherl, Peter Bartenstein & Sebastian Lehner

  2. Medical Department I-Cardiology, University Hospital, LMU Munich, Munich, Germany

    Nick L. Beetz, Ulrich Grabmaier, Bruno Huber & Stefan Brunner

  3. Ambulatory Healthcare Center Dr. Neumaier & Colleagues, Radiology, Nuclear Medicine, Radiation Therapy, Regensburg, Germany

    Sebastian Lehner

Authors
  1. Andrei Todica
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  2. Nick L. Beetz
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  3. Lisa Günther
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  8. Stefan Brunner
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Correspondence to Andrei Todica.

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Todica, A., Beetz, N.L., Günther, L. et al. Monitoring of Cardiac Remodeling in a Mouse Model of Pressure-Overload Left Ventricular Hypertrophy with [18F]FDG MicroPET. Mol Imaging Biol 20, 268–274 (2018). https://doi.org/10.1007/s11307-017-1114-6

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  • DOI: https://doi.org/10.1007/s11307-017-1114-6

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