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Abstract
Purpose
Children born with single ventricle physiology demonstrate poor growth rate and suffer from malnutrition, which lead to increased morbidity and mortality in this population. We assume that an anabolic steroid, oxandrolone, will promote growth in these infants by improving myocardial energy utilization. The purpose of this paper is to study the efficacy of oxandrolone on myocardial energy consumption in these infants.
Materials and Methods
We modeled single ventricle physiology in a lamb by prenatally shunting the aorta to the pulmonary artery and then postnatally, we monitored cardiac energy utilization by quantitatively measuring the first order reaction rate constant, kf of the creatine-kinase reaction in the heart using magnetization transfer 31P magnetic resonance spectroscopy, home built 1H/31P transmit/receive double tuned coil, and transmit/receive switch. We also performed cine MRI to study the structure and dynamic function of the myocardium and the left ventricular chamber. The spectroscopy data were processed using home-developed python software, while cine data were analyzed using Argus software.
Results
We quantitatively measured both the first order reaction rate constant and ejection fraction in the control, shunted, and the oxandrolone-treated lambs. Both kf and ejection fraction were found to be more significantly reduced in the shunted lambs compared to the control lambs, and they are increased in oxandrolone-treated lambs.
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Fig. 3.
(a) Circuit diagram and (b) photograph of 1H/31P dual tuned RF coils. The 31P loop consisted of a butterfly loop and an inner rectangular loop decoupled geometrically for a quadrature mode. The outer rectangular loop was 1H RF coil whose surface area was made large to minimize the coupling with 31P rectangular loop, and positioned such that it was in quadrature mode with 31P butterfly loop.
Fig. 4.
(a) A scout image with 1D CSI grid with green rectangle as a shim region. Saturation bands were used on the chest wall to avoid the contamination on the 31P signal of heart from the chest wall. (b-e) in-vivo stacked plots of 31P MR spectra o of control (triplet), shunted (twin), and ox-treated control (twin) lamb. Blue, green and red spectra indicate M PCr (equilibrium), TR ss MPCr (saturation pulse for 3.5 second and pre-saturation time of 2.5 second), and M PCr (saturation pulse for two seconds), respectively. The arrows indicate the positions where saturation pulse is applied. (f) 31P spectra with (green) and without (blue) RF bleed-over effect. There is a decrease in PCr peak due to RF bleed-over effect.
Fig. 5.
Representative short axis images of shunted lamb with (a) diastolic and (b) systolic contours (red) drawn using Argus software.
Table 1.
The 1D MT-CSI Protocol for the Lambs’ Hearts
| ΔfMT (ppm) | TR (s) | NMzSat | tpreSat (s) | tMT (s) | |
|---|---|---|---|---|---|
| PCr Mo | 0 | 20 | 0 | 0 | 0 |
| ss MPCr | –2.7 | minimum | 0 | 2.5 | 3.5 |
| Tsat MPCr | –2.7 | minimum | 2 | 0 | 2 |
Table 2.
kf, Signal to Noise Ratio (SNR) of M Ejection Fraction (EF) of Different Groups of Lambs PCr o, End Diastolic Volume (EDV), End Systolic Volume (ESV), Systolic Volume (SV), and
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