Background
Diffusion-Tensor cardiovascular magnetic resonance (DT-CMR) is capable of mapping myocardial fiber orientation [1,2]. It has been demonstrated in myocardial infarction (MI) murine models that DT-CMR can identify the effects of stem cell therapy on myocardial fiber orientation [3]. However, it remains to be seen if this recent work is translatable to large animal and clinical studies. We propose the application of a well-established in vivo cardiac DT-CMR technique [4] to characterize myocardial fiber orientation before and after the novel regenerative therapy of using intramyocardial injection of exosomes from cardiosphere-derived cells (CDCs) in a MI porcine model.
Methods
MI was induced in 7 Yucatan mini pigs by balloon occlusion of the mid-LAD for 2.5 hours. The MI was allowed to heal for 4 weeks for all pigs defining baseline. Group 1 (N = 4) were treated with exosome proteins derived from CDCs. Group 2 was given a placebo.
CMR was performed at baseline and 4 weeks after treatment on a 3T Siemens Verio with the following: whole-heart 2D multi-slice (WH) morphological CMR, WH function CINE CMR, 3 short axis slice DT-CMR (STEAM, 6 dir, b = 350 s/mm2, 8 avg, 2 avg/BH), and WH viability CMR (LGE PSIR, TI = 315 ms). Viability and function CMR yielded scar size (SS) and ejection fraction (EF) [5], respectively. For in vivo DT-CMR, mean diffusivity (MD), fractional anisotropy (FA), and helix angle (HA) maps were calculated. HA transmurality slope (HATS) was calculated by radially sampling the transmural HA along 36 chords and fitting the slope of a linear regression between HA and transmural depth.
Wilcoxon signed-rank test was performed to evaluate the difference between mean slice values (G1 N = 12, G2 N = 9) before and after treatment (p < 0.017 significance). Change (Δ) in MD, FA, and HATS were correlated (R^2) with ΔSS and ΔEF.
Results
For Group 1 (treated), EF, MD, FA, and HATS did not significantly change (Δ: -1 ± 2%, -0.1 ± 0.2 um2/ms, 0.01 ± 0.03, and 0.05 ± 0.15°/%depth, respectively), while SS was significantly reduced (Δ: -3 ± 2%, p < 0.01). In contrast, Group 2 (placebo) exhibited significant (p < 0.01) adverse changes with decreased EF (Δ: -4 ± 2%), increased SS (Δ: 3 ± 1%), decreased FA (Δ: -0.03 ± 0.02), and less helical HATS (-1.2 ± 0.1 vs -0.9 ± 0.2°/%depth). ΔMD and ΔFA weakly correlated with ΔEF (R^2: 0.02 and 0.27, respectively) and ΔSS (R^2: 0.03 and 0.08, respectively). However, ΔHATS significantly (p < 0.01) correlated highly with ΔEF (R^2: 0.85) and ΔSS (R^2: 0.67).
Conclusions
In a MI porcine model, in vivo DT-CMR revealed that myocardial fiber orientation was preserved with CDC-derived exosome treatment and adversely changed with placebo treatment consistent with observed viability and function changes. Furthermore, changes in helix transmurality highly correlated with changes in viability and function.
References
Reese : MRM. 1995
Sosnovik : JCMR. 2009
Sosnovik : Circ. 2014
Tunnicliffe : JCMR. 2014
Malliaras : Circ. 2013
Author information
Authors and Affiliations
Rights and permissions
This article is published under an open access license. Please check the 'Copyright Information' section either on this page or in the PDF for details of this license and what re-use is permitted. If your intended use exceeds what is permitted by the license or if you are unable to locate the licence and re-use information, please contact the Rights and Permissions team.
About this article
Cite this article
Nguyen, C.T., Dawkins, J., Tunnicliffe, E.M. et al. Characterization of myocardial fiber orientation to assess therapeutic exosomes from cardiosphere-derived cells (CDCs) in myocardial infarcted porcine with in vivo diffusion-tensor CMR on a clinical scanner. J Cardiovasc Magn Reson 18 (Suppl 1), Q62 (2016). https://doi.org/10.1186/1532-429X-18-S1-Q62
Published:
DOI: https://doi.org/10.1186/1532-429X-18-S1-Q62