Using MRI for studying cardiac function in rat models of radiation-therapy is important for better understanding of cardiotoxicity. In this study, we developed an optimized cardiac functional MRI protocol for rat imaging, and investigated the effects of changing imaging parameters on cardiac measurements. The results showed that blood-to-myocardium contrast-to-noise ratio in the cine images significantly affects ejection-fraction measurements, whereas reduced resolution has less effect on ejection-fraction. However, reduced resolution in the tagged images has significant effect on strain measurements, whereas tagline density has less effect, as long as sufficient resolution is maintained and more than one tagline intersects the myocardium.
Small-animal, e.g. rats, MR imaging is essential for better understanding of cardiac dysfunction development in different cardiovascular diseases, as specific animal models can be studied under controlled conditions and the imaging parameters can be compared to histology results. Specifically, cardiac MR imaging of rat models of cancer, for better understanding of chemotherapy or radiation-therapy (RT) cardiotoxicity, is challenging as the animals are quite sick with deteriorated cardiac function and inconsistent breathing pattern. Further, due to small anatomy in rats, image averaging is typically conducted to maintain adequate signal-to-noise ratio (SNR).
In this study, we developed an optimized MRI protocol for evaluating both global and regional cardiac function in RT rat models, and investigated the effects of different imaging parameters on image quality and cardiac measurements.
Adult female rats (n=6; both RT and control) were scanned on 9.4T Bruker Biospec MRI scanner with 30-cm bore diameter and equipped with 4-element surface coil. The RT rats received image-guided localized whole-heart RT to 24Gy using 3 equally-weighted fields. The MRI scan included both cine and tagging sequences. Both short-axis and long-axis images were acquired using fast low-angle shot (FLASH) pulse sequence with both cardiac and respiratory gating. Total scan time<1 hour.
The cine imaging parameters were as follows: TR=7ms, TE=2.1ms, flip angle=15⁰, matrix=176x176, FOV=40x40mm2, slice thickness=1mm, acquisition bandwidth=526Hz/pixel, #averages=2, #cardiac phases=20, and scan time/slice ~2:30 minutes. The effects of changing the following parameters on image quality and measured ejection-fraction (EF) were studied: #averages, imaging flip angle, imaging matrix, slice thickness, fat saturation, and TR.
The tagging imaging parameters were as follows: TR=7ms, TE=2.5ms, flip angle=15⁰, matrix=256x256, FOV=40x40 mm2, slice thickness=1mm, acquisition bandwidth=376Hz/pixel, #averages=3, #cardiac phases=20, and scan time/slice ~5 minutes. The effects of changing the following parameters on image quality and measured myocardial strain were studied: #averages, tagline width, and tag separation.
The cine images were processed by delineating the endocardial and epicardial contours, from which regional (in a certain slice) or global (whole heart) EF was measured. The tagged images were analyzed using the harmonic phase (HARP) technique to measure myocardial strain.
Optimal cine and tagging imaging parameters are listed in Table-1. Figure-1 shows an optimal cine image and the effects of changing SNR and blood-to-myocardium contrast-to-noise ratio (CNR) on the results. Reducing or increasing SNR by up-to 50% did not significantly affect image quality and the measured EF. Reducing #averages in half resulted in ≤5% change in EF, while increasing #averages from 2 to 3 resulted in ≤1% in EF. Increasing the flip angle resulted in improved blood-to-myocardium CNR at the cost of reduced SNR. Increasing the flip angle up-to 40⁰ resulted in ≤1% change in EF, while reducing the flip angle resulted in decreased CNR, and at 5⁰ flip angle, EF changed by >10%.
Figure-2 shows the effects of partial-volume averaging and image artifacts on image quality and FE. Reducing the imaging matrix in half (to 86x86) resulted in EF underestimation by 4-5%, while increasing the imaging matrix above 176x176 resulted in ≤1% change in EF. Increasing slice thickness resulted in partial-volume effect and EF underestimation by 3-4%. Adding fat saturation slightly affected image quality, but EF did not change. Increasing TR>10ms resulted in signal inhomogeneity artifacts and up-to 10% change in EF. Reducing FOV resulted in wrap-around artifacts that affected EF depending on the artifact severity.
Figure-3 shows an optimal tagging image, and the effects of changing SNR and resolution on strain measurements. Reducing #averages<3 resulted in 2-3% change in strain. Reducing image resolution in half (matrix=128x128) resulted in 7-10% change in strain, while further reduction in resolution resulted in unrealistic strain values. Figure-4 shows the effects of tagging profile on strain. Increasing tagline width to 50% of the tag separation resulted in ≤2% change in strain. Increasing the tagline density resulted in blurred tags and up-to 10% change in strain, whereas increasing tag separation resulted in significant change in measurements, such that unrealistic strain values were obtained when only one tagline intersected the myocardium.
Based on results from this study, blood-to-myocardium CNR and image artifacts in the cine images significantly affect EF measurements, whereas resolution has less effect on EF. On the other hand, reduced resolution in the tagged images has significant effect on strain measurements, whereas tagline density has less effect on strain, as long as sufficient image resolution is maintained and more than one tagline intersects the myocardium.
In conclusion, this study provides an optimized cardiac functional MRI protocol for imaging rats, which ensures accurate measurements while minimizing scan time to be tolerated by sick animals.
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