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Development and feasibility of quantitative dynamic cardiac imaging for mice using μSPECT

  • ORIGINAL ARTICLE
  • Published:
Journal of Nuclear Cardiology Aims and scope

Abstract

Background

Despite growing interest in coronary microvascular disease (CMVD), there is a dearth of mechanistic understanding. Mouse models offer opportunities to understand molecular processes in CMVD. We have sought to develop quantitative mouse imaging to assess coronary microvascular function.

Methods

We used 99mTc-sestamibi to measure myocardial blood flow in mice with MILabs U-SPECT+ system. We determined recovery and crosstalk coefficients, the influx rate constant from blood to myocardium (K1), and, using microsphere perfusion, constraints on the extraction fraction curve. We used 99mTc and stannous pyrophosphate for red blood cell imaging to measure intramyocardial blood volume (IMBV) as an alternate measure of microvascular function.

Results

The recovery coefficients for myocardial tissue (RT) and left ventricular arterial blood (RA) were 0.81 ± 0.16 and 1.07 ± 0.12, respectively. The assumption RT = 1 − FBV (fraction blood volume) does not hold in mice. Using a complete mixing matrix to fit a one-compartment model, we measured K1 of 0.57 ± 0.08 min−1. Constraints on the extraction fraction curve for 99mTc-sestamibi in mice for best-fit Renkin–Crone parameters were α = 0.99 and β = 0.39. Additionally, we found that wild-type mice increase their IMBV by 22.9 ± 3.3% under hyperemic conditions.

Conclusions

We have developed a framework for measuring K1 and change in IMBV in mice, demonstrating non-invasive µSPECT-based quantitative imaging of mouse microvascular function.

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Abbreviations

CMVD:

Coronary microvascular disease

FOV:

Field of view

FBV:

Fractional blood volume

IMBV:

Intramyocardial blood volume

LV:

Left ventricle

MBF:

Myocardial blood flow

ROI:

Region of interest

SPECT:

Single-photon emission-computed tomography

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Acknowledgments

We would like to acknowledge the Penn Cardiovascular Institute Mouse Physiology core for microsphere experiments. Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR001878 and Institute for Translational Medicine and Therapeutics’ Transdisciplinary Program in Translational Medicine and Therapeutics. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. MG was supported by K08HL136890. LCJ was supported by T32HL007954.

Disclosure

M. A. Guerraty, L. C. Johnson, E. Blankemeyer, D. J. Rader, S. C. Moore, and S. D. Metzler report no relevant disclosures.

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Authors and Affiliations

  1. Division of Cardiovascular Medicine, Department of Medicine, University of Pennsylvania, 11-145 South Perelman Tower, 3400 Civic Center Blvd, Philadelphia, PA, 19104, USA

    M. A. Guerraty MD, PhD

  2. Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA

    L. C. Johnson PhD, E. Blankemeyer BS, S. C. Moore PhD & S. D. Metzler PhD

  3. Division of Human Genetics and Translational Medicine, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    D. J. Rader MD

  4. Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA

    D. J. Rader MD

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  1. M. A. Guerraty MD, PhD
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  3. E. Blankemeyer BS
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  4. D. J. Rader MD
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  6. S. D. Metzler PhD
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Correspondence to M. A. Guerraty MD, PhD.

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Guerraty, M.A., Johnson, L.C., Blankemeyer, E. et al. Development and feasibility of quantitative dynamic cardiac imaging for mice using μSPECT. J. Nucl. Cardiol. 28, 2647–2656 (2021). https://doi.org/10.1007/s12350-020-02082-8

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