Quantification of doxorubicin-induced interstitial myocardial fibrosis in a beagle model using equilibrium contrast-enhanced computed tomography: A comparative study with cardiac magnetic resonance T1-mapping

Abstract

Background: The noninvasive equilibrium contrast-enhanced cardiac computed tomography(CCT) has potential for myocardial tissue characterization. The objective of this study was to test the feasibility of CCT-based extracellular volume (ECV) fraction in beagle models of doxorubicin-induced interstitial myocardial fibrosis, with cardiac magnetic resonance (CMR) as the reference. Methods: This study was approved by local ethics committee. Thirteen beagles were included with ECV quantified by CCT and CMR at baseline, 16 and 24 weeks after modeling. Spearman correlation analysis was used to determine the association between CT ECV, CMR ECV, collagen volume fraction (CVF), LVEF and serum fibrosis index (Hyaluronic acid [HA], Laminin [LN] and Type-III procollagen [PCIII]). Results: Median ECV values in CT and CMR at 16 and 24 weeks were significantly higher than those at baseline (CT ECV: 34.4% and 37.7% vs. 25.2%; CMR ECV: 32.2% and 37.4% vs. 22.7%; P < 0.001). A strong correlation was found between CCT and CMR for ECV (r = 0.899, P < 0.001). Both correlated well with CVF (r = 0.951 and 0.879 for CT and MR ECV vs. CVF, P < 0.001), serum fibrosis index (r = 0.830–0.907 for CT and MR ECV vs. HA, LN, PCIII, respectively, P < 0.05) and were inversely related to LVEF (r = −0.846 and −0.804 for CCT and CMR, P < 0.001). Bland-Altman analysis showed a small bias (1.5%), with 95% limits of agreement of −2.7% and 5.6%. Conclusions: CCT-derived ECV correlates well with CMR, histology and serum fibrosis index, suggesting that CCT is capable of myocardial tissue characterization.