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Comparison of canine ECV measurements derived from CMR: bolus injection vs. slow infusion of Gd-BOPTA

Background

Myocardial extracellular volume (ECV) fraction [1], derived from pre- and post-contrast cardiac T1 measurements, is an emerging biomarker of diffuse cardiac fibrosis. The major benefits of ECV over post-contrast cardiac T1 is that the former is less sensitive to confounders such as contrast agent type and dosage, specific delayed imaging time, renal function, and magnetic field strength. Recent studies using inversion-recovery (IR) based T1 mapping in control human subjects[2] and patients[3] reported that ECV measured with a bolus injection of contrast agent agrees well with ECV measured with a slow infusion of contrast agent. It is unknown if this approximation holds in canines which are frequently used in preclinical research. We sought to compare canine ECV measurements derived from bolus and slow infusion protocols.

Methods

Eighteen mongrel dogs with normal myocardium were imaged at 3T (Verio, Siemens). Cardiac T1 maps were acquired in 3 short-axis planes (base, mid, and apex) using the arrhythmia-insensitive-rapid (AIR) cardiac T1 mapping pulse sequence based on B1-insensitive saturation-recovery of magnetization preparation [4], with the following imaging parameters: spatial resolution = 1.4 × 1.4 × 7.0 mm, temporal resolution = 217 ms, saturation-recovery time = 600 ms. The AIR acquisition was performed with "paired" consecutive phase-encoding steps in centric k-space ordering to minimize image artifacts due to eddy currents. Cardiac T1 maps were acquired pre-contrast, 15 min after a bolus injection of Gd-BOPTA (MultiHance; 0.15 mmol/kg), and 30 min after slow infusion of Gd-BOPTA (0.002 mmol/kg/min). Blood samples were drawn during MRI for hematocrit calculation. For image analysis, myocardium and blood pool were manually segmented, and myocardial and blood T1 were calculated. Subsequently, ECV was calculated as ECV=(1-hematocrit)x(ΔR1, myocardium/ΔR1, blood), where R1 is T1-1, and Δ is the difference between post- and pre-contrast. Linear regression and Bland-Altman analyses were performed to compare the results, and magnitude of effect size of the observed difference was calculated using Cohen's d from t-tests.

Results

As shown in Figure 1, ECV measurements derived from the two different injection protocols were strongly correlated (Pearson's R = 0.93, p < 0.001) and in fair agreement (mean difference = 0.011, upper and lower 95% limits = 0.027 and -0.0045), which corresponds to a medium effect size in difference (d = 0.55).

Figure 1
figure1

(left) Linear regression and (right) Bland-Altman analyses comparing ECV measurements between bolus and slow infusion protocols.

Conclusions

This study suggests that the contrast agent kinetics between canines and humans are slightly different and that in canines 15 min after a bolus injection may not be dynamic equilibrium.

Funding

Ben B. and Iris M. Margolis Foundation.

References

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Correspondence to Kyungpyo Hong.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Hong, K., Kholmovski, E.G., McGann, C.J. et al. Comparison of canine ECV measurements derived from CMR: bolus injection vs. slow infusion of Gd-BOPTA. J Cardiovasc Magn Reson 16, P64 (2014). https://doi.org/10.1186/1532-429X-16-S1-P64

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Keywords

  • Contrast Agent
  • Bolus Injection
  • Slow Infusion
  • Agent Kinetic
  • Follow Imaging Parameter